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Sample records for aulacomya atra atra

  1. Cytoprotective Effects of Lysophospholipids from Sea Cucumber Holothuria atra.

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    Yoshifumi Nishikawa

    Full Text Available Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography-time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress.

  2. Accelerator-driven transmutation reactor analysis code system (ATRAS)

    Energy Technology Data Exchange (ETDEWEB)

    Sasa, Toshinobu; Tsujimoto, Kazufumi; Takizuka, Takakazu; Takano, Hideki [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-03-01

    JAERI is proceeding a design study of the hybrid type minor actinide transmutation system which mainly consist of an intense proton accelerator and a fast subcritical core. Neutronics and burnup characteristics of the accelerator-driven system is important from a view point of the maintenance of subcriticality and energy balance during the system operation. To determine those characteristics accurately, it is necessary to involve reactions at high-energy region, which are not treated on ordinary reactor analysis codes. The authors developed a code system named ATRAS to analyze the neutronics and burnup characteristics of accelerator-driven subcritical reactor systems. ATRAS has a function of burnup analysis taking account of the effect of spallation neutron source. ATRAS consists of a spallation analysis code, a neutron transport codes and a burnup analysis code. Utility programs for fuel exchange, pre-processing and post-processing are also incorporated. (author)

  3. Radiologic features of all-trans-retinoic acid syndrome (ATRAS) - case report

    International Nuclear Information System (INIS)

    Konarzewska, J.; Bianek-Bodzak, A.; Szatkowski, D.; Szarmach, D.

    2007-01-01

    ATRA Syndrome appears as a side effect of acute promyelocytic leukemia treatment with ATRA, vitamin A derivative. The etiopathogenesis of the syndrome remains unclear. Fever, generalized edema, pleural or pericardial effusion, respiratory distress, coagulation disorders and sometimes renal failure are the most common clinical symptoms of ATRAS. Radiological features of the syndrome are very diverse. Early diagnosis followed by introduction of appropriate treatment (corticosteroids) prevents worsening of the patients' condition and significantly reduces the risk of death. Although clinical symptomatology of ATRAS has been widely described, there are still few descriptions of its radiological manifestation. A 53-year-old female was referred to the Hematology Department for further detailed diagnostics and appropriate therapy from the district hospital, where she had been primarily admitted due to weakness, easy fatigue, loss of appetite and blood extravasations on the skin of the extremities. The patient's general condition on admission was assessed as quite good. Acute promyelocytic leukemia (AML M3 according to FAB classification) was diagnosed. The introduced treatment included ATRA. On the second day of treatment, the patient developed fever, dyspnea, generalized edema, and coagulation disorders increased. Chest X-ray findings reminded ARDS. The diagnosis of ATRAS was established, which resulted in ATRA withdrawal. After administration of corticosteroids, the patient's condition improved gradually within a few days. ATRA was reintroduced then, since the signs of leukemia had intensified. The patient remains in charge of the Hematology Department. Changes of chest X-ray pictures in AML patients treated with ATRA should be interpreted in clinical context due to lack of radiological features specific for ATRAS. (author)

  4. Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso

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    Gelcimar Moresco

    2011-06-01

    Full Text Available O presente relato apresenta o caso clínico de uma paciente com leucemia promie-locítica aguda tratada com ácido todo-transretinoico (ATRA, que apresentou suspeita de síndrome do ácido transreti-noico (síndrome de ATRA. Com a ocor-rência de leucopenia febril inespecífica, foram associados ao tratamento antimi-crobianos e antifúngicos. A diminuição da função renal, observada inicialmente, contribuiu para a suspeita de síndrome de ATRA, que foi agravada pelos antifúngi-cos. Assim, o uso de ATRA foi suspenso, mas somente 8 dias depois foi caracteriza-da pneumonia e descartada a hipótese de síndrome de ATRA. Nesse contexto, foi discutida a nefrotoxicidade do ATRA e a potencialização desse efeito adverso pelo uso de antifúngicos nefrotóxicos, em par-ticular da anfotericina B, assim como a im-portância do diagnóstico diferencial entre síndrome de ATRA e doença infecciosa.

  5. Differential Effects of Naja naja atra Venom on Immune Activity

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    Jian-Qun Kou

    2014-01-01

    Full Text Available Previous studies reported that Naja naja atra venom (NNAV inhibited inflammation and adjuvant arthritis. Here we investigated the role of NNAV in regulation of immune responses in mice. Oral administration of NNAV to normal mice showed significant increase in natural killer cell activity, B lymphocyte proliferation stimulated by lipopolysaccharides, and antibody production in response to sheep red blood cells. Meanwhile, NNAV markedly decreased T lymphocyte proliferation stimulated by concanavalin A, arrested the cell cycle at G0/G1 phase, and suppressed CD4 and CD8 T cell divisions. Furthermore, NNAV inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reaction. This modulation of immune responses may be partly attributed to the selective increase in Th1 and Th2 cytokines (IFN-γ, IL-4 secretion and inhibition of Th17 cytokine (IL-17 production. In dexamethasone-induced immunosuppressed mice, NNAV restored the concentration of serum IgG and IgM, while decreasing the percentage of CD4 and CD8 T-cell subsets. These results indicate that NNAV enhances the innate and humoral immune responses while inhibiting CD4 Th17 and CD8 T cell actions, suggesting that NNAV could be a potential therapeutic agent for autoimmune diseases.

  6. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    International Nuclear Information System (INIS)

    Akter, Jesmin; Takatori, Atsushi; Islam, Md. Sazzadul; Nakazawa, Atsuko; Ozaki, Toshinori; Nagase, Hiroki; Nakagawara, Akira

    2014-01-01

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas

  7. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Akter, Jesmin [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Takatori, Atsushi, E-mail: atakatori@chiba-cc.jp [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Islam, Md. Sazzadul [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakazawa, Atsuko [Department of Pathology, National Center for Child Health and Development, Tokyo (Japan); Ozaki, Toshinori, E-mail: tozaki@chiba-cc.jp [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nagase, Hiroki [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakagawara, Akira [Saga Medical Centre, 840-8571 (Japan)

    2014-10-10

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

  8. Timing of reproduction and fledging success in the coot Fulica atra : evidence for a causal relationship

    NARCIS (Netherlands)

    Brinkhof, Martin W.G.; Cavé, Anton J.; Hage, Fred J.; Verhulst, Simon

    1993-01-01

    1. We investigated the relationship between hatching date and fledging success in the European coot (Fulica atra). 2. The production of fledglings per brood increased in the first half of the season and decreased in the second half, independent of clutch size or egg size. We tested experimentally

  9. Discovery of Salamandra atra aurorae (Trevisan, 1982 on the Altopiano di Vezzena, Trentino (Northeastern Italy

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    Wouter Beukema

    2008-05-01

    Full Text Available Aurora’s Alpine Salamander is a limited distributed subspecies endemic to the Altopiano di Asiago, Veneto. In the current paper the occurrence of Salamandra atra aurorae is described for the Altopiano di Vezzena, Trentino. The aim of this paper is to review the distribution as well as to comment on the conservational status of the subspecies in Trentino.

  10. The effect of all-trans retinoic acid (ATRA) on the expression of ...

    African Journals Online (AJOL)

    Administrator

    2011-09-28

    Sep 28, 2011 ... ATRA on the expression of VEGF and its receptors in LoVo cells, and its possible mechanisms. LoVo .... Tween 20 (PBS-T) and 5% non-fat milk for temperature, the ... The frequencies of positive cells were compared using the. Chi-square test .... curative surgery alone ultimately relapse and die of metastatic ...

  11. Megadenus atrae n. sp., an endoparasitic eulimid gastropod (Mollusca) from the black sea cucumber Holothuria atra Jaeger (Aspidochirotida: Holothuriidae) in the Indo-West Pacific.

    Science.gov (United States)

    Takano, Tsuyoshi; Warén, Anders; Kano, Yasunori

    2017-07-01

    An eulimid gastropod, Megadenus atrae n. sp., endoparasitic in the cloacal chamber of the black sea cucumber Holothuria atra Jaeger is described from Okinawa, Japan, as the fifth species of the genus. Conspecific specimens have also been found from southeast India, northeast Australia and New Caledonia. The generic assignment is justified by the presence of (i) a thick, long proboscis that bears a large fold (pseudopallium) near the base and a collar-like structure at the middle, (ii) a thin, globose shell that is covered by the pseudopallium, and (iii) sexual dimorphism with the female generally larger than the male. The new species is distinguishable from the four previously described congeners by its cauldron-shaped pseudopallium, moderately-developed collar of the proboscis and rounded basal lip of the shell. The comparisons of the size and sex of solitary and paired individuals support a previous hypothesis that the species of Megadenus Rosén, 1910 are protandrous with environmental sex determination. The present species occurs mostly as monogamous pairs despite its very low population density, implying that the presence of a conspecific individual acts as a cue for larval settlement. Both mechanisms would increase individual reproductive success in such permanent parasites with low prevalence and abundance as the species of Megadenus.

  12. Atrações e prazeres visuais em um pornô feminino

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    Mariana Baltar

    2015-08-01

    Full Text Available Este artigo correlaciona os conceitos de excesso e atrações como estratégicos para refletir sobre processos de engajamento e afetação no campo da pornografia que desestabilizam morais tradicionais em direção a uma política de gêneros. Nesse sentido, mobiliza-se uma lógica de excesso de atrações que estabelece um jogo ambivalente de recusa e adesão aos códigos genéricos mais básicos da pornografia. Os argumentos são empreendidos a partir da análise de Dirty Diaries, um projeto declaradamente associado ao campo da pornografia feminista empreendido com apoio do Swedish Film Institut.

  13. Anticancer potency of black sea cucumber (Holothuria atra) from Mentawai Islands, Indonesia

    OpenAIRE

    Mieke Hemiawati Satari; Utmi Arma; Syafruddin Ilyas; Dian Handayani

    2017-01-01

    ABSTRACT Introduction: The source of bioactive compounds believed to have strong anticancer potency is derived from sea cucumber. Black sea cucumber (Holothuria atra) is a dominant species in Mentawai Islands, West Sumatera, Indonesia. Key factor compound that acts as anticancer in sea cucumber extract is tritepenoid also known as Frondoside A. The purpose of this study was to determine the effectiveness of the active compound taken from black sea cucumber as anticancer. Methods: Methods u...

  14. Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling study

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    Hermanova Marketa

    2010-05-01

    Full Text Available Abstract Background We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2 and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA and inhibitors of lipoxygenases (LOX and cyclooxygenases (COX. This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells. Methods Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes. Results Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2 or SH-SY5Y after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX in combination with ATRA in both cell lines. Conclusions Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.

  15. Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling study.

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    Chlapek, Petr; Redova, Martina; Zitterbart, Karel; Hermanova, Marketa; Sterba, Jaroslav; Veselska, Renata

    2010-05-11

    We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA) and inhibitors of lipoxygenases (LOX) and cyclooxygenases (COX). This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells. Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes. Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2) or SH-SY5Y) after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX) in combination with ATRA in both cell lines. Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.

  16. Studies on Multifunctional Effect of All-Trans Retinoic Acid (ATRA on Matrix Metalloproteinase-2 (MMP-2 and Its Regulatory Molecules in Human Breast Cancer Cells (MCF-7

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    Anindita Dutta

    2009-01-01

    Full Text Available Background. Vitamin A derivative all-trans retinoic acid (ATRA is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We studied the effect of ATRA on MMP-2 in MCF-7, human breast cancer cells, and the probable signaling pathways which are affected by ATRA on regulating pro-MMP-2 activity and expression. Methods. Gelatin zymography, RT-PCR, ELISA, Western blot, Immunoprecipitation, and Cell adhesion assay are used. Results. Gelatin zymography showed that ATRA caused a dose-dependent inhibition of pro-MMP-2 activity. ATRA treatment downregulates the expression of MT1-MMP, EMMPRIN, FAK, NF-kB, and p-ERK. However, expression of E-cadherin, RAR, and CRABP increased upon ATRA treatment. Binding of cells to extra cellular matrix (ECM protein fibronectin reduced significantly after ATRA treatment. Conclusions. The experimental findings clearly showed the inhibition of MMP-2 activity upon ATRA treatment. This inhibitory effect of ATRA on MMP-2 activity in human breast cancer cells (MCF-7 may result due to its inhibitory effect on MT1-MMP, EMMPRIN, and upregulation of TIMP-2. This study is focused on the effect of ATRA on MMP, MMP-integrin-E-cadherin interrelationship, and also the effect of the drug on different signaling molecules which may involve in the progression of malignant tumor development.

  17. Beneficial effect of all-trans retinoic acid (ATRA) on glomerulosclerosis rats via the down-regulation of the expression of alpha-smooth muscle actin: a comparative study between ATRA and benazepril.

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    Hu, Peng; Qin, Yuan Han; Pei, Juan; Lei, Feng Ying; Hu, Bo; Lu, Ling

    2010-08-01

    Although ATRA is a potent renoprotective agent, relatively little is known regarding the mechanisms of its action. The present study was designed to further elucidate the mechanisms of ATRA's action to GS rats and compare that with the beneficial effect of benazepril. Male SD rats weighting 160 to 200g were used in this study. GS was induced by unilateral nephrectomy and intravenous injection of adriamycin (6mg/kg). They were divided randomly 20 ones per group into GS group, GS treated with ATRA (20mg/kg/day) group, and GS treated with benazepril (10mg/kg/day) group. The other 20 ones were taken as sham-operation group, injected normal saline into caudal vein. 12weeks later, all rats were subjected to sacrifice. As expected, the GS group exhibited significant lower serum TP and Alb, and higher BUN, Cr and proteinuria than those of the sham group. Administration of ATRA or benazepril did ameliorate these above disorders of biochemical parameters in GS rats. Extensive renal damage was observed in the GS group, such as mononuclear infiltration, mesangial proliferation, focal segment glomerular sclerosis, and tubulointerstitial fibrosis. The pathological changes in both ATRA and benazepril group were alleviated remarkably. Semiquantitative GSI was used to evaluate the degree of GS in all groups. GSI was significantly higher in the GS group than in sham group. GSI decreased from 21.9+/-6.7 in the GS group to 6.9+/-2.8 in the ATRA group and 7.0+/-2.7 in benazepril group respectively. However, no significant difference in GSI between rats treated with ATRA and rats treated with benazepril was found. RT-PCR analysis revealed the renal expression of alpha-SMA mRNA was induced substantially in GS group as compared to sham group, which could be offset completely by ATRA or benazepril administration. However, expression level of alpha-SMA mRNA in GS rats treated with ATRA was identical to that in GS rats treated with benazepril. We also examined immunohistochemical staining

  18. Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon.

