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Sample records for p57

  1. Antigenic and functional characterization of p57 produced by Renibacterium salmoninarum

    Science.gov (United States)

    Weins, G.; Chien, M.S.; Winton, J.R.; Kaatari, S.L.

    1999-01-01

    Renibacterium salmoninarum, the causative agent of bacterial kidney disease, produces large quantities of a 57-58 kDa protein (p57) during growth in broth culture and during infection of salmonid fish. Biological activities of secreted p57 include agglutination of salrnonid leucocytes and rabbit erythrocytes. We define the location of epitopes on p57 recognized by agglutination-blocking monoclonal antibodies (MAbs) 4Cl1, 4H8 and 4D3, and demonstrate that the majority of secreted p57 is a nlonomer that retains salrnonid leucocyte agglutinat~ng activity. The 3 MAbs bound a recombinant, amino-terminal fragment of p57 (211 aa) but not a carboxy-terminal fragment (315 aa) demonstrating that the neutralizing epitopes are located within the amino-terminal portion of p57. When combinations of the MAbs were used in an antigen capture ELISA. the epitopes recognized by the 3 MAbs were shown to be sterically separate. However, when the same MAb was used as both the coating and detection MAb, binding of the biotinylated detection MAb was not observed. These data indicate that the epitopes recognized by the 3 agglutination-blocking antibodies are functionally available only once per molecule and that native p57 exists as a monomer Similar ELISA results were obtained when kidney tissues from 3 naturally infected chinook salmon were assayed. Finally, a p57 monomer was purified using anion exchange and size exclusion chromatography that retained in vitro agglutinating activity. A model in which p57 is released from R. salmoninarum as a biologically active monomer during infection of salmonid fish is proposed.

  2. Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57 immunohistochemistry and molecular genotyping) improve morphologic diagnosis.

    Science.gov (United States)

    Vang, Russell; Gupta, Mamta; Wu, Lee-Shu-Fune; Yemelyanova, Anna V; Kurman, Robert J; Murphy, Kathleen M; Descipio, Cheryl; Ronnett, Brigitte M

    2012-03-01

    Distinction of hydatidiform moles (HMs) from nonmolar specimens (NMs) and subclassification of HMs as complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are important for clinical practice and investigational studies; yet, diagnosis based solely on morphology is affected by interobserver variability. Molecular genotyping can distinguish these entities by discerning androgenetic diploidy, diandric triploidy, and biparental diploidy to diagnose CHMs, PHMs, and NMs, respectively. Eighty genotyped cases (27 CHMs, 27 PHMs, and 26 NMs) were selected from a series of 200 potentially molar specimens previously diagnosed using p57 immunostaining and genotyping. Cases were classified by 3 gynecologic pathologists on the basis of H&E slides (masked to p57 immunostaining and genotyping results) into 1 of 3 categories (CHM, PHM, or NM) during 2 diagnostic rounds; a third round incorporating p57 immunostaining results was also conducted. Consensus diagnoses (those rendered by 2 of 3 pathologists) were determined. Genotyping results were used as the gold standard for assessing diagnostic performance. Sensitivity of a diagnosis of CHM ranged from 59% to 100% for individual pathologists and from 70% to 81% by consensus; specificity ranged from 91% to 96% for individuals and from 94% to 98% by consensus. Sensitivity of a diagnosis of PHM ranged from 56% to 93% for individual pathologists and from 70% to 78% by consensus; specificity ranged from 58% to 92% for individuals and from 74% to 85% by consensus. The percentage of correct classification of all cases by morphology ranged from 55% to 75% for individual pathologists and from 70% to 75% by consensus. The κ values for interobserver agreement ranged from 0.59 to 0.73 (moderate to good) for a diagnosis of CHM, from 0.15 to 0.43 (poor to moderate) for PHM, and from 0.13 to 0.42 (poor to moderate) for NM. The κ values for intraobserver agreement ranged from 0.44 to 0.67 (moderate to good). Addition of the p57

  3. EGCG-targeted p57/KIP2 reduces tumorigenicity of oral carcinoma cells: Role of c-Jun N-terminal kinase

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuya; Digumarthi, Hari; Aranbayeva, Zina; Wataha, John; Lewis, Jill; Messer, Regina; Qin, Haiyan; Dickinson, Douglas; Osaki, Tokio; Schuster, George S.; Hsu, Stephen

    2007-01-01

    The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene expression differentially in tumor and normal cells. In normal human primary epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in NHEK, but not in epithelial cancer cells. In humans, reduced expression of p57 often is associated with advanced tumors, and tumor cells with inactivated p57 undergo apoptosis when exposed to EGCG. The mechanism of p57 induction by EGCG is not well understood. Here, we show that in NHEK, EGCG-induces p57 via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In p57-negative tumor cells, JNK signaling mediates EGCG-induced apoptosis, and exogenous expression of p57 suppresses EGCG-induced apoptosis via inhibition of c-Jun N-terminal kinase (JNK). We also found that restoration of p57 expression in tumor cells significantly reduced tumorigenicity in athymic mice. These results suggest that p57 expression may be an useful indicator for the clinical course of cancers, and could be potentially useful as a target for cancer therapies

  4. Insulin-like growth factor 2 (IGF2) modulates murine hematopoietic stem cell maintenance through upregulation of p57

    Science.gov (United States)

    Thomas, Dolly D.; Sommer, Andreia Gianotti; Balazs, Alejandro B.; Beerman, Isabel; Murphy, George J.; Rossi, Derrick; Mostoslavsky, Gustavo

    2017-01-01

    Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found Insulin-like growth factor 2 (IGF2) to be predominantly expressed within long-term HSC. This study examines IGF2 expression patterns and the effects of the gene in HSC. Through the overexpression and knockdown of IGF2 within purified HSC, we demonstrate that IGF2 expression increases HSC-derived multilineage colonies in vitro and enhances hematopoietic contribution in vivo upon competitive bone marrow transplantation. The effects of IGF2 are mediated by direct upregulation of the CDKi p57, exclusively within long-term HSC, via activation of the PI3K-Akt pathway. Increased expression of p57 resulted in a concomitant increase of HSC in the G0/G1 stage of the cell cycle. Analysis of genomic DNA methylation revealed that HSC exhibited a hypomethylated state within the promoter region of the CDKN1C (p57) gene, providing a potential mechanism for the exclusive effects of IGF2 within HSC. Our studies demonstrate a novel role for IGF2 in regulating HSC cell cycle and illustrate potential novel therapeutic targets for hematological diseases. PMID:26872540

  5. Downregulated CDKN1C/p57kip2 drives tumorigenesis and associates with poor overall survival in breast cancer.

    Science.gov (United States)

    Qiu, Zhu; Li, Yunhai; Zeng, Beilei; Guan, Xiaoqin; Li, Hongzhong

    2018-02-26

    CDKN1C, also known as p57 kip2 , is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKN1C was significantly associated with poor overall survival (OS) in the TCGA cohort and validated cohort composed of 1402 patients. Multivariate Cox regression analysis indicated that CDKN1C was an independent prognostic factor for worse OS (HR = 1.78, 95% CI: 1.09-2.89, p = 0.020). Furthermore, gene set enrichment analysis (GSEA) revealed that CDKN1C was significantly correlated with gene signatures involving DNA repair, cell cycle, glycolysis, adipogenesis, and two critical signaling pathways mTORC1 and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKN1C in the tumorgenesis of breast cancer. Targeting CDKN1C may be a promising strategy for anticancer therapeutics. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer

    International Nuclear Information System (INIS)

    Larson, Pamela S; Schlechter, Benjamin L; King, Chia-Lin; Yang, Qiong; Glass, Chelsea N; Mack, Charline; Pistey, Robert; Morenas, Antonio de las; Rosenberg, Carol L

    2008-01-01

    CDKN1C (also known as p57 KIP2 ) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21 CIP1 and B/p27 KIP1 ) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status. CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor

  7. Effect of X-irradiation on the protein expression of P57kip2 and TGF-β1 in lung cancer cell stain A549

    International Nuclear Information System (INIS)

    Zou Huawei; Tan Yonggang; Zhang Heying

    2008-01-01

    Objective: To analyze the effect of X-irradiation on the proteins expression of p57 kip2 and TGF-β1 in lung cancer cell stain A549 and its clinical significance. Methods: Lung cancer cell stain A549 was cultivated and cell, protein was extracted at 6,12,24,36 and 48 hours after X-irradiation by different doses(2,4, 8 and 12 Gy). The expression of p57 kip2 and TGF-β1 proteins were examined by Western blot. Results: The expression of p57 kip2 in lung cancer cell stain A549 was very low before X-irradiation, and increased significantly after irradiation with different doses and reached the peak level at 12 hours after irradiation (P kip2 and TGF-β1 proteins which increased with certain doses, p57 kip2 and TGF-β1 could be used to predict the damage degree of cancer cells by X-ray. (authors)

  8. Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57 immunohistochemistry and molecular genotyping) improve morphologic diagnosis for both recently trained and experienced gynecologic pathologists.

    Science.gov (United States)

    Gupta, Mamta; Vang, Russell; Yemelyanova, Anna V; Kurman, Robert J; Li, Fanghong Rose; Maambo, Emily C; Murphy, Kathleen M; DeScipio, Cheryl; Thompson, Carol B; Ronnett, Brigitte M

    2012-12-01

    Distinction of hydatidiform moles from nonmolar specimens (NMs) and subclassification of hydatidiform moles as complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) are important for clinical practice and investigational studies; however, diagnosis based solely on morphology is affected by interobserver variability. Molecular genotyping can distinguish these entities by discerning androgenetic diploidy, diandric triploidy, and biparental diploidy to diagnose CHMs, PHMs, and NMs, respectively. Eighty genotyped cases (27 CHMs, 27 PHMs, 26 NMs) were selected from a series of 200 potentially molar specimens previously diagnosed using p57 immunohistochemistry and genotyping. Cases were classified by 6 pathologists (3 faculty level gynecologic pathologists and 3 fellows) on the basis of morphology, masked to p57 immunostaining and genotyping results, into 1 of 3 categories (CHM, PHM, or NM) during 2 diagnostic rounds; a third round incorporating p57 immunostaining results was also conducted. Consensus diagnoses (those rendered by 2 of 3 pathologists in each group) were also determined. Performance of experienced gynecologic pathologists versus fellow pathologists was compared, using genotyping results as the gold standard. Correct classification of CHMs ranged from 59% to 100%; there were no statistically significant differences in performance of faculty versus fellows in any round (P-values of 0.13, 0.67, and 0.54 for rounds 1 to 3, respectively). Correct classification of PHMs ranged from 26% to 93%, with statistically significantly better performance of faculty versus fellows in each round (P-values of 0.04, <0.01, and <0.01 for rounds 1 to 3, respectively). Correct classification of NMs ranged from 31% to 92%, with statistically significantly better performance of faculty only in round 2 (P-values of 1.0, <0.01, and 0.61 for rounds 1 to 3, respectively). Correct classification of all cases combined ranged from 51% to 75% by morphology and 70% to 80

  9. Determination of the appetite suppressant P57 in Hoodia gordonii plant extracts and dietary supplements by liquid chromatography/electrospray ionization mass spectrometry (LC-MSD-TOF) and LC-UV methods.

    Science.gov (United States)

    Avula, Bharathi; Wang, Yan-Hong; Pawar, Rahul S; Shukla, Yatin J; Schaneberg, Brian; Khan, Ikhlas A

    2006-01-01

    Hoodia gordonii is traditionally used in South Africa for its appetite suppressant properties. P57AS3 (P57), an oxypregnane steroidal glycoside, is the only reported active constituent from this plant as an appetite suppressant. Effective quality control of these extracts or products requires rapid methods to determine P57 content. New methods of liquid chromatography/mass spectrometry (LC/MS) and LC-UV for analysis of P57 from H. gordonii have been developed. The quantitative determination of P57 was achieved with a Phenomenex Gemini (Torrance, CA) reversed-phase column using gradient mobile phase of water and acetonitrile, both containing 0.1% acetic acid. The method was validated for linearity, repeatability, and limits of detection and quantification. Good results were obtained in terms of repeatability (relative standard deviation <5.0%) and recovery (98.5-103.5%). The developed methods were applied to the determination of P57 for H. gordonii plant samples, one related genus (Opuntia ficus-indica), and dietary supplements that claim to contain H. gordonii.

  10. Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57.

    Science.gov (United States)

    Zhang, E; He, X; Yin, D; Han, L; Qiu, M; Xu, T; Xia, R; Xu, L; Yin, R; De, W

    2016-02-25

    Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.

  11. Long Intergenic Noncoding RNA 00511 Acts as an Oncogene in Non–small-cell Lung Cancer by Binding to EZH2 and Suppressing p57

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    Cheng-Cao Sun

    2016-01-01

    Full Text Available Long noncoding RNAs (lncRNAs play crucial roles in carcinogenesis. However, the function and mechanism of lncRNAs in human non–small-cell lung cancer (NSCLC are still remaining largely unknown. Long intergenic noncoding RNA 00511 (LINC00511 has been found to be upregulated and acts as an oncogene in breast cancer, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Herein, we identified LINC00511 as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found LINC00511 was upregulated and associated with oncogenesis, tumor size, metastasis, and poor prognosis in NSCLC. Moreover, LINC00511 affected cell proliferation, invasiveness, metastasis, and apoptosis in multiple NSCLC cell lines. Mechanistically, LINC00511 bound histone methyltransferase enhancer of zeste homolog 2 ((EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2, a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3, and acted as a modular scaffold of EZH2/PRC2 complexes, coordinated their localization, and specified the histone modification pattern on the target genes, including p57, and consequently altered NSCLC cell biology. Thus, LINC00511 is mechanistically, functionally, and clinically oncogenic in NSCLC. Targeting LINC00511 and its pathway may be meaningful for treating patients with NSCLC.

  12. Development of a nested polymerase chain reaction for amplification of a sequence of the p57 gene of Renibacterium salmoninarum that provides a highly sensitive method for detection of the bacterium in salmonid kidney

    Science.gov (United States)

    Chase, D.M.; Pascho, R.J.

    1998-01-01

    Nucleic acid-based assays have shown promise for diagnosing Renibacterium salmoninarum in tissues and body fluids of salmonids. DeVelopment of a nested polymerase chain reaction (PCR) method to detect a 320 bp DNA segment of the gene encoding the p57 protein of R. salmoninarum is described. Whereas a conventional PCR for a 383 bp segment of the p57 gene reliably detected 1000 R. salmoninarum cells per reaction in kidney tissue, the nested PCR detected as few as 10 R. salmoninarum per reaction in kidney tissue. Two DNA extraction methods for the nested PCR were compared and the correlation between replicate samples was generally higher in samples extracted by the QIAamp system compared with those extracted by the phenol/chloroform method. The specificity of the nested PCR was confirmed by testing DNA extracts of common bacterial fish pathogens and a panel of bacterial species reported to cause false-positive reactions in the enzyme-linked immunosorbent assay (ELISA) and the fluorescent antibody test (FAT) for R. salmoninarum. Kidney samples from 74 naturally infected chinook Salmon were examined by the nested PCR, the ELISA, and the FAT, and the detected prevalences of R. salmoninarum were 61, 47, and 43%, respectively.

  13. Excitation of the 5p57p levels of xenon by electron impact

    International Nuclear Information System (INIS)

    Sharma, L.; Sharma, L.; Srivastava, R.; Stauffer, A.D.

    2011-01-01

    We have used our relativistic distorted-wave method to calculate cross sections for the electron-impact excitation of the ground state of xenon to all the 5p 5 7p fine-structure levels. The results are compared with the recent experimental measurements of Jung et al. [Phys. Rev. A 80, 062708 (2009)]. We show that the measured cross sections of Jung et al. for excitation of the levels with angular momentum J odd are dominated by cascading from higher-lying levels. Analytic fits to our cross sections are also provided for use in plasma modeling studies

  14. SU-E-P-57: Radiation Doses Assessment to Paediatric Patients for Some Digital Diagnostic Radiology Examination in Emergency Department in Qatar

    Energy Technology Data Exchange (ETDEWEB)

    Abdallah, I; Aly, A; Al Naemi, H [Hamad Medical Corporation, Doha (Qatar)

    2015-06-15

    Purpose: The aim of this study was to evaluate radiation doses to pediatric patients undergoing standard radiographic examinations using Direct Digital Radiography (DDR) in Paediatric emergency center of Hamad General Hospital (HGH) in state of Qatar and compared with regional and international Dose Reference Levels (DRLs). Methods: Entrance Skin Dose (ESD) was measured for 2739 patients for two common X-ray examinations namely: Chest AP/PA, Abdomen. Exposure factors such as kV, mAs and Focal to Skin Distance (FSD) were recorded for each patient. Tube Output was measured for a range of selected kV values. ESD for each individual patient was calculated using the tube output and the technical exposure factors for each examination. The ESD values were compared with the some international Dose Reference Levels (DRL) for all types of examinations. Results: The most performed procedure during the time of this study was chest PA/PA (85%). The mean ESD values obtained from AP chest, PA chest and AP abdomen ranged 91–120, 80–84 and 209 – 659 µGy per radiograph for different age’s groups respectively. Two protocols have been used for chest AP and PA using different radiological parameters, and the different of ESD values for chest PA and were 41% for 1 years old child, 57% for 5 years old for chest AP. Conclusion: The mean ESD were compared with those found in literature and were found to be comparable. The radiation dose can be reduced more for Chest AP and PA examination by optimization of each investigation and hence more studies are required for this task. The results presented will serve as a baseline data needed for deriving local reference doses for pediatric X-ray examinations in this local department and hence it can be applied in the whole Qatar.

  15. Human ecology, statistical analysis, and the logic of valid correlations DOI:10.5007/2175-7984.2011v10n19p57

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    Fernando Dias de Avila-Pires

    2011-10-01

    Full Text Available Human health ecology is an expanding field of interdisciplinary research, combining knowledge drawn from distinct areas. Human ecology is essentially interdisciplinary. The search for the origin and distribution of diseases demands a combination of theories and methods from both natural and social sciences. There is a limit to the replication and repetition of observations and experiments in scientific research: hence the importance of statistics. As a tool, statistical analyses are usually based upon selected samples and samples must be representative of the whole. Irrelevant, erroneous, false, and misleading, information based on flawed interpretation of statistics has always plagued scientific publications. In some cases, not only professional ethics has been breached, but risks to well-being and health has been fostered. In this article I will not deal with fraud, but with bona fide errors of judgment and the use of erroneous statistical concepts. My objective in this article is to caution against a common practice adopted by researchers while using qualitative as well as quantitative methods of analysis to establish demographic categories.

  16. La imagen de la mujer en el ámbito científicoDOI:10.5007/1807-1384.2011v8n2p57

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    Silvia Domínguez Gutiérrez

    2011-12-01

    Full Text Available Las mujeres no se imaginan a sí mismas como científicas. Cuando se les preguntó a 58 estudiantes (22 hombres y 36 mujeres de pregrado de la Universidad de Guadalajara (U. de G., México, que escribieran la primer idea que tuvieran cuando escuchaban la palabra “científico”, la mayoría informó imaginarse principalmente a un hombre, vistiendo bata blanca, con anteojos, grande de edad. Sólo una estudiante visualizó a una mujer como científica. Este hecho es notorio, ya que los alumnos informantes son del Centro Universitario de Ciencias de la Salud de diferentes carreras que en su mayoría están compuestas por mujeres (Enfermería, Psicología, Nutrición, Odontología, Medicina y Cultura Física y Deportes. Para obtener dicha información se utilizó un cuestionario de preguntas asociativas consolidado con entrevistas semi-estructuradas, instrumentos que fueron analizados a través de técnicas inductivo/deductivas y por análisis de contenido de corte cualitativo. A pesar de que se ha observado que el papel de las mujeres es fundamental en el desarrollo de los países, la presencia femenina ha sido relegada u obviada como soporte hacia sus “grandes hombres” lo cual tiene relación con la cultura, la educación y con una tradición patriarcal, la cual puede ser observada en casi cualquier área de la investigación.

  17. Processo de gestão e liderança nas empresas familiares http://dx.doi.org/10.15601/1983-7631/rt.v9n16p57-69

    Directory of Open Access Journals (Sweden)

    Patricia Silva da Silva

    2016-06-01

    Full Text Available O Brasil tem entre 6 a 8 milhões de empresas, sendo que 90% delas são empresas familiares, configurando papel significativo no desenvolvimento econômico, social e mesmo político no país (SEBRAE, 2015. Este artigo analisa a gestão e o exercício da liderança nas empresas familiares a partir de estudo de caso. Os objetivos da investigação são compreender o processo de gestão e desenvolvimento dos líderes nestas organizações O método adotado é qualitativo-descritivo, a partir de estudo de caso em empresa do setor varejista. A empresa analisada caracteriza-se pela gestão centralizada, observando-se dificuldades de comunicação. Na visão dos participantes, as empresas familiares possibilitam maior crescimento profissional e reconhecimento, pela proximidade com a direção, em oposição às corporações de controle acionário. A resistência à mudança pelos gestores familiares implica em tempo ampliado para algumas ações, o que preocupa as lideranças em relação ao futuro da empresa, diante do cenário externo altamente competitivo.

  18. Estudo de toxicologia clínica de um produto crioterápico em voluntários saudáveis do sexo masculino - doi:10.5020/18061230.2005.p57

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    Aline Kércia Alves Soares

    2012-01-01

    Full Text Available Gelomed® é uma emulsão congelada composta de salicilato de metila, cânfora e mentol com indicação para a terapia de processos inflamatórios, especialmente os determinados por traumatismos. A associação desses princípios ativos promove uma ação antiinflamatória tópica explicada por uma vasoconstrição inicial, seguida de resposta vasodilatadora reflexa. O desenho do estudo foi de um ensaio clínico não randomizado de modalidade de controle “bias” aberto. O projeto foi aprovado pelo comitê de ética em pesquisa da Universidade Federal do Ceará. Foram selecionados 25 voluntários saudáveis do sexo masculino, que receberam topicamente a aplicação de 50g de Gelomed® por 20min, duas vezes ao dia, durante 14 dias ininterruptos. Os voluntários foram incluídos no estudo somente quando considerados saudáveis após avaliação clínica, exame físico e exames laboratoriais que antecederam o estudo. As avaliações foram repetidas na 1ª e 2ª semanas e 7 dias após o fim da administração do medicamento. A formulação Gelomed® foi bem tolerada pelos voluntários, entretanto, eventos adversos foram relatados por 24% dos voluntários, somente dois desses eventos foram relacionados a formulação (prurido e dor no local da aplicação, todos de intensidade leve que cederam sem medicação adicional. Os exames clínicos, eletrocardiográficos e laboratoriais efetuados antes, durante e após o ensaio não evidenciaram sinais de toxicidade nos diversos órgãos e sistemas avaliados. O ensaio clínico de fase I confirmou segurança da formulação na amostra avaliada, permitindo que o produto possa ser empregado em populações maiores para determinação de sua eficácia terapêutica.