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    Shi, Yi-Jun; Chen, Ying-Jung; Hu, Wan-Ping; Chang, Long-Sen

    2017-01-07

    This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5'- and 3'-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A₂-coralyne-A₂ coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs.

  19. CDDO and ATRA Instigate Differentiation of IMR32 Human Neuroblastoma Cells

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    Namrata Chaudhari

    2017-09-01

    Full Text Available Neuroblastoma is the most common solid extra cranial tumor in infants. Improving the clinical outcome of children with aggressive tumors undergoing one of the multiple treatment options has been a major concern. Differentiating neuroblastoma cells holds promise in inducing tumor growth arrest and treating minimal residual disease. In this study, we investigated the effect of partial PPARγ agonist 2-cyano-3,12-dioxooleana-1,9(11-dien-28-oic acid (CDDO on human neuroblastoma IMR32 cells. Our results demonstrate that treatment with low concentration of CDDO and particularly in combination with all trans retinoic acid (ATRA induced neurite outgrowth, increased the percentage of more than two neurites bearing cells, and decreased viability in IMR32 cells. These morphological changes were associated with an increase in expression of bonafide differentiation markers like β3-tubulin and Neuron Specific Enolase (NSE. The differentiation was accompanied by a decrease in the expression of MYCN whose amplification is known to contribute to the pathogenesis of neuroblastoma. MYCN is known to negatively regulate NMYC downstream-regulated gene 1 (NDRG1 in neuroblastomas. MYCN down-regulation induced by CDDO correlated with increased expression of NDRG1. CDDO decreased Anaplastic Lymphoma Kinase (ALK mRNA expression without affecting its protein level, while ATRA significantly down-regulated ALK. Antagonism of PPARγ receptor by T0070907 meddled with differentiation inducing effects of CDDO as observed by stunted neurite growth, increased viability and decreased expression of differentiation markers. Our findings indicate that IMR32 differentiation induced by CDDO in combination with ATRA enhances, differentiation followed by cell death via cAMP-response-element binding protein (CREB independent and PPARγ dependent signaling mechanisms.

  20. ÚLCERAS ESCROTALES SECUNDARIAS A TRATAMIENTO CON ÁCIDO TRANSRETINOICO (ATRA

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    Cuevas-Ruiz MV

    2011-01-01

    Full Text Available El ácido trans retinoico es el fármaco de elección en el tratamiento de la Leucemia Promielocítica Aguda. El efecto secundario más grave del fármaco es el síndrome de diferenciación, pero puede ocasionar lesiones en piel y úlceras escrotales. Presentamos el caso de un varón con leucemia promielocítica aguda que recibió ATRA y presentó úlceras escrotales

  1. Agama atra

    African Journals Online (AJOL)

    show a well-defined breeding season (Fitch 1970; Van Wyk. 1983). Oocyte development in ... biuret reaction method described by Mattenheimer (1971) was used to determine the total plasma protein concentration. Plasma protein fractions ...

  2. Antifungal effect of Sticophus hermanii and Holothuria atra extract and its cytotoxicity on gingiva-derived mesenchymal stem cell

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    Kristanti Parisihni

    2013-12-01

    Full Text Available Background: Sea cucumber had been acknowledged to have some medical properties Sticophus hermanii and Holothuria atra are species of sea cucumber which has been known to have antifungal properties thus potentially explored as therapeutic agent in oral candidiasis. Purpose: The aim of this study was to examine the antifungal property Sticophus hermanii and Holothuria atra extract against Candida albicans and its cytotoxicity to human gingiva-derived mesenchymal stem cell. Methods: The study was an experimental laboratories research with post test only control group design. Methanolic extract of Sticophus hermanii and Holothuria atra in concentrations of 1%, 0.5%; 0.25%; 0.13%, 0.07%; 0.03%, 0.02% and 0.01%; were tested its cytotoxicity on gingiva-derived mesenchymal stem cell. Cell viability were measured by MTT assay. The antifungal property against Candida albicans was tested by disk diffusion method. Data were analyzed by ANOVA followed by LSD. Results: Extract of Sticophus hermanii showed no cytotoxicity in all concentrations (p>0.05, while Holothuria atra showed toxicity in the concentration of 1% and not cytotoxic in the concentrations below (p<0.05. Both sea cucumber extract could inhibit the growth Candida albicans, in vitro, proved by the clear zone around the disc in all concentrations (p<0.05. Conclusion: Stichopus hermanii and Holothuria atra extract had the antifungal effect against Candida albicans. Sea cucumber extract were not cytotoxic togingiva-derived mesenchymal stem cell in the concentration of Sticophus hermanii ≤ 1% and Holothuria atra ≤ 0.5%.Latar belakang: Teripang telah diketahui mempunyai berbagai khasiat medis. Sticophus hermanii dan Holothuria atra adalah spesies teripang yang telah diketahui mempunyai sifat anti jamur sehingga santat potensial untuk diekplorasi sebagai agen terapeutik pada infeksi di rongga mulut. Tujuan: Tujuan dari penelitian ini adalah untuk meneliti sifat anti jamur ekstrak Sticophus hermanii

  3. Sirenophila ovis-atra a new species of maritime Teloschistaceae from the Southern Hemisphere

    DEFF Research Database (Denmark)

    Søchting, Ulrik; Søgaard, Majbrit Zeuthen; Sancho, Leopoldo G.

    2016-01-01

    A new species, Sirenophila ovis-atra is described from maritime rocks of southern Patagonia, the Falkland Islands and Macquarie Island, where it grows in the upper part of the black ‘Verrucaria-zone’, most often on members of the genus Hydropunctaria. It is so far the only known species of Sireno......A new species, Sirenophila ovis-atra is described from maritime rocks of southern Patagonia, the Falkland Islands and Macquarie Island, where it grows in the upper part of the black ‘Verrucaria-zone’, most often on members of the genus Hydropunctaria. It is so far the only known species...

  4. Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom

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    Shu-Zhi Wang

    2018-02-01

    Full Text Available Naja naja atra venom (NNAV is composed of various proteins, peptides, and enzymes with different biological and pharmacological functions. A number of previous studies have reported that NNAV exerts potent analgesic effects on various animal models of pain. The clinical studies using whole venom or active components have confirmed that NNAV is an effective and safe medicine for treatment of chronic pain. Furthermore, recent studies have demonstrated that NNAV has anti-inflammatory and immune regulatory actions in vitro and in vivo. In this review article, we summarize recent studies of NNAV and its components on inflammation and immunity. The main new findings in NNAV research show that it may enhance innate and humoral immune responses while suppressing T lymphocytes-mediated cellular immunity, thus suggesting that NNAV and its active components may have therapeutic values in the treatment of inflammatory and autoimmune diseases.

  5. Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

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    J. C. Troiano

    2006-01-01

    Full Text Available A comparative study on the sensitivity of erythrocytes from different vertebrate species (avian, mammalian and reptilian to the hemolytic action caused by cardiotoxin isolated from Naja naja atra venom was carried out. Cardiotoxin was able to induce direct hemolysis in washed erythrocytes from several animals, except for llama. The EC50 values from hemolysis of the most sensitive (cat and the most resistant (snake animal varied approximately tenfold. According to the cell behavior, it was possible to characterize four types of behavior: The first was observed in cat, horse and human cells; the second in rat, rabbit and dog erythrocytes; and the third only in llama erythrocytes, which were resistant to cardiotoxin concentrations up to 300 µg/ml. Finally, avian and reptilian erythrocytes were more resistant to cardiotoxin III-induced hemolysis than those of the mammalian species.

  6. Naja naja atra venom ameliorates pulmonary fibrosis by inhibiting inflammatory response and oxidative stress.

    Science.gov (United States)

    Cui, Kui; Kou, Jian-Qun; Gu, Jin-Hua; Han, Rong; Wang, Guanghui; Zhen, Xuechu; Qin, Zheng-Hong

    2014-12-02

    Naja naja atra venom (NNAV) displays diverse pharmacological actions including analgesia, anti-inflammation and immune regulation.In this study, we investigated the effects of NNAV on pulmonary fibrosis and its mechanisms of action. To determine if Naja naja atra venom (NNAV) can produce beneficial effects on pulmonary fibrosis, two marine models of pulmonary fibrosis were produced with bleomycin (BLM) and lipopolysaccharide (LPS). NNAV (30, 90, 270 μg/kg) was orally administered once a day started five days before BLM and LPS until to the end of experiment. The effects of NNAV treatment on pulmonary injury were evaluated with arterial blood gas analysis, hydroxyproline (HYP) content assessment and HE/Masson staining. The effects of NNAV treatment on inflammatory related cytokines, fibrosis related TGF-β/Smad signaling pathway and oxidative stress were examined. The results showed that NNAV improved the lung gas-exchange function and attenuated the fibrotic lesions in lung. NNAV decreased IL-1β and TNF-α levels in serum in both pulmonary fibrosis models. NNAV inhibited the activation of NF-κB in LPS-induced and TGF-β/Smad pathway in BLM-induced pulmonary fibrosis. Additionally, NNAV also increased the levels of SOD and GSH and reduced the levels of MDA in BLM-induced pulmonary fibrosis model. The present study indicates that NNAV attenuates LPS- and BLM-induced lung fibrosis. Its mechanisms of action are associated with inhibiting inflammatory response and oxidative stress. The study suggests that NNAV might be a potential therapeutic drug for treatment of pulmonary fibrosis.

  7. Novel Naja atra cardiotoxin 1 (CTX-1 derived antimicrobial peptides with broad spectrum activity.

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    Andrea Sala

    Full Text Available Naja atra subsp. atra cardiotoxin 1 (CTX-1, produced by Chinese cobra snakes, belonging to Elapidae family, is included in the three-finger toxin family and exerts high cytotoxicity and antimicrobial activity too. Using as template mainly the tip and the subsequent β-strand of the first "finger" of this toxin, different sequences of 20 amino acids linear peptides have been designed in order to avoid toxic effects but to maintain or even strengthen the partial antimicrobial activity already seen for the complete toxin. As a result, the sequence NCP-0 (Naja Cardiotoxin Peptide-0 was designed as ancestor and subsequently 4 other variant sequences of NCP-0 were developed. These synthesized variant sequences have shown microbicidal activity towards a panel of reference and field strains of Gram-positive and Gram-negative bacteria. The sequence named NCP-3, and its variants NCP-3a and NCP-3b, have shown the best antimicrobial activity, together with low cytotoxicity against eukaryotic cells and low hemolytic activity. Bactericidal activity has been demonstrated by minimum bactericidal concentration (MBC assay at values below 10 μg/ml for most of the tested bacterial strains. This potent antimicrobial activity was confirmed even for unicellular fungi Candida albicans, Candida glabrata and Malassezia pachydermatis (MBC 50-6.3 μg/ml, and against the fast-growing mycobacteria Mycobacterium smegmatis and Mycobacterium fortuitum. Moreover, NCP-3 has shown virucidal activity on Bovine Herpesvirus 1 (BoHV1 belonging to Herpesviridae family. The bactericidal activity is maintained even in a high salt concentration medium (125 and 250 mM NaCl and phosphate buffer with 20% Mueller Hinton (MH medium against E. coli, methicillin resistant Staphylococcus aureus (MRSA and Pseudomonas aeruginosa reference strains. Considering these in vitro obtained data, the search for active sequences within proteins presenting an intrinsic microbicidal activity could provide a

  8. Reduced RAR-β gene expression in Benzo(a)Pyrene induced lung cancer mice is upregulated by DOTAP lipo-ATRA treatment.

    Science.gov (United States)

    Viswanathan, S; Berlin Grace, V M

    2018-05-16

    Molecular targeted therapy for specific genes is an emerging research. Retinoic Acid Receptor (RAR-β) is a key tumor suppressor which is found to be lost drastically during much cancer progression. We hence, analyzed the expression level of RAR-β gene during B(a)P induced lung cancer development in mice and studied the lung cancer targeted action of All Trans Retinoic Acid (ATRA) in DOTAP liposomal formulation. The effect of its treatment on lung cancer was determined by histopathological analysis. RAR-β gene expression was assessed by RT-PCR and qPCR. A distinct band for RAR-β gene (density - 0.5123 for lung and 0.5160 for liver) was observed in normal mice, whereas no visible band was observed in cancer induced group, indicating loss of RAR-β gene expression. Both ATRA and lipo-ATRA treated groups showed detectable RAR-β expression with relatively lesser density than the normal group. The expression was more intense in lipo-ATRA treatment (density-0.2973) compared with free ATRA treatment (density-0.1549) in lung tissues. The qPCR results also have highlighted a highly significant (p ≤ 0.01) variation RQ values between lipo-ATRA group (15.46 ± 1.54) and free ATRA group (7.58 ± 1.30) in lung tissue sample on 30th day. The mean RQ value for normal lung on 30th day was 20.86 ± 2.58 against the cancer control. The 120th day mice also showed the similar RAR-β expression pattern with further declined expression levels as there was no treatment given after 30 days. Interestingly, the lipo-ATRA treatment could show a highly significant (p ≤ 0.001) expression (12.00 ± 2.31) when compared with free ATRA treatment (3.31 ± 0.58) which implies that the lipo-ATRA formulation could result in sustained delivery of ATRA in target site. Histopathology of lung and liver on 120th day also revealed an effective therapeutic indication in lipo-ATRA treatment compared to free ATRA treatment due to lipo-ATRA's stealth property and it

  9. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

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    Cao-Xin Chen

    2015-01-01

    Full Text Available Cardiotoxin (CTX from Naja naja atra venom (NNAV reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis.

  10. Effect of All-Trans Retinoic Acid (ATRA against expression of Matrix Metalloproteinase-2 (MMP-2 in model mice (Rattus norvegicus periodontitis

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    Ilma Soraya

    2017-08-01

    Full Text Available Introduction: Periodontitis is a condition of inflammation of the tooth supporting tissues generally caused by bacteria Phorphyromonas gingivalis (Pg. and is usually characterized by the occurrence of the alveolar bone resorption. Matrix metalloproteinase-2 (MMP-2 is an enzyme that plays an important role in inflammatory conditions. All-trans retinoic acid (ATRA is a metabolite of vitamin A which plays a role in healing the inflamed tissue and maintain the immune system. The purpose of this study was to determine the effect of ATRA on the expression of MMP-2 in mouse models Rattus norvegicus of periodontitis. Methods: Experimental laboratory by using post test only with control group design. This study used 25 male Wistar mice (Rattus norvegicus that divided into 5 groups. Group 1 (G1 is a group of healthy mice, group 2 (G2 is a group of sick mice as induced periodontitis without treatment, group 3 (G3 is a group of periodontitis mice treated with 5 mg/kg dose of ATRA, group 4 (G4 is a group of periodontitis mice treated with 10 mg/kg dose of ATRA, group 5 (G5 is a group of periodontitis mice treated with 20 mg/kg dose of ATRA. Periodontitis induction was induced by Pg. bacteria every 3 days for 28 days and followed by administration of ATRA for 7 days. Expression of MMP-2 from gingival tissues and periodontal ligament was obtained by immunohistochemical methods. Results were analyzed using the Shapiro-Wilk Test and Mann-Whitney Test. Results: The results showed there were significant differences in the positive area of MMP-2 and MMP-2 color intensity (p < 0.05 between groups. Conclusion: ATRA dose of 20 mg/kg is the most effective dose in inhibiting the expression of MMP-2 in mice models of periodontitis when compared with the dose on other groups.

  11. Hierarchical structure and mechanical properties of snake (Naja atra) and turtle (Ocadia sinensis) eggshells.

    Science.gov (United States)

    Chang, Yin; Chen, Po-Yu

    2016-02-01

    After hundreds of million years of evolution, natural armors have evolved in various organisms, and has manifested in diverse forms such as eggshells, abalone shells, alligator osteoderms, turtle shells, and fish scales. Eggshells serve as multifunctional shields for successful embryogenesis, such as protection, moisture control and thermal regulation. Unlike calcareous avian eggshells which are brittle and hard, reptilians have leathery eggshells that are tough and flexible. Reptilian eggshells can withstand collision damages when laid in holes and dropped onto each other, and reduce abrasion caused by buried sand. In this study, we investigate structure and mechanical properties of eggshells of Taiwan cobra snake (Naja atra) and Chinese striped-neck turtle (Ocadia sinensis). From Acid Fuchsin Orange G (AFOG) staining and ATR-FTIR examination, we found that both eggshells are mainly composed of keratin. The mechanical properties of demineralized snake and turtle eggshells were evaluated by tensile and fracture tests and show distinctly difference. Turtle eggshells are relatively stiff and rigid, while snake eggshells behave as elastomers, which are highly extensible and reversible. The exceptional deformability (110-230% tensile strain) and toughness of snake eggshells are contributed by the wavy and random arrangement of keratin fibers as well as collagen layers. Multi-scale toughening mechanisms of snake eggshells were observed and elucidated, including crack deflection and twisting, fibers reorientation, sliding and bridging, inter-laminar shear effect, as well as the α-β phase transition of keratin. Inspirations from the structural and mechanical designs of reptilian eggshells may lead to the synthesis of tough, extensible, lightweight composites which could be further applied in the flexible devices, packaging and bio-medical fields. Amniotic eggshells serve as multifunctional shields for successful embryogenesis. The avian eggshells have been extensively

  12. Potencial de árvores frutíferas para a atração de aves

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    Leonardo Ribeiro Góes-Silva

    2012-04-01

    Full Text Available O objetivo deste trabalho é avaliar o potencial atrativo de aves presente em oito espécies de árvores frutíferas: Callicarpa reevesii Wall.ex Walp., Ficus microcarpa L.f., Ficus tomentella Miq., Michelia champaca L., Morus nigra L., Nectandra nitidula Nees, Schinus terebinthifolius Raddi e Syagrus romanzoffiana Cham. A interação de aves-plantas foi observada no município de Ouro Fino (MG, nos domínios da Serra da Mantiqueira. As referentes árvores foram observadas durante 24 horas nos períodos em que estavam frutificando, entre julho de 2007 a abril de 2008. Com o uso de ferramentas de análise de diversidade biológica, pode-se constatar que as espécies com maiores potenciais de atração de aves foram Ficus microcarpa, Ficus tomentella, Morus nigra, Nectandra nitidula e Schinus terebinthifolius e as espécies de aves que apresentaram alto índice de interação com as árvores foram Dacnis cayana, Elaenia flavogaster, Tangara cayana, Tersina viridis, Thraupis sayaca, Turdus amaurochalinus e Turdus rufiventris.

  13. Changes in Sediment Fatty Acid Composition during Passage through the Gut of Deposit Feeding Holothurians: Holothuria atra (Jaeger, 1883 and Holothuria leucospilota (Brandt, 1835

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    Prosper L. Mfilinge

    2016-01-01

    Full Text Available Sea cucumbers Holothuria atra and Holothuria leucospilota play an important role in the bioturbation of sediment in coral reef and rocky intertidal ecosystems. This study investigated changes in sediment fatty acid (FA composition during gut passage in H. atra and H. leucospilota. The FA composition did not differ significantly between species. Comparison of FA composition in ambient sediment (AS, foregut (FG, midgut (MG, hindgut (HG, and faecal pellets (FPs indicated that marked changes in FA composition occurred during passage through the gut of H. atra and H. leucospilota. Saturated fatty acids (SAFAs, monounsaturated fatty acids (MUFAs, polyunsaturated fatty acids (PUFAs, and branched fatty acids (BrFAs were significantly higher in FG than in AS, suggesting that both species selectively ingested nutrient rich particles. Significant reduction of SAFAs, MUFAs, PUFAs, and BrFAs occurred in MD and HD, with complete elimination of most PUFAs in FPs. A decrease in PUFAs 20:5ω3, 18:4ω3, 22:5ω3, 22:6ω3, 18:2ω6, 18:3ω3, 18:3ω6, odd-numbered BrFAs, and MUFA 18:1ω7 indicated that algal detritus and bacteria were important part of diet. These results have implications for the fate of specific dietary FAs, especially ω3 and ω6, and the contribution holothurian FPs make to the FA composition of coral reef and rocky intertidal ecosystems.

  14. Changes in Sediment Fatty Acid Composition during Passage through the Gut of Deposit Feeding Holothurians: Holothuria atra (Jaeger, 1883) and Holothuria leucospilota (Brandt, 1835)

    Science.gov (United States)

    Tsuchiya, Makoto

    2016-01-01

    Sea cucumbers Holothuria atra and Holothuria leucospilota play an important role in the bioturbation of sediment in coral reef and rocky intertidal ecosystems. This study investigated changes in sediment fatty acid (FA) composition during gut passage in H. atra and H. leucospilota. The FA composition did not differ significantly between species. Comparison of FA composition in ambient sediment (AS), foregut (FG), midgut (MG), hindgut (HG), and faecal pellets (FPs) indicated that marked changes in FA composition occurred during passage through the gut of H. atra and H. leucospilota. Saturated fatty acids (SAFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and branched fatty acids (BrFAs) were significantly higher in FG than in AS, suggesting that both species selectively ingested nutrient rich particles. Significant reduction of SAFAs, MUFAs, PUFAs, and BrFAs occurred in MD and HD, with complete elimination of most PUFAs in FPs. A decrease in PUFAs 20:5ω3, 18:4ω3, 22:5ω3, 22:6ω3, 18:2ω6, 18:3ω3, 18:3ω6, odd-numbered BrFAs, and MUFA 18:1ω7 indicated that algal detritus and bacteria were important part of diet. These results have implications for the fate of specific dietary FAs, especially ω3 and ω6, and the contribution holothurian FPs make to the FA composition of coral reef and rocky intertidal ecosystems. PMID:27042355

  15. Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats.

    Science.gov (United States)

    Esmat, Amr Y; Said, Mahmoud M; Soliman, Amel A; El-Masry, Khaled S H; Badiea, Elham Abdel

    2013-01-01

    The identification of the active phenolic compounds in the mixed extract of sea cucumber (Holothuria atra) body wall by high-performance liquid chromatography and an assessment of its hepatoprotective activity against thioacetamide-induced liver fibrosis in rats. Female Swiss albino rats were divided into four groups: normal controls; oral administration of a sea cucumber mixed extract (14.4 mg/kg of body weight) on days 2, 4, and 6 weekly for 8 consecutive weeks; intoxication with thioacetamide (200 mg/kg of body weight, intraperitoneally) on days 2 and 6 weekly for 8 wk; and oral administration of a sea cucumber extract and then intoxication with thioacetamide 2 h later for 8 wk. High-performance liquid chromatographic analysis of the sea cucumber mixed extract revealed the presence of some phenolic components, such as chlorogenic acid, pyrogallol, rutin, coumaric acid, catechin, and ascorbic acid. In vitro studies have shown that the extract has a high scavenging activity for the nitric oxide radical, a moderate iron-chelating activity, and a weak inhibitory effect of lipid peroxidation. The subchronic oral administration of sea cucumber extract to the rats did not show any toxic side effects but increased hepatic superoxide dismutase and glutathione peroxidase activities. The coadministration of sea cucumber extract and thioacetamide (protection modality) normalized serum direct bilirubin, alanine and aspartate aminotransferases, hepatic malondialdehyde, and hydroxyproline concentrations and antioxidant enzyme activities. In addition, the histologic examination of liver sections from the protection group that were stained with hematoxylin and eosin showed substantial attenuation of the degenerative cellular changes and regressions in liver fibrosis and necrosis induced by the thioacetamide intoxication. Sea cucumber mixed extract contains physiologically active phenolic compounds with antioxidant activity, which afforded a potential hepatoprotective activity

  16. Atração e desligamento voluntário de jovens empregados: um estudo de caso no setor jornalístico

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    Lucia Barbosa de Oliveira

    2014-12-01

    Full Text Available Neste estudo de caso de natureza exploratória, desenvolvido em uma grande empresa do setor jornalístico, o objetivo foi analisar fatores de atração e perda de jovens que voluntariamente optaram por deixar a organização. A fundamentação teórica para a pesquisa foi construída a partir dos seguintes pilares: aspirações de trabalho e carreira da chamada geração Y, fatores de atração e retenção e cultura organizacional, tendo em vista a identificação da necessidade de adaptação da cultura da empresa aos novos desafios estratégicos e competitivos que vem enfrentando. O levantamento de dados foi feito por meio de 17 entrevistas em profundidade com jovens da geração Y que pediram demissão após pelo menos um ano de estágio e/ou trabalho na empresa. Como principais fatores de atração, destacaram-se a imagem e a reputação do principal jornal da empresa, que muito contribui para a construção de sua marca empregadora. Por outro lado, alguns traços da cultura organizacional apresentaram contraste com aspectos valorizados pelos participantes, indicando incongruência de valores, que pode estar levando a organização a perder jovens talentos, considerados importantes ante a necessidade de renovar seu quadro funcional e sua cultura. Com relação às motivações pessoais para deixar a empresa, foram identificados três grupos de jovens – idealistas, carreiristas e imediatistas –, orientados por anseios e perspectivas profissionais distintos.

  17. NMR structure of navel orangeworm moth pheromone-binding protein (AtraPBP1): implications for pH-sensitive pheromone detection.

    Science.gov (United States)

    Xu, Xianzhong; Xu, Wei; Rayo, Josep; Ishida, Yuko; Leal, Walter S; Ames, James B

    2010-02-23

    The navel orangeworm, Amyelois transitella (Walker), is an agricultural insect pest that can be controlled by disrupting male-female communication with sex pheromones, a technique known as mating disruption. Insect pheromone-binding proteins (PBPs) provide fast transport of hydrophobic pheromones through the aqueous sensillar lymph and promote sensitive delivery of pheromones to receptors. Here we present the three-dimensional structure of a PBP from A. transitella (AtraPBP1) in solution at pH 4.5 determined by nuclear magnetic resonance (NMR) spectroscopy. Pulsed-field gradient NMR diffusion experiments, multiangle light scattering, and (15)N NMR relaxation analysis indicate that AtraPBP1 forms a stable monomer in solution at pH 4.5 in contrast to forming mostly dimers at pH 7. The NMR structure of AtraPBP1 at pH 4.5 contains seven alpha-helices (alpha1, L8-L23; alpha2, D27-F36; alpha3, R46-V62; alpha4, A73-M78; alpha5, D84-S100; alpha6, R107-L125; alpha7, M131-E141) that adopt an overall main-chain fold similar to that of PBPs found in Antheraea polyphemus and Bombyx mori. The AtraPBP1 structure is stabilized by three disulfide bonds formed by C19/C54, C50/C108, and C97/C117 and salt bridges formed by H69/E60, H70/E57, H80/E132, H95/E141, and H123/D40. All five His residues are cationic at pH 4.5, whereas H80 and H95 become neutral at pH 7.0. The C-terminal helix (alpha7) contains hydrophobic residues (M131, V133, V134, V135, V138, L139, and A140) that contact conserved residues (W37, L59, A73, F76, A77, I94, V111, and V115) suggested to interact with bound pheromone. Our NMR studies reveal that acid-induced formation of the C-terminal helix at pH 4.5 is triggered by a histidine protonation switch that promotes rapid release of bound pheromone under acidic conditions.

  18. Protective effects of sea cucumber (Holothuria atra) extract on testicular dysfunction induced by immune suppressant drugs in Wistar rats.

    Science.gov (United States)

    Saad, D Y; Soliman, M M; Mohamed, A A; Youssef, G B

    2018-04-23

    The current study was aimed to evaluate the protective effect of Holothurian atra (HA) extract; naturally occurring marine resource, against methotrexate (MTX) induced testicular dysfunction. Mature rats received either MTX (20 mg/kg, intraperitoneally) or saline on the 7th day of experiment al design. Seven days prior and after MTX-injection, rats received HA at dose of 300 mg/kg intragastrically (HA + MTX group; HA group alone). Serum was extracted and testicular tissues were examined for the changes in serum biochemistry (liver & kidney biomarkers, testicular hormones and antioxidants), molecular and histopthological alterations using RT-PCR and immunohistochemistry. MTX-injected rats induced alteration in all testicular parameters. Prior administration of HA ameliorated the MTX-induced oxidative stress. HA administration normalised MTX-induced decrease in serum levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), reproductive hormones (FSH, LH and testosterone) and antioxidants GST, SOD and catalase. MTX-injected rats down-regulated mRNA expression of GST, SOD, steroidogenesis associated genes, IFN-γ, Bcl2 and NFKB. MTX up-regulated BAX expression and caspase 9 immunoreactivity that were ameliorated in HA + MTX group. Collectively, HA ameliorated and restored all altered genes. In conclusion, HA is a promising supplement that is helpful in protection against testicular cytotoxicity and dysfunction induced by methotrexate. © 2018 Blackwell Verlag GmbH.