  19. Peacekeeping: A Selected Bibliography

    Science.gov (United States)

    2009-07-01

    UN Missions and Local People. Bloom - field: Kumarian Press, 2006. 295pp. (JZ6374 .P57 2006) Serafino, Nina M. The Global Peace Operations...28pp. http://www.gao.gov/new.items/d06331.pdf Periodical Articles Arancibia-Clavel, Felipe. “ Chile and Argentina: From Measures of Trust to

  20. Notes on Gobioid fishes : 6. On the synonymy of some species from the Indo-Australian Archipelago

    NARCIS (Netherlands)

    Koumans, F.P.

    1935-01-01

    Bathygobius fuscus (Rüpp.) Gobius fuscus Rüppell, Atl. Reise N. Afr. Fische 1828, p. 137. Gobius punctillatus Rüppell, l.c., p. 138. Gobius soporator Cuvier & Valenciennes, Hist. Nat. Poissons XII. 1837, p. 56. Gobius albopunctatus Cuvier & Valenciennes, l.c., p. 57. Gobius nebulopunctatus Cuvier &

  1. Combating Human Trafficking: Evolution of State Legislation and the Policies of the United Kingdom and France

    Science.gov (United States)

    2011-12-01

    18 Pajnik, M. (2010). Media framing of trafficking. International Feminist Journal of Politics, 12(1). p. 57 19 Friesendorf, Cornelius. 2007...of trafficking. International Feminist Journal of Politics, 12(1). 53 28 Trafficking of Children in Albania. International Labour Organization...successfully reintegrate into their native country. It contributes to their reintegration through medical, psychological , and legal help: family and

  2. Over Dicaeum sanguinolentum sanguinolentum Temm. en Dicaeum sanguinolentum ablutum Rob. & Kloss van West- en Oost-Java

    NARCIS (Netherlands)

    Hoogerwerf, A.

    1947-01-01

    In 1923 splitsten Robinson en Kloss voor Oost-Java de ondersoort ablutum af naar aanleiding van twee huidjes verkregen nabij het langs het Idjen-gebergte gelegen Tamansari (Journ. Fed. Mal. States Mus., vol. II, 1923. P. 57), waarbij de volgende diagnose werd gepubliceerd. „Male. Like D. s.

  3. Development of mice without Cip/Kip CDK inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Tateishi, Yuki; Matsumoto, Akinobu; Kanie, Tomoharu [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); Hara, Eiji [Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakayama, Keiko [Department of Developmental Genetics, Center for Translational and Advanced Animal Research, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Nakayama, Keiichi I., E-mail: nakayak1@bioreg.kyushu-u.ac.jp [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Mice lacking Cip/Kip CKIs (p21, p27, and p57) survive until embryonic day 13.5. Black-Right-Pointing-Pointer Proliferation of MEFs lacking all three Cip/Kip CKIs appears unexpectedly normal. Black-Right-Pointing-Pointer CDK2 kinase activity of the triple mutant MEFs is increased in G0 phase. -- Abstract: Timely exit of cells from the cell cycle is essential for proper cell differentiation during embryogenesis. Cyclin-dependent kinase (CDK) inhibitors (CKIs) of the Cip/Kip family (p21, p27, and p57) are negative regulators of cell cycle progression and are thought to be essential for development. However, the extent of functional redundancy among Cip/Kip family members has remained largely unknown. We have now generated mice that lack all three Cip/Kip CKIs (TKO mice) and compared them with those lacking each possible pair of these proteins (DKO mice). We found that the TKO embryos develop normally until midgestation but die around embryonic day (E) 13.5, slightly earlier than p27/p57 DKO embryos. The TKO embryos manifested morphological abnormalities as well as increased rates of cell proliferation and apoptosis in the placenta and lens that were essentially indistinguishable from those of p27/p57 DKO mice. Unexpectedly, the proliferation rate and cell cycle profile of mouse embryonic fibroblasts (MEFs) lacking all three Cip/Kip CKIs did not differ substantially from those of control MEFs. The abundance and kinase activity of CDK2 were markedly increased, whereas CDK4 activity and cyclin D1 abundance were decreased, in both p27/p57 DKO and TKO MEFs during progression from G{sub 0} to S phase compared with those in control MEFs. The extents of the increase in CDK2 activity and the decrease in CDK4 activity and cyclin D1 abundance were greater in TKO MEFs than in p27/p57 DKO MEFs. These results suggest that p27 and p57 play an essential role in mouse development after midgestation, and that p21 plays only an auxiliary role in

  4. USAF/SCEEE Summer Faculty Research Program (1979). Volume 2

    Science.gov (United States)

    1979-12-01

    K. Schwarzschild , Math. Phys, Kiasse, Grottingen Nachrichten, p. 41 (1906). . 28-21 I -. 4; 1979 USAF - SCEEE SUMMER FACULTY RESEARCH PROGRAM...Wollam, 1968, p. 57. 22. Richard H. Hall, Organizations Structure and Process (New Jersey: Prentice-Hall, Inc., 2nd ed., 1978). 23. Karl E. Weick, The...The Analysis of the U.S. Army Aircraft Maintenance System, Battelle Memorial Institute, 1970. (AD703839) Weick, Karl E. The Social Psychology of

  5. Experiment WA1 (CDHS Neutrino Experiment)

    CERN Multimedia

    CERN PhotoLab

    1977-01-01

    Experiment WA1, also known under CDHS (CERN, Dortmund, Heidelberg, Saclay; spokesman Jack Steinberger), was the first neutrino experiment on the SPS, in its West Area. Magnetized iron (with a toroidal field) forms the core of the detector. On its outside we see drift chambers and photomultipliers (detecting the light from the plastic scintillators further in). Peter Schilly is wearing a white coat. See also CERN Annual Report 1976, p.57.

  6. CSIR Annual report 2003

    CSIR Research Space (South Africa)

    CSIR

    2003-01-01

    Full Text Available ACHIEVEMENTS OF OUR PEOPLE 14 THE STATE OF SCIENCE AND TECHNOLOGY IN THE CSIR 15 ANNUAL FINANCIAL STATEMENTS 20 CORPORATE GOVERNANCE 20 CSIR BOARD MEMBERS 24 REPORT OF THE AUDIT COMMITTEE 26 REPORT OF THE AUDITOR GENERAL 27 EXECUTIVE REPORT 28 FIVE..., which followed research and development of new technology related to the Hoodia plant, dubbed P57. Clinical trials relating to the product continue internationally. World-class genomics research > The African Centre for Gene Technologies, established...

  7. Cizinci jako obtížně dosažitelná populace

    Czech Academy of Sciences Publication Activity Database

    Bernard, Josef; Leontiyeva, Yana

    2013-01-01

    Roč. 7, č. 1 (2013), s. 57-80 ISSN 1802-8152 R&D Projects: GA ČR GAP404/12/1014 Institutional support: RVO:68378025 Keywords : migration research * hard-to-reach populations * sampling methods Subject RIV: AO - Sociology, Demography http://dav.soc.cas.cz/uploads/cfffba873645374315170573eab28d219c81ce85_DaV_2013-1_p57-80_Bernard_Leontiyeva.pdf

  8. Setting Priorities in the Age of Austerity: British, French, and German Experiences

    Science.gov (United States)

    2013-01-01

    overseas—it raises the cost of recruitment by an unknown amount, as the military will have to raise salaries and spend money on advertising and various...Mechanized Infantry Division: The Division in Eastern Germany],” in Heeresführungskommando, Sankt Augustin: CPM Communication Presse, 2009, p. 57...Sankt Augustin: CPM Communication Presse, 2009, p. 44. 76 Timo Noetzel and Martin Zapfe, “Force Structure Requirements for Complex and Conventional

  9. Single-dilution enzyme-linked immunosorbent assay for quantification of antigen-specific salmonid antibody

    Science.gov (United States)

    Alcorn, S.W.; Pascho, R.J.

    2000-01-01

    An enzyme-linked immunosorbent assay (ELISA) was developed on the basis of testing a single dilution of serum to quantify the level of antibody to the p57 protein of Renibaclerium salmoninarum in sockeye salmon (Oncorhynchus nerka). The levels of antibody were interpolated from a standard curve constructed by relating the optical densities (OD) produced by several dilutions of a high-titer rainbow trout (O. mykiss) antiserum to the p57 protein. The ELISA OD values produced by as many as 36 test sera on each microplate were compared with the standard curve to calculate the antigen-specific antibody activity. Repeated measurements of 36 samples on 3 microplates on each of 6 assay dates indicated that the mean intraassay coefficient of variation (CV) was 6.68% (range, 0-23%) and the mean interassay CV was 8.29% (range, 4-16%). The antibody levels determined for the serum sample from 24 sockeye salmon vaccinated with a recombinant p57 protein generally were correlated with the levels determined by endpoint titration (r2 = 0.936) and with results from another ELISA that was based on extrapolation of antibody levels from a standard curve (r2 = 0.956). The single-dilution antibody ELISA described here increases the number of samples that can be tested on each microplate compared with immunoassays based on analysis of several dilutions of each test serum. It includes controls for interassay standardization and can be used to test fish weighing <3 g.

  10. Transgenic expression of BRCA1 disturbs hematopoietic stem and progenitor cells quiescence and function

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Lin; Shi, Guiying; Zhang, Xu; Dong, Wei; Zhang, Lianfeng, E-mail: zhanglf@cnilas.org

    2013-10-15

    The balance between quiescence and proliferation of HSCs is an important regulator of hematopoiesis. Loss of quiescence frequently results in HSCs exhaustion, which underscores the importance of tight regulation of proliferation in these cells. Studies have indicated that cyclin-dependent kinases are involved in the regulation of quiescence in HSCs. BRCA1 plays an important role in the repair of DNA double-stranded breaks, cell cycle, apoptosis and transcription. BRCA1 is expressed in the bone marrow. However, the function of BRCA1 in HSCs is unknown. In our study, we generated BRCA1 transgenic mice to investigate the effects of BRCA1 on the mechanisms of quiescence and differentiation in HSCs. The results demonstrate that over-expression of BRCA1 in the bone marrow impairs the development of B lymphocytes. Furthermore, BRCA1 induced an increase in the number of LSKs, LT-HSCs, ST-HSCs and MPPs. A competitive transplantation assay found that BRCA1 transgenic mice failed to reconstitute hematopoiesis. Moreover, BRCA1 regulates the expression of p21{sup waf1}/cip1 and p57{sup kip2}, which results in a loss of quiescence in LSKs. Together, over-expression of BRCA1 in bone marrow disrupted the quiescent of LSKs, induced excessive accumulation of LSKs, and disrupted differentiation of the HSCs, which acts through the down-regulated of p21{sup waf1}/cip1 and p57{sup kip2}. - Highlights: • Over-expression of BRCA1 results in impaired B lymphocyte development. • BRCA1 transgenic mice disrupted the quiescent of LSKs, induced excessive accumulation of LSKs. • BRCA1 impairs the function of HSCs through the down-regulated of p21{sup waf1/cip1} and p57{sup kip2}.

  11. Transgenic expression of BRCA1 disturbs hematopoietic stem and progenitor cells quiescence and function

    International Nuclear Information System (INIS)

    Bai, Lin; Shi, Guiying; Zhang, Xu; Dong, Wei; Zhang, Lianfeng

    2013-01-01

    The balance between quiescence and proliferation of HSCs is an important regulator of hematopoiesis. Loss of quiescence frequently results in HSCs exhaustion, which underscores the importance of tight regulation of proliferation in these cells. Studies have indicated that cyclin-dependent kinases are involved in the regulation of quiescence in HSCs. BRCA1 plays an important role in the repair of DNA double-stranded breaks, cell cycle, apoptosis and transcription. BRCA1 is expressed in the bone marrow. However, the function of BRCA1 in HSCs is unknown. In our study, we generated BRCA1 transgenic mice to investigate the effects of BRCA1 on the mechanisms of quiescence and differentiation in HSCs. The results demonstrate that over-expression of BRCA1 in the bone marrow impairs the development of B lymphocytes. Furthermore, BRCA1 induced an increase in the number of LSKs, LT-HSCs, ST-HSCs and MPPs. A competitive transplantation assay found that BRCA1 transgenic mice failed to reconstitute hematopoiesis. Moreover, BRCA1 regulates the expression of p21 waf1 /cip1 and p57 kip2 , which results in a loss of quiescence in LSKs. Together, over-expression of BRCA1 in bone marrow disrupted the quiescent of LSKs, induced excessive accumulation of LSKs, and disrupted differentiation of the HSCs, which acts through the down-regulated of p21 waf1 /cip1 and p57 kip2 . - Highlights: • Over-expression of BRCA1 results in impaired B lymphocyte development. • BRCA1 transgenic mice disrupted the quiescent of LSKs, induced excessive accumulation of LSKs. • BRCA1 impairs the function of HSCs through the down-regulated of p21 waf1/cip1 and p57 kip2

  12. Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

    DEFF Research Database (Denmark)

    Maddika, S; Ande, SR; Panigrahi, S

    2007-01-01

    )), and the Cip1/Waf1/Kip1-2-family (p21(Cip1/Waf1), p27(Kip1), p57(Kip2)) are shown both in the context of proliferation regulators and as contributors to the apoptotic machinery. Bcl2-family members (i.e. Bcl2, Bcl-X(L) Mcl-1(L); Bax, Bok/Mtd, Bak, and Bcl-X(S); Bad, Bid, Bim(EL), Bmf, Mcl-1(S)) are highlighted...... approaches that would involve redirecting over-active survival and proliferation pathways towards induction of apoptosis in cancer cells....

  13. Absorption of food cobalamins assessed by the double isotope method in healthy volunteers and in patients with chronic diarrhoea

    International Nuclear Information System (INIS)

    Kittang, B.; Hamborg, B.; Schjoensby, H.

    1985-01-01

    To make a food preparation containing radioactively labelled cobalamins, rabbits were given repeated injections with 57 Co-labelled cyanocobalamin. The liver was removed, homogenized and fried for one min. or boiled for 30 min. Of the radioactivity in the fried homogenate, 41.7% was recovered in the centrifuged supernatant compared with 50.8% in the boiled homogenate. The radioactivity in the supernatants had a molecular size close to that of free 57 Co-labelled cyanocobalamin. 42% of the radioactivity in the whole homogenate had been incorporated into 5-deoxyadenosyl-, 10% into methyl-and 16.5% into hydroxy-cobalamin. To assess the validity of a double-isotope method for measuring the intestinal absorption of doses of 57 Co-labelled liver cobalamins, 51 CrCl 3 was used as a non-absorbable marker. In 14 healthy volunteers the correlation coefficient between the absorption measured by the double-isotope technique and the faecal excretion test was highly significant (r = 0.96, p 57 Co/ 51 Cr ratio in successive stool collections. In 11 patients with chronic diarrhoea there was a significant correlation between the absorption measured by the double-isotope technique and the faecal excretion test (r = 0.92, p 57 / 51 Cr ratio in successive stool collections

  14. Expression of androgen receptor target genes in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Kesha Rana

    2014-10-01

    Full Text Available We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (ARΔZF2 versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57 Kip2, Igf2 and calcineurin Aa, was increased in AR∆ZF2 muscle, and the expression of all but p57 Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

  15. Synthesis of functionally graded bioactive glass-apatite multistructures on Ti substrates by pulsed laser deposition

    International Nuclear Information System (INIS)

    Tanaskovic, D.; Jokic, B.; Socol, G.; Popescu, A.; Mihailescu, I.N.; Petrovic, R.; Janackovic, Dj.

    2007-01-01

    Functionally graded glass-apatite multistructures were synthesized by pulsed laser deposition on Ti substrates. We used sintered targets of hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2 , or bioglasses in the system SiO 2 -Na 2 O-K 2 O-CaO-MgO-P 2 O 5 with SiO 2 content of either 57 wt.% (6P57) or 61 wt.% (6P61). A UV KrF* (λ = 248 nm, τ > 7 ns) excimer laser source was used for the multipulse laser ablation of the targets. The hydroxyapatite thin films were obtained in H 2 O vapors, while the bioglass layers were deposited in O 2 . Thin films of 6P61 were deposited in direct contact with Ti, because Ti and this glass have similar thermal expansion behaviors, which ensure good bioglass adhesion to the substrate. This glass, however, is not bioactive, so yet more depositions of 6P57 bioglass and/or hydroxyapatite thin films were performed. All structures with hydroxyapatite overcoating were post-treated in a flux of water vapors. The obtained multistructures were characterized by various techniques. X-ray investigations of the coatings found small amounts of crystalline hydroxyapatite in the outer layers. The scanning electron microscopy analyses revealed homogeneous coatings with good adhesion to the Ti substrate. Our studies showed that the multistructures we had obtained were compatible with further use in biomimetic metallic implants with glass-apatite coating applications

  16. The role of organelle proteins in carotenoid droplet dispersion in goldfish xanthophore

    International Nuclear Information System (INIS)

    Wu, B.Y.

    1988-01-01

    In this study, I report on the evidence for the possible role of two carotenoid droplet (CD) proteins in CD dispersion. In order to identify the target of the ATP analogue 8-N 3 ATP, CDs, one of the major components in permeabilized xanthophore residues, were isolated by sucrose density gradient centrifugation and were tested for ATPase activity. An ATPase activity was found associated with CDs. Polypeptides analysis of the two subpopulations of 3 H-leucine labeled CDs by one dimensional and two dimensional polyacrylamide gel electrophoresis showed that there is more actin associated with HCD than with LCD, suggesting that the CD-ATPase may be an apparent actin activated ATPase. The properties of the CD-ATPase have been partially characterized with regard to its ionic requirement and the effects of known ATPase inhibitors and potential activators. Monoclonal antibodies were generated against CD proteins. The major monoclonal antibodies obtained are anti-p57s. The effects of these anti-p57s on dispersion of CDs in permeabilized xanthophores were determined and it was found that some inhibit CD dispersion while others do not

  17. The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy.

    Science.gov (United States)

    Andeen, Nicole K; Nguyen, Tri Q; Steegh, Floor; Hudkins, Kelly L; Najafian, Behzad; Alpers, Charles E

    2015-11-01

    Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.

  18. Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Barone

    Full Text Available BACKGROUND: Celiac Disease (CD is both a frequent disease (1:100 and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs

  19. Synthesis and characterization of Taurine

    Directory of Open Access Journals (Sweden)

    B Bayarmaa

    2014-10-01

    Full Text Available Have been obtained 2-aminoethanesulfonic acid (taurine from ethanolamine, sulfuric acid and sodium sulfite during the synthesis in laboratory condition. The process involves two steps of reactions, the first was esterification of ethanolamine with sulfuric acid to produce the intermediate product of 2-aminoethyl ester which than was extended to the second step by sulfonation with sodium sulfite to produce 2-aminoethanesulfonic acid. Resulting product was analyzed using 1H-NMR, IR, FAB-MS analysis and examined purity characterizations of the synthesized products. DOI: http://dx.doi.org/10.5564/mjc.v14i0.200 Mongolian Journal of Chemistry 14 (40, 2013, p57-60

  20. Diagnóstico del sector primario citrícola de Entre Ríos

    OpenAIRE

    González, María del Carmen

    1994-01-01

    p.57-68 En la producción citrícola mesopotámica es el comercio de la fruta fresca la actividad organizadora del subsistema. La estrategia de desarrollo de la citricultura se ha basado en la especialización regional, observándose la dominancia de Tucumán en la producción de limón, mientras que la producción de naranja y mandarina está localizada fundamentalmente en la Mesopotamia, y la de pomelo en la Mesopotamia y en Salta. Se observa un incremento entre el Censo Citrícola 1978 y 1987 de l...

  1. Economia solidária: possibilidade de (rehumanização do trabalho

    Directory of Open Access Journals (Sweden)

    Clesar Luiz Loch

    2008-07-01

    Full Text Available http://dx.doi.org/10.5007/2175-8069.2008v10n20p57 Este ensaio teórico busca suscitar algumas reflexões acerca do trabalho compreendido como elemento constitutivo do homem, porém, condicionado pela formação societal onde se insere. O trabalho pode ser concebido como fonte de criação, transformação e emancipação humana, como pode também assumir seus aspectos mais negativos, aqueles relacionados a tripalium. No modo de produção capitalista, onde o trabalho é concebido essencialmente como mero fator de produção, emergem suas conotações negativas. Por outro lado, princípios de modelos alternativos como o da economia solidária, de igualdade, de autonomia, por exemplo, podem representar um resgate da humanização do trabalho.

  2. Inside ISIS II

    CERN Multimedia

    1981-01-01

    ISIS stands for Identification of Secondaries by Ionization Sampling. It was a drift chamber with an active volume of about 40 m3 built by Oxford University as a particle identifier for the European Hybrid Spectrometer (EHS). The photo shows the electrostatic grading structure and the central anode-wire plane, with Roger Giles standing just under it (Annual Report 1981 p. 57, Fig. 4). ISIS-II differed from the prototype ISIS-I only in the depth of the track (4 m instead of 1 m) thus extending the momentum range for particle identification to 50 GeV/c. See Nucl. Instr. and Meth. 224 (1984) 396, and Nucl. Instr. and Meth. 258 (1987) 26.

  3. "Measuring up to measure" dysmorphophobia as a language game.

    Science.gov (United States)

    Faccio, Elena; Centomo, Chiara; Mininni, Giuseppe

    2011-09-01

    We look into the transformation of meanings in psychotherapy and suggest a clinical application for Wittgenstein's intuitions concerning the role of linguistic practices in generating significance. In post-modern theory, therapy does not necessarily change reality as much as it does our way of experiencing it by intervening in the linguistic-representational rules responsible for constructing the text which expresses the problem. Since "states of mind assume the truths and forms of the language devices that we use to represent them" (Foucault, 1963, p. 57), therapy may be intended as a narrative path toward a new naming of one's reified experiences. The clinical problem we consider here, the pervasive feeling of inadequacy due to one's excessive height (dysmorphophobia), is an excellent example of "language game" by which a "perspicuous representation" (the "therapy" proposed by Wittgenstein in the 1953) may bring out alternatives to linguistically-built "traps", putting the blocked semiotic mechanism back into motion.

  4. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  5. Hes1 is required for appropriate morphogenesis and differentiation during mouse thyroid gland development.