  19. Atração e refração na educação a distância: constatações sobre o isolacionismo e a evasão do aluno

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    Gisela Biacchi Emanuelli

    2011-06-01

    Full Text Available http://dx.doi.org/10.5007/1983-4535.2011v4n2p205   A Lei de Diretrizes e Bases da Educação no Brasil incentiva a educação a distância como meio econômico e abrangente de acesso ao ensino e à aprendizagem. O método apresenta vantagens, mas não são suficientes para evitar que a auto-didática conduza à evasão dos alunos dos cursos. Amostra coletada junto à Instituição de Ensino Superior do Distrito Federal confirma o paradoxo da atração que a EaD exerce por sua economicidade e flexibilidade e a refração dos alunos por força do isolamento e pela necessidade do professor. Para demonstrar o binômio atração – refração do aluno ao ensino a distância partiu-se dessa amostragem para conclusões gerais, endossadas por outras pesquisas. O resultado coincide com a preocupação do Ministério da Educação de ser a Educação a Distância um meio de ensino no qual há índices significativos de evasão.

  20. Atração e penetração de Meloidogyne javanica e Heterodera glycines em raízes excisadas de soja Attraction and penetration of Meloidogyne javanica and Heterodera glycines in excised soybean roots

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    Hercules Diniz Campos

    2011-09-01

    Full Text Available Com vista ao estudo de atração e penetração de Meloidogyne javanica (Treub Chitwood e Heterodera glycines (Ichinoe em soja (Glycine max L., desenvolveu-se uma técnica empregando-se segmento de raiz com 2cm de comprimento. Nos segmentos de raiz de soja infectados, observou-se que a penetração de juvenis de segundo estádio (J2 de M. javanica ocorre pela coifa seguida de migração entre os feixes vasculares do cilindro central. Juvenis de H. glycines penetraram, aproximadamente, 15mm da coifa. A região seccionada da raiz de soja atraiu três vezes mais J2 de M. javanica do que a região da coifa, mas esta não foi tão atrativa para J2 de H. glycines. A obstrução conjunta da coifa e do local seccionado reduziu (83% a penetração de J2, tanto de M. javanica quanto de H. glycines. Quando apenas um desses locais foi obstruído, a outra extremidade livre compensou o processo atrativo. Portanto, as substâncias atrativas são liberadas por essas extremidades. A penetração de J2 de M. javanica foi maior no segmento de raiz quando comparada com a plântula intacta de soja. Entretanto, os J2 de H. glycines penetraram menos em segmentos de raiz e em plântulas sem folhas, quando comparados com plântulas intactas e com as seccionadas no colo. Portanto, na cultivar de soja "Embrapa 20", a atração e os locais de penetração de J2 de H. glycines e M. javanica são diferenciados. Esta técnica poderá ser útil nos estudos de atração e penetração de outros nematoides endoparasitas.To study the attraction and penetration of Meloidogyne javanica (Treub Chitwood and Heterodera glycines (Ichinoe in soybean (Glycine max L., a technique using 2-cm long root segments was developed. In infected soybean root segments penetration of second stage juveniles (J2 of M. javanica occured through the root cap following migration between the vascular bundles of the central cylinder. Juveniles of H. glycines penetrated about 15mm from the root cap. The cut

  1. Fatores condicionantes da atração e retenção de jovens profissionais e Âncoras de Carreira: estudo com engenheiros de empresa construtora de obras de infraestrutura de Minas Gerais.

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    Eliane Sereno de Mattos Cabral

    2017-04-01

    Full Text Available São expostos neste artigo os resultados de estudo de caso que objetivou identificar os fatores condicionantes da atração e retenção de engenheiros recém-formados e sua vinculação com as âncoras de carreira de Schein (1978. Pretendeu-se, ainda, verificar se esses fatores se configuram também como fatores de retenção e acompanhar a evolução das âncoras. Em uma abordagem de natureza quali e quanti, foram realizadas entrevistas e utilizadas versões adaptadas dos inventários de Schein (1996, Demo (2008 e Cia de Talentos (2011. As âncoras mais proeminentes foram Desafio Puro, Estilo de Vida e Competência Técnica Funcional, que também se revelaram influentes na adaptação e retenção do grupo pesquisado.

  2. A Gestão de Pessoas e as Estratégias de Atração, Desenvolvimento e Retenção de Profissionais: O Caso Petrobras

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    Nildes Pitombo Leite

    2013-12-01

    Full Text Available Este estudo de caso, ancorado na abordagem qualitativa e com nível de análise organizacional, investigou a gestão de pessoas dentro de unidades com estruturas organizacionais remotas (i.e., longe dos centros urbanos e não remotas da PETROBRAS – Petróleo Brasileiro S/A. A pesquisa foi realizada em três plataformas marítimas, três bases e na unidade operacional da selva Amazônica, envolvendo 31 respondentes, entre diretores, gerentes, profissionais de RH, supervisores e coordenadores. Esses respondentes são representativos para o nível de análise escolhido, bem como para a estratégia de pesquisa. Seu foco esteve voltado para dois problemas principais, considerados igualmente relevantes: Como gerenciar pessoas em unidades distantes das principais sedes da organização? Como gerenciar essas pessoas de modo a assegurar os objetivos estratégicos de atrair, desenvolver e reter o capital humano valorizado nessas unidades? A coleta dos dados primários foi feita por meio de entrevistas em profundidade e observações; a dos dados secundários, por meio de análise de documentos. Trabalhou-se com as estratégias das análises de conteúdo, documental e reflexiva. Seus resultados indicaram as especificidades de políticas e práticas de gestão de pessoas, oriundas das estratégias de atração, desenvolvimento e retenção de profissionais nessas unidades, especificidades essas que representam contribuição para a área de gestão de pessoas. DOI:10.5585/riae.v12i4.2043

  3. DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy

    International Nuclear Information System (INIS)

    Grishina, Olga; Schmoor, Claudia; Döhner, Konstanze; Hackanson, Björn; Lubrich, Beate; May, Annette M.; Cieslik, Caroline; Müller, Michael J.; Lübbert, Michael

    2015-01-01

    Acute myeloid leukemia (AML) is predominantly a disease of older patients with a poor long-term survival. Approval of decitabine (DAC) in the European Union (EU) in 2012 for the treatment of patients with AML ≥65 years marks the potential for hypomethylating agents in elderly AML. Nevertheless the situation is dissatisfactory and the quest for novel treatment approaches, including combination epigenetic therapy is actively ongoing. The given randomized trial should be helpful in investigating the question whether combinations of DAC with the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and/or all-trans retinoic acid (ATRA), which in vitro show a very promising synergism, are superior to the DAC monotherapy. The accompanying translational research project will contribute to find surrogate molecular end points for drug efficacy and better tailor epigenetic therapy. An additional aim of the study is to investigate the prognostic value of geriatric assessments for elderly AML patients treated non-intensively. DECIDER is a prospective, randomized, observer blind, parallel group, multicenter, Phase II study with a 2x2 factorial design. The primary endpoint is objective best overall response (complete remission (CR) and partial remission (PR)). The target population is AML patients aged 60 years or older and unfit for standard induction chemotherapy. Patients are randomized to one of the four treatment groups: DAC alone or in combination with VPA or ATRA or with both add-on drugs. One interim safety analysis was planned and carried out with the objective to stop early one or more of the treatment arms in case of an unacceptable death rate. This analysis showed that in all treatment arms the critical stopping rule was not reached. No important safety issues were observed. The Data Monitoring Committee (DMC) recommended continuing the study as planned. The first patient was included in December 2011. A total of 189 out of 200 planned patients were randomized

  4. A história da ciência na formação do professor de física: subsídios para um curso sobre o tema atração gravitacional visando às mudanças de postura na ação docente History of Science in teaching education: suggestions for a course plan on gravitational attraction aiming to change teachers' attitudes

    Directory of Open Access Journals (Sweden)

    Sandra Regina Teodoro Gatti

    2004-12-01

    Full Text Available O objetivo desta pesquisa foi estudar como a evolução histórica dos modelos de atração entre corpos, tendo como pano de fundo a evolução dos modelos de mundo, pode auxiliar na formação inicial do docente de Física. Para tanto, sugerimos um planejamento de curso sobre o tema atração gravitacional, destinado principalmente a docentes de Física que atuam no ensino médio. O planejamento do curso foi baseado: em dados sobre a evolução dos modelos de mundo, buscando evidenciar como o conceito de atração gravitacional desenvolveu-se historicamente; nas concepções alternativas mais comuns encontradas na literatura, incluindo um breve esboço de noções diagnosticadas em uma amostra de docentes de Física de ensino médio; e em sugestões de leituras de resultados de pesquisas recentes sobre os processos de ensino e aprendizagem de ciências. Pretende-se fornecer aos docentes elementos de reflexão que lhes proporcionem mudanças de postura, através do questionamento da visão de ciência enquanto processo de construção e sobre sua própria prática de ensino. Partindo de resultados recentes da pesquisa em Ensino de Ciências, a metodologia sugerida privilegia o trabalho coletivo, com a realização de debates e sínteses. As atividades mencionadas são acompanhadas de justificativas sobre a escolha do tema e objetivos.The main purpose of this research was to study how the attraction among bodies, having as background the evolution of models of the world, can help prospective teachers' education. To reach this goal, we suggest a course plan on gravitational attraction, addressed mainly to High School Physics teachers. This course was based: on data about world models' evolution, searching to make clear how the concept of gravitational attraction was historically developed; on the most common alternative conceptions found in the literature, including a brief outline of notions found among in-service High School Physics teachers

  5. Estratégias fenológicas de Senna cana (Nees & Mart. H.S. Irwin & Barneby (Fabaceae: Caesalpinioideae como mecanismo eficiente para atração de polinizadores Phenological strategies of Senna cana (Nees & Mart. H.S. Irwin & Barneby (Fabaceae: Caesalpinioideae as efficient mechanisms for attracting pollinators

    Directory of Open Access Journals (Sweden)

    Isys Mascarenhas Souza

    2012-06-01

    Full Text Available Este trabalho verificou a importância das estratégias fenológicas de Senna cana na atração de visitantes e polinizadores na mata ciliar do rio Lençóis, Chapada Diamantina, Bahia. As observações fenológicas foliares (queda foliar e brotamento e reprodutivas (botão, flor, fruto imaturo e fruto maduro foram mensais (18 meses em 10 indivíduos marcados. Para a biologia floral observou-se: antese, duração das flores, receptividade estigmática, viabilidade polínica, presença de osmóforos e pigmentos que refletem raios ultravioleta. Foram realizados testes de autopolinização manual, espontânea e polinização cruzada. Os visitantes e polinizadores foram determinados observando-se: horário, duração, freqüência das visitas e comportamento de forrageio. Senna cana é uma espécie perenifólia episódica, com eventos reprodutivos sazonais e altamente sincrônicos (floração intermediária no período chuvoso e frutificação longa no período seco. Tais características na floração, somadas à síndrome de melitofilia, configuram importantes estratégias para atração de visitantes florais, dentre os quais Xylocopa frontalis e X. grisescens foram classificadas enquanto potenciais polinizadores. A autoincompatibilidade e o máximo de frutos produzidos após polinização cruzada são mecanismos reprodutivos favorecidos pelas estratégias fenológicas e síndrome de polinização apresentadas pela espécie.The present work evaluated the importance of the phenological strategies of Senna cana in attracting floral visitors and pollinators in an riparian forest along the Lençóis River, in Chapada Diamantina, Bahia, Brazil. Vegetative and reproductive phenological observations (leaf fall, leaf flushing, flowering, and fruiting were made on a monthly basis among a group of 10 individuals. The floral biology patterns observed included: anthesis, duration of the flowers, stigma receptivity, pollen viability, and the presence of

  6. Orchid bee baits attracting bees of the genus Megalopta (Hymenoptera, Halictidae in Bauru region, São Paulo, Brazil: abundance, seasonality, and the importance of odors for dim-light bees Abelhas do gênero Megalopta (Hymenoptera, Halictidae atraídas por iscas químicas usadas para euglossíneos na região de Bauru, SP: abundância, sazonalidade e importância de odores para abelhas crepusculares

    Directory of Open Access Journals (Sweden)

    Fátima R. N. Knoll

    2012-12-01

    Full Text Available Nocturnal bees in the genus Megalopta Smith, 1853 are generally collected using artificial light sources. However, between 1993 and 2000, a total of 946 females (no males were captured were captured using aromatic baits commonly used for orchid bees (Euglossini in five localities in Bauru region, São Paulo, Brazil. Aromatic compounds used in bait traps were: benzyl acetate, eucalyptol, eugenol, skatole, methyl salicylate, and vanillin. The Megalopta species collected were: M. guimaraesi (71.2% of total number of specimens, M. amoena (28.1%, and M. aegis (0.6%. Using the data from these traps, we showed that there was a positive and significant correlation between the abundance of individuals and meteorological factors, rainfall and temperature. Bees were more commonly collected in the spring (September to December and summer (December to March than in the autumn and winter, the latter characterized for being a drier and colder period. Variations in the abundance were also detected among localities and years. The most attractive compounds were eugenol (54%, methyl salicylate (22%, and eucalyptol (16%. The ability to detect smells may have an important role in searching for flowers during dim-light conditions. We suggest the use of aromatic compounds in future studies on the biology of Megalopta in the Neotropical region.Abelhas noturnas do gênero Megalopta (Smith, 1853 são geralmente coletadas usando fontes artificiais de luz. Porém entre os anos de 1993 e 2000, um total de 946 fêmeas de Megalopta foram capturadas (machos não foram capturados usando iscas aromáticas frequentemente usadas para atração de machos de Euglossini, em cinco localidades na região de Bauru, São Paulo, Brasil. Os compostos aromáticos utilizados foram: acetato de benzila, eucaliptol, eugenol, escatol, salicilato de metila e vanilina. As espécies encontradas foram M. guimaraesi (71.2% do total de indivíduos, M. amoena (28.1% and M. aegis (0.6%. De modo geral

  7. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era

    Science.gov (United States)

    Ramadan, Safaa M.; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

    2012-01-01

    The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed. PMID:22689684

  8. A new approach for surveying the Alpine Salamander (Salamandra atra in Austria

    Directory of Open Access Journals (Sweden)

    Ursula Reinthaler-Lottermoser

    2010-12-01

    Full Text Available The Alpine Salamander is a small pitch black amphibian which is endemic to the European Alps and the Dinarides. It is strictly protected according to the European FFH guidelines. Despite its central role in the alpine ecosystem our actual published record in Austria is small. In order to resolve this shortcoming our project explores its distribution in Austria. It uses a participatory and community based approach to gather data. Everybody can enter and look at Alpine Salamander observations on our website www.alpensalamander.eu. This approach also allows us to establish an “oral history” of Salamander observations in the past 50 years by conducting interviews in the local community. Since July 2009 the website and salamander report database are online. From the actual data (more than 5600 records we already obtained an overview about the present distribution and data quality. The data are an excellent basis for detailed scientific studies on these remarkable amphibians. With this new and highly interactive approach science and education are combined to initiate protection measures with the public.

  9. Cobrotoxin from Naja naja atra Venom Ameliorates Adriamycin Nephropathy in Rats

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    Shu-Zhi Wang

    2015-01-01

    Full Text Available Chronic kidney disease (CKD becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR- induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β. These findings suggest that CTX may be a potential drug for chronic kidney diseases.

  10. Seasonal variation in food supply and breeding success in European Coots Fulica atra

    NARCIS (Netherlands)

    Brinkhof, M.W.G.

    1997-01-01

    Chick survival in the European Coot typically shows a convex seasonal pattern. Previous experiments revealed that this pattern is directly linked to hatching date and that food supply within the first ten days after hatching is a causal factor in this relationship. However, the precise mechanism

  11. Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

    Directory of Open Access Journals (Sweden)

    Zhao Junfeng

    2012-03-01

    Full Text Available Abstract The testicular yolk sac tumor (TYST is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

  12. Characterization of the mechanical properties of tough biopolymer fibres from the mussel byssus of Aulacomya ater.

    Science.gov (United States)

    Troncoso, O P; Torres, F G; Grande, C J

    2008-07-01

    Byssus fibres are tough biopolymer fibres produced by mussels to attach themselves to rocks. In this communication, we present the mechanical properties of the byssus from the South American mussel Aulacomya ater which have not been previously reported in the literature. The mechanical properties of the whole threads were assessed by uniaxial tensile tests of dry and hydrated specimens. Elastoplastic and elastomeric stress-strain curves were found for byssal threads from A. ater in the dry and hydrated state, respectively. The results obtained from mechanical tests were modelled using linear, power-law-type and Mooney-Rivlin relationships. These methods for dealing with tensile measurements of mussel byssus have the potential to be used with other stretchy biomaterials.

  13. Marketing Digital e Turismo: Uso de Websites para Atração de Turistas nos Municípios do Rio Grande Do Sul/ Brasil

    Directory of Open Access Journals (Sweden)

    Dalva Maria Righi Dotto

    2015-12-01

    Full Text Available Com a utilização cada vez mais frequente da internet na busca de informações para a escolha dentre as opções de turismo disponíveis, a otimização dos websites turísticos por parte dos municípios pode ser uma ferramenta importante para o desenvolvimento do turismo. Informações  claras sobre os atrativos turísticos facilitam aos turistas escolher o destino, assim como informações sobre a disponibilidade de hotéis e, também, a gastronomia que o local oferece. Com o objetivo de analisar qualitativamente os websites de municípios do Rio Grande do Sul, este estudo, através de uma pesquisa exploratória, pretende disponibilizar aos gestores um diagnóstico comparativo, no intuito de auxiliar na visibilidade do atrativo turístico e sensibilização dos turistas potenciais, para incremento do setor e da economia local.

  14. Turismo e Idosos: o patrimônio imaterial como fator de atração para o turismo cultural no espaço rural

    Directory of Open Access Journals (Sweden)

    Lívia Morais Garcia Lima

    2011-01-01

    Full Text Available A pesquisa tem por objetivo investigar e analisar as formas pelas quais propriedades rurais históricas paulistas se preocupam em proporcionar atividades voltadas para idosos, trabalhando o turismo cultural com uma preocupação voltada à educação patrimonial não-formal e sob um enfoque qualitativo. O método biográfico ou da História Oral é utilizado tanto para a coleta de informações sobre o patrimônio imaterial, como para levantar as demandas do público idoso. Ela é sempre acompanhada da realização de um diário de campo em associação com registros fotográficos das atividades educacionais e turísticas observadas em duas fazendas selecionadas. Para melhor avaliar programas para o público idoso é necessário uma efetiva conexão entre os elementos encontrados em cada fazenda participante, visando à articulação de ações efetivas para o turismo cultural no espaço rural e às diretrizes da Gerontologia.

  15. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Skavland, J; Jørgensen, K M [Hematology Section, Institute of Medicine, University of Bergen, Bergen (Norway); Hadziavdic, K [Department of Informatics, University of Bergen, Bergen (Norway); Hovland, R [Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen (Norway); Jonassen, I [Department of Informatics, University of Bergen, Bergen (Norway); Computational Biology Unit, Bergen Centre for Computational Science, University of Bergen, Bergen (Norway); Bruserud, Ø; Gjertsen, B T, E-mail: bjorn.gjertsen@med.uib.no [Hematology Section, Institute of Medicine, University of Bergen, Bergen (Norway); Hematology Section, Department of Medicine, Haukeland University Hospital, Bergen (Norway)

    2011-02-01

    Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial.

  16. Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Binkowski, Łukasz J., E-mail: ljbinkowski@gmail.com [Institute of Biology, Pedagogical University of Cracow, Podbrzezie 3, 31-054 Cracow (Poland); Sawicka-Kapusta, Katarzyna, E-mail: katarzyna.sawicka-kapusta@uj.edu.pl [Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387 Cracow (Poland); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland); Strzyżewska, Emilia, E-mail: emijel@wp.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland); Felsmann, Mariusz, E-mail: felsmann.mariusz@wp.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland)

    2013-04-15

    Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n = 60) and Coot (n = 50). Free living birds were collected by hunters in years 2006–2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n = 5) and high concentrations (Mallards n = 18 and Coots n = 17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions. - Highlights: ► High levels of Cd and Pb were found in liver and kidneys of Mallard and Coot. ► Lower concentrations were found in young birds. ► Amount of metals exceeded the safety threshold established for edible poultry. ► Histopathological alterations were found in studied tissues. ► Lesions in birds with the highest concentrations of metals were numerous.

  17. Atração e desenvolvimento de Leptoglossus gonagra (Fabr. (Hemiptera: Coreidae em cultivares de abóbora e moranga

    Directory of Open Access Journals (Sweden)

    Baldin Edson Luiz Lopes

    2002-01-01

    Full Text Available As plantas da família Cucurbitaceae são seriamente prejudicadas pelo ataque de insetos, sendo que os danos ocorrem desde a germinação até a colheita e podem ser observados em todas as partes da planta. Dentre os insetos sugadores que atacam a abóbora (Cucurbita moschata e a moranga (C. maxima, as formas jovens e adultas do percevejo Leptoglossus gonagra (Fabr. (Hemiptera: Coreidae merecem destaque por sugarem a seiva das folhas, ramos e frutos novos, nos quais causam necroses, reduzindo a produção. Visando comparar a atratividade de plântulas de cultivares de abóbora e moranga a adultos deste percevejo e os efeitos desses materiais sobre a biologia de ninfas dessa espécie, realizaram-se ensaios sob condições de laboratório. Em teste de atratividade, o cultivar de abóbora BRA015113 destacou-se como o menos atrativo em relação ao cultivar de moranga Exposição, enquanto que o cultivar de abóbora BRA003531 foi o mais atrativo. Todos os cultivares provocaram 100% de mortalidade das ninfas, indicando a presença de componentes antibióticos, adversos ao desenvolvimento de L. gonagra.

  18. Atração e distração na publicidade externa dos candidatos à eleição em 2014

    Directory of Open Access Journals (Sweden)

    Sérgio Trein

    2015-12-01

    CÉSAR, Newton. Direção de arte em propaganda. São Paulo: Futura, 2004. COLLARO, Antonio Celso. Projeto Gráfico Teoria e Prática da Diagramação. São Paulo: Summus Editorial, 1987.  DONDIS, Donis A.. Sintaxe da linguagem visual. 2. ed. São Paulo: Martins Fontes, 2003.  HILLMAN, James. Cidade & alma. São Paulo: Studio Nobel, 1993. HURLBURT, Allen. Layout o design da página impressa. São Paulo: Nobel, 2002. MOLES, Abraham Antoine. O cartaz. São Paulo: Perspectiva, 1974. MÜLLER, Josef Brockmann. History of visual communication. Teufen: Nigli, 1971. PÈNINOU, Georges. Semiótica de la publicidad. Barcelona: Gustavo Gili, 1976.   Site consultado: Outdoor.com. Acessado em: 26 de março de 2015.   Disponível em:  Url: http://opendepot.org/2703/   Abrir em (para melhor visualização em dispositivos móveis - Formato Flipbooks: Issuu / Calameo

  19. Branding de países e atração de investimento direto estrangeiro : o papel do soft power

    OpenAIRE

    Alves, Ana Cristina Leitão Santos

    2013-01-01

    Mestrado em Marketing Nas últimas décadas, deu-se uma mudança no paradigma internacional e na maneira como os países se interrelacionam. Estas relações, cada vez mais económicas, exigem uma nova abordagem por parte dos países. Neste sentido, o conceito de soft power de Joseph Nye, enquanto poder de atracção de um país e que pode ser encontrado na sua cultura, valores e políticas externas, ao invés de hard power, considerado como poder de coerção e que pode ser económico ou militar, ganha u...

  20. Transcriptome profiling to identify ATRA-responsive genes in human iPSC-derived endoderm for high-throughput point of departure analysis (SOT Annual Meeting)

    Science.gov (United States)

    Toxicological tipping points occur at chemical concentrations that overwhelm a cell’s adaptive response leading to permanent effects. We focused on retinoid signaling in differentiating endoderm to identify developmental pathways for tipping point analysis. Human induced pluripot...

  1. Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy

    NARCIS (Netherlands)

    Martinez-Cuadron, D.; Montesinos, P.; Vellenga, E.; Bernal, T.; Salamero, O.; Holowiecka, A.; Brunet, S.; Gil, C.; Benavente, C.; Ribera, J. M.; Perez-Encinas, M.; De la Serna, J.; Esteve, J.; Rubio, V.; Gonzalez-Campos, J.; Escoda, L.; Amutio, M. E.; Arnan, M.; Arias, J.; Negri, S.; Lowenberg, B.; Sanz, M. A.

    Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk-and age-adapted protocol (Programa Espanol de

  2. Educando a Estudiantes con Diversidades Linguisticas y Culturales (Educating Linguistically and Culturally Diverse Students). Que Ningun Nino se Quede Atras (No Child Left Behind).

    Science.gov (United States)

    Office of English Language Acquisition, Language Enhancement, and Academic Achievement for Limited English Proficient Students (ED), Washington, DC.

    The brochure, written in Spanish, briefly outlines the U.S. Department of Education's most recent policy on educating students with diverse linguistic and cultural backgrounds. It states the Department's mission, describes today's student population, and outlines the role of the Office of English Language Acquisition, Language Enhancement and…

  3. Fouling community dominated by Metridium senile (Cnidaria: Anthozoa: Actiniaria in Bahía San Julián (southern Patagonia, Argentina

    Directory of Open Access Journals (Sweden)

    Juan Pablo Martin

    2015-06-01

    Full Text Available The objective of this study is to provide information about a harbour-fouling community dominated by Metridium senile in southern Patagonia. Several steel tubes from the wharf of Puerto San Julián were extracted to perform repair tasks, allowing the attached benthic community to be studied. Sampling was conducted at three levels: lower intertidal, 3-4 m depth and 6-7 m depth. In the lower intertidal, M. senile had a relative abundance of 43%, the most abundant accompanying species being Perumytilus purpuratus, Mytilus edulis platensis and Aulacomya atra atra. At subtidal level, the anemone showed relative abundances of 64% and 65%, and was accompanied by Monocorophium insidiosum at 3-4 m depth and by polychaetes of families Sabellidae and Syllidae at 6-7 m at depth. In the lower intertidal, epibiosis was more frequent on P. purpuratus, A. atra atra and M. edulis platensis, while in the subtidal, the richness of substrate-organisms increased significantly and the anemone was fixed to A. atra atra, M. edulis platensis, Paramolgula gregaria, Crepipatella dilatata, Austromegabalanus psittacus, Hiatella arctica, Polyzoa opuntia, Pyura sp. and Sabellidae tubes. The ability of M. senile to settle on many different organisms, along with other strategies, makes it a colonizer able to displace other species that could compete with it for substratum. Given the cosmopolitan nature of M. senile, the fact that this species has not been previously reported in the coastal zone of the region, and the results of our study, we discuss the possibility that this sea anemone is an invasive alien species in southern Patagonia, or at least a cryptogenic species.

  4. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) on Aulacomya ater (Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of Organophosphate Pesticide Exposition

    Science.gov (United States)

    Führer, Eduardo; Rudolph, Anny; Espinoza, Claudio; Díaz, Rodrigo; Gajardo, Marisol; Camaño, Nuria

    2012-01-01

    The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L−1 (LC50−96 hours). Concentrations between 0.2 and 1.61 μg L−1 were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L−1 stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N) ratio, with respect to the control group. A. ater proved to be a species sensitive to pesticide exposure and easy to handle in lab conditions. Thus, it is recommended as a bioindicator for use in programs of environmental alertness in the Eastern South Pacific coastal zone. PMID:22619673

  5. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 1.- anallsis cuantitativo.

    Directory of Open Access Journals (Sweden)

    Juana María Coha

    2014-06-01

    Full Text Available Se ha determinado, cuantitativamente, presencia de organismos Coliformes y Enterococos en el molusco Aulacomya ater "choro", como índice de contaminación entérica humana, en cada etapa de su preparación hasta "cebiche". Se han pracesado 1,152 especímenes de mercados de Lima y Callao. Los resultados reportan mayores promedios de contaminación para ambos grupos m'crobianos, en choros crudos (etapa a, de mercados ubicados en zonas de menor higiene y mayor población. La temperatura ambiental en meses de verano, demuestra gran incremento de esta microflora. La temperatura de cocción de la fracción previa al "cebiche" (etapa b, efímina totalmente los contaminantes, reapareciendo Coliformes en éste (etapa el, por los aditivos. El jugo de limón no actuó como bactericida eficaz.

  6. Evidence for absorption of kelp detritus by the ribbed mussel Aulacomya ater using a new 51Cr-labelled microsphere technique

    International Nuclear Information System (INIS)

    Stuart, V.; Field, J.G.