    Directory of Open Access Journals (Sweden)

    Aurore Carre

    Full Text Available Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis. To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1(-/- mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05 at E9.5 and at E11.5. Moreover, Hes1(-/- mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60% compared to wild type mice at all study time points (E9.5-E16.5. In both Hes1(-/- and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1(-/- mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice. After fusion of thyroid anlages, hypoplastic Hes1(-/- thyroids revealed a significantly decreased labelling area for T4 (-78% and calcitonin (-65% normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%. These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

  6. Prolonged mechanical ventilation induces cell cycle arrest in newborn rat lung.

    Directory of Open Access Journals (Sweden)

    Andreas A Kroon

    Full Text Available RATIONALE: The molecular mechanism(s by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. OBJECTIVE: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. METHODS: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg⁻¹. MEASUREMENT AND MAIN RESULTS: Ventilation for 24 h (h decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27(Kip1 was significantly increased. Mechanical ventilation for 24 h also increased levels of p57(Kip2, decreased that of p16(INK4a, while the levels of p21(Waf/Cip1 and p15(INK4b were unchanged. Increased p27(Kip1 expression coincided with reduced phosphorylation of p27(Kip1 at Thr¹⁵⁷, Thr¹⁸⁷ and Thr¹⁹⁸ (p<0.05, thereby promoting its nuclear localization. Similar -but more rapid- changes in cell cycle regulators were noted when 7-day rats were ventilated with high tidal volume (40 mL.kg⁻¹ and when fetal lung epithelial cells were subjected to a continuous (17% elongation cyclic stretch. CONCLUSION: This is the first demonstration that prolonged (24 h of mechanical ventilation causes cell cycle arrest in newborn rat lungs; the arrest occurs in G₁ and is caused by increased expression and nuclear localization of Cdk inhibitor proteins (p27(Kip1, p57(Kip2 from the Kip family.

  7. Parietal podocytes in normal human glomeruli.

    Science.gov (United States)

    Bariety, Jean; Mandet, Chantal; Hill, Gary S; Bruneval, Patrick

    2006-10-01

    Although parietal podocytes along the Bowman's capsule have been described by electron microscopy in the normal human kidney, their molecular composition remains unknown. Ten human normal kidneys that were removed for cancer were assessed for the presence and the extent of parietal podocytes along the Bowman's capsule. The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested. In addition, six normal fetal kidneys were studied to track the ontogeny of parietal podocytes. The podocyte protein labeling detected parietal podocytes in all of the kidneys, was found in 76.6% on average of Bowman's capsule sections, and was prominent at the vascular pole. WT1 and p57 were expressed in some parietal cells, whereas PAX2 was present in all or most of them, so some parietal cells coexpressed WT1 and PAX2. Furthermore, parietal podocytes coexpressed WT1 and podocyte proteins. Cytokeratin-positive cells covered a variable part of the capsule and did not express podocyte proteins. Tuft-capsular podocyte bridges were present in 15.5 +/- 3.7% of the glomerular sections. Parietal podocytes often covered the juxtaglomerular arterioles and were present within the extraglomerular mesangium. Parietal podocytes were present in fetal kidneys. Parietal podocytes that express the same epitopes as visceral podocytes do exist along Bowman's capsule in the normal adult kidney. They are a constitutive cell type of the Bowman's capsule. Therefore, their role in physiology and pathology should be investigated.

  8. Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources.

    Science.gov (United States)

    Kaverina, Natalya V; Eng, Diana G; Schneider, Remington R S; Pippin, Jeffrey W; Shankland, Stuart J

    2016-06-01

    The current studies used genetic fate mapping to prove that adult podocytes can be partially replenished following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated to permanently label podocytes with the ZsGreen reporter. Experimental focal segmental glomerulosclerosis (FSGS) was induced with a cytotoxic podocyte antibody. On FSGS day 7, immunostaining for the podocyte markers p57, synaptopodin, and podocin were markedly decreased by 44%, and this was accompanied by a decrease in ZsGreen fluorescence. The nuclear stain DAPI was absent in segments of reduced ZsGreen and podocyte marker staining, which is consistent with podocyte depletion. Staining for p57, synaptopodin, podocin, and DAPI increased at FSGS day 28 and was augmented by the ACE inhibitor enalapril, which is consistent with a partial replenishment of podocytes. In contrast, ZsGreen fluorescence did not return and remained significantly low at day 28, indicating replenishment was from a nonpodocyte origin. Despite administration of bromodeoxyuridine (BrdU) thrice weekly throughout the course of disease, BrdU staining was not detected in podocytes, which is consistent with an absence of proliferation. Although ZsGreen reporting was reduced in the tuft at FSGS day 28, labeled podocytes were detected along the Bowman's capsule in a subset of glomeruli, which is consistent with migration from the tuft. Moreover, more than half of the migrated podocytes coexpressed the parietal epithelial cell (PEC) proteins claudin-1, SSeCKS, and PAX8. These results show that although podocytes can be partially replenished following abrupt depletion, a process augmented by ACE inhibition, the source or sources are nonpodocyte in origin and are independent of proliferation. Furthermore, a subset of podocytes migrate to the Bowman's capsule and begin to coexpress PEC markers. Copyright © 2016 the American Physiological Society.

  9. Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension

    International Nuclear Information System (INIS)

    Yu Lunyin; Quinn, Deborah A.; Garg, Hari G.; Hales, Charles A.

    2006-01-01

    The balance between cell proliferation and cell quiescence is regulated delicately by a variety of mediators, in which cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) play a very important role. Heparin which inhibits pulmonary artery smooth muscle cell (PASMC) proliferation increases the levels of two CDKIs, p21 and p27, although only p27 is important in inhibition of PASMC growth in vitro and in vivo. In the present study we investigated the expression profile of all the cell cycle regulating genes, including all seven CDKIs (p21, p27, p57, p15, p16, p18, and p19), in the lungs of mice with hypoxia-induced pulmonary hypertension. A cell cycle pathway specific gene microarray was used to profile the 96 genes involved in cell cycle regulation. We also observed the effect of heparin on gene expression. We found that (a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p18 activity, showing a 98% decrease in p27 and 81% increase in p18; (b) other CDKIs, p21, p57, p15, p16, and p19 were not affected significantly in response to hypoxia; (c) heparin treatment restored p27 expression, but did not influence p18; (d) ERK1/2 and p38 were mediators in heparin upregulation of p27. This study provides an expression profile of cell cycle regulating genes under hypoxia in mice with hypoxia-induced pulmonary hypertension and strengthens the previous finding that p27 is the only CDKI involved in heparin regulation of PASMC proliferation and hypoxia-induced pulmonary hypertension

  10. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  11. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byeong-Moo [Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Choi, Michael Y., E-mail: mchoi@partners.org [Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Harvard Stem Cell Institute, Boston, MA 02114 (United States)

    2012-09-21

    Highlights: Black-Right-Pointing-Pointer Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. Black-Right-Pointing-Pointer miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. Black-Right-Pointing-Pointer miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. Black-Right-Pointing-Pointer miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. Black-Right-Pointing-Pointer miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3 Prime -untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.

  12. Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development

    Science.gov (United States)

    Carre, Aurore; Rachdi, Latif; Tron, Elodie; Richard, Bénédicte; Castanet, Mireille; Schlumberger, Martin; Bidart, Jean-Michel

    2011-01-01

    Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1 −/− mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1 −/− mouse embryos showed a significantly smaller total thyroid surface area (−40 to −60%) compared to wild type mice at all study time points (E9.5−E16.5). In both Hes1 −/− and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1 −/− mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1 −/− thyroids revealed a significantly decreased labelling area for T4 (−78%) and calcitonin (−65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (−69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells. PMID:21364918

  13. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    International Nuclear Information System (INIS)

    Kim, Byeong-Moo; Choi, Michael Y.

    2012-01-01

    Highlights: ► Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. ► miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. ► miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. ► miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. ► miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3′-untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.

  14. Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

    Science.gov (United States)

    Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

    2017-09-01

    Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

  15. Arbitrary amplitude electrostatic wave propagation in a magnetized dense plasma containing helium ions and degenerate electrons

    Science.gov (United States)

    Mahmood, S.; Sadiq, Safeer; Haque, Q.; Ali, Munazza Z.

    2016-06-01

    The obliquely propagating arbitrary amplitude electrostatic wave is studied in a dense magnetized plasma having singly and doubly charged helium ions with nonrelativistic and ultrarelativistic degenerate electrons pressures. The Fermi temperature for ultrarelativistic degenerate electrons described by N. M. Vernet [(Cambridge University Press, Cambridge, 2007), p. 57] is used to define ion acoustic speed in ultra-dense plasmas. The pseudo-potential approach is used to solve the fully nonlinear set of dynamic equations for obliquely propagating electrostatic waves in a dense magnetized plasma containing helium ions. The upper and lower Mach number ranges for the existence of electrostatic solitons are found which depends on the obliqueness of the wave propagation with respect to applied magnetic field and charge number of the helium ions. It is found that only compressive (hump) soliton structures are formed in all the cases and only subsonic solitons are formed for a singly charged helium ions plasma case with nonrelativistic degenerate electrons. Both subsonic and supersonic soliton hump structures are formed for doubly charged helium ions with nonrelativistic degenerate electrons and ultrarelativistic degenerate electrons plasma case containing singly as well as doubly charged helium ions. The effect of propagation direction on the soliton amplitude and width of the electrostatic waves is also presented. The numerical plots are also shown for illustration using dense plasma parameters of a compact star (white dwarf) from literature.

  16. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    KAUST Repository

    Lissanu Deribe, Yonathan

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  17. Retrospective Analysis of the Accuracy of Ultrasound-Guided Magnetic Resonance Arthrogram Injections of the Hip in the Office Setting.

    Science.gov (United States)

    Jernick, Michael; Walker Gallego, Edward; Nuzzo, Michael

    2017-12-01

    Ultrasound (US)-guided intra-articular hip injections have been proposed in the literature to be accurate, reliable, and safe alternatives to fluoroscopy-guided injections. To evaluate the accuracy of US-guided magnetic resonance (MR) arthrogram injections of the hip performed in the office setting by a single orthopaedic surgeon and elucidate the potential effects that patient age, sex, and body mass index (BMI) have on contrast placement. Case series; Level of evidence, 4. From a review of the senior author's office database, 89 patients (101 hips) who had US-guided MR arthrogram injections performed between December 2014 and June 2016 were identified. Official radiology reports were evaluated to determine whether extra-articular contrast was noted. Patient variables, including BMI, age, and sex, were evaluated between patients who had inappropriately placed contrast and those who did not. Of the 101 hip injections, there were 6 cases that demonstrated inadequate contrast placement within the joint, likely secondary to extravasation or incorrect placement; however, an MR arthrogram was adequately interpreted in all cases. There were no significant differences noted between those with appropriate versus inappropriate contrast placement when evaluating BMI ( P = .57), age ( P = .33), or sex ( P = .67), and neither group had an adverse event. US-guided injections are safe and accurate alternatives to fluoroscopy-guided injections in the office setting, with 94% accuracy. Furthermore, BMI, age, and sex did not play a statistically significant role among patients with inappropriately placed contrast.

  18. Influence of conjunctive use of coffee effluent and fresh water on performance of robusta coffee and soil properties.

    Science.gov (United States)

    Salakinkop, S R; Shivaprasad, P

    2012-01-01

    A field experiment was conducted to study the influence of treated coffee effluent irrigation on performance of established robusta coffee, nutrient contribution and microbial activities in the soil. The results revealed that the field irrigated with coffee effluent from aerobic tank having COD of 1009 ppm, did not affect the yield of clean coffee (1309 kg/ha) and it was statistically similar (on par) with the plots irrigated with fresh water (1310 kg/ha) with respect to clean coffee yield. Effluent irrigation increased significantly the population bacteria, yeast, fungi, actinomycetes and PSB (122, 52, 12, 34 and 6 x 104/g respectively)) in the soil compared to the soil irrigated with fresh water (87, 22, 5, 24 and 2 x 10(4)/g respectively). The organic carbon (2.60%), available nutrients in the soil like P (57.2 kg/ha), K (401.6 kg/ha, Ca (695.3 ppm), S (5.3 ppm),Cu (4.09 ppm) and Zn(4.78 ppm) were also increased due to effluent irrigation compared to fresh water irrigation. Thus analysis of coffee effluent for major and minor plant nutrients content revealed its potential as source of nutrients and water for plant growth.

  19. Testing a path-analytic mediation model of how motivational enhancement physiotherapy improves physical functioning in pain patients.

    Science.gov (United States)

    Cheing, Gladys; Vong, Sinfia; Chan, Fong; Ditchman, Nicole; Brooks, Jessica; Chan, Chetwyn

    2014-12-01

    Pain is a complex phenomenon not easily discerned from psychological, social, and environmental characteristics and is an oft cited barrier to return to work for people experiencing low back pain (LBP). The purpose of this study was to evaluate a path-analytic mediation model to examine how motivational enhancement physiotherapy, which incorporates tenets of motivational interviewing, improves physical functioning of patients with chronic LBP. Seventy-six patients with chronic LBP were recruited from the outpatient physiotherapy department of a government hospital in Hong Kong. The re-specified path-analytic model fit the data very well, χ (2)(3, N = 76) = 3.86, p = .57; comparative fit index = 1.00; and the root mean square error of approximation = 0.00. Specifically, results indicated that (a) using motivational interviewing techniques in physiotherapy was associated with increased working alliance with patients, (b) working alliance increased patients' outcome expectancy and (c) greater outcome expectancy resulted in a reduction of subjective pain intensity and improvement in physical functioning. Change in pain intensity also directly influenced improvement in physical functioning. The effect of motivational enhancement therapy on physical functioning can be explained by social-cognitive factors such as motivation, outcome expectancy, and working alliance. The use of motivational interviewing techniques to increase outcome expectancy of patients and improve working alliance could further strengthen the impact of physiotherapy on rehabilitation outcomes of patients with chronic LBP.

  20. Outcomes associated with a structured prenatal counseling program for shoulder dystocia with brachial plexus injury.

    Science.gov (United States)

    Daly, Mary Veronica; Bender, Christina; Townsend, Kathryn E; Hamilton, Emily F

    2012-08-01

    We examined outcomes that were associated with a novel program to identify patients who are at high risk for shoulder dystocia with brachial plexus injury. The program included a checklist of key risk factors and a multifactorial algorithm to estimate risk of shoulder dystocia with brachial plexus injury. We examined rates of cesarean delivery and shoulder dystocia in 8767 deliveries by clinicians who were enrolled in the program and in 11,958 patients of clinicians with no access to the program. Key risk factors were identified in 1071 of 8767 mothers (12.2%), of whom 40 of 8767 women (0.46%) had results in the high-risk category. The rate of primary cesarean delivery rate was stable (21.2-20.8%; P = .57). Shoulder dystocia rates fell by 56.8% (1.74-0.75%; P = .002). The rates of shoulder dystocia and cesarean birth showed no changes in the group with no access to the program. With the introduction of this program, overall shoulder dystocia rates fell by more than one-half with no increase in the primary cesarean delivery rate. Copyright © 2012 Mosby, Inc. All rights reserved.

  1. [Results of an experience with the Bentall procedure].

    Science.gov (United States)

    Gallego, Javier; Ferreira, R; Roque, J; Guerra, N; Gennari, M; Serpa, C; Mendes, S; Mendes, M; Lucero, R; Lemos, A; Pereira, R; Nobre, A; Cravino, J

    2008-01-01

    The authors report a retrospective study of patients who underwent a Bentall procedure in the Cardio-Thoracic Surgery Department of Hospital Santa Maria, Lisbon. Data were obtained from 42 patients who underwent the Bentall procedure between 1991 and 2008. Different parameters were compared as well as the short and long term results. The median age was 58,5 years being 88% of patients of male gender. 32 (76,27%) presented with ascending aorta degenerative aneurism, 6 p (14,3%) with type A aortic dissection and 4p (9,5%) with Marfan syndrome. 10p(23.8%) had associated coronary artery disease and there were 6p (14.3%) who underwent emergency surgery. Among the risk factors associated, 24 p (57,1%) had hypertension, 12 p (28,6%) dyslipidemia, 4p (9,5%) had history of smoking, 7 p (16,7%) diabetes, 6 p (14,3%) CPOD, 2 p (4,8%) renal dysfunction and 2 had a recent myocardial infarction. There were 7p (16,7%) with left ventricular dysfunction (EFBentall procedure obtained good results in short and long term and, despite the emerging of new and more complex techniques like remodelling and reimplantation, our results support the maintenance of this procedure as the preferential treatment for aortic root and valvular disease.

  2. Identification of the protein kinase C phosphorylation site in neuromodulin

    International Nuclear Information System (INIS)

    Apel, E.D.; Byford, M.F.; Au, D.; Walsh, K.A.; Storm, D.R.

    1990-01-01

    Neuromodulin (P-57, GAP-43, B-50, F-1) is a neurospecific calmodulin binding protein that is phosphorylated by protein kinase C. Phosphorylation by protein kinase C has been shown to abolish the affinity of neuromodulin for calmodulin and the authors have proposed that the concentration of free CaM in neurons may be regulated by phosphorylation and dephosphorylation of neuromodulin. The purpose of this study was to identify the protein kinase C phosphorylation site(s) in neuromodulin using recombinant neuromodulin as a substrate. Toward this end, it was demonstrated that recombinant neuromodulin purified from Escherichia coli and bovine neuromodulin were phosphorylated with similar K m values and stoichiometries and that protein kinase C mediated phosphorylation of both proteins abolished binding to calmodulin-Sepharose. Recombinant neuromodulin was phosphorylated by using protein kinase C and [γ- 32 P]ATP and digested with trypsin, and the resulting peptides were separated by HPLC. Only one 32 P-labeled tryptic peptide was generated from phosphorylated neuromodulin. They conclude that serine-41 is the protein kinase C phosphorylation site of neuromodulin and that phosphorylation of this amino acid residue blocks binding of calmoculin to neuromodulin. The proximity of serine-41 to the calmodulin binding domain in neuromodulin very likely explains the effect of phosphorylation on the affinity of neuromodulin for calmodulin

  3. El arte paleolítico en El Carnicero de Chabrol.

    Directory of Open Access Journals (Sweden)

    Lombo Montañés, Alberto

    2015-12-01

    Full Text Available El cine de ficción ha recreado las grafías paleolíticas de muy diversas formas. Las reproducciones fílmicas han servido para enseñar a los niños (Viaje a la Prehsitoria, Cesta do praveku, 1954 de Karel Zeman, para fantasear acerca de los extraterrestres (Prometheus, Ridley Scott, 2012; pero sólo Chabrol lo ha utilizado para estructurar la historia de unos crímenes. Claude Chabrol (1930-2010 era uno de los críticos de Cahiers de cinèma que, junto con otros reconocidos directores de la Nouvelle Vague como François Truffaut, Jean-Luc Godard o Eric Rohmer, pasó a la dirección de películas. En sus numerosos films Chabrol dio gran importancia a la estructura narrativa y a las apariencias que se esconden tras la realidad física cotidiana (Viganò, 1999, p. 23 y 30. Además, los personajes de Chabrol no reflejan un individuo particular, sino a toda la humanidad (Viganò, 1999, p. 57. Estas tres características, herederas en gran medida del cine de Alfred Hitchcock, son fundamentales para comprender la presencia del arte paleolítico en la película que nos ocupa.

  4. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    International Nuclear Information System (INIS)

    Joseph, Bertrand; Hermanson, Ola

    2010-01-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  5. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Bertrand [Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, Stockholm (Sweden)

    2010-05-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  6. Loss of ATRX in chondrocytes has minimal effects on skeletal development.

    Directory of Open Access Journals (Sweden)

    Lauren A Solomon

    Full Text Available BACKGROUND: Mutations in the human ATRX gene cause developmental defects, including skeletal deformities and dwarfism. ATRX encodes a chromatin remodeling protein, however the role of ATRX in skeletal development is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: We induced Atrx deletion in mouse cartilage using the Cre-loxP system, with Cre expression driven by the collagen II (Col2a1 promoter. Growth rate, body size and weight, and long bone length did not differ in Atrx(Col2cre mice compared to control littermates. Histological analyses of the growth plate did not reveal any differences between control and mutant mice. Expression patterns of Sox9, a transcription factor required for cartilage morphogenesis, and p57, a marker of cell cycle arrest and hypertrophic chondrocyte differentiation, was unaffected. However, loss of ATRX in cartilage led to a delay in the ossification of the hips in some mice. We also observed hindlimb polydactily in one out of 61 mutants. CONCLUSIONS/SIGNIFICANCE: These findings indicate that ATRX is not directly required for development or growth of cartilage in the mouse, suggesting that the short stature in ATR-X patients is caused by defects in cartilage-extrinsic mechanisms.

  7. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.

    Science.gov (United States)

    Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B; Wu, Chia-Chin; Akdemir, Kadir C; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T; Welch, Heidi C E; Garraway, Levi A; Chin, Lynda

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2(E824)*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57(KIP2)). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  8. Temporal compression of soil erosion processes. A regional analysis of USLE database; La compresion temporal de los procesos de erosion del suelo. Un analisis regional de la base de datos USLE

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Hidalgo, J. C.; Luis, M.; Lopez-Bermudez, F.

    2009-07-01

    When John Thornes and Denis Brunsden wrote in 1977 How often one hears the researcher (and no less the undergraduate) complain that after weeks of observation nothing happened only to learn that, the day after his departure, a flood caused unprecedented erosion and channel changes (Thrones and Brunsden, 1977, p. 57), they were focussing to important problems in Geomorphology: the extreme events and time compression of geomorphological processes. Time compression is a fundamental characteristic of geomorphological processes, some times produced by extreme events. Extreme events are rare events, defined by deviation from mean values. But from magnitude-frequency analysis we know that few events, not necessarily extreme, are able to produce a high amount of geomorphological work. finally time compression of geomorphological processes can be focused by the analysis of largest events defined by ranks, not magnitude. We have analysed the effects of largest events on total soil erosion by using 594 erosion plots from USLE database. Plots are located in different climate regions of USA and have different length of records. The 10 largest daily events mean contribution value is 60% of total soil erosion. There exist a relationship between such percentage and total daily erosive events recorded. The pattern seems to be independent of climate conditions. We discuss the nature of such relationship and the implications in soil erosion research. (Author) 17 refs.

  9. Against Contextualism: Belief, Evidence, & the Bank Cases

    Directory of Open Access Journals (Sweden)

    Logan Paul Gage

    2013-04-01

    Full Text Available http://dx.doi.org/10.5007/1808-1711.2013v17n1p57 Contextualism (the view that ‘knowledge’ and its variants are context-sensitive has been supported in large part through appeal to intuitions about Keith DeRose’s Bank Cases. Recently, however, the contextualist construal of these cases has come under fire from Kent Bach and Jennifer Nagel who question whether the Bank Case subject’s confidence can remain constant in both low- and high-stakes cases. Having explained the Bank Cases and this challenge to them, I argue that DeRose has given a reasonable reply to this initial challenge. However, I proceed to argue that the current stalemate can be broken. Seeking to extend the Bach–Nagel critique, I offer a novel interpretation of the Bank Cases according to which the subject’s evidence changes between low- and high-stakes cases. If I am correct, then, given the amount of support the Bank Cases have been thought to lend contextualism, the case for contextualism is seriously weakened.

  10. The Unique Hoyle State of the Carbon Atom

    Directory of Open Access Journals (Sweden)

    Thorvaldsen, Steinar

    2015-05-01

    Full Text Available The famous astronomer Fred Hoyle (1915-2001 started his research career as an atheist. Hoyle’s most important contribution to astrophysics is the theory of nucleosynthesis, i.e. the idea that chemical elements such as carbon can form in stars on the basis of hydrogen and helium. Essentially here was his prediction that the carbon core has a state with a specific energy which is precisely adapted to the basic fusion process. This result was one of the most important breakthroughs in modern astrophysics, and the so called Hoyle state has become a cornerstone for state-ofthe- art nuclear theory. The calculations he made, eventually revealed a fine-tuning of the universe. Hoyle’s work in this area supported the anthropic principle that the universe was fine-tuned so that intelligent life would be possible. It is said that what really made him conclude that creation demanded intelligence, were his calculations of the special properties of the carbon atom. This shook his atheism fundamentally [1, p. 57]. In this paper we describe this discovery.

  11. Tracking the stochastic fate of cells of the renin lineage after podocyte depletion using multicolor reporters and intravital imaging.

    Directory of Open Access Journals (Sweden)

    Natalya V Kaverina

    Full Text Available Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS. Because cells of the renin lineage (CoRL serve as adult podocyte and parietal epithelial cell (PEC progenitor candidates, we generated Ren1cCre/R26R-ConfettiTG/WT and Ren1dCre/R26R-ConfettiTG/WT mice to determine CoRL clonality during podocyte replacement. Four CoRL reporters (GFP, YFP, RFP, CFP were restricted to cells in the juxtaglomerular compartment (JGC at baseline. Following abrupt podocyte depletion in experimental FSGS, all four CoRL reporters were detected in a subset of glomeruli at day 28, where they co-expressed de novo four podocyte proteins (podocin, nephrin, WT-1 and p57 and two glomerular parietal epithelial cell (PEC proteins (claudin-1, PAX8. To monitor the precise migration of a subset of CoRL over a 2w period following podocyte depletion, intravital multiphoton microscopy was used. Our findings demonstrate direct visual support for the migration of single CoRL from the JGC to the parietal Bowman's capsule, early proximal tubule, mesangium and glomerular tuft. In summary, these results suggest that following podocyte depletion, multi-clonal CoRL migrate to the glomerulus and replace podocyte and PECs in experimental FSGS.

  12. Effect of primary air content on formation of nitrogen oxides during combustion of Ehkibastuz coal

    Energy Technology Data Exchange (ETDEWEB)

    Kotler, V.R.; Imankulov, Eh.R.

    1986-01-01

    Investigations are discussed carried out in a pilot plant at the Kaz. Power Engineering Scientific Research Institute into the effect of the amount of primary air in coal-dust flame on the final concentration of nitrogen oxides in flue gases. The tests were carried out in a 7500 mm high, 1600 mm dia vertical cylindrical combustion chamber having type P-57 burner, and air dispersed fuel plus additional air supplies located at the top. Amounts of coal dust fed by a drum feeder along the air pipe varied from 100-600 kg/h. The required air was supplied by 5000 m/sup 3//h Type TK-700/5 blowers at 0.04 MPa. Ehkibastuz coal samples contained: 1.3% moisture; 48.1% ash; 38.02% carbon; 2.56% hydrogen; 0.73% sulfur; 0.60% nitrogen; heat of combustion was 14.3 MJ/kg. Results obtained indicate that variations in the amount of primary air in swirl flow burners affect formation of fuel nitrogen; there is an optimum volume at which minimum quantities of nitrogen oxides are formed. Either an increase or decrease in the primary air results in a rise in nitrogen oxide concentration. 3 references.

  13. DISCOVERY OF HIGH-ENERGY GAMMA-RAY EMISSION FROM THE BINARY SYSTEM PSR B1259-63/LS 2883 AROUND PERIASTRON WITH FERMI

    International Nuclear Information System (INIS)

    Abdo, A. A.; Ackermann, M.; Ajello, M.; Allafort, A.; Bechtol, K.; Berenji, B.; Blandford, R. D.; Borgland, A. W.; Buehler, R.; Cameron, R. A.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Buson, S.; Bellazzini, R.; Bregeon, J.; Bonamente, E.; Brigida, M.; Bruel, P.; Caliandro, G. A.

    2011-01-01

    We report on the discovery of ≥100 MeV γ-rays from the binary system PSR B1259-63/LS 2883 using the Large Area Telescope (LAT) on board Fermi. The system comprises a radio pulsar in orbit around a Be star. We report on LAT observations from near apastron to ∼128 days after the time of periastron, t p , on 2010 December 15. No γ-ray emission was detected from this source when it was far from periastron. Faint γ-ray emission appeared as the pulsar approached periastron. At ∼t p + 30 days, the ≥100 MeV γ-ray flux increased over a period of a few days to a peak flux 20-30 times that seen during the pre-periastron period, but with a softer spectrum. For the following month, it was seen to be variable on daily timescales, but remained at ∼(1-4) x 10 -6 cm -2 s -1 before starting to fade at ∼t p + 57 days. The total γ-ray luminosity observed during this period is comparable to the spin-down power of the pulsar. Simultaneous radio and X-ray observations of the source showed no corresponding dramatic changes in radio and X-ray flux between the pre-periastron and post-periastron flares. We discuss possible explanations for the observed γ-ray-only flaring of the source.

  14. Blood harmane concentrations in 497 individuals relative to coffee, cigarettes, and food consumption on the morning of testing.

    Science.gov (United States)

    Louis, Elan D; Factor-Litvak, Pam; Gerbin, Marina; Jiang, Wendy; Zheng, Wei

    2011-01-01

    Harmane, a potent neurotoxin linked with several neurological disorders, is present in many foods, coffee, and cigarettes. We assessed whether morning food/coffee consumption and smoking were reflected in blood harmane concentrations (BHCs) we obtained in an epidemiologic sample (n = 497). Participants who smoked on the morning of phlebotomy had similar logBHCs to those who had not smoked (P = .57); there was no correlation between logBHCs and number of cigarettes (P = .59). Among the coffee drinkers, there was no correlation between number of cups and logBHCs (P = .98). Participants who had eaten on the morning of phlebotomy had similar logBHCs to those who had not (P = .49); logBHCs did not correlate with the time latency between last food consumption and phlebotomy (P = .74). BHCs in this sample of ~500 individuals did not covary with recent smoking, coffee, or food consumption, suggesting that our inability to withhold these exposures on the morning of phlebotomy was not reflected in the BHCs we measured.

  15. Temporal compression of soil erosion processes. A regional analysis of USLE database

    International Nuclear Information System (INIS)

    Gonzalez-Hidalgo, J. C.; Luis, M.; Lopez-Bermudez, F.

    2009-01-01

    When John Thornes and Denis Brunsden wrote in 1977 How often one hears the researcher (and no less the undergraduate) complain that after weeks of observation nothing happened only to learn that, the day after his departure, a flood caused unprecedented erosion and channel changes (Thrones and Brunsden, 1977, p. 57), they were focussing to important problems in Geomorphology: the extreme events and time compression of geomorphological processes. Time compression is a fundamental characteristic of geomorphological processes, some times produced by extreme events. Extreme events are rare events, defined by deviation from mean values. But from magnitude-frequency analysis we know that few events, not necessarily extreme, are able to produce a high amount of geomorphological work. finally time compression of geomorphological processes can be focused by the analysis of largest events defined by ranks, not magnitude. We have analysed the effects of largest events on total soil erosion by using 594 erosion plots from USLE database. Plots are located in different climate regions of USA and have different length of records. The 10 largest daily events mean contribution value is 60% of total soil erosion. There exist a relationship between such percentage and total daily erosive events recorded. The pattern seems to be independent of climate conditions. We discuss the nature of such relationship and the implications in soil erosion research. (Author) 17 refs.

  16. Efficacy and safety of the trans-obturator TVT-Abbrevo device in normal weight compared to overweight patients affected by stress urinary incontinence.

    Science.gov (United States)

    Tommaselli, Giovanni A; Napolitano, Valerio; Di Carlo, Costantino; Formisano, Carmen; Fabozzi, Annamaria; Nappi, Carmine

    2016-02-01

    To investigate if TVT-Abbrevo has similar outcomes in normal weight and overweight patients. Retrospective evaluation of 205 (105 normal weight women and 100 overweight women with BMI ≥ 25 kg/m(2)) undergone TVT-Abbrevo positioning with 12 month follow-up. Primary outcomes were objective cure rate (defined as no leakage during CST) and subjective cure rate ("very much improved"/"much improved" at PGI-I), secondary outcomes were intra-operative and post-operative complications. Objective cure rates in the normal and overweight groups were 96.2% and 94%, respectively (p=.47). Subjective cure rates in the normal and overweight groups were 90.5% and 88%, respectively (p=.57). ICIQ-SF, I-QoL and PGI-S scores significantly improved in both groups with no differences between the two groups. No serious intra- or post-operative complications were observed. No differences were observed in pain VAS scores and number of analgesic vials administered. TVT-Abbrevo seems to have similar efficacy and safety in normal weight and overweight women. More studies are needed to assess the efficacy of this device in frankly obese women and long-term outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Exogam with its ancillary detectors

    International Nuclear Information System (INIS)

    Theisen, Ch.

    2004-01-01

    The goal of the meeting was to discuss the status of experiments using Exogam and its ancillary detectors. Presentations include details of experiments already run and those in preparation. This document gathers most of the slides presented at the meeting. The results of 7 experiments are described. There are 9 contributions as it follows: 1) presentation of the Vamos spectrometer p.1-15, 2) the Clara (detector) and Prisma (spectrometer) setup: status and perspectives p.16-33, 3) experiment E344aS: shape coexistence near the N=Z line and collective properties of Kr isotopes investigated by low-energy Coulomb excitation p.34-56, 4) experiment E389: study of effective charges at Sm 100 via the nuclear lifetime measurements in Pd 96 and Cd 98 p.57-68, 5) experiment E375: spectroscopy of trans-fermium nuclei p.69-91, 6) experiment E408S: He 8 on Pb 208 and Bi 209 p.92-102, 7) experiment E462: very neutron rich calcium isotopes at N=32, structure of magic Ca 54 studied by gamma-spectroscopy with deep inelastic reactions p.103-115, 8) experiment E451: searching for T=D pairing and a new coupling scheme in Pd 92 and Ru 88 p.116-141, and 9) experiment E404aS: identification of gamma rays in nuclei around the drip-line nucleus Sm 130 , probing the maximally deformed light rare earth region

  18. Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ERα.

    Science.gov (United States)

    Tsang, Wing Pui; Zhang, Fengjie; He, Qiling; Cai, Waijiao; Huang, Jianhua; Chan, Wai Yee; Shen, Ziyin; Wan, Chao

    2017-01-16

    Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of mESCs self-renewal is characterized by increased population in S-phase of cell cycle, elevation of Cylin E and Cyclin-dependent kinase 2 (CDK2) and downregulation of p21, p27 and p57. PCR array screening reveals that caudal-related homeobox 2 (Cdx2) and Rbl2/p130 are remarkably suppressed in mESCs treated with Icaritin. siRNA knockdown of Cdx2 or Rbl2/p130 upregulates the expression of Cyclin E, OCT4 and SOX2, and subsequently increases cell proliferation and colony forming efficiency of mESCs. We then demonstrate that Icaritin co-localizes with estrogen receptor alpha (ERα) and activates its nuclear translocation in mESCs. The promotive effect of Icaritin on cell cycle and pluripotency regulators are eliminated by siRNA knockdown of ERα in mESCs. The results suggest that Icaritin enhances mESCs self-renewal by regulating cell cycle machinery and core pluripotency transcription factors mediated by ERα.

  19. CDK2 phosphorylation of Smad2 disrupts TGF-beta transcriptional regulation in resistant primary bone marrow myeloma cells.

    Science.gov (United States)

    Baughn, Linda B; Di Liberto, Maurizio; Niesvizky, Ruben; Cho, Hearn J; Jayabalan, David; Lane, Joseph; Liu, Fang; Chen-Kiang, Selina

    2009-02-15

    Resistance to growth suppression by TGF-beta1 is common in cancer; however, mutations in this pathway are rare in hematopoietic malignancies. In multiple myeloma, a fatal cancer of plasma cells, malignant cells accumulate in the TGF-beta-rich bone marrow due to loss of both cell cycle and apoptotic controls. Herein we show that TGF-beta activates Smad2 but fails to induce cell cycle arrest or apoptosis in primary bone marrow myeloma and human myeloma cell lines due to its inability to activate G(1) cyclin-dependent kinase (CDK) inhibitors (p15(INK4b), p21(CIP1/WAF1), p27(KIP1), p57(KIP2)) or to repress c-myc and Bcl-2 transcription. Correlating with aberrant activation of CDKs, CDK-dependent phosphorylation of Smad2 on Thr(8) (pT8), a modification linked to impaired Smad activity, is elevated in primary bone marrow myeloma cells, even in asymptomatic monoclonal gammopathy of undetermined significance. Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2. Our findings provide the first direct evidence that pT8 Smad2 couples dysregulation of CDK2 to TGF-beta resistance in primary cancer cells, and they suggest that disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-beta resistance in multiple myeloma.

  20. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    KAUST Repository

    Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B.; Wu, Chia-Chin; Akdemir, Kadir C.; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T.; Welch, Heidi C. E.; Garraway, Levi A.; Chin, Lynda

    2016-01-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  1. Fast sodium ion conductivity in supertetrahedral phosphidosilicates.

    Science.gov (United States)

    Johrendt, Dirk; Haffner, Arthur; Hatz, Anna Katharina; Moudrakovski, Igor; Lotsch, Bettina Valeska

    2018-04-03

    Fast sodium ion conductors are key components of sodium-based all-solid-state batteries which hold promise as safe systems for large-scale storage of electrical power. Here, we report the synthesis, crystal structure determination and Na+ ion conductivities of six new sodium ion conductors, the phosphidosilicates Na19Si13P25, Na23Si19P33, Na23Si28P45, Na23Si37P57, LT-NaSi2P3 and HT-NaSi2P3, which are entirely based on earth-abundant elements. The new structures exhibit SiP4 tetrahedra assembling interpenetrating networks of T3 to T5 supertetrahedral clusters which can be hierarchically assigned to sphalerite- or diamond-type structures. 23Na solid-state NMR spectra and geometrical pathway analysis indicate Na+ ion mobility between the supertetrahedral cluster networks. Electrochemical impedance spectroscopy revealed Na+ ion conductivities up to σ (Na+) = 4 ∙ 10-4 Scm-1 with an activation energy of Ea = 0.25 eV in HT-NaSi2P3 at 25 °C. The conductivities increase with the size of the supertetrahedral clusters due to the dilution of Na+ ions as the charge density of the anionic supertetrahedral networks decreases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Eficácia e toxicidade do pó comercial de Hoodia gordonii (Masson swet ex decne utilizado no tratamento da obesidade Efficacy and toxicity of Hoodia gordonii commercial powder used to combat obesity

    Directory of Open Access Journals (Sweden)

    C.A. Pereira

    2012-01-01

    Full Text Available A obesidade é atualmente o principal problema de saúde em países desenvolvidos e em desenvolvimento. Diversos recursos terapêuticos têm sido empregados para o tratamento da obesidade destacando-se os fitoterápicos, consagrados pelo conhecimento popular. Nesse contexto, a planta Hoodia gordonii tem despertado atualmente grande interesse mundial, principalmente pelas recentes descobertas e comprovações científicas da inibição do apetite e da sede pelo glicosídeo ativo P57 isolado de espécies da planta. Apesar disso, tais efeitos ainda não foram avaliados e comprovados em amostras comerciais do pó de H. gordonii (PHG, não existindo evidências científicas que garantam a sua eficácia e segurança. Portanto, o objetivo deste trabalho foi realizar ensaios biológicos com ratos para avaliar a atividade farmacológica e a toxicidade de amostras comerciais do pó de H. gordonii. As amostras foram administradas por gavagem em doses equivalentes a 20 vezes as recomendadas para humanos em ratas Wistar durante 4 semanas sendo avaliados os parâmetros indicadores do efeito terapêutico. Após as 4 semanas, os animais foram sacrificados, e amostras de sangue e órgãos foram coletados e submetidos à avaliação dos indicadores metabólicos, endócrinos, hematológicos e histopatológicos. Os resultados demonstraram que para todos os parâmetros avaliados não houve diferenças significativas entre o grupo controle que recebeu somente solução salina estéril e os grupos tratados com PHG indicando que os mesmos, apesar de não apresentarem quaisquer indícios de toxicidade, são incapazes de produzir os supostos efeitos de inibição de apetite e consequente tratamento da obesidade.Obesity is currently the main health problem in developed and developing countries. Several therapeutic methods have been employed for the treatment of obesity, especially herbal medicines, highlighted by popular knowledge. In this context, the plant Hoodia

  3. A randomized, blinded, prospective clinical trial of postoperative rehabilitation in dogs after surgical decompression of acute thoracolumbar intervertebral disc herniation.

    Science.gov (United States)

    Zidan, Natalia; Sims, Cory; Fenn, Joe; Williams, Kim; Griffith, Emily; Early, Peter J; Mariani, Chris L; Munana, Karen R; Guevar, Julien; Olby, Natasha J

    2018-05-01

    Experimental evidence shows benefit of rehabilitation after spinal cord injury (SCI) but there are limited objective data on the effect of rehabilitation on recovery of dogs after surgery for acute thoracolumbar intervertebral disc herniations (TL-IVDH). Compare the effect of basic and intensive post-operative rehabilitation programs on recovery of locomotion in dogs with acute TL-IVDH in a randomized, blinded, prospective clinical trial. Thirty non-ambulatory paraparetic or paraplegic (with pain perception) dogs after decompressive surgery for TL-IVDH. Blinded, prospective clinical trial. Dogs were randomized (1:1) to a basic or intensive 14-day in-house rehabilitation protocol. Fourteen-day open field gait score (OFS) and coordination (regulatory index, RI) were primary outcomes. Secondary measures of gait, post-operative pain, and weight were compared at 14 and 42 days. Of 50 dogs assessed, 32 met inclusion criteria and 30 completed the protocol. There were no adverse events associated with rehabilitation. Median time to walking was 7.5 (2 - 37) days. Mean change in OFS by day 14 was 6.13 (confidence intervals: 4.88, 7.39, basic) versus 5.73 (4.94, 6.53, intensive) representing a treatment effect of -0.4 (-1.82, 1.02) which was not significant, P=.57. RI on day 14 was 55.13 (36.88, 73.38, basic) versus 51.65 (30.98, 72.33, intensive), a non-significant treatment effect of -3.47 (-29.81, 22.87), P = .79. There were no differences in secondary outcomes between groups. Early postoperative rehabilitation after surgery for TL-IVDH is safe but doesn't improve rate or level of recovery in dogs with incomplete SCI. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  4. Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors.

    Science.gov (United States)

    Eymin, Béatrice; Gazzeri, Sylvie; Brambilla, Christian; Brambilla, Elisabeth

    2002-04-18

    Pathways involving p53 and pRb tumor suppressor genes are frequently deregulated during lung carcinogenesis. Through its location at the interface of these pathways, Mdm2 can modulate the function of both p53 and pRb genes. We have examined here the pattern of expression of Mdm2 in a series of 192 human lung carcinomas of all histological types using both immunohistochemical and Western blot analyses and four distinct antibodies mapping different epitopes onto the Mdm2 protein. Using Immunohistochemistry (IHC), Mdm2 was overexpressed as compared to normal lung in 31% (60 out of 192) of all tumors analysed, whatever their histological types. Western blotting was performed on 28 out of the 192 tumoral samples. Overexpression of p85/90, p74/76 and p57 Mdm2 isoforms was detected in 18% (5 out of 28), 25% (7 out of 28) and 39% (11 out of 28) of the cases respectively. Overall, overexpression of at least one isoform was observed in 14 out of 28 (50%) lung tumors and concomittant overexpression of at least two isoforms in 7 out of 28 (25%) cases. A good concordance (82%) was observed between immunohistochemical and Western blot data. Interestingly, a highly significant inverse relationship was detected between p14(ARF) loss and Mdm2 overexpression either in NSCLC (P=0.0089) or in NE lung tumors (P1 ratio was correlated with a high grade phenotype among NE tumors overexpressing Mdm2 (P=0.0021). Taken together, these data strongly suggest that p14(ARF)and Mdm2 act on common pathway(s) to regulate p53 and/or pRb-dependent or independent functions and that the Mdm2 : p14(ARF) ratio might act as a rheostat in modulating the activity of both proteins.

  5. Levantamento de estoques da ostra Crassostrea sp. em bancos naturais no litoral paranaense

    Directory of Open Access Journals (Sweden)

    Euler Batista Erse

    2011-09-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2008v21n2p57 A importância econômica de diversas espécies de ostras nativas, em especial a Crassostrea sp., torna atrativa a exploração desta espécie pelas comunidades litorâneas. A explotação deste recurso natural, baseada somente no extrativismo não sustentável acaba por ameaçar os estoques naturais com a sobrepesca. Baseado neste fato, uma avaliação das condições dos estoques naturais desse animal torna-se importante para futuros projetos de conservação e manejo sustentáveis do recurso. Neste trabalho foram levantados dados referentes aos estoques da ostra Crassostrea sp. de três bancos naturais distintos, sendo estes, um na Ilha da Cotinga, na foz do Rio Maciel e outro na foz do Rio Biguaçú. Em cada banco, foram feitas três amostragens aleatórias durante a maré baixa sizígia utilizando-se de um quadrado de amostragem com dimensão de 30x30 cm. Observamos também neste trabalho que, dos locais de estoques naturais da ostra nativa Cras- sostrea sp. presentes na Baía de Paranaguá, o da Ilha da Cotinga apresenta signifi cativamente os maiores valores quanto ao tamanho se comparados com a o Rio Maciel e o Rio Biguaçú, sendo que, entre os dois últimos, o primeiro apresentou maiores valores. Porém, não houve diferenças signifi cativas nos valores biométricos encontrados entre os bancos amostrados nos respectivos bosques.

  6. The effect of staff training on agitation and use of restraint in nursing home residents with dementia: a single-blind, randomized controlled trial.