    1983-01-01

    A modification of the 51 Cr: 14 C twin-labelling technique is described in which the food source is labelled with 14 C but the 51 Cr is enclosed in a polymeric resin membrane and presented as microspheres of a similar diameter to the food particles. This eliminates the major uptake of 51 Cr which is transferred to the ctenidia and palps of the suspension-feeding mussel Aulacomya ater (Molina) from detritus labelled with 51 Cr. The results suggest that althoug bacterial cultures based on isolates of kelp bacteria can be absorbed with an efficiency of 67 to 70%, the debris itself is also absorbed with an efficiency of approximately 50%. The kelp debris, which forms an important component of the particulate matter potentially available for consumers, may thus represent an important source of carbon for the filter feeding community adjacent to kelp beds. In contrast to the results obtained in other studies with artificial food sources, the data for kelp debris suggest that A. ater is able to maintain a positive scope for grwoth at the concentrations of suspended organic matter which occur under natural conditions in the kelp bed environment. (orig.)

  7. (N)um lugar ao sol: contributos do turismo para as dinâmicas criativas e para a atração da classe criativa no Algarve

    OpenAIRE

    Cruz, Ana Rita Pereira Marques da

    2016-01-01

    Tese de Doutoramento, Turismo, Faculdade de Economia, Universidade do Algarve, 2016 Os destinos turísticos ficam frequentemente reféns do seu próprio sucesso. Apesar dos efeitos positivos do turismo, produtos turísticos dominantes tornam-se muitas vezes demasiado importantes para as economias regionais e promovem uma especialização excessiva, concentrando recursos financeiros e humanos num número limitado de atividades. Este foi o caso de várias regiões na Europa e é uma situação que carac...

  8. Interações entre Protodiscelis (Colletidae, Neopasiphaeinae) e plantas aquáticas e a importância de odores florais na atração de polinizadores.

    OpenAIRE

    Carvalho, Airton Torres

    2012-01-01

    Abelhas são os principais polinizadores das plantas com flores. Plantas são sésseis e a reprodução sexuada cruzada somente ocorre através de vetores de pólen. Sendo assim, flores zoofílicas provêm pistas para o encontro interespecífico, são polinizadas e fornecem recursos florais aos polinizadores. O principal recurso coletado por abelhas herbívoros Apiformes é pólen, o principal alimento larval. Para as plantas, entretanto, existe um balanço entre recurso fornecido e quantidade de grão...

  9. Ten Facts Every Parent Should Know about the No Child Left Behind Act = Diez datos que cada padre debe saber sobre La Ley. Que Ningun Nino Se Quede Atras.

    Science.gov (United States)

    Department of Education, Washington, DC.

    The No Child Left Behind Act (NCLB) is President George W. Bush's education reform law passed by Republicans and Democrats in Congress. This flier, in both English and Spanish, details 10 facts concerning NCLB to inform parents as to the goals of the Act and how they will affect their child's school. The flier highlights how the Act: (1) gives…

  10. Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2009-02-01

    Full Text Available Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1. CRBP-1 is a key regulator of All-trans retinoic acid (ATRA through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion

  11. Bradycardia during Induction Therapy with All-trans Retinoic Acid in Patients with Acute Promyelocytic Leukemia: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Pin-Zi Chen

    2018-01-01

    Full Text Available A 41-year-old man with newly diagnosed acute promyelocytic leukemia (APL received induction chemotherapy, containing all-trans retinoic acid (ATRA, idarubicin, and arsenic trioxide. On the 11th day of therapy, he experienced complete atrioventricular (AV block; therefore, ATRA and arsenic trioxide were immediately postponed. His heart rate partially recovered, and ATRA was rechallenged with a half dose. However, complete AV block as well as differentiation syndrome recurred on the next day. ATRA was immediately discontinued, and a temporary pacemaker was inserted. Two days after discontinuing ATRA, AV block gradually improved, and ATRA was uneventfully rechallenged again. The Naranjo adverse drug reaction probability scale was 7 for ATRA, suggesting it was the probable cause of arrhythmia. A literature search identified 6 other cases of bradycardia during ATRA therapy, and all of them occurred during APL induction therapy, with onset ranging from 4 days to 25 days. Therefore, monitoring vital signs and performing electrocardiogram are highly recommended during the first month of induction therapy with ATRA. ATRA should be discontinued if complete AV block occurs. Rechallenging with ATRA can be considered in fully recovered and clinically stable patients.

  12. All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages.

    Science.gov (United States)

    Seifart, C; Muyal, J P; Plagens, A; Yildirim, A Ö; Kohse, K; Grau, V; Sandu, S; Reinke, C; Tschernig, T; Vogelmeier, C; Fehrenbach, H

    2011-08-01

    All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 μg · kg(-1) body weight) versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1β, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-α, nuclear factor-κB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

  13. Clinical study of a retinoic acid-loaded microneedle patch for seborrheic keratosis or senile lentigo.

    Science.gov (United States)

    Hirobe, Sachiko; Otsuka, Risa; Iioka, Hiroshi; Quan, Ying-Shu; Kamiyama, Fumio; Asada, Hideo; Okada, Naoki; Nakagawa, Shinsaku

    2017-01-01

    Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people>50years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all-trans retinoic acid (ATRA) is an attractive option for self-treatment at home. We have developed an ATRA-loaded microneedle patch (ATRA-MN) and confirmed the pharmacological effects of ATRA-MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA-MN in subjects with seborrheic keratosis or senile lentigo. ATRA-MN was applied to the lesion site of each subject for 6h once per week for 4weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA-MN, the desquamation and whitening ability of the investigational skin was observed. Desquamation of the stratum corneum was observed following four ATRA-MN applications at 1-week intervals, but ATRA-MN applications did not induce severe local or systemic adverse effects. These results showed that ATRA-MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Increased catalase activity by all-trans retinoic acid and its effect on radiosensitivity in rat glioma cells

    International Nuclear Information System (INIS)

    Jin, Hua; Jeon, Ha Yeun; Park, Woo Yoon; Kim, Won Dong; Ahn, Hee Yul; Yu, Jae Ran

    2005-01-01

    It has been reported that all-trans retinoic acid (ATRA) can inhibit glioma growing in vitro. However, clinical trials with ATRA alone in gliomas revealed modest results. ATRA has been shown to increase radiosensitivity in other tumor types, so combining radiation and ATRA would be one of alternatives to increase therapeutic efficacy in malignant gliomas. Thus, we intended to know the role of catalase, which is induced by ATRA, for radiosensitivity. If radiation-reduced reactive oxygen species (ROS) is removed by catalase, the effect of radiation will be reduced. A rat glioma cell line (36B10) was used for this study. The change of catalase activity and radiosensitivity by ATRA, with or without 3-amino-1, 2, 4-triazole (ATZ), a chemical inhibitor of catalase were measured. Catalase activity was measured by the decomposition of H 2 O 2 spectrophotometrically. Radiosensitivity was measured with clonogenic assay. Also ROS was measured using a 2, 7-dichlorofluores-cein diacetate spectrophotometrically. When 36B10 cells were exposed to 10, 25 and 50 μ M of ATRA for 48 h, the expression of catalase activity were increased with increasing concentration and incubation time of ATRA. Catalase activity was decreased with increasing the concentration of AT (1, 10 mM) dose-dependently. ROS was increased with ATRA and it was augmented with the combination of ATRA and radiation. ATZ decreased ROS production and increased cell survival in combination of ATRA and radiation despite the reduction of catalase. The increase of ROS is one of the reasons for the increased radiosensitivity in combination with ATRA. The catalase that is induced by ATRA doesn't decrease ROS production and radiosensitivity

  15. Potential for all-trans retinoic acid (tretinoin) to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma.

    Science.gov (United States)

    Kast, Richard E

    2008-10-01

    This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid (ATRA, also termed tretinoin) exerts an anti-viral effect against hepatitis C virus (HCV) in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-a activity in treating chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementally enhance interferon-a responses in these cancers.

  16. Population structure, growth and production of a recent brachiopod from the Chilean fjord region

    KAUST Repository

    Baumgarten, Sebastian

    2013-12-04

    Magellania venosa, the largest recent brachiopod, occurs in clusters and banks in population densities of up to 416 ind m-2 in Comau Fjord, Northern Chilean fjord region. Below 15 m, it co-occurs with the mytilid Aulacomya atra and it dominates the benthic community below 20 m. To determine the question of why M. venosa is a successful competitor, the in situ growth rate of the brachiopod was studied and its overall growth performance compared with that of other brachiopods and mussels. The growth in length was measured between February 2011 and March 2012 after mechanical tagging and calcein staining. Settlement and juvenile growth were determined from recruitment tiles installed in 2009 and from subsequent photocensus. Growth of M. venosa is best described by the general von Bertalanffy growth function, with a maximum shell length (L∞) of 71.53 mm and a Brody growth constant (K) of 0.336 year-1. The overall growth performance (OGP index = 5.1) is the highest recorded for a rynchonelliform brachiopod and in the range of that for Mytilus chilensis (4.8-5.27), but lower than that of A. atra (5.74). The maximal individual production (PInd) is 0.29 g AFDM ind-1 year-1 at 42 mm shell length and annual production ranges from 1.28 to 89.25 g AFDM year-1 m-2 (1-57% of that of A. atra in the respective fjords). The high shell growth rate of M. venosa, together with its high overall growth performance may explain the locally high population density of this brachiopod in Comau Fjord. However, the production per biomass of the population (P/B--ratio) is low (0.535) and M. venosa may play only a minor role in the food chain. Settling dynamics indicates that M. venosa is a pioneer species with low juvenile mortality. The coexistence of the brachiopod and bivalve suggests that brachiopod survival is affected by neither the presence of potential brachiopod predators nor that of space competitors (i.e. mytilids).

  17. Growth increments of the recent brachiopod Magellania venosa mechanically marked in Paso Comau and Comau Fjord, Chile, 2011/2012, supplement to: Baumgarten, Sebastian; Laudien, Jürgen; Jantzen, Carin; Häussermann, Verena; Försterra, Günter (2013): Population structure, growth and production of a recent brachiopod from the Chilean fjord region. Marine Ecology, 35(4), 401-413

    KAUST Repository

    Baumgarten, Sebastian

    2015-01-01

    Magellania venosa, the largest recent brachiopod, occurs in clusters and banks in population densities of up to 416 ind/m**2 in Comau Fjord, Northern Chilean fjord region. Below 15 m, it co-occurs with the mytilid Aulacomya atra and it dominates the benthic community below 20 m. To determine the question of why M. venosa is a successful competitor, the in situ growth rate of the brachiopod was studied and its overall growth performance compared with that of other brachiopods and mussels. The growth in length was measured between February 2011 and March 2012 after mechanical tagging and calcein staining. Settlement and juvenile growth were determined from recruitment tiles installed in 2009 and from subsequent photocensus. Growth of M. venosa is best described by the general von Bertalanffy growth function, with a maximum shell length (Linf) of 71.53 mm and a Brody growth constant (K) of 0.336/year. The overall growth performance (OGP index = 5.1) is the highest recorded for a rynchonelliform brachiopod and in the range of that for Mytilus chilensis (4.8-5.27), but lower than that of A. atra (5.74). The maximal individual production (PInd) is 0.29 g AFDM/ind/year at 42 mm shell length and annual production ranges from 1.28 to 89.25 g AFDM/year/m**2 (1-57% of that of A. atra in the respective fjords). The high shell growth rate of M. venosa, together with its high overall growth performance may explain the locally high population density of this brachiopod in Comau Fjord. However, the production per biomass of the population (P/B-ratio) is low (0.535) and M. venosa may play only a minor role in the food chain. Settling dynamics indicates that M. venosa is a pioneer species with low juvenile mortality. The coexistence of the brachiopod and bivalve suggests that brachiopod survival is affected by neither the presence of potential brachiopod predators nor that of space competitors (i.e. mytilids).

  18. Critical determinant of intestinal permeability and oral bioavailability of pegylated all trans-retinoic acid prodrug-based nanomicelles: Chain length of poly (ethylene glycol) corona.

    Science.gov (United States)

    Li, Zhenbao; Han, Xiaopeng; Zhai, Yinglei; Lian, He; Zhang, Dong; Zhang, Wenjuan; Wang, Yongjun; He, Zhonggui; Liu, Zheng; Sun, Jin

    2015-06-01

    Pegylation method is widely used to prolong the blood circulation time of proteins and nanoparticles after intravenous administration, but the effect of surface poly (ethylene glycol) (PEG) chain length on oral absorption of the pegylated nanoparticles is poorly reported. The aim of our study was to investigate the influence of PEG corona chain length on membrane permeability and oral bioavailability of the amphiphilic pegylated prodrug-based nanomicelles, taking all trans-retinoic acid (ATRA) as a model drug. The amphiphilic ATRA-PEG conjugates were synthesized by esterification reaction between all trans-retinoic acid and mPEGs (mPEG500, mPEG1000, mPEG2000, and mPEG5000). The conjugates could self-assemble in aqueous medium to form nanomicelles by emulsion-solvent evaporation method. The resultant nanomicelles were in spherical shape with an average diameter of 13-20 nm. The drug loading efficiency of ATRA-PEG500, ATRA-PEG1000, ATRA-PEG2000, and ATRA-PEG5000 was about 38.4, 26.6, 13.1, and 5.68 wt%, respectively. With PEG chain length ranging from 500 to 5000, ATRA-PEG nanomicelles exhibited a bell shape of chemical stability in different pH buffers, intestinal homogenate and plasma. More importantly, they were all rapidly hydrolyzed into the parent drug in hepatic homogenate, with the half-time values being 0.3-0.4h. In comparison to ATRA solution and ATRA prodrug-based nanomicelles, ATRA-PEG1000 showed the highest intestinal permeability. After oral administration, ATRA-PEG2000 and ATRA-PEG5000 nanomicelles were not nearly absorbed, while the oral bioavailability of ATRA-PEG500 and ATRA-PEG1000 demonstrated about 1.2- and 2.0-fold higher than ATRA solution. Our results indicated that PEG1000 chain length of ATRA-PEG prodrug nanomicelles has the optimal oral bioavailability probably due to improved stability and balanced mucus penetration capability and cell binding, and that the PEG chain length on a surface of nanoparticles cannot exceed a key threshold with

  19. GSK3 is a regulator of RAR-mediated differentiation

    Science.gov (United States)

    Gupta, K; Gulen, F; Sun, L; Aguilera, R; Chakrabarti, A; Kiselar, J; Agarwal, MK; Wald, DN

    2015-01-01

    Acute myeloid leukemia (AML) is the most common form of leukemia in adults. Unfortunately, the standard therapeutic agents used for this disease have high toxicities and poor efficacy. The one exception to these poor outcomes is the use of the retinoid, all-trans retinoic acid (ATRA), for a rare subtype of AML (APL). The use of the differentiation agent, ATRA, in combination with low-dose chemotherapy leads to the long-term survival and presumed cure of 75–85% of patients. Unfortunately ATRA has not been clinically useful for other subtypes of AML. Though many non-APL leukemic cells respond to ATRA, they require significantly higher concentrations of ATRA for effective differentiation. Here we show that the combination of ATRA with glycogen synthase kinase 3 (GSK3) inhibition significantly enhances ATRA-mediated AML differentiation and growth inhibition. These studies have revealed that ATRA's receptor, the retinoic acid receptor (RAR), is a novel target of GSK3 phosphorylation and that GSK3 can impact the expression and transcriptional activity of the RAR. Overall, our studies suggest the clinical potential of ATRA and GSK3 inhibition for AML and provide a mechanistic framework to explain the promising activity of this combination regimen. PMID:22222598

  20. A case of all-trans retinoic acid-induced myositis in the treatment of acute promyelocytic leukaemia.

    Science.gov (United States)

    Chan, K H; Yuen, S L S; Joshua, D

    2005-12-01

    The use of all-trans retinoic acid (ATRA) is now standard therapy for the treatment of acute promyelocytic leukaemia (APML). There have been increasing reports of ATRA-induced myositis, with its frequent association with retinoic acid syndrome and Sweet's syndrome. We report a case of a young man with APML who developed ATRA-induced myositis characterized by unexplained fevers, bilateral leg swelling and a non-painful purpuric, petechial rash, with prompt resolution of symptoms and signs with high-dose steroids and cessation of ATRA. Rapid recognition of this adverse reaction and prompt institution of steroids is of prime importance given its potentially fatal course.