    Science.gov (United States)

    Testad, Ingelin; Ballard, Clive; Brønnick, Kolbjørn; Aarsland, Dag

    2010-01-01

    Agitation is common in dementia and is associated with use of restraints and use of psychotropic drugs. The aim of this study was to determine whether an education and supervision intervention could reduce agitation and the use of restraints and antipsychotic drugs in nursing homes. Four Norwegian nursing homes were randomly allocated to receive either treatment as usual or an intervention consisting of a 2-day educational seminar and monthly group guidance for 6 months. One hundred forty-five residents with dementia (based on medical records and corroborated with a Functional Assessment Staging score >or= 4) completed baseline and 6-month intervention assessments and were included in the analyses. The co-primary outcome measures were the proportion of residents subject to interactional restraint and the severity of agitation using the Cohen-Mansfield Agitation Inventory (CMAI). Patients were assessed at baseline, immediately after completion of the intervention at 6 months, and 12 months after baseline. Comparison of change in the 2 groups was made using repeated-measures analysis of variance (CMAI) and Mann-Whitney test (restraints). The study was conducted from 2003 to 2004. The proportion of residents starting new restraint was lower in the intervention than in the control group at 6-month evaluation (P = .02), but no statistically significant differences were found at 12-month assessment (P = .57). The total CMAI score declined from baseline to 6 and 12 months' follow-up in the intervention homes compared to a small increase in the control homes (F2,176 = 3.46, P = .034). There were no statistically significant differences in use of antipsychotic drugs. A brief 2-day staff education program followed by continued monthly guidance was able both to improve quality of care by reducing the frequency of interactional restraints and to reduce severity of agitation. ©Copyright 2010 Physicians Postgraduate Press, Inc.

  7. Performance of five plant species in removal of nitrogen and phosphorus from an experimental phytoremediation system in the Ningxia irrigation area.

    Science.gov (United States)

    Chen, Chongjuan; Zhao, Tiancheng; Liu, Ruliang; Luo, Liangguo

    2017-09-10

    Agricultural non-point source (ANPS) pollution is an important contributor to elevated nitrogen (N) and phosphorus (P) in surface waters, which can cause serious environmental problems. Considerable effort has therefore gone into the development of methods that control the ANPS input of N and P to surface waters. Phytoremediation has been extensively used because it is cost-effective, environmentally friendly, and efficient. The N and P loads from agricultural drainage are a potential threat to the water quality of the Yellow River in Ningxia, China. Yet, phytoremediation has only rarely been applied within the Ningxia irrigation area. In an experimental set-up, five species (Ipomoea aquatica, IA; Lactuca sativa, LS; Oryza sativa, OS; Typha latifolia, TL; Zizania latifolia, ZL) were evaluated for their ability to reduce N and P loads over 62 days and five observation periods. Total N and P concentrations, plant biomass, and nutrient content were measured. The results showed that OS, LS, and IA performed better than ZL and TL in terms of nutrients removal, biomass accumulation, and nutrients storage. The highest overall removal rates of N and P (57.7 and 57.3%, respectively) were achieved by LS treatment. In addition, plant uptake contributed significantly to nutrient removal, causing a 25.9-72.0% reduction in N removal and a 54.3-86.5% reduction in P removal. Thus, this study suggests that OS, LS, and IA would be more suitable than ZL and TL for controlling nutrient loads in the Ningxia irrigation area using phytoremediation.

  8. Perceived Fall Risk and Functional Decline: Gender Differences in Patient's Willingness to Discuss Fall Risk, Fall History, or to Have a Home Safety Evaluation.

    Science.gov (United States)

    Greenberg, Marna Rayl; Moore, Elizabeth C; Nguyen, Michael C; Stello, Brian; Goldberg, Arnold; Barraco, Robert D; Porter, Bernadette G; Kurt, Anita; Dusza, Stephen W; Kane, Bryan G

    2016-06-01

    The CDC reports that among older adults, falls are the leading cause of injury-related death and rates of fall-related fractures among older women are twice those of men. We set out to 1) determine patient perceptions (analyzed by gender) about their perceived fall risk compared to their actual risk for functional decline and death and 2) to report their comfort level in discussing their fall history or a home safety plan with their provider. Elders who presented to the Emergency Department (ED†) were surveyed. The survey included demographics, the Falls Efficacy Scale (FES) and the Vulnerable Elders Survey (VES); both validated surveys measuring fall concern and functional decline. Females had higher FES scores (mean 12.3, SD 5.9) than males (mean 9.7, SD 5.9 p = .007) in the 146 surveys analyzed. Females were more likely to report an increased fear of falling, and almost three times more likely to have a VES score of 3 or greater than males (OR = 2.86, 95% CI: 1.17-7.00, p = .02). A strong correlation was observed between FES and VES scores (r = 0.80, p fall risk with a provider; there was no difference between genders (p = .57). In this study, irrespective of gender, there appears to be a high association between subjects' perceived fall risk and risk for functional decline and death. The majority of patients are likely willing to discuss their fall risk with their provider. These findings may suggest a meaningful opportunity for fall risk mitigation in this setting.

  9. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).

    Science.gov (United States)

    Zhang, Tiening; Cai, Xun; Li, Qi; Xue, Peng; Chen, Zhixiao; Dong, Xiao; Xue, Ying

    2016-07-05

    Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.

  10. Thermal comparison of Infiniti OZil and Signature Ellips phacoemulsification systems.

    Science.gov (United States)

    Schmutz, Joseph S; Olson, Randall J

    2010-05-01

    To determine thermal characteristics of Signature Ellips (Abbott Medical Optics) and Infiniti OZil (Alcon, Inc.) transverse ultrasound and compare both with longitudinal ultrasound in clinically relevant scenarios. Laboratory investigation. Temperature increase over baseline after 60 seconds was measured in water at positions in 90-degree increments around the sleeve near the proximal needle shaft in an artificial chamber for Ellips and OZil on continuous ultrasound with aspiration blocked and unblocked. This was also done with Signature using longitudinal ultrasound, with and without micropulse (6 ms on, 12 ms off), with aspiration blocked and unblocked, and at the OZil sleeve tip on continuous transverse mode with aspiration unblocked. OZil (8.1 +/- 0.3 C) had greater temperature increase than Ellips (5.2 +/- 0.3 C; P < .0001) with aspiration unblocked and blocked (29.3 +/- 1.0 C vs 12.2 +/- 0.7 C; P < .0001). OZil had uneven distribution of heat around the shaft (30.1 +/- 0.5 C vs 28.5 +/- 0.6 C; P < .0001), whereas Ellips did not (P = .57). OZil was cooler at the tip (6.6 +/- 0.2 C; P < .0001). Friction in a cadaver eye incision only increased these numbers by 10% (OZil, irrigation blocked). Metal stress probably creates heat at the proximal needle junction for both transverse methods. Heat generation differences between OZil and Ellips result from the manner in which they create needle motion. Incision burns may occur, especially for OZil, under nonpulsed settings during fragment removal with occlusion when reaching across the anterior chamber such that the proximal needle shaft came near the wound. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Evaluation of microbial contamination of canine plasma eyedropper bottles following clinical use in canine patients.

    Science.gov (United States)

    Strauss, Rachel A; Genschel, Ulrike; Allbaugh, Rachel A; Sebbag, Lionel; Ben-Shlomo, Gil

    2018-05-24

    To investigate microbial contamination of canine plasma eye drops when used clinically and to compare the effect of two different eyedropper bottles on contamination rate. Forty-six bottles containing plasma were randomly dispensed for use on 42 dogs with ulcerative keratitis. Of these, 23 were standard eyedropper bottles and 23 were Novelia ® bottles designed to prevent contamination. After use for up to 2 weeks, samples for bacterial culture were obtained from a drop of plasma, the bottle tip, the plasma inside the bottle, and the corneal surface. Fungal culture was performed from a drop of plasma. The overall microbial contamination rate was 17.4% (8/46 bottles); however, only one bottle had growth from the plasma inside the bottle. There was a lower contamination rate of Novelia ® bottles (3/23 = 13.0%) compared to standard bottles (5/23 = 21.7%), but this difference was not statistically significant (P = .57). There were also no significant differences in contamination rate of bottles used greater than 7 days compared to less than or equal to 7 days, or in bottles used greater than 4 times daily compared to 4 times daily or less. Three corneal samples (6.5%) had bacterial growth, but none matched contamination from the bottles. Novelia ® bottles may decrease contamination of plasma eye drops used clinically. However, while microbial contamination of plasma bottles was documented, no clinically relevant complications were observed. This study supports safe use of plasma eye drops for up to 2 weeks when refrigerated and dispensed from either Novelia ® or standard eyedropper bottles. © 2018 American College of Veterinary Ophthalmologists.

  12. Accuracy of three hemoglobin A1c point-of-care systems for glucose monitoring in patients with diabetes mellitus.

    Science.gov (United States)

    Torregrosa, María-Eugenia; Molina, Juan; Argente, Carlos R; Ena, Javier

    2015-12-01

    Use of hemoglobin A1c point-of-care devices in physician offices provides immediate results and reduces inconveniences for the patients. We compared the analytical performances of 3 point-of-care HbA1c analyzers to high pressure liquid chromatography (HPLC). We preselected a pool of 40 EDTA-preserved whole blood samples from our laboratory with HbA1c results obtained by HPLC (mean 6.6% [49 mmol/mol] and range: 4.6-9.9% [27-87 mmol/mol]). Aliquots of theses samples were tested by Afinion AS100, DCA Vantage and In2it point-of-care systems. According the Clinical Laboratory Standards Institute EP-09 protocol we determined linearity (linear regression and correlation coefficient between point-of-care and reference methods), bias (Bland-Altman analysis) and coefficient of variation (%). We used the acceptability criteria endorsed by the National Glycohemoglobin Standardization Program. The calculated correlation coefficients (r) were 0.98, 0.98 and 0.83 for Afinion AS100, DCA Vantage and In2it systems, respectively. The 95% confidence interval of the error between point-of-care systems and the reference method was -0.41% and +0.34% (p =.22) for Afinion AS100, -0.62% and +0.05% (p =.57) for DCA Vantage, and -1.15% and +1.26% (p<.001) for the In2it. The coefficients of variation for Afinion AS100, DCA Vantage and In2it systems were 1.80, 3.74 and 7.14%, respectively. Only the Afinion AS100 point-of-care system met all NGSP performance criteria. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  13. A celiac cellular phenotype, with altered LPP sub-cellular distribution, is inducible in controls by the toxic gliadin peptide P31-43.

    Directory of Open Access Journals (Sweden)

    Merlin Nanayakkara

    Full Text Available Celiac disease (CD is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP gene was identified as strongly associated with CD using genome-wide association studies (GWAS. The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis.

  14. Optimal Order of Successive Office Hysteroscopy and Endometrial Biopsy for the Evaluation of Abnormal Uterine Bleeding: A Randomized Controlled Trial.

    Science.gov (United States)

    Sarkar, Papri; Mikhail, Emad; Schickler, Robyn; Plosker, Shayne; Imudia, Anthony N

    2017-09-01

    To estimate the optimal order of office hysteroscopy and endometrial biopsy when performed successively for evaluation of abnormal uterine bleeding. Patients undergoing successive office hysteroscopy and endometrial biopsy were included in a single-blind, prospective, randomized trial. The primary outcome was to evaluate the effect of order of procedures on patients' pain score. Prespecified secondary outcomes include procedure duration, hysteroscopic visualization of the uterine cavity, endometrial sample adequacy, and number of attempts at biopsy. Pain scores were assessed using a visual analog scale from 0 to 10 and endometrial sample adequacy was determined from the histopathology report. Hysteroscopy images were recorded. Sample size of 34 per group (n=68) was determined to be adequate to detect a difference of 20% in visual analog scale score between hysteroscopy first (group A) and biopsy first (group B) at α of 0.05 and 80% power. Between October 2015 and January 2017, 78 women were randomized to group A (n=40) and group B (n=38). There was no difference in global pain perception [7 (0-10) vs 7 (0-10); P=.57, 95% CI 5.8-7.1]. Procedure duration [3 (1-9) vs 3 (2-10), P=.32, 95% CI 3.3-4.1] and endometrial sample adequacy (78.9% vs 75.7%, P=.74) were similar in both groups. Group A patients had better endometrial visualization (Pabnormal uterine bleeding, the global pain perception, and time required are independent of the order in which procedures are performed. Performing hysteroscopy first ensures better image, whereas biopsy first yields adequate tissue sample with fewer attempts. ClinicalTrials.gov, NCT02472184.

  15. RURAL TEACHERS IN SINALOA: PEDAGOGUES, HEALTH PROMOTERS AND SOCIO-POLITICAL ACTIVISTS

    Directory of Open Access Journals (Sweden)

    Rafael Santos-Cenobio

    2017-07-01

    Full Text Available The objective of this article is to study the formation of the postrevolutionary Mexican State based on the actions undertaken by rural teachers belonging to the Ministry of Public Education (SEP. From these actors a cultural revolution was programmed and undertaken at the national level, which established as a mission to integrate and incorporate the masses of peasants and workers into the national culture. In this sense, the teachers functioned as articulators between the communities and the national State, they became pedagogues, organizers of peasants and workers; promoters of unity and legitimacy through songs, dances, theater and oratory, introducing the new heroes and principles of the Revolution to political processes and local artistic expressions. (Kay, 1997, p.57 The work consists of two sections. In the first one it refers to the educational actions undertaken by the State as manifestations against alcoholism, Day and Tree Week. These projects were executed by state governors, municipal presidents, teachers and students, who were responsible for touring the streets shouting and shouting slogans against alcoholism and the damage it caused. The second section refers to the work of teachers, especially in their respective communities where they organized clean-up campaigns, sporting events, tree planting and formation of parent committees to raise funds for the construction of schools. At the same time, teachers are analyzed as articulators between the national State and rural communities. To realize the socialist project, the professors organized plays, founded night schools, chaired meetings and gave lectures to the citizens of the community. Likewise, the professors became popular leaders, because they advised and founded labor unions; In addition, they created Agrarian Committees, of which they themselves were established as leaders.

  16. Affective reactivity to daily stressors is associated with elevated inflammation.

    Science.gov (United States)

    Sin, Nancy L; Graham-Engeland, Jennifer E; Ong, Anthony D; Almeida, David M

    2015-12-01

    Inflammation increases the risk of chronic diseases, but the links between emotional responses to daily events and inflammation are unknown. We examined individual differences in affective reactivity to daily stressors (i.e., changes in positive and negative affect in response to stressors) as predictors of inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP). A cross-sectional sample of 872 adults from the National Study of Daily Experiences (substudy of Midlife in the United States II) reported daily stressors and affect during telephone interviews for 8 days. Blood samples were obtained at a separate clinic visit and assayed for inflammatory markers. Multilevel models estimated trait affective reactivity slopes for each participant, which were inputted into regression models to predict inflammation. People who experienced greater decreases in positive affect on days when stressors occurred (i.e., positive affect reactivity) had elevated log IL-6, independent of demographic, physical, psychological, and behavioral factors (B = 1.12, SE = 0.45, p = .01). Heightened negative affect reactivity was associated with higher log CRP among women (p = .03) but not men (p = .57); health behaviors accounted for this association in women. Adults who fail to maintain positive affect when faced with minor stressors in everyday life appear to have elevated levels of IL-6, a marker of inflammation. Women who experience increased negative affect when faced with minor stressors may be at particular risk of elevated inflammation. These findings add to growing evidence regarding the health implications of affective reactivity to daily stressors. (c) 2015 APA, all rights reserved).

  17. High-Temperature Nucleosynthesis Processes on the Proton-Rich Side of Stability: the Alpha-Rich Freezeout and the rp^2-Process

    Science.gov (United States)

    Meyer, Bradley S.

    2001-10-01

    Nucleosynthesis on the proton-rich side of stability has at least two intriguing aspects. First, the most abundant of the stable iron-group isotopes, such as ^48Ti, ^52Cr, and ^56,57Fe, are synthesized as proton-rich, radioactive parents in alpha-rich freezeouts from equilibrium. The production of these radioactive progenitors depends in large measure on reactions on the proton-rich side of stability. The second intriguing aspect is that explosive nucleosynthesis in a hydrogen-rich environment (namely, the rp-process) may be associated with exotic astrophysical settings, such as x-ray bursts, and may be responsible for production of some of the light p-process nuclei (for example, ^92,94Mo and ^96,98Ru). We have developed web-based tools to help nuclear physicists determine which nuclear reactions on the proton-rich side of stability govern the nucleosynthesis in these processes. For the alpha-rich freezeout, one may determine the effect of any one of 2,140 reactions on the yield of any isotope in the nuclear reaction network with the web calculator. As a relevant example, I will discuss the governing role of ^57Ni (n,p)^57Co in the synthesis of the important astronomical observable ^57Co. As for explosive, proton-rich burning, I will discuss the synthesis of p-process nuclei in the repetitive rp-process (the rp^2-process). movies/rp.html>Movies of the rp^2-process illustrate its important features and give some indications of the important nuclear reactions.

  18. (3He,α) reaction mechanism at high energy and neutron inner shell structure

    International Nuclear Information System (INIS)

    Wiele, J. van de.

    1980-01-01

    The ( 3 He,α) reaction on 12 C, 16 O, 28 Si, 58 Ni, 90 Zr, 118 Sn, 124 Sn and 208 Pb targets has been studied at Esub( 3 He) = 217 MeV (or 205 MeV) in order to investigate the reaction mechanism at high energy and large momentum transfer. The reaction yields large cross sections at very forward angles and strongly enhances the largest orbital momentum transfer. The angular distribution shapes are well reproduced in the frame-work of the Z-R- D.W.B.A. analysis if we use a unique empirical α-potential: Vsub(α)(Esub(α)) = Vsub( 3 He)(3/4 Esub(α)) + Vsub(n)(1/4 Esub(α)). The excitation energy spectra have been measured up to 100 MeV in the residual light and medium nuclei and up to about 16 MeV in heavy nuclei. In addition to the well-known low-lying levels, peaks or broad structures are observed for each nucleus at higher excitation energies. They are attributed to pick up from inner shells: 1s( 11 C and 15 O), 1p( 27 Si), 1d5/2 + 1p( 57 Ni), 1f7/2( 89 Zr) 1g9/2 117 Sn, 123 Sn and 1h11/2( 207 Pb). Selectivity and localization of direct and indirect pick up ( 3 He,α) reactions were studied. Finite range calculations show that this reaction is not very sensitive to the details of the range from function but only to D 0 coefficient and range R. A microscopic α-nucleus optical potential calculated with n-n dependent and independent density forces is able to reproduce both elastic scattering and pick up reaction angular distributions [fr

  19. In the Modern Treatment Era, Is Breast Conservation Equivalent to Mastectomy in Women Younger Than 40 Years of Age? A Multi-Institution Study

    Energy Technology Data Exchange (ETDEWEB)

    Frandsen, Jonathan; Ly, David [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah School of Medicine, Salt Lake City, Utah (United States); Cannon, George [Department of Radiation Oncology, Intermountain Medical Center, Murray, Utah (United States); Suneja, Gita [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah School of Medicine, Salt Lake City, Utah (United States); Matsen, Cindy [Department of General Surgery, Huntsman Cancer Hospital, University of Utah School of Medicine, Salt Lake City, Utah (United States); Gaffney, David K. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah School of Medicine, Salt Lake City, Utah (United States); Wright, Melissa [Oncology Clinical Program, Intermountain Healthcare, Salt Lake City, Utah (United States); Kokeny, Kristine E. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah School of Medicine, Salt Lake City, Utah (United States); Poppe, Matthew M., E-mail: matthew.poppe@hci.utah.edu [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah School of Medicine, Salt Lake City, Utah (United States)

    2015-12-01

    Purpose: Mastectomy is often recommended for women ≤40 years of age with breast cancer, as young women were under-represented in the landmark trials comparing breast conservation therapy (BCT) to mastectomy. We hypothesized that, in the modern treatment era, BCT and mastectomy result in equivalent local control rates in young women. Methods and Materials: Breast cancer cases arising between 1975 and 2013 in women ≤40 years old were collected from the tumor registries of 2 large healthcare systems in Utah. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze freedom from locoregional recurrence (FFLR), overall survival (OS), and relapse-free survival (RFS). Results: This analysis identified 853 BCT candidates. A comparison of BCT to mastectomy after 2000 showed FFLR, RFS, and OS were all similar. Rate for FFLR at 10 years was 94.9% versus 92.1% for BCT and mastectomy, respectively (P=.57). For women whose cancer was diagnosed after 2000, who received BCT, FFLR and RFS rates were improved compared to those whose cancer was diagnosed prior to 2000 (P<.05), whereas OS (P=.46) rates were similar. Among those who underwent mastectomy, FFLR, OS, and RFS were significantly improved (P<.05) with diagnosis after 2000. Conclusions: FFLR rates for young women, ≤40 years of age, have significantly improved for BCT and mastectomy over time. If patients were treated after 2000, BCT appears to be safe and equivalent to mastectomy at 10 years in terms of FFLR, OS, and RFS.

  20. Low pH induces co-ordinate regulation of gene expression in oesophageal cells.

    Science.gov (United States)

    Duggan, Shane P; Gallagher, William M; Fox, Edward J P; Abdel-Latif, Mohammed M; Reynolds, John V; Kelleher, Dermot

    2006-02-01

    The development of gastro-oesophageal reflux disease (GORD) is known to be a causative risk factor in the evolution of adenocarcinoma of the oesophagus. The major component of this reflux is gastric acid. However, the impact of low pH on gene expression has not been extensively studied in oesophageal cells. This study utilizes a transcriptomic and bioinformatic approach to assess regulation of gene expression in response to low pH. In more detail, oesophageal adenocarcinoma cell lines were exposed to a range of pH environments. Affymetrix microarrays were used for gene-expression analysis and results were validated using cycle limitation and real-time RT-PCR analysis, as well as northern and western blotting. Comparative promoter transcription factor binding site (TFBS) analysis (MatInspector) of hierarchically clustered gene-expression data was employed to identify the elements which may co-ordinately regulate individual gene clusters. Initial experiments demonstrated maximal induction of EGR1 gene expression at pH 6.5. Subsequent array experimentation revealed significant induction of gene expression from such functional categories as DNA damage response (EGR1-4, ATF3) and cell-cycle control (GADD34, GADD45, p57). Changes in expression of EGR1, EGR3, ATF3, MKP-1, FOSB, CTGF and CYR61 were verified in separate experiments and in a variety of oesophageal cell lines. TFBS analysis of promoters identified transcription factors that may co-ordinately regulate gene-expression clusters, Cluster 1: Oct-1, AP4R; Cluster 2: NF-kB, EGRF; Cluster 3: IKRS, AP-1F. Low pH has the ability to induce genes and pathways which can provide an environment suitable for the progression of malignancy. Further functional analysis of the genes and clusters identified in this low pH study is likely to lead to new insights into the pathogenesis and therapeutics of GORD and oesophageal cancer.