  1. A atração da educação : o impacto do estereótipo nacional na intenção de escolha do destino de estudo no contexto do ensino superior europeu: o caso de Portugal

    OpenAIRE

    Duarte, António Alexandre de Oliveira

    2014-01-01

    Tese de doutoramento em Ciências da Comunicação (área de especialização em Comunicação Organizacional e Estratégica) Este estudo aborda a relação entre os conceitos de imagem e de estereótipos dos países e a atratividade dos seus sistemas de Ensino Superior, analisando o caso português, no contexto da educação universitária europeia. A crescente importância da mobilidade académica, facilitada pelas decisões políticas que a estimulam; pela globalização; pela preferência das orga...

  2. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

    Science.gov (United States)

    Platzbecker, Uwe; Avvisati, Giuseppe; Cicconi, Laura; Thiede, Christian; Paoloni, Francesca; Vignetti, Marco; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Fazi, Paola; Sborgia, Marco; Di Bona, Eros; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; La Nasa, Giorgio; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian H; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Pogliani, Enrico Maria; Fozza, Claudio; D'Arco, Alfonso Maria; Di Renzo, Nicola; Cortelezzi, Agostino; Fabbiano, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Ehninger, Gerhard; Schlenk, Richard F; Lo-Coco, Francesco

    2017-02-20

    Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10 9 /L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

  3. Effect of retinoic acid on the radiosensitivity of normal human oral keratinocyte

    International Nuclear Information System (INIS)

    Lee, Jean; Heo, Min Suk; Lee, Sam Sun; Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; Lee, Sul Mi; Choi, Hang Moon

    2003-01-01

    To evaluate the effect of all-trans-retinotic acid (ATRA) on the radiosensitivity of normal human oral keratinocyte (NHOK). Relative cell survival fraction including SF2 (survival fraction at 2 Gy) was calculated on the basis of colony formation assay. Data were fitted to the linear-quadratic model to establish the survival curve and calculate α and β values. Using flow cytometry at 1, 2, 3, 4, and 5 days after exposure to 2 and 10 Gy irradiation, cell cycle arrest and apoptosis were analysed. To understand the molecular mechanism of the radiosensitization of ATRA on NHOK, proteins related with apoptosis and cell cycle arrest were investigated by Western blot analysis. Treatment with ATRA resulted in a significant decrease of SF2 value for NHOK from 0.63 to 0.27, and increased α and β value, indicating that ATRA increased radiosensitivity of NHOK. ATRA increased LDH significantly, but increasing irradiation dose decreased LDH, suggesting that the radiosensitizing effect of ATRA is not directly related with increasing cell necrosis by ATRA. ATRA did not induce appotosis but increased G2 arrest after 10 Gy irradiation, implying that the increased radiosensitivity of NHOK may be due to a decrease in mitosis caused by increasing G2 arrest. ATRA inhibited the reduction of p53 at 3 days after 10 Gy irradiation and increased p21 at 1 day after 10 Gy irradiation. Further study is required to determine the precise relationship between this effect and the radiosensitizing effect of ATRA. These results suggested that ATRA increase radiosensitivity by inhibiting mitosis caused by increasing G2 arrest.

  4. Paradoxical reproduction and body size in the rock lizard, Agama ...

    African Journals Online (AJOL)

    1993-07-05

    Jul 5, 1993 ... The rock lizard Agama atra atra from Namaqualand differs in both body size and reproduction from other populations of this species occurring elsewhere in southern Africa. Both sexes from Namaqualand are significantly larger than their counterparts in the south-western Cape. While reproduction in this ...

  5. In vitro induction and differentiation of umbilical cord mesenchymal stem cells into neuron-like cells by all-trans retinoic acid

    Directory of Open Access Journals (Sweden)

    Wei Jin

    2015-04-01

    Full Text Available AIM: To determine the optimal concentration for inducing the differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs into neuron-like cells, although it is understood that all-trans retinoic acid (ATRA regulates cell proliferation in the nervous system by modulating the balance between mitosis and apoptosis. METHODS: The abilities of ATRA to promote apoptosis as well as neural differentiation were assessed in cultured hUC-MSCs by morphological observation, MTT assay, annexin V-FITC/PI flow cytometry and immunocytochemistry. RESULTS: The data showed that low concentrations of ATRA (0.5 µmol, 0.25 µmol had no effect on the number of cells. However, treatment with 1.0 µmol or 2.0 µmol ATRA induced a 24.16% and 52.67% reduction in cell number, respectively, compared with vehicle-treated cultures. Further, 4.0 µmol ATRA had a potent effect on cell number, with almost no adherent cells recovered after 24h. We further showed that 0.5 µmol ATRA caused these cells to express characteristic markers of neuronal progenitor cells. CONCLUSION: Taken together, we conclude that ATRA has a dose-dependent influence on the neural differentiation and apoptosis of hUC-MSCs. These findings have implications on the use of ATRA-differentiated hUC-MSCs for the study of neural degeneration diseases.

  6. Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Jin Man Kim; Sang Wook Kang; Su-Mi Shin; Duck Su Kim; Kyong-Kyu Choi; Eun-Cheol Kim; Sun-Young Kim

    2014-01-01

    All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and-9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and-9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 mmol?L21 ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.

  7. DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia

    NARCIS (Netherlands)

    Glasow, Annegret; Barrett, Angela; Petrie, Kevin; Gupta, Rajeev; Boix-Chornet, Manuel; Zhou, Da-Cheng; Grimwade, David; Gallagher, Robert; von Lindern, Marieke; Waxman, Samuel; Enver, Tariq; Hildebrandt, Guido; Zelent, Arthur

    2008-01-01

    The retinoic acid receptor (RAR) alpha gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARalpha2) isoform increases with myelomonocytic differentiation and appears to be

  8. DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia

    NARCIS (Netherlands)

    A. Glasow (Annegret); A. Barrett (Angela); K. Petrie (Kevin); R. Gupta (Rajeev); M. Boix-Chornet (Manuel); D.C. Zhou; D. Grimwade (David); R. Gallagher (Robert); M.M. von Lindern (Marieke); S. Waxman (Sergio); T. Enver (Tariq); G. Hildebrandt (Guido); A. Zelent (Arthur)

    2008-01-01

    textabstractThe retinoic acid receptor (RAR) α gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARα2) isoform increases with myelomonocytic differentiation and appears to be

  9. Catalase Induced by All-Trans Retinoic Acid Is Involved in Antiproliferation of 36B10 Cells

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Yu, Jae Ran

    2010-01-01

    All-trans retinoic acid (ATRA) has antiproliferative effects against brain tumor cells. Recently, ATRA has been reported to induce catalase. We investigated whether catalase induction by ATRA is associated with its antiproliferative effects. 36B10 cells were exposed to 0-50μM ATRA for 24 or 48 hours and mRNA, protein, and activity of catalase were measured. Reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescin diacetate. A clonogenic assay was used to confirm the cytotoxic effect. The mRNA, protein, and activity of catalase were found to increase in a concentration- and incubation- time-dependent manner. The increase in catalase activity induced by ATRA was decreased by the addition of 3-amino-1,2,4-triazole (ATZ). ROS was also increased with ATRA and decreased by the addition of ATZ. The decrease in cell survival induced by ATRA was partly rescued by ATZ. Catalase induction by ATRA is involved in ROS overproduction and thus inhibits the proliferation of 36B10 cells.

  10. Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management

    Directory of Open Access Journals (Sweden)

    K. Govind Babu

    2016-01-01

    Full Text Available Background. Acute promyelocytic leukemia is characterized by t(15;17. This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA, a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

  11. Ultrasound-enhanced delivery of doxorubicin/all-trans retinoic acid-loaded nanodiamonds into tumors.

    Science.gov (United States)

    Li, Huanan; Zeng, Deping; Wang, Zhenyu; Fang, Liaoqiong; Li, Faqi; Wang, Zhibiao

    2018-03-14

    To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm 2 . Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. DOX-ATRA-NDs demonstrate great potential in clinical applications.

  12. Eosinophils from Murine Lamina Propria Induce Differentiation of Naïve T Cells into Regulatory T Cells via TGF-β1 and Retinoic Acid.

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    Hong-Hu Chen

    Full Text Available Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP that displayed high aldehyde dehydrogenase (ALDH activity, a rate-limiting step during all-trans retinoic acid (ATRA synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.

  13. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  14. The retinoic acid-induced up-regulation of insulin-like growth factor 1 and 2 is associated with prolidase-dependent collagen synthesis in UVA-irradiated human dermal equivalents.

    Science.gov (United States)

    Shim, Joong Hyun; Shin, Dong Wook; Lee, Tae Ryong; Kang, Hak Hee; Jin, Sun Hee; Noh, Minsoo

    2012-04-01

    Ultraviolet (UV) A irradiation causes the degeneration of extracellular matrix in the skin dermis, mainly due to disrupted collagen homeostasis, resulting in the photo-aging of human skin. All-trans retinoic acid (ATRA) improves photo-aged human skin in vivo. Although the effects of ATRA on collagen synthesis and MMP regulation are well known, the effects of ATRA on other collagen homeostasis-associated genes have not been elucidated. This study was aimed to study the factors that are pharmacologically associated with the effect of ATRA on collagen homeostasis. The gene transcription profile of collagen homeostasis-associated genes was systematically evaluated in three-dimensional human dermal equivalents (HDEs) following UVA-irradiation and/or ATRA treatment. In addition to the expected changes in MMPs and collagen synthesis in HDEs in response to ATRA, prolidase, an important enzyme in the recycling of proline and hydroxyproline from degraded collagen molecules, was significantly decreased by UVA irradiation, and its down-regulation was antagonized by ATRA. Transfection with a prolidase-specific siRNA led to a significant decrease in procollagen synthesis in human fibroblasts. ATRA inhibited the UVA irradiation-induced decrease in prolidase activity through an insulin-like growth factor (IGF) receptor signaling pathway in HDEs. ARTA increased IGF1 and IGF2 production in HDEs, and neutralizing IGFs with anti-IGF antibodies abolished the effect of ATRA on proliase activity. These data demonstrate that ATRA regulates prolidase activity in HDEs via IGF receptor signaling, suggesting one of the pharmacological mechanisms by which improves photo-aged human skin. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Oleic Acid enhances all-trans retinoic Acid loading in nano-lipid emulsions.

    Science.gov (United States)

    Chinsriwongkul, Akhayachatra; Opanasopit, Praneet; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Sila-On, Warisada; Ruktanonchai, Uracha

    2010-01-01

    The aim of this study was to investigate the enhancement of all-trans retinoic acid (ATRA) loading in nano-lipid emulsions and stability by using oleic acid. The effect of formulation factors including initial ATRA concentration and the type of oil on the physicochemical properties, that is, percentage yield, percentage drug release, and photostability of formulations, was determined. The solubility of ATRA was increased in the order of oleic acid > MCT > soybean oil > water. The physicochemical properties of ATRA-loaded lipid emulsion, including mean particle diameter and zeta potential, were modulated by changing an initial ATRA concentration as well as the type and mixing ratio of oil and oleic acid as an oil phase. The particles of lipid emulsions had average sizes of less than 250 nm and negative zeta potential. The addition of oleic acid in lipid emulsions resulted in high loading capacity. The photodegradation rate was found to be dependent on the initial drug concentration but independent of the type of oily phase used in this study. The release rates were not affected by initial ATRA concentration but were affected by the type of oil, where oleic acid showed the highest release rate of ATRA from lipid emulsions.

  16. An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.

    Science.gov (United States)

    Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D

    2017-10-30

    In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.

  17. Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia.

    Science.gov (United States)

    Jin, Jianjun; Li, Xiaozhen; Xing, Luqi; Chang, Yongchao; Wu, Lijuan; Jin, Zhe; Su, Xiuli; Bai, Yanli; Zheng, Yufeng; Jiang, Yalin; Zhao, Xiao; Lu, Lan; Gao, Qiang

    2015-04-01

    To investigate the efficacy of all-trans retinoic acid (ATRA) in human gastric dysplasia. In this double-blind study, patients with precancerous gastric dysplasia with or without intestinal metaplasia (IM) received either conventional treatment consisting of omeprazole and sucralfate (control group) or conventional treatment plus ATRA. Gastric mucosal biopsies were performed before and after drug treatment and were analysed histologically; expression of retinoblastoma (Rb) protein and HER2 protein in gastric mucosa were measured using immunohistochemistry. A total of 122 patients were included in the study, 63 in the ATRA group and 59 in the control group. In the ATRA group, dysplasia was attenuated in 43 out of 63 patients (68%) compared with 22 out of 59 patients (37%) in the control group; however, IM was not affected by treatment in either group. ATRA treatment was associated with significantly increased Rb expression and decreased HER2 expression in gastric mucosa. The use of conventional therapy plus ATRA for gastric dysplasia was associated with improved efficacy compared with conventional therapy alone. It was also accompanied by increased Rb expression and decreased HER2 expression in gastric mucosa. The addition of ATRA to conventional therapy for gastritis may improve the prognosis of gastric dysplasia. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Li Xiang-Xin

    2014-01-01

    Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

  19. Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor.