  1. E-cigarettes and National Adolescent Cigarette Use: 2004-2014.

    Science.gov (United States)

    Dutra, Lauren M; Glantz, Stanton A

    2017-02-01

    E-cigarette use is rapidly increasing among adolescents in the United States, with some suggesting that e-cigarettes are the cause of declining youth cigarette smoking. We hypothesized that the decline in youth smoking changed after e-cigarettes arrived on the US market in 2007. Data were collected by using cross-sectional, nationally representative school-based samples of sixth- through 12th-graders from 2004-2014 National Youth Tobacco Surveys (samples ranged from 16 614 in 2013 to 25 324 in 2004). Analyses were conducted by using interrupted time series of ever (≥1 puff) and current (last 30 days) cigarette smoking. Logistic regression was used to identify psychosocial risk factors associated with cigarette smoking in the 2004-2009 samples; this model was then applied to estimate the probability of cigarette smoking among cigarette smokers and e-cigarette users in the 2011-2014 samples. Youth cigarette smoking decreased linearly between 2004 and 2014 (P = .009 for ever smoking and P = .05 for current smoking), with no significant change in this trend after 2009 (P = .57 and .23). Based on the psychosocial model of smoking, including demographic characteristics, willingness to wear clothing with a tobacco logo, living with a smoker, likelihood of smoking in the next year, likelihood of smoking cigarettes from a friend, and use of tobacco products other than cigarettes or e-cigarettes, the model categorized e-cigarette-only users (between 11.0% in 2012 and 23.1% in 2013) as current smokers. The introduction of e-cigarettes was not associated with a change in the linear decline in cigarette smoking among youth. E-cigarette-only users would be unlikely to have initiated tobacco product use with cigarettes. Copyright © 2017 by the American Academy of Pediatrics.

  2. Vitamin E levels in preeclampsia placenta tissue and its correlation with oxidative stress injury and apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Li

    2017-04-01

    Full Text Available Objective: To study the vitamin E levels in preeclampsia placenta tissue and its correlation with oxidative stress injury and apoptosis. Methods: A total of 60 pregnant women with preeclampsia who received treatment and gave birth in our hospital between July 2012 and January 2016 were collected and divided into mild preeclampsia group (n=41 and severe preeclampsia group (n=19 according to the disease severity; 38 normal pregnant women who received pregnancy test and gave birth in our hospital during the same period were selected as healthy control group. The placental tissue samples of three groups of research subjects were retained, high performance liquid chromatograph-mass spectrometry was used to detect VitE levels in tissue grinding fluid, automatic biochemical analyzer was used to detect the levels of oxidative stress injury indexes, and fluorescence quantitative PCR method was used to detect the mRNA expression of apoptosis molecules. Results: VitE, SOD and CAT levels in grinding fluid of severe preeclampsia group were lower than those of mild preeclampsia group and healthy control group while ROS and AOPP levels were higher than those of mild preeclampsia group and healthy control group; Fas, caspase and Apaf-1 mRNA expression were higher than those of mild preeclampsia group and healthy control group while anti-apoptotic molecules Bcl-2, Bcl-xl, Mcl-2 and p57kip2 mRNA expression were lower than those of mild preeclampsia group and healthy control group. Spearman correlation analysis showed that VitE level in the preeclampsia placenta tissue was directly correlated with oxidative stress injury and cell apoptosis. Conclusion: VitE deficiency is the direct factor that results in oxidative stress and cell apoptosis in patients with preeclampsia, and the VitE supplementation in time is expected to become the auxiliary treatment means for patients with preeclampsia.

  3. Synthesis of Chalcone and Flavanone Compound Using Raw Material of Acetophenone and Benzaldehyde Derivative

    Directory of Open Access Journals (Sweden)

    Ismiyarto Ismiyarto

    2010-06-01

    Full Text Available Synthesis of flavanoid compounds of chalcone and flavanone groups have been conducted. Flavanoid Is one of the group natural products which is mostly found in plants and have been proved to have physiological activity as drug. In this research, chalcone proup compounds that being synthesized are: chalcone, 3,4-dimethoxychalcone, 2'-hidroxy-3,4-dimethoxychalcone where as compound of flavanone group that being synthesized is 3',4'-dimethoxyflavanone. The synthesis of chalcone group are carried out based on Claisen-Schmidt reaction by using raw material of aromatic aldehydes and aromatic ketones. The synthesis in carried out by stirring at the room temperature using alkali solution as catalyst and ethanol as solvent. The synthesis of 3',4'-dimethoxyflanone is made based on the nucleophilic 1,4 addition of the unsaturated α,β ketone. The synthesis is made by refluxing 2'-hydroxy-3,4-dimethoxychalcone in alkali condition for 12 hours. The identification of flavanoid compound is carried out by using spectroscopic IR, GC-MS and 1H-NMR methods. The result of each synthesis chalcone group are follows: chalcone as yellowish solid with m.p= 50 °C and the yield is 83.39%; 3,4-dimethoxychalcone as yellow solid with m.p= 57°C and the yield is 76.00% ; 2'-hydroxy-3,4-dimethoxychalcone as orange solid with m.p= 90 °C and the yield is 74.29%, for 3',4'-dimethoxyflavanone as pale yellow solid with m.p= 80 °C and the yield is 72.00%.

  4. Anabolic/androgenic steroid administration during adolescence and adulthood differentially modulates aggression and anxiety.

    Science.gov (United States)

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2015-03-01

    Anabolic/androgenic steroid (AAS) use remains high in both teens and adults in the U.S. and worldwide despite studies showing that AAS use is associated with a higher incidence of aggression and anxiety. Recently we showed that chronic exposure to AAS through adolescence increases aggression and decreases anxious behaviors, while during AAS-withdrawal aggression is lowered to species-normative levels and anxiety increases. AAS exposure is known to differentially alter behaviors and their underlying neural substrates between adults and adolescents and thus the current study investigated whether exposure to AAS during adulthood affects the relationship between aggression and anxiety in a manner similar to that previously observed in adolescents. Male hamsters were administered a moderate dose of AAS (5.0mg/kg/day×30days) during adolescence (P27-56) or young adulthood (P65-P94) and then tested for aggression and anxiety during AAS exposure (i.e., on P57 or P95) and during AAS withdrawal (i.e., 30days later on P77 or P115). Adolescent exposure to AAS increased aggressive responding during the AAS exposure period and anxiety-like responding during AAS withdrawal. Neither behavior was similarly influenced by adult exposure to AAS. Adult AAS exposure produced no difference in aggressive responding during AAS exposure (P95) or AAS withdrawal (P115); however, while AAS exposure during adulthood produced no difference in anxiety-like responding during AAS exposure, adult hamsters administered AAS were less anxious than vehicle control animals following AAS withdrawal. Together these data suggest that the aggression and anxiety provoking influence of AAS are likely a developmental phenomenon and that adult exposure to AAS may be anxiolytic over the long term. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. The 57Co excretion and resorption test in the diagnosis of iron deficiency anemia

    International Nuclear Information System (INIS)

    Bekier, A.; Holdener, E.; Kantonsspital Sankt Gallen

    1976-01-01

    1971 Sorbie et al. described a simple 57 Co-excretion test (16) as an aid in the diagnosis of iron deficiency anemia. The authors found that renal excretion of a tracer dosis of 0,5 μCi 57 CoCl 2 was significantly elevated in patients with iron deficiency anemia (31% of the adminstered dose in 24 hours' urine) as compared with the controls (18%). Between 1972-1974 we performed the 57 Co-excretion test in 29 patients with different kind of anemia and in 10 healthy volunteers. The test was modified by measurement of the serum activity 1, 2, 3, 7, 11 and 24 hours after the oral administration of the test dosis. In all anemias as well as in the control group we found the maximum of serum activity three hours after the oral administration of the tracer. The three hours serum activity was elevated in patients with iron deficiency anemia (5.53%/l serum) as compared with the control group (1.92%/l) and renal, tumor and infectious anemia (1.20%/l) p 57 Co excretion was moderately elevated in most of the patients with iron deficiency anemia (average 31.5% 57 Co-activity in 24 hours' urine) in comparison to the healthy controls (average 25.30%). Contrary to the results obtained by Sorbie et al. we found a wide range of fluctuation of the Co-excretion test in each group of patients with a poor statistical significance of p > 0.05. (orig.) [de

  6. Is there a doctor in the house? . . . Or the Senate? Physicians in US Congress, 1960-2004.

    Science.gov (United States)

    Kraus, Chadd K; Suarez, Thomas A

    2004-11-03

    The legislative and fiscal influences of Congress, as well as the continuing overall growth in health care spending as a portion of the gross domestic product, make congressional representation by physicians important because physicians have unique expertise in the impact of legislation on patient care and medical practice. To describe physician representation in the US Congress between 1960 and 2004 and relate the results to past representation of physicians in Congress. A retrospective observational study of members of the US Congress from all 50 states and all represented territories, who served from January 1960 to April 2004 (including 108th Congress), using data available in public access databases and congressional biographical records. Physician representation in Congress, including occupation before taking office, state/territory of representation, sex, party affiliation, and time served. During the past 44 years, 25 (1.1%) of 2196 members of Congress were physicians. Physicians in Congress were more likely to be members of the Republican Party (60% vs 45.1% of all members, P = .007) and were similar to other members of Congress in mean years of service (9.2 years for physicians vs 12.3 years for all members, P = .09) and in sex distribution (4.0% female physicians vs 6.8% all female members, P = .57). Physicians in Congress represented 17 states, the Virgin Islands, and Puerto Rico. Physician representation in Congress is low and is in stark contrast with physician roles during the first century of the United States. However, the 8 physicians currently serving in Congress may be indicative of a shift toward more direct influence of physicians in national politics.

  7. O dictionnaire suisse romand e a lexicografia diferencial

    Directory of Open Access Journals (Sweden)

    René G. Strehler

    2013-08-01

    Full Text Available http://dx.doi.org/10.5007/2175-7968.2013v2n32p57 A noção de lexicografia diferencial está pouco difundida fora da francofonia. O objetivo do presente trabalho é apresentar as peculiaridades da lexicografia diferencial através do Dictionnairesuisseromande (DSR. Baseado em considerações teóricas de Coseriu, Völker ou Glessgen, nós admitimos que a variação faz parte do sistema. Em lexicografia, cabe verificar como as variações (diatópica, diacrónica... se articulam em volta de um nível linguístico chamado não marcado. A variante normalizada do francês, o français standard, foi elaborada essencialmente pelos grammairiens do século XVII, como Vaugelas ou Bouhours, por exemplo. Na lexicografia francófona, que verdadeiramente apareceu com os dicionários de Richelet (1680 e Furetière (1690, o français standard continua a referência, mas em muitos dicionários, o français standard, embora supranacional, é explicado em função do uso da França. É nesse contexto que aparece a metodologia da lexicografia diferencial. A noção de diferencial se manifesta na seleção da nomenclatura, pois são apresentados no dicionário apenas os lexemas com uso divergente em comparação com dicionários gerais que fornecem um francês de referência, mas não a norma. Em resumo, o DSR consagra uma norma regional, ou subnorma, correspondendo às peculiaridades do francês suíço. Outras obras diferenciais corroboram essa observação: o francês se compõe de um français standard e de normas regionais descritas pela lexicografia diferencial – situação diferente daquela do português, para o qual existe uma norma culta brasileira e uma norma culta de Portugal

  8. A role for smoothened during murine lens and cornea development.

    Directory of Open Access Journals (Sweden)

    Janet J Y Choi

    Full Text Available Various studies suggest that Hedgehog (Hh signalling plays roles in human and zebrafish ocular development. Recent studies (Kerr et al., Invest Ophthalmol Vis Sci. 2012; 53, 3316-30 showed that conditionally activating Hh signals promotes murine lens epithelial cell proliferation and disrupts fibre differentiation. In this study we examined the expression of the Hh pathway and the requirement for the Smoothened gene in murine lens development. Expression of Hh pathway components in developing lens was examined by RT-PCR, immunofluorescence and in situ hybridisation. The requirement of Smo in lens development was determined by conditional loss-of-function mutations, using LeCre and MLR10 Cre transgenic mice. The phenotype of mutant mice was examined by immunofluorescence for various markers of cell cycle, lens and cornea differentiation. Hh pathway components (Ptch1, Smo, Gli2, Gli3 were detected in lens epithelium from E12.5. Gli2 was particularly localised to mitotic nuclei and, at E13.5, Gli3 exhibited a shift from cytosol to nucleus, suggesting distinct roles for these transcription factors. Conditional deletion of Smo, from ∼E12.5 (MLR10 Cre did not affect ocular development, whereas deletion from ∼E9.5 (LeCre resulted in lens and corneal defects from E14.5. Mutant lenses were smaller and showed normal expression of p57Kip2, c-Maf, E-cadherin and Pax6, reduced expression of FoxE3 and Ptch1 and decreased nuclear Hes1. There was normal G1-S phase but decreased G2-M phase transition at E16.5 and epithelial cell death from E14.5-E16.5. Mutant corneas were thicker due to aberrant migration of Nrp2+ cells from the extraocular mesenchyme, resulting in delayed corneal endothelial but normal epithelial differentiation. These results indicate the Hh pathway is required during a discrete period (E9.5-E12.5 in lens development to regulate lens epithelial cell proliferation, survival and FoxE3 expression. Defective corneal development occurs

  9. Radiation Therapy Risk Factors for Development of Lymphedema in Patients Treated With Regional Lymph Node Irradiation for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Ravi A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Miller, Cynthia L. [Harvard Medical School, Boston, Massachusetts (United States); Skolny, Melissa N. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Warren, Laura E.G. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Horick, Nora [Department of Biostatistics, Massachusetts General Hospital, Boston, Massachusetts (United States); Jammallo, Lauren S.; Sadek, Betro T.; Shenouda, Mina N. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); O' Toole, Jean [Department of Physical and Occupational Therapy, Massachusetts General Hospital, Boston, Massachusetts (United States); Specht, Michelle C. [Division of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-03-15

    Purpose: We previously evaluated the risk of breast cancer-related lymphedema (LE) with the addition of regional lymph node irradiation (RLNR) and found an increased risk when RLNR is used. Here we analyze the association of technical radiation therapy (RT) factors in RLNR patients with the risk of LE development. Methods and Materials: From 2005 to 2012, we prospectively screened 1476 women for LE who underwent surgery for breast cancer. Among 1507 breasts treated, 172 received RLNR and had complete technical data for analysis. RLNR was delivered as supraclavicular (SC) irradiation (69% [118 of 172 patients]) or SC plus posterior axillary boost (PAB) (31% [54 of 172]). Bilateral arm volume measurements were performed pre- and postoperatively. Patients' RT plans were analyzed for SC field lateral border (relative to the humeral head), total dose to SC, RT fraction size, beam energy, and type of tangent (normal vs wide). Cox proportional hazards models were used to analyze associated risk factors for LE. Results: Median postoperative follow-up was 29.3 months (range: 4.9-74.1 months). The 2-year cumulative incidence of LE was 22% (95% confidence interval [CI]: 15%-32%) for SC and 20% (95% CI: 11%-37%) for SC plus PAB (SC+PAB). None of the analyzed variables was significantly associated with LE risk (extent of humeral head: P=.74 for <1/3 vs >2/3, P=.41 for 1/3 to 2/3 vs >2/3; P=.40 for fraction size of 1.8 Gy vs 2.0 Gy; P=.57 for beam energy 6 MV vs 10 MV; P=.74 for tangent type wide vs regular; P=.66 for SC vs SC+PAB). Only pretreatment body mass index (hazard ratio [HR]: 1.09; 95% CI: 1.04-1.15, P=.0007) and the use of axillary lymph node dissection (HR: 7.08, 95% CI: 0.98-51.40, P=.05) were associated with risk of subsequent LE development. Conclusions: Of the RT parameters tested, none was associated with an increased risk of LE development. This study underscores the need for future work investigating alternative RLNR risk factors for LE.

  10. APPLICATION OF PHYTOREMEDIATION FOR HERBAL MEDICINE WASTE AND ITS UTILIZATION FOR PROTEIN PRODUCTION

    Directory of Open Access Journals (Sweden)

    Danny Soetrisnanto

    2012-11-01

    bertujuan untuk mengevaluasi penggunaan tanaman air (enceng gondok dan teratai untukmereduksi kontaminan dalam limbah obat jamu. Phytoremediasi dilakukan selama 4-8 hari dan tinggicairan dalam reaktor dijaga pada 5 cm. Keluaran dari phytoremediasi pertama menggunakantanaman air digunakan sebagai medium di phytoremediasi menggunakan mikroalga Spirulina. Untukmendapakan pertumbuhan yang optimum, maka ditambahakan juga nutrient dan menunjukkan bahwaSpirulina tumbuh dengan sangat baik dalam medium ini. Pertumbuhan terbaik diperoleh dariphytoremediasi menggunakan teratai selama 3 hari dan kecepatan pertumbuhan 0,271/hari denganperbandingan C:N:P = 57,790:9,28:1.

  11. Common miR-590 Variant rs6971711 Present Only in African Americans Reduces miR-590 Biogenesis.

    Directory of Open Access Journals (Sweden)

    Xiaoping Lin

    Full Text Available MicroRNAs (miRNAs are recognized as important regulators of cardiac development, hypertrophy and fibrosis. Recent studies have demonstrated that genetic variations which cause alterations in miRNA:target interactions can lead to disease. We hypothesized that genetic variations in miRNAs that regulate cardiac hypertrophy/fibrosis might be involved in generation of the cardiac phenotype in patients diagnosed with hypertrophic cardiomyopathy (HCM. To investigate this question, we Sanger sequenced 18 miRNA genes previously implicated in myocyte hypertrophy/fibrosis and apoptosis, using genomic DNA isolated from the leukocytes of 199 HCM patients. We identified a single nucleotide polymorphism (rs6971711, C57T SNP at the 17th position of mature miR-590-3p (= 57th position of pre-miR-590 that is common in individuals of African ancestry. SNP frequency was higher in African American HCM patients (n = 55 than ethnically-matched controls (n = 100, but the difference was not statistically significant (8.2% vs. 6.5%; p = 0.5. Using a cell culture system, we discovered that presence of this SNP resulted in markedly lower levels of mature miR-590-5p (39 ± 16%, p<0.003 and miR-590-3p (20 ± 2%, p<0.003, when compared with wild-type (WT miR-590, without affecting levels of pri-miR-590 and pre-miR-590. Consistent with this finding, the SNP resulted in reduced target suppression when compared to WT miR-590 (71% suppression by WT vs 60% suppression by SNP, p<0.03. Since miR-590 can regulate TGF-β, Activin A and Akt signaling, SNP-induced reduction in miR-590 biogenesis could influence cardiac phenotype by de-repression of these signaling pathways. Since the SNP is only present in African Americans, population studies in this patient population would be valuable to investigate effects of this SNP on myocyte function and cardiac physiology.

  12. Time compression of soil erosion by the effect of largest daily event. A regional analysis of USLE database.

    Science.gov (United States)

    Gonzalez-Hidalgo, J. C.; Batalla, R.; Cerda, A.; de Luis, M.

    2009-04-01

    When Thornes and Brunsden wrote in 1977 "How often one hears the researcher (and no less the undergraduate) complain that after weeks of observation "nothing happened" only to learn that, the day after his departure, a flood caused unprecedent erosion and channel changes!" (Thornes and Brunsden, 1977, p. 57), they focussed on two different problems in geomorphological research: the effects of extreme events and the temporal compression of geomorphological processes. The time compression is one of the main characteristic of erosion processes. It means that an important amount of the total soil eroded is produced in very short temporal intervals, i.e. few events mostly related to extreme events. From magnitude-frequency analysis we know that few events, not necessarily extreme by magnitude, produce high amount of geomorphological work. Last but not least, extreme isolated events are a classical issue in geomorphology by their specific effects, and they are receiving permanent attention, increased at present because of scenarios of global change. Notwithstanding, the time compression of geomorphological processes could be focused not only on the analysis of extreme events and the traditional magnitude-frequency approach, but on new complementary approach based on the effects of largest events. The classical approach define extreme event as a rare event (identified by its magnitude and quantified by some deviation from central value), while we define largest events by the rank, whatever their magnitude. In a previous research on time compression of soil erosion, using USLE soil erosion database (Gonzalez-Hidalgo et al., EGU 2007), we described a relationship between the total amount of daily erosive events recorded by plot and the percentage contribution to total soil erosion of n-largest aggregated daily events. Now we offer a further refined analysis comparing different agricultural regions in USA. To do that we have analyzed data from 594 erosion plots from USLE

  13. Visual and refractive outcomes of LASIK with the SCHWIND ESIRIS and WaveLight ALLEGRETTO WAVE Eye-q excimer lasers: a prospective, contralateral study.

    Science.gov (United States)

    Mearza, Ali A; Muhtaseb, Mohammed; Aslanides, Ioannis M

    2008-11-01

    To compare the safety, efficacy, and predictability of LASIK with the SCHWIND ESIRIS and WaveLight ALLEGRETTO WAVE Eye-Q excimer laser platforms. This prospective study comprised 44 eyes of 22 consecutive patients who were treated with LASIK using the Moria M2 microkeratome. One eye was treated with the SCHWIND ESIRIS laser and the fellow eye treated with the WaveLight ALLEGRETTO WAVE Eye-Q laser. All eyes operated with the SCHWIND ESIRIS were treated with standard aspheric ablation, whereas the eyes operated with the WaveLight ALLEGRETTO WAVE Eye-Q received treatment with three different ablation types according to the common practice at our clinic. Outcome measures were uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, and proximity to target refraction at 6-month follow-up. At 6 months postoperative, mean decimal UCVA was 0.96+/-0.22 (range: 0.3 to 1.2) for ESIRIS eyes and 0.98+/-0.17 (range: 0.6 to 1.2) for ALLEGRETTO eyes (P=.57). Mean postoperative spherical equivalent refraction was -0.02+/-0.28 diopters (D) (range: -0.75 to +0.75 D) for ESIRIS eyes and 0.11+/-0.91 D (range: -1.00 to +3.88 D) for ALLEGRETTO eyes (P=.49). Of the ESIRIS eyes, 20/22 (91%) were within +/-1.00 D of target refraction and 20/22 (91%) were within +/-0.50 D of target refraction. Of the ALLEGRETTO eyes, 20/22 (91%) and 19/22 (86%) were within +/-1.00 D and +/-0.50 D, respectively, of target refraction. No patient lost > or =2 lines of BSCVA in either group. No differences were seen in safety and efficacy outcome parameters between the SCHWIND ESIRIS and WaveLight ALLEGRETTO WAVE Eye-Q excimer lasers when used according to a previously established treatment algorithm at our clinic in the treatment of refractive error.

  14. OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

    Science.gov (United States)

    Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

    2017-10-01

    Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC

  15. Should Women Younger Than 40 Years of Age With Invasive Breast Cancer Have a Mastectomy?: 15-Year Outcomes in a Population-Based Cohort

    International Nuclear Information System (INIS)

    Cao, Jeffrey Q.; Truong, Pauline T.; Olivotto, Ivo A.; Olson, Robert; Coulombe, Genevieve; Keyes, Mira; Weir, Lorna; Gelmon, Karen; Bernstein, Vanessa; Woods, Ryan; Speers, Caroline; Tyldesley, Scott

    2014-01-01

    Purpose: Optimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM). Methods and Materials: Women aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary outcomes of breast cancer–specific survival (BCSS), overall survival (OS) and secondary outcomes of local relapse–free survival (LRFS), locoregional relapse–free survival (LRRFS), and distant relapse–free survival (DRFS) were calculated using Kaplan-Meier methods and compared between BCT and MRM cohorts using log-rank tests. A planned subgroup analysis was performed on patients considered “ideal” for BCT (ie, T1N0, negative margins and no extensive ductal carcinoma in situ) and in whom local therapy may have the largest impact on survival because of low systemic risk. Results: 965 patients were identified; 616 had BCT and 349 had MRM. The median follow-up time was 14.4 years (range, 8.4-23.3 years). Overall, 15-year rates of BCSS (76.0% vs 74.1%, P=.62), OS (74.2% vs 73.0%, P=.75), LRFS (85.4% vs 86.5%, P=.95), LRRFS (82.2% vs 81.6%, P=.61), and DRFS (74.4% vs 71.6%, P=.40) were similar between the BCT and MRM cohorts. In the “ideal” for BCT subgroup, there were 219 BCT and 67 MRM patients with a median follow-up time of 15.5 years. The 15-year BCSS (86.1% vs 82.9%, P=.57), OS (82.6% vs 82.9%, P=.89), LRFS (86.2% vs 84.2%, P=.50), LRRFS (83.1% vs 78.3%, P=.24), and DRFS (84.8% vs 79.1%, P=.17) were similar in the BCT and MRM cohorts. Conclusions: This population-based analysis with long-term follow-up confirmed that women younger than 40 years treated with BCT had similar 15-year outcomes compared with MRM. Young age alone is not a contraindication to BCT

  16. A survey of selected neutron-activation reactions with short-lived products of importance to fusion reactor technology

    International Nuclear Information System (INIS)

    Ward, R.C.; Gomes, I.C.; Smith, D.L.

    1994-11-01

    The status of the cross sections for production of short-lived radioactivities in the intense high-energy neutron fields associated with D-T fusion reactors is investigated. The main concerns relative to these very radioactive isotopes are with radiation damage to sensitive components such as superconducting magnets, the decay-heat problem and the safety of personnel during operation of the facility. The present report surveys the status of nuclear data required to assess these problems. The study is limited to a few high-priority nuclear reactions which appear to be of critical concern in this context. Other reactions of lesser concern are listed but are not treated in the present work. Among the factors that were considered in defining the relevant reactions and setting priorities are: quantities of the elemental materials in a fusion reactor, isotopic abundances within elemental categories, the decay properties of the induced radioactive byproducts, the reaction cross sections, and the nature of the decay radiations. Attention has been focused on radioactive species with half lives in the range from about 1 second to 15 minutes. Available cross-section and reaction-product decay information from the literature has been compiled and included in the report. Uncertainties have been estimated by examining several sets of experimental as well as evaluated data. Comments on the general status of data for various high-priority reactions are offered. On the basis of this investigation, it has been found that the nuclear data are in reasonably good shape for some of the most important reactions but are unacceptable for others. Based on this investigation, the reactions which should be given the greatest attention are: 16 O(n,p) 16 N, 55 Mn(n,p) 55 Cr, 57 Fe(n,p) 57 Mn, 186 W(n,2n) 185m W, and 207 Pb(n,n') 207m Pb. However, the development of fusion power would benefit from an across-the-board refinement in these nuclear data so that a more accurate quantitative

  17. Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke.

    Science.gov (United States)

    Stone, David H; Nolan, Brian W; Schanzer, Andres; Goodney, Philip P; Cambria, Robert A; Likosky, Donald S; Walsh, Daniel B; Cronenwett, Jack L

    2010-03-01

    Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke

  18. LLE Review Quarterly Report January - March 2012. Volume 130

    Energy Technology Data Exchange (ETDEWEB)

    Shvydky, Alex [Univ. of Rochester, NY (United States). Lab. for Laser Energetics

    2012-03-01

    This volume of the LLE Review, covering January–March 2012, features “OMEGA Polar-Drive Target Designs,” by P. B. Radha, J. A. Marozas, F. J. Marshall, A. Shvydky, T. J. B. Collins, V. N. Goncharov, R. L. McCrory, P. W. McKenty, D. D. Meyerhofer, T. C. Sangster, and S. Skupsky. This article (p. 57) describes low-adiabat, cryogenic-deuterium–tritium, and warm-plastic-shell polar-drive (PD)–implosion designs for the OMEGA laser. The designs are at two different on-target laser intensities, each at a different in-flight aspect ratio (IFAR). The first design permits one to study implosion energetics and target performance closer to ignition-relevant intensities (7 X 1014 W/cm2 at the quarter-critical surface), where nonlocal heat conduction and laser–plasma interactions can play an important role, but at lower values of IFAR (~22). The second design permits one to study implosion energetics and target performance at a lower intensity (3 X 1014 W/cm2) but at higher IFAR (~32), where the shell instability can play an important role. The higher IFAR designs are accessible on the existing OMEGA Laser System only at lower intensities. Implosions at ignition-relevant intensities can be obtained only by reducing target radius, although only at smaller values of IFAR. Polar-drive geometry requires repointing the laser beams to improve shell symmetry. The higher-intensity designs optimize target performance by repointing beams to a lesser extent and compensate for the reduced equatorial drive by increasing beam energies for the repointed beams and using custom beam profiles that improve equatorial illumination at the expense of irradiation at higher latitudes. These designs will be studied when new phase plates for the OMEGA Laser System, corresponding to the smaller target radii and custom beam profiles, are obtained. Implosion results from the combined set of high-intensity and high-IFAR implosions should yield valuable

  19. Prevalence and Factors Associated with Hydatidiform Mole among Patients Undergoing Uterine Evacuation at Mbarara Regional Referral Hospital

    Directory of Open Access Journals (Sweden)

    Olivier Mulisya

    2018-01-01

    Full Text Available Objective. We sought to determine the prevalence of and factors associated with hydatidiform molar gestations amongst patients undergoing uterine evacuation at Mbarara Regional Referral Hospital (MRRH, Mbarara, Uganda. Methods. This was a cross-sectional study carried out from November 2016 to February 2017. All patients admitted for uterine evacuation for nonviable pregnancy were included. The study registered 181 patients. Data were collected on sociodemographics, medical conditions, obstetrics, and gynecological factors. The evacuated tissue received a full gross and histopathologic examination. Cases of pathologically suspected complete hydatidiform mole were confirmed by p57 immunohistochemistry. Data were analyzed using STATA 13. Results. The prevalence of hydatidiform mole was 6.1% (11/181. All detected moles were complete hydatidiform moles, and there were no diagnosed partial hydatidiform moles. Clinical diagnosis of molar pregnancy was suspected in 13 patients, but only 69.2% (9/13 were confirmed as molar pregnancies histologically. Two cases were clinically unsuspected. Factors that had a significant relationship with complete hydatidiform mole included maternal age of 35 years and above (aOR 13.5; CI: 1.46–125.31; p=0.00, gestational age beyond the first trimester at the time of uterine evacuation (aOR 6.2; CI: 1.07–36.14; p=0.04, and history of previous abortion (aOR 4.3; CI: 1.00–18.57; p=0.05. Conclusion. The prevalence of complete hydatidiform mole was high at 6.1%. Associated risk factors included advanced maternal age (35 years and above, history of previous abortions, and gestational age beyond the first trimester at the time of evacuations. Recommendations. We recommend putting in place capacity to do routine histopathological examination of all products of conception especially those at high risk for a molar gestation either by clinical suspicion or by risk factors including advanced maternal age, advanced gestational

  20. Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer

    International Nuclear Information System (INIS)

    Lemaire, Maryse; Chabot, Guy G; Raynal, Noël JM; Momparler, Louise F; Hurtubise, Annie; Bernstein, Mark L; Momparler, Richard L

    2008-01-01

    The inactivation of tumor suppressor genes (TSGs) by aberrant DNA methylation plays an important role in the development of malignancy. Since this epigenetic change is reversible, it is a potential target for chemotherapeutic intervention using an inhibitor of DNA methylation, such as 5-aza-2'-deoxycytidine (DAC). Although clinical studies show that DAC has activity against hematological malignancies, the optimal dose-schedule of this epigenetic agent still needs to be established. Clonogenic assays were performed on leukemic and tumor cell lines to evaluate the in vitro antineoplastic activity of DAC. The reactivation of TSGs and inhibition of DNA methylation by DAC were investigated by reverse transcriptase-PCR and Line-1 assays. The in vivo antineoplastic activity of DAC administered as an i.v. infusion was evaluated in mice with murine L1210 leukemia by measurement of survival time, and in mice bearing murine EMT6 mammary tumor by excision of tumor after chemotherapy for an in vitro clonogenic assay. Increasing the DAC concentration and duration of exposure produced a greater loss of clonogenicity for both human leukemic and tumor cell lines. The reactivation of the TSGs (p57KIP2 in HL-60 leukemic cells and p16CDKN2A in Calu-6 lung carcinoma cells) and the inhibition of global DNA methylation in HL-60 leukemic cells increased with DAC concentration. In mice with L1210 leukemia and in mice bearing EMT6 tumors, the antineoplastic action of DAC also increased with the dose. The plasma level of DAC that produced a very potent antineoplastic effect in mice with leukemia or solid tumors was > 200 ng/ml (> 1 μM). We have shown that intensification of the DAC dose markedly increased its antineoplastic activity in mouse models of cancer. Our data also show that there is a good correlation between the concentrations of DAC that reduce in vitro clonogenicity, reactivate TSGs and inhibit DNA methylation. These results suggest that the antineoplastic action of DAC is

  1. Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid Transporter Signals.

    Science.gov (United States)

    Tian, Tian; Ni, Hong; Sun, Bao-liang

    2015-10-01

    The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy in adults, but it has not been extensively tested for its efficacy in neonatal seizure-induced brain damage. We have previously shown altered expression of zinc/lipid metabolism-related genes in hippocampus following penicillin-induced developmental model of epilepsy. In this study, we further investigated the effect of KD on the neurobehavioral and cognitive deficits, as well as if KD has any influence in the activity of zinc/lipid transporters such as zinc transporter 3 (ZnT-3), MT-3, ApoE, ApoJ (clusterin), and ACAT-1 activities in neonatal rats submitted to flurothyl-induced recurrent seizures. Postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizure group (EXP) and control group (CONT). On P28, they were further randomly divided into the seizure group without ketogenic diet (EXP1), seizure plus ketogenic diet (EXP2), the control group without ketogenic diet (CONT1), and the control plus ketogenic diet (CONT2). Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed from P35 to P49. Morris water maze test was performed during P51-P57. Then hippocampal mossy fiber sprouting and the protein levels of ZnT3, MT3, ApoE, CLU, and ACAT-1 were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced neurobehavioral toxicology and aberrant mossy fiber sprouting were blocked by KD. In parallel with these behavioral changes, rats treated with KD (EXP2) showed a significant down-regulated expression of ZnT-3, MT-3, ApoE, clusterin, and ACAT-1 in hippocampus when compared with the non-KD-treated EXP1 group. Our findings provide support for zinc/lipid transporter signals being potential targets for the treatment of neonatal seizure-induced brain damage by KD.

  2. Assessing significance of peripheral blood indicators for differential diagnosis and prognosis of thrombotic complications in polycythemia vera and secondary erythrocytosis

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    Kostiukevych O.M.

    2014-03-01

    Full Text Available The aim of the study – determining of changes in peripheral blood (PB in patients with secondary erythrocytosis (SE and polycythemia vera (PV, detection of discriminatory parameters levels of PB indicators and analyzing of their operating characteristics for differentiation of erythrocytosis and predicting of thrombotic events in patients with PV. Materials and methods. The material for the study was the results of clinical trials of 210 patients with erythrocytosis who underwent differential diagnosis between PV and SE. Results and discussion. The optimal threshold for differential diagnosis of red blood cells content between PV and SE is >6.08•1012/ L, the diagnostic value of the marker equals to the level of a good diagnostic marker (AUC=0.82; 95% CI=0.77-0.87, p 57.5% with its capacity – 0.72 (0.66-0.78, p 8.9•109/L, and the boundary of marker is consistent with a good level of efficiency (AUC=0.79, 95% CI=0.72-0.84, p287•109 /L" to differentiate erythrocytosis is 0.90 (0.86-0.94, p 55%" and "WBC >12.3•109 /L", according to the AUC (AUC=0.65; 95% CI=0.52-0.79, p=0.021 and AUC=0.66; 95% CI=0.55-0.77, p=0.003, respectively, corresponds to the average power level. Conclusion. Hemoglobin has not confirmed its value for the differential diagnosis between PV and SE. Using other parameters of PB with the aim of differentiating PV and SE is rational, but their discriminatory power levels greatly depend on the group erythrocytosis. In our cohort were obtained the following most appropriate criteria for inclusion of patients in the group of patients with PV: "WBC >8.9•109/L", "red blood cells >6.08•1012/L" and "hematocrit >57.5%". The most significant marker of general clinical blood test to differentiate between PV and SE is "platelets >287•109/L". Hematocrit over 55% and WBC over 12.3•109/L are valuable prognostic markers of thrombosis in PV patients, but their use is appropriate only in a cohort of patients with PV without

  3. Disease-specific self-efficacy in spasmodic dysphonia patients.

    Science.gov (United States)

    Hu, Amanda; Isetti, Derek; Hillel, Allen D; Waugh, Patricia; Comstock, Bryan; Meyer, Tanya K

    2013-03-01

    Self-efficacy (SE) is an optimistic self-belief that one can perform a novel task. This concept involves empowerment, self-esteem, and adaptation to a stressful situation. SE is a strong predictor of health behaviors. Our objectives were to study SE in spasmodic dysphonia (SD) and to develop a disease-specific SE-SD scale. Prospective study. Academic hospital. Disease-specific SE-SD items were developed with laryngologists, speech pathologists, and SD patients. These items, General SE Scale, Voice Handicap Index-10 (VHI-10), Consensus Auditory Perceptual Evaluation of Voice (CAPE-V), and Hospital Anxiety and Depression Scale (HADS), were administered to SD patients who presented for botulinum toxin injections. One hundred forty-five SD patients (mean age 59.5 ± 13.6 years) had a general SE score (Cronbach's α = 0.894) of 33.4 ± 5.2 out of 40. This was negatively correlated with HADS-A (r = -0.42, P < 0.001) and HADS-D (r = -0.42, P < .001), but not correlated with VHI-10 (r = -0.098, P = .243) and CAPE-V (r = -0.047, P = .57). Factor analysis selected 8 items from the general SE scale and 5 disease-specific SE-SD items to generate a 13-item disease-specific SE-SD scale (Cronbach's α = 0.907). Disease-specific SE-SD score was 42.1 ± 6.9 out of 52 and was negatively correlated with VHI-10 (r = -0.19, P = .005), HADS-A (r = -0.43, P < .001), and HADS-D (r = -0.57, P < .001), but not correlated with CAPE-V (r = -0.024, P = .60). SD patients established on botulinum toxin injections have high degrees of general and disease-specific SE. Patients with higher SE-SD demonstrate lower vocal handicap and lower levels of anxiety and depression. A 13-item disease-specific SE-SD scale has been developed.

  4. Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

    Science.gov (United States)

    Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

    2018-05-01

    Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

  5. Intelligence May Moderate the Cognitive Profile of Patients with ASD.

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    Nanda Rommelse

    Full Text Available The intelligence of individuals with Autism Spectrum Disorder (ASD varies considerably. The pattern of cognitive deficits associated with ASD may differ depending on intelligence. We aimed to study the absolute and relative severity of cognitive deficits in participants with ASD in relation to IQ.A total of 274 children (M age = 12.1, 68.6% boys participated: 30 ASD and 22 controls in the below average Intelligence Quotient (IQ group (IQ115. Matching for age, sex, Full Scale IQ (FSIQ, Verbal IQ (VIQ, Performance IQ (PIQ and VIQ-PIQ difference was performed. Speed and accuracy of social cognition, executive functioning, visual pattern recognition and basic processing speed were examined per domain and as a composite score.The composite score revealed a trend significant IQ by ASD interaction (significant when excluding the average IQ group. In absolute terms, participants with below average IQs performed poorest (regardless of diagnosis. However, in relative terms, above average intelligent participants with ASD showed the most substantial cognitive problems (particularly for social cognition, visual pattern recognition and verbal working memory since this group differed significantly from the IQ-matched control group (p < .001, whereas this was not the case for below-average intelligence participants with ASD (p = .57.In relative terms, cognitive deficits appear somewhat more severe in individuals with ASD and above average IQs compared to the below average IQ patients with ASD. Even though high IQ ASD individuals enjoy a certain protection from their higher IQ, they clearly demonstrate cognitive impairments that may be targeted in clinical assessment and treatment. Conversely, even though in absolute terms ASD patients with below average IQs were clearly more impaired than ASD patients with average to above average IQs, the differences in cognitive functioning between participants with and without ASD on the lower end of the IQ spectrum were

  6. FOXO1 is a direct target of EWS-Fli1 oncogenic fusion protein in Ewing's sarcoma cells

    International Nuclear Information System (INIS)

    Yang, Liu; Hu, Hsien-Ming; Zielinska-Kwiatkowska, Anna; Chansky, Howard A.

    2010-01-01

    Research highlights: → Inducible and reversible siRNA knockdown of an oncogenic fusion protein such as EWS-Fli1 is feasible and more advantageous than other siRNA methods. → The tumor suppressor gene FOXO1 is a new EWS-Fli1 target. → While trans-activators are known for the FOXO1 gene, there has been no report on negative regulators of FOXO1 transcription. → This study provides first evidence that the EWS-Fli1 oncogenic fusion protein can function as a transcriptional repressor of the FOXO1 gene. -- Abstract: Ewing's family tumors are characterized by a specific t(11;22) chromosomal translocation that results in the formation of EWS-Fli1 oncogenic fusion protein. To investigate the effects of EWS-Fli1 on gene expression, we carried out DNA microarray analysis after specific knockdown of EWS-Fli1 through transfection of synthetic siRNAs. EWS-Fli1 knockdown increased expression of genes such as DKK1 and p57 that are known to be repressed by EWS-Fli1 fusion protein. Among other potential EWS-Fli1 targets identified by our microarray analysis, we have focused on the FOXO1 gene since it encodes a potential tumor suppressor and has not been previously reported in Ewing's cells. To better understand how EWS-Fli1 affects FOXO1 expression, we have established a doxycycline-inducible siRNA system to achieve stable and reversible knockdown of EWS-Fli1 in Ewing's sarcoma cells. Here we show that FOXO1 expression in Ewing's cells has an inverse relationship with EWS-Fli1 protein level, and FOXO1 promoter activity is increased after doxycycline-induced EWS-Fli1 knockdown. In addition, we have found that direct binding of EWS-Fli1 to FOXO1 promoter is attenuated after doxycycline-induced siRNA knockdown of the fusion protein. Together, these results suggest that suppression of FOXO1 function by EWS-Fli1 fusion protein may contribute to cellular transformation in Ewing's family tumors.

  7. Identification of key amino acid residues modulating intracellular and in vitro microcin E492 amyloid formation

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    Paulina eAguilera

    2016-01-01

    Full Text Available Microcin E492 (MccE492 is a pore-forming bacteriocin produced and exported by Klebsiella pneumoniae RYC492. Besides its antibacterial activity, excreted MccE492 can form amyloid fibrils in vivo as well as in vitro. It has been proposed that bacterial amyloids can be functional playing a biological role, and in the particular case of MccE492 it would control the antibacterial activity. MccE492 amyloid fibril’s morphology and formation kinetics in vitro have been well characterized, however it is not known which amino acid residues determine its amyloidogenic propensity, nor if it forms intracellular amyloid inclusions as has been reported for other bacterial amyloids. In this work we found the conditions in which MccE492 forms intracellular amyloids in E. coli cells, that were visualized as round-shaped inclusion bodies recognized by two amyloidophillic probes, 2-4´-methylaminophenyl benzothiazole and thioflavin-S. We used this property to perform a flow cytometry-based assay to evaluate the aggregation propensity of MccE492 mutants, that were designed using an in silico prediction of putative aggregation hotspots. We established that the predicted amino acid residues 54-63, effectively act as a pro-amyloidogenic stretch. As in the case of other amyloidogenic proteins, this region presented two gatekeeper residues (P57 and P59, which disfavor both intracellular and in vitro MccE492 amyloid formation, preventing an uncontrolled aggregation. Mutants in each of these gatekeeper residues showed faster in vitro aggregation and bactericidal inactivation kinetics, and the two mutants were accumulated as dense amyloid inclusions in more than 80% of E. coli cells expressing these variants. In contrast, the MccE492 mutant lacking residues 54-63 showed a significantly lower intracellular aggregation propensity and slower in vitro polymerization kinetics. Electron microscopy analysis of the amyloids formed in vitro by these mutants revealed that, although

  8. The evaluation of the statistical monomineral thermobarometric methods for the reconstruction of the lithospheric mantle structure

    Science.gov (United States)

    Ashchepkov, I.; Vishnyakova, E.

    2009-04-01

    The modified versions of the thermobarometers for the mantle assemblages were revised sing statistical calibrations on the results of Opx thermobarometry. The modifications suggest the calculation of the Fe# of coexisting olivine Fe#Ol according to the statistical approximations by the regressions obtained from the xenoliths from kimberlite data base including >700 associations. They allow reproduces the Opx based TP estimates and to receive the complete set of the TP values for mantle xenoliths and xenocrysts. For GARNET Three variants of barometer give similar results. The first is published (Ashchepkov, 2006). The second is calculating the Al2O3 from Garnet for Orthopyroxene according to procedure: xCrOpx=Cr2O3/CaO)/FeO/MgO/500 xAlOpx=1/(3875*(exp(Cr2O3^0.2/CaO)-0.3)*CaO/989+16)-XcrOpx Al2O3=xAlOp*24.64/Cr2O3^0.2*CaO/2.+FeO*(ToK-501)/1002 And then it suppose using of the Al2O3 in Opx barometer (McGregor, 1974). The third variant is transformation of the G. Grutter (2006) method by introducing of the influence of temperature. P=40+(Cr2O3)-4.5)*10/3-20/7*CaO+(ToC)*0.0000751*MgO)*CaO+2.45*Cr2O3*(7-xv(5,8)) -Fe*0.5 with the correction for P>55: P=55+(P-55)*55/(1+0.9*P) Average from this three methods give appropriate values comparable with determined with (McGregor,1974) barometer. Temperature are estimating according to transformed Krogh thermometer Fe#Ol_Gar=Fe#Gar/2+(T(K)-1420)*0.000112+0.01 For the deep seated associations P>55 kbar T=T-(0.25/(0.4-0.004*(20-P))-0.38/Ca)*275+51*Ca*Cr2-378*CaO-0.51)-Cr/Ca2*5+Mg/(Fe+0.0001)*17.4 ILMENITE P= ((TiO2-23.)*2.15-(T0-973)/20*MgO*Cr2O3 and next P=(60-P)/6.1+P ToK is determined according to (Taylor et al , 1998) Fe#Ol_Chr =(Fe/(Fe+Mg)ilm -0.35)/2.252-0.0000351*(T(K)-973) CHROMITE The equations for PT estimates with chromite compositions P=Cr/(Cr+Al)*T(K)/14.+Ti*0.10 with the next iteration P=-0.0053*P^2+1.1292*P+5.8059 +0.00135*T(K)*Ti*410-8.2 For P> 57 P=P+(P-57)*2.75 Temperature estimates are according to the O

  9. Fertilidad y extracción de nutrientes en la asociación maíz-pastos en suelos ácidos del piedemonte Llanero de Colombia

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    Rincón Álvaro

    2008-08-01

    Full Text Available

    En un oxisol del Centro de Investigaciones La Libertad de Corpoica, a 17 km de Villavicencio, se estableció la asociación de maíz con los pastos B. decumbens, Mulato 1 y Toledo, como medio para recobrar la productividad de una pradera degradada. Los minerales aplicados 45 días antes de la siembra fueron: Ca, 555 kg ha-1; Mg, 88 kg ha-1; P, 35 kg ha-1 y S, 45 kg ha- 1, utilizando como fuente cal dolomítica, roca fosfórica y yeso agrícola; al momento de la siembra se aplicaron: 31 kg ha-1 de P, 27 de N (fuente fosfato diamónico; 37,5 de K (fuente cloruro de potasio; 3 de Zn; 0,1 de Cu; 0,5 de B y 1,2 de S (fuente borozinco. A los 15 después de la siembra (dds se aplicaron 37,5 kg ha-1 de K. La aplicación de N se fraccionó en dosis de 100 y 200 kg ha-1 a los 15 y 35 dds, respectivamente. Los análisis de suelos realizados después de la cosecha del maíz demostraron un mejoramiento de la fertilidad, ya que la saturación de bases aumentó de 24% inicial a 47%, el P disponible pasó de 2 ppm a 11,8 ppm, el S aumentó de 3 ppm a 6 ppm. En el momento de la cosecha, la mayor extracción de N fue la hicieron el grano de maíz y los pastos (43 y 45 kg ha-1, respectivamente, mientras que el P se presentó en mayor concentración en el grano de maíz (12,7 kg ha-1. Los pastos y la soca de maíz (tallos y hojas después de la cosecha se caracterizaron por un mayor contenido de K (40 y 27 kg ha-1, respectivamente. El Ca, Mg y S fueron más extraídos por los pastos (9; 8 y 6 kg ha-1, respectivamente; los minerales extraídos en mayor cantidad por el maíz y los pastos fueron N (91%, P (57% y K (58%, mientras que los de menor extracción fueron Ca (2,2% y Mg (16%.

  10. Da educação das meninas por Fénelon (1852 - The education of girls by Fénelon (1852

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    Maria Helena Camara Bastos, Brasil

    2012-03-01

    época. Além disso, fazendo uso das palavras de Calvino (2006, p. 137, Fénelon foi “autor de um afresco do seu tempo”, construindo um texto repleto de conteúdos/ mensagens, pleno de sentidos e marcando uma concepção de educação de que “a virtude pode ser ensinada e que o vício é conseqüência da ignorância” (Brum, 1995, p. 57.

  11. Modelos de educação geral na experiência universitária americana

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    José Camilo dos Santos Filho

    2010-06-01

    Full Text Available http://dx.doi.org/10.5007/1983-4535.2010v3n1p57   Em conseqüência da descentralização e da flexibilidade do sistema de educação superior e da grande autonomia das instituições universitárias nos Estados Unidos, não há obrigação legal de adoção de um programa de educação geral comum ou padrão para todo o país ou para todo um Estado da Federação. Por um lado, as instituições gozam de ampla liberdade e autonomia para conceberem seus programas de educação geral, o que tem levado a uma considerável variedade de abordagens institucionais da educação geral. Por outro lado, esse processo não impositivo tem levado ao longo do tempo a uma progressiva homogeneização básica de pressuposições e padrões semelhantes, mediante o processo de imitação dos programas das instituições de maior prestígio nacional. Robert Newton (2000 destaca esse caráter descentralizador e flexível da educação superior americana e a existência de quase tantos programas de educação geral quantos são os `colleges` e universidades do país. No entanto, acredita que, descartando-se os detalhes desses programas, podem emergir certas pressuposições e padrões esclarecedores. Desse modo, Newton propõe três abordagens que, no seu entender, podem fornecer um contexto para o planejamento, a compreensão e o aprimoramento de programas de educação geral. Os três modelos de educação geral dominantes atualmente nas universidades e ´colleges´ americanos são: o modelo centrado na disciplina acadêmica, o centrado nos Grandes Livros e o centrado na formação do cidadão efetivo. O propósito deste trabalho é analisar esses três modelos de educação geral adotados por essas instituições, destacando suas raízes históricas e as características básicas de cada um, à luz dos princípios subjacentes aos programas de educação geral. Cabe salientar que a discussão teórica e a prática efetiva de mais de cem anos de educação geral

  12. Methylation profiles of thirty four promoter-CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma

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    Wang Yifei

    2004-09-01

    Full Text Available Abstract Background Astrocytoma is a common aggressive intracranial tumor and presents a formidable challenge in the clinic. Association of altered DNA methylation patterns of the promoter CpG islands with the expression profile of cancer-related genes, has been found in many human tumors. Therefore, DNA methylation status as such may serve as an epigenetic biomarker for both diagnosis and prognosis of human tumors, including astrocytoma. Methods We used the methylation specific PCR in conjunction with sequencing verification to establish the methylation profile of the promoter CpG island of thirty four genes in astrocytoma tissues from fifty three patients (The WHO grading:. I: 14, II: 15, III: 12 and IV: 12 cases, respectively. In addition, compatible tissues (normal tissues distant from lesion from three non-astrocytoma patients were included as the control. Results Seventeen genes (ABL, APC, APAF1, BRCA1, CSPG2, DAPK1, hMLH1, LKB1, PTEN, p14ARF, p15INK4b, p27KIP1, p57KIP2, RASSF1C, RB1, SURVIVIN, and VHL displayed a uniformly unmethylated pattern in all the astrocytoma and non-astrocytoma tissues examined. However, the MAGEA1 gene that was inactivated and hypermethylated in non-astrocytoma tissues, was partially demethylated in 24.5% of the astrocytoma tissues (co-existence of the hypermethylated and demethylated alleles. Of the astrocytoma associated hypermethylated genes, the methylation pattern of the CDH13, cyclin a1, DBCCR1, EPO, MYOD1, and p16INK4a genes changed in no more than 5.66% (3/53 of astrocytoma tissues compared to non-astrocytoma controls, while the RASSF1A, p73, AR, MGMT, CDH1, OCT6,, MT1A, WT1, and IRF7 genes were more frequently hypermethylated in 69.8%, 47.2%, 41.5%, 35.8%, 32%, 30.2%, 30.2%, 30.2% and 26.4% of astrocytoma tissues, respectively. Demethylation mediated inducible expression of the CDH13, MAGEA1, MGMT, p73 and RASSF1A genes was established in an astrocytoma cell line (U251, demonstrating that expression of

  13. Editor's welcome, PORTAL, Vol. 1, No. 1, January 2004

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    Paul Allatson

    2004-01-01

    Full Text Available Welcome to the inaugural issue of PORTAL On behalf of the Executive Editorial Committee of PORTAL Journal of Multidisciplinary International Studies, it is a great pleasure to announce the virtual birth of this fully peer-reviewed journal under the auspices of UTSePress, the exciting new electronic publishing enterprise housed at the central library at the University of Technology, Sydney (UTS, Australia. PORTAL itself is edited by staff from the Institute for International Studies, a dynamic research and teaching centre at UTS. The launch of PORTAL's inaugural issue will take place simultaneously in Sydney, Australia, and Guadalajara, México, on January 28 (Sydney / 27 (Guadalajara 2004. The trans-Pacific axial enabling this twin launch is emblematic of the many axes of dialogue that, it is to be hoped, will characterize the content and reception of this and future issues of Portal. We are grateful to the many people at the Center for Social Sciences and Humanities at la Universidad de Guadalajara, México, for their provision of the technologies and tequila that will facilitate Portal's digital launch in a different space and timezone to its 'homebirth' in Sydney, Australia. As PORTAL's 'Focus and Scope' statement indicates, the journal is dedicated to publishing scholarship by practitioners of-and dissenters from-international, regional, area, migration, and ethnic studies. PORTAL is also committed to providing a space for cultural producers interested in the internationalization of cultures. With these aims in mind we have conceived PORTAL as a "multidisciplinary venture," to use Michel Chaouli's words. That is, PORTAL signifies "a place where researchers [and cultural producers] are exposed to different ways of posing questions and proffering answers, without creating out of their differing disciplinary languages a common theoretical or methodological pidgin" (2003, p. 57. Our hope is that scholars working in the humanities

  14. LLE Review 114 (January-March 2008)

    International Nuclear Information System (INIS)

    Zuegel, J.D.

    2008-01-01

    This volume of the LLE Review, covering January-March 2008, features 'Cryogenic Targets: Current Status and Future Development', by D. R. Harding, D. H. Edgell, M. D. Wittman, L. M. Elasky, S. J. Verbridge, A. J. Weaver, L. D. Lund, W. Seka, W. T. Shmayda, R. T. Janezic, M. J. Shoup III, M. Moore, R. Junquist, and A. V. Okishev. In this article (p. 57), the authors report on the status of layering cryogenic DT and D 2 targets at LLE for inertial confinement fusion (ICF) targets. This critical effort achieves the important milestone of routinely providing cryogenic DT targets that meet the 1.0-(micro)m (rms) OMEGA ice-quality-surface specification. The best D 2 -ice layers produced so far (rms roughness of 1.1 (micro)m) are approaching the quality typically achieved in DT targets. Efforts to improve the consistency of this process are reported along with investigations supporting the National Ignition Campaign studying issues relevant to indirect-drive and direct-drive cryogenic targets. Additional highlights of recent research presented in this issue include the following: (1) an improved laser speckle smoothing scheme that augments the current NIF 1-D SSD system by using multiple-FM modulators (MultiFM 1-D SSD) (p. 73). With a judicious choice of modulator frequencies, MultiFM 1-D SSD smoothes resonances produced at the higher spatial frequencies and can attain similar or even faster smoothing rates compared to the baseline NIF 2-D SSD system. DRACO simulations have shown that MultiFM 1-D SSD beam smoothing is sufficient for the direct-drive-ignition targets and pulse shapes analyzed thus far, and may even allow reducing the bandwidth enough to eliminate the need for dual-tripler frequency conversion on the NIF. (2) describes a time-gated, monoenergetic proton radiography that provides unique measurements of implosion dynamics of spherical targets in direct-drive inertial confinement fusion (ICF) (p. 81). Radiographs obtained at different implosion times, from

  15. Communities of Practice. Niches voor de samenwerking tussen ervaringswerkers en professionals bij gebiedsgericht werken

    Directory of Open Access Journals (Sweden)

    Gerda Scholtens

    2015-03-01

    takes place in a setting where communication is horizontal rather than hierarchical.It was in this context that the organization for mental health clients in Eindhoven launched a project to form Communities of Practice (CoPs in different areas of Eindhoven and its surroundings in 2011. A CoP is a learning group of professionals with different backgrounds who work on the same case, and who improve their competencies by regularly sharing and exchanging knowledge and experience. The main aim of a CoP is to learn from and with each other (social learning. Good relationships form the basis for these learning processes and the development of competencies.The community provides a framework for the learning processes of the participants. Ideally, CoPs should be based on existing voluntary networks since these are informal and self-managing. Such networks can be found in the social support systems of Eindhoven and surroundings, and professionals and experts already have experience of working together in these networks.The contribution of experts-by-experience lends an extra dimension to the CoP. Their approach is known as the “recovery” approach. Recovery is a concept developed by clients in mental health care. According to Wilma Boevink, a prominent member of the recovery movement, “recovery means finding a meaningful life with or without the mental illness.” (Boevink, Prinsen, Elfers, Dröes, Tiber & Wilrycx, 2009, in Dröes & Witsenburg, 2012, p. 57The motivation for the formation of a CoP is the idea that learning from each other’s practices can promote cooperation between professionals and between professionals and experts-by-experience. Cooperation within the CoP also promotes the professional development of the skills needed to work in the community.The programme of CoP meetings involves getting to know each other and each other’s work. Meetings in the learning group have a positive effect on cooperation and the most important aspect of the programme is case

  16. 3D Quaternary deformation pattern in the central Po Plain (Northern Italy)

    Science.gov (United States)

    Sileo, G.; Mueller, K.; Michetti, A. M.; Livio, F.; Berlusconi, A.; Carcano, C.; Rogledi, S.; Vittori, E.

    2009-04-01

    ., Zerboni A., Cremaschi M., Trombino L, Mueller K., Vittori E., Carcano C., Rogledi S. (2008) - Holocene Surface Faulting At Monte Netto, Brescia, And The Christmas 1222 (Io = Ix Mcs) Earthquake In The Po Plain, Italy: What Does It Mean "Blind Fault"? Geophysical Research Abstracts, 10, Egu2008-A-00000, 2008 Egu General Assembly 2008. Mueller, K. & Talling, P. (1997) - Geomorphic Evidence For Tear Faults Accommodating Lateral Propagation Of An Active Fault-Bend Fold, Wheeler Ridge, California. Journal Of Structural Geology, 19, 3-4, p. 397-411. Muttoni G., Carcano, C., Garzanti, E., Ghielmi, M., Piccin, A., Pini, R., Rogledi, S., Sciunnach, D. (2002) - Onset Of Major Pleistocene Galciations In The Alps. Geology. - 2003. - 11 : 31. - p. 989-992. Salvini, F. & Storti, F. (2002) - Three-Dimensional Architecture Of Growth Strata Associated To Fault-Bend, Fault-Propagation, And Decollement Anticlines In Non-Erosional Environments. Sedimentary Geology, 146, p 57 - 73 Scardia, G., Muttoni, G. & Sciunnach, D. (2006) - Subsurface Magnetostratigraphy Of Pleistocene Sediments From The Po Plain (Italy): Constraints On Rates Of Sedimentation And Rock Uplift. GSA Bulletin 118, 11/12, p.1299-1312.

  17. Is journalism failing on climate?

    Science.gov (United States)

    Rahmstorf, Stefan

    2012-12-01

    year likened those who accept the facts of global warming to mass murderers (Hickman 2012). Yet the public also needs to understand the background story about where the 'climate sceptics' claims originate and who finances their dissemination. Let us hope that the study by Painter and Ashe will help to initiate a critical discussion on climate science coverage in the media, particularly in 'Anglo-Saxon' countries, and help to improve it in future. There are so many science journalists out there who work hard every day, striving for quality under most difficult working conditions. Their efforts should not be in vain. References Anderegg W R L et al 2010 Expert credibility in climate change Proc. Natl Acad. Sci. USA 107 12107-9 Boykoff M T and Boykoff J M 2004 Balance as bias: global warming and the US prestige press Glob. Environ. Change—Human Policy Dimen. 14 125-36 Doran P and Kendall Zimmerman M 2009 Examining the scientific consensus on climate change EOS Trans. Am. Geophys. Union 90 22 Gerlach T 2011 Volcanic versus anthropogenic carbon dioxide EOS Trans. Am. Geophys. Union 92 201-8 Hickman L 2012 Heartland Institute compares belief in global warming to mass murder Guardian (www.guardian.co.uk/environment/blog/2012/may/04/heartland-institute-global-warming-murder) Leiserowitz A et al 2011 Global Warming's Six Americas, May 2011 (New Haven, CT: Yale University and George Mason University) p 57(http:/environment.yale.edu/climate/files/SixAmericasMay2011.pdf) Oreskes N 2004 Beyond the ivory tower—the scientific consensus on climate change Science 306 1686 Painter J and Ashe T 2012 Cross-national comparison of the presence of climate scepticism in the print media in six countries, 2007-10 Environ. Res. Lett. 7 044005 Rahmstorf S 2004 The climate skeptics Weather Catastrophes and Climate Change—Is There Still Hope for Us? ed Re Munich (Munich: Munich Re) pp 76-83 Wikipedia 2012 The Great Global Warming Swindle (http

  18. 6th International Symposium on Molecular Allergology (ISMA

    Directory of Open Access Journals (Sweden)

    Christiane Hilger

    2016-10-01

    depletion approach to access IgE cross-reactivity Diana Silva, Teresa Vieira, Ana Maria Pereira, André Moreira, Luís Delgado P54 Olive pollen allergens: what are we missing? Sara Prates, Cátia Alves, Elena Finelli, Paula Leiria Pinto P55 Purified Alt a 1 extract in Alternaria alternata allergy diagnosis Bárbara Kong Cardoso, Cíntia Cruz, Filipa Semedo, Elza Tomaz, Filipe Inácio P56 Use of specific IgE Bos d8 (casein to aid early introduction of dietary baked milk in children with cows’ milk allergy James Gardner, Santanu Maity, Giuseppina Rotiroti, Minal Gandhi P57 Molecular characterisation and immunoreactivity of a peanut ingredient for use in oral food challenges Ivona Baricevic-Jones, Justin T. Marsh, Phil E. Johnson, Anuradha Balasundaram, Anya-May Hope, Aafke Taekema, Angela Simpson, Aida Semic-Jusufagic, E.N. Clare Mills P58 Specific IgE to recombinant allergens of hazelnut and oral food challenge in children Gourdon Dubois Nelly, Sellam Laetitia, Pereira Bruno, Michaud Elodie, Messaoudi Khaled, Evrard Bertrand, Fauquert Jean-Luc Poster session 7/8: miscellaneous P59 What defines a protein as an allergen? A discussion of sources and sufficiency Richard E. Goodman P60 Cat allergy: relationship between clinical and molecular diagnostic María Cecilia Martín Fernández De Basoa, Antón Fernández Ferreiro, Elena Rodríguez Plata P61 Anaphylaxis to rabbit: the cat came in last Luis Amaral, Borja Bartolomé, Alice Coimbra, Jose L Placido P62 Dog allergy: relationship between clinical and molecular diagnostic María Cecilia Martín Fernández De Basoa, Antón Fernández Ferreiro, Elena Rodríguez Plata P63 Correlation of serum timothy grass-pollen specific IgE levels determined by two immunoblot test systems Mariana Vieru, Florin-Dan Popescu, Florin-Adrian Secureanu, Carmen Saviana Ganea P64 Development of oral food challenge formulations for diagnosis of fish allergy using powdered fish ingredients Carol Ann Costello, Ivona Baricevic-Jones, Martin Sorensen, Clare

  19. Selected Abstracts of the 13th International Workshop on Neonatology; Cagliari (Italy; October 25th-28th, 2017

    Directory of Open Access Journals (Sweden)

    --- Various Authors

    2017-10-01

    . IMBALANCE OF PRO- AND ANTI-INFLAM­MA­TORY CYTOKINES IN COMMUNITY ACQUIRED PNEUMONIA OF CHILDREN WITH DIFFERENT LEVELS OF PHYSICAL DEVELOPMENT • T.V. Frolova, O.S. BorodinaABS 56. THINK FIRST ABOUT WHAT’S COMMON • C. Spiga, F. Ferendeles, N. Garau, R. Mazzitti, S. Ibba, A. Cirina, A. Atzei, P. Neroni, M. Puddu, G. OttonelloABS 57. A COMPLEX CASE OF ANOMALOUS LEFT CORONARY ARTERY ORIGIN FROM THE PULMONARY ARTERY (ALCAPA • F. Bardanzellu, P. Neroni, P.P. Bassareo, M. Puddu, G. OttonelloABS 58. SLEEP-DISORDERED BREATHING IN CHIL­DREN WITH RECURRENT WHEEZING/ASTHMA: A SINGLE CENTRE STUDY • M. Zaffanello, E. Gasperi, L. Tenero, M. Piazza, A. Pietrobelli, L. Sacchetto, F. Antoniazzi, G. PiacentiniABS 59. UNUSUAL GLOMERULAR SHAPE IN TRISOMY 21 • A. Ravarino, C. Rossi, L. Ippolito, C. Gerosa, V. Marinelli, V. Fanos, Y. Gibo, G. FaaABS 60. A STEP TOWARDS A SAFER DISCHARGE: THE EVALUATION OF CARDIORESPIRATORY STABILITY IN PRETERM NEWBORN • E. Maggiora, E. Cocchi, F. Logrippo, A. Pirra, C. Plazzotta, S. Viola, R. Bagna, A. Coscia, E. Bertino, F. CresiABS 61. NASAL OBSTRUCTION AND SLEEP DIS­OR­DERED BREATHING DURING CLINICAL PRAC­TICE IN CHILDREN • M. Zaffanello, E. Gasperi, L. Tenero, M. Piazza, S. Bonafini, L. Nosetti, L. Sacchetto, G. PiacentiniABS 62. IS THE BODY POSITION REALLY HELPFUL FOR THE STABILIZATION OF PRETERM BABIES WITH PATENT OF DUCTUS ARTERIOSUS IN NURSING CARE? A LITERATURE REVIEW • F. De Matteis, C. Taberna, M Ariotti, P. Murru, E. BertinoABS 63. P57 EXPRESSION IN MALE AND FEMALE PLACENTAS • E. Di Felice, C. Rossi, L.Vinci, C. GerosaABS 64. IRON SUPPLEMENTATION IN PRETERM NEW­BORNS: SULFATE OR BISGLYCINATE CHELATE IRON? • S. Viola, E. Maggiora, R. Bagna, E. Spada, E. BertinoABS 65. LIVER BIOPSY INTERPRETATION IN WILSON DISEASE IN CHILDHOOD: A REPORT OF 12 CASES • V. Vallascas, M. Moi, C. Gerosa, A.M. Nurchi, P. Van Eyken, D. FanniABS 66. A NEW APPROACH TO REDUCE CHILDREN’S FEAR • M. Aprile, C. Pala, C. Cuscusa, S. Puggioni, G. Bogo