    Directory of Open Access Journals (Sweden)

    Aurore Gely-Pernot

    2015-10-01

    Full Text Available All-trans retinoic acid (ATRA is instrumental to male germ cell differentiation, but its mechanism of action remains elusive. To address this question, we have analyzed the phenotypes of mice lacking, in spermatogonia, all rexinoid receptors (RXRA, RXRB and RXRG or all ATRA receptors (RARA, RARB and RARG. We demonstrate that the combined ablation of RXRA and RXRB in spermatogonia recapitulates the set of defects observed both upon ablation of RAR in spermatogonia. We also show that ATRA activates RAR and RXR bound to a conserved regulatory region to increase expression of the SALL4A transcription factor in spermatogonia. Our results reveal that this major pluripotency gene is a target of ATRA signaling and that RAR/RXR heterodimers are the functional units driving its expression in spermatogonia. They add to the mechanisms through which ATRA promote expression of the KIT tyrosine kinase receptor to trigger a critical step in spermatogonia differentiation. Importantly, they indicate also that meiosis eventually occurs in the absence of a RAR/RXR pathway within germ cells and suggest that instructing this process is either ATRA-independent or requires an ATRA signal originating from Sertoli cells.

  20. Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. II. Effects after intrathecal administration

    Science.gov (United States)

    Alique, M; Lucio, F J; Herrero, J F

    2006-01-01

    Background and purpose: In our previous study (see accompanying paper) we observed that all-trans retinoic acid (ATRA) p.o. induces changes in spinal cord neuronal responses similar to those observed in inflammation-induced sensitization. In the present study we assessed the it. effects of ATRA, and its mechanisms of action. Experimental approach: The effects of all drugs were studied after it. administration in nociceptive withdrawal reflexes using behavioural tests in awake male Wistar rats. Key results: The administration of ATRA in normal rats induced a dose-dependent enhancement of nociceptive responses to noxious mechanical and thermal stimulation, as well as responses to innocuous stimulation. The intensity of the responses was similar to that observed in non-treated animals after carrageenan-induced inflammation. The effect induced by ATRA was fully prevented by the previous administration of the retinoic acid receptor (RAR) pan-antagonist LE540 but not by the retinoid X receptor (RXR) pan-antagonist HX531, suggesting a selective action on spinal cord RARs. The COX inhibitor dexketoprofen and the interleukin-1 receptor antagonist IL-1ra inhibited ATRA effect. The results indicate that COX and interleukin-1 are involved in the effects of ATRA in the spinal cord, similar to that seen in inflammation. Conclusions and implications: In conclusion, ATRA induces changes in the spinal cord similar to those observed in inflammation. The sensitization-like effect induced by ATRA was mediated by RARs and associated with a modulation of COX-2 and interleukin-1 activities. ATRA might be involved in the mechanisms underlying the initiation and/or maintenance of sensitization in the spinal cord. PMID:16847438

  1. All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein

    Directory of Open Access Journals (Sweden)

    Taguchi Takahiro

    2010-12-01

    Full Text Available Abstract Background Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for irresectable and metastasized gastrointestinal stromal tumor (GIST patients. Unfortunately, most patients responding to imatinib will eventually exhibit imatinib-resistance, the cause of which is not fully understood. The serious clinical problem of imatinib-resistance demands alternative therapeutic strategy. This study was conducted to investigate the effect of all-trans retinoic acid (ATRA on GIST cell lines. Methods Cell proliferation was determined by trypan blue dye exclusion test. Western blot analysis was performed to test the expression of activated KIT, its downstream proteins, and apoptosis associated proteins. The cytotoxic interactions of imatinib with ATRA were evaluated using the isobologram of Steel and Peckham. Results and conclusion In this work, for the first time we have demonstrated that ATRA affected on cell proliferation of GIST-T1 and GIST-882 cell line through inhibition of cell growth in a dose dependent manner and induced apoptosis. High dose of ATRA induced morphologic change in GIST-T1 cells, rounded-up cells, and activated the caspase-3 protein. In further examination, we found that the ATRA-induced apoptosis in GIST-T1 cells was accompanied by the down-regulated expression of survivin and up-regulated expression of Bax protein. Moreover, ATRA suppressed the activity of KIT protein in GIST-T1 cells and its downstream signal, AKT activity, but not MAPK activity. We also have demonstrated that combination of ATRA with imatinib showed additive effect by isobologram, suggesting that the combination of ATRA and imatinib may be a novel potential therapeutic option for GIST treatment. Furthermore, the scracht assay result suggested that ATRA was a potential reagent to prevent the invasion or metastasis of GIST cells.

  2. Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Xu, Qin; Zhang, Zhiyuan; Zhang, Ping; Chen, Wantao

    2008-01-01

    Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo. In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined. Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues. The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma

  3. All-trans retinoic acid increases the expression of oxidative myosin heavy chain through the PPARδ pathway in bovine muscle cells derived from satellite cells.

    Science.gov (United States)

    Kim, Jongkyoo; Wellmann, Kimberly B; Smith, Zachary K; Johnson, Bradley J

    2018-04-24

    All-trans retinoic acid (ATRA) has been associated with various physiological phenomenon in mammalian adipose tissue and skeletal muscle. We hypothesized that ATRA may affect skeletal muscle fiber type in bovine satellite cell culture through various transcriptional processes. Bovine primary satellite cell (BSC) culture experiments were conducted to determine dose effects of ATRA on expression of genes and protein levels related to skeletal muscle fiber type and metabolism. The semimembranosus from crossbred steers (n = 2 steers), aged approximately 24 months, were used to isolate BSC for 3 separate assays. Myogenic differentiation was induced using 3% horse serum upon cultured BSC with increasing doses (0, 1, 10, 100, 1000 nM) of ATRA. After 96 h of incubation, cells were harvested and used to measure the gene expression of protein kinase B (Akt), AMP-activated protein kinase alpha (AMPK), glucose transporter 4 (GLUT4), myogenin, lipoprotein lipase (LPL), myosin heavy chain (MHC) I, MHC IIA,MHC IIX, insulin like growth factor -1 (IGF-1), Peroxisome proliferator activated receptor gamma (PPARγ), PPARδ, and Smad transcription factor 3 (SMAD3) mRNA relative to ribosomal protein subunit 9 (RPS9). The mRNA expression of LPL was increased (P < 0.05) with 100 and 1000nM of ATRA. Expression of GLUT4 was altered (P < 0.05) by ATRA. The treatment of ATRA (1000nM) also increased (P < 0.05) mRNA gene expression of SMAD3. The gene expression of both PPARδ and PPARγ were increased (P < 0.05) with 1000nM of ATRA. Protein level of PPARδ was also affected (P < 0.05) by 1000nM of ATRA and resulted in a greater (P < 0.05) protein level of PPARδ compared to CON. All-trans retinoic acid (10nM) increased gene expression of MHC I (P < 0.05) compared to CON. Expression of MHC IIA was also influenced (P < 0.05) by ATRA. The mRNA expression of MHC IIX was decreased (P < 0.05) with 100 and 1000nM of ATRA.In muscle cells, ATRA may cause muscle fibers to transition towards the MHC

  4. Development of a novel microemulsion for oral absorption enhancement of all-trans retinoic acid.

    Science.gov (United States)

    Subongkot, Thirapit; Ngawhirunpat, Tanasait

    2017-01-01

    This study was aimed to develop a novel microemulsion that contained oleth-5 as a surfactant to enhance the oral absorption of all-trans retinoic acid (ATRA). The prepared microemulsion was evaluated for its particle size, shape, zeta potential, in vitro release, in vitro intestinal absorption, intestinal membrane cytotoxicity and stability. The obtained microemulsion was spherical in shape with a particle size of microemulsion was best fit with the zero-order model. This microemulsion significantly improved the intestinal absorption of ATRA. Confocal laser scanning microscopy analysis using a fluorescent dye-loaded microemulsion also confirmed the intestinal absorption result. The intestinal membrane cytotoxicity of the ATRA-loaded microemulsion did not differ from an edible oil (fish oil). Stability testing showed that the ATRA-loaded microemulsion was more stable at 25°C than 40°C.

  5. Biodegradation of Crude-oil by Fungi Isolated from Cow ...

    African Journals Online (AJOL)

    ... fungi identified from the contaminated soils include; Bdellospora helicoides, Aspergillus fumigatus, Gonadobotricum apiculata, Aspergillus niger, Trichoderma viridae, Pleurothecium recurvatum, Streptothrix atra, Thysarophora longispora, Candida albicans, Aspergillus flavus, Helminthosporium velutinum, Botrytis cinerea, ...

  6. Plaat

    Index Scriptorium Estoniae

    2008-01-01

    Laseringi kauplustes müügilolevatest heliplaatidest: Bizarre "Cafe De Flor", Hocico "Memorias Atras", Portishead "Third", Alanis Morissette "Flavors Of Entanglement", Radiohead "The Best Of", Kelder "Vikerkaar ja latimeeria"

  7. Comparising the Succinylcholine onset effect with Atracurium - Alfentanyl in patient underwent rapid sequence Induction

    Directory of Open Access Journals (Sweden)

    hasan Teimouri

    2005-12-01

    Conclusion: According to results, use of Atra + Alfen method can replace the standard method (succinylcholine for contraindicated condition. Mild vocal cord movement and mild bucking in the Atracurium + Alfentanyl can be control by that a increase in Atracurium dose.

  8. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning [Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Wang, Miao [Department of Oral and Maxillofacial Surgery, Kiang Wu Hospital, Macao (China); Chen, Mu [Department of Stomatology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen (China); Hou, Jinsong [Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Huang, Hongzhang, E-mail: drhuang52@163.com [Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China); Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055 (China)

    2016-08-26

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. - Highlights: • atRA exposure on E12.0 induced MEE persistence and cleft palate. • Notch1 was up-regulated in MEE cells in the atRA-treated embryos. • atRA inhibits MEE degradation, which in turn induces cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway.

  9. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice

    International Nuclear Information System (INIS)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning; Wang, Miao; Chen, Mu; Hou, Jinsong; Huang, Hongzhang

    2016-01-01

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. - Highlights: • atRA exposure on E12.0 induced MEE persistence and cleft palate. • Notch1 was up-regulated in MEE cells in the atRA-treated embryos. • atRA inhibits MEE degradation, which in turn induces cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway.

  10. The Role of Tumor Metastases Suppressor Gene, Drg-1, in Breast Cancer

    Science.gov (United States)

    2009-03-01

    regulates NM23 in hepatocarcinoma cells. Increased adhesion to ECM in vitro Inhibits the growth of xenograft tumors and gastric cancer cell metastasis to...expression of NM23 was also shown to be up-regulated by ATRA in human hepatocarcinoma cell line and gastric cancer cell lines [226,227]. Liu et al...invasion of human hepatocarcinoma cell line [226]. Furthermore, Wu et al. examined the effect of ATRA treatment in xenografted nude mice and found that

  11. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia

    Science.gov (United States)

    Boutzen, Héléna; Saland, Estelle; Larrue, Clément; de Toni, Fabienne; Gales, Lara; Castelli, Florence A.; Cathebas, Mathilde; Zaghdoudi, Sonia; Stuani, Lucille; Kaoma, Tony; Riscal, Romain; Yang, Guangli; Hirsch, Pierre; David, Marion; De Mas-Mansat, Véronique; Delabesse, Eric; Vallar, Laurent; Delhommeau, François; Jouanin, Isabelle; Ouerfelli, Ouathek; Le Cam, Laurent; Linares, Laetitia K.; Junot, Christophe; Portais, Jean-Charles; Vergez, François; Récher, Christian

    2016-01-01

    Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD–Scid–IL2rγnull mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies. PMID:26951332

  12. Oral absorption and oxidative metabolism of atrazine in rats evaluated by physiological modeling approaches

    International Nuclear Information System (INIS)

    McMullin, Tami S.; Hanneman, William H.; Cranmer, Brian K.; Tessari, John D.; Andersen, Melvin E.

    2007-01-01

    Atrazine (ATRA) is metabolized by cytochrome P450s to the chlorinated metabolites, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1, 3, 5-triazine (ISO), and diaminochlorotriazine (DACT). Here, we develop a set of physiologically based pharmacokinetic (PBPK) models that describe the influence of oral absorption and oxidative metabolism on the blood time course curves of individual chlorotriazines (Cl-TRIs) in rat after oral dosing of ATRA. These models first incorporated in vitro metabolic parameters to describe time course plasma concentrations of DACT, ETHYL, and ISO after dosing with each compound. Parameters from each individual model were linked together into a final composite model in order to describe the time course of all 4 Cl-TRIs after ATRA dosing. Oral administration of ISO, ETHYL and ATRA produced double peaks of the compounds in plasma time courses that were described by multiple absorption phases from gut. An adequate description of the uptake and bioavailability of absorbed ATRA also required inclusion of additional oxidative metabolic clearance of ATRA to the mono-dealkylated metabolites occurring in GI a tract compartment. These complex processes regulating tissue dosimetry of atrazine and its chlorinated metabolites likely reflect limited compound solubility in the gut from dosing with an emulsion, and sequential absorption and metabolism along the GI tract at these high oral doses

  13. All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

    International Nuclear Information System (INIS)

    Li Ang; He Meilan; Wang Hui; Qiao Bin; Chen Ping; Gu Hua; Zhang Mengjie; He Shengxiang

    2007-01-01

    NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

  14. Promotive Effect of Minoxidil Combined with All-trans Retinoic Acid (tretinoin) on Human Hair Growth in Vitro

    Science.gov (United States)

    Kwon, Oh Sang; Pyo, Hyun Keol; Oh, Youn Jin; Han, Ji Hyun; Lee, Se Rah; Chung, Jin Ho; Eun, Hee Chul

    2007-01-01

    Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21. PMID:17449938

  15. Temperature-controlled continuous production of all-trans retinoic acid-loaded solid lipid nanoparticles using static mixers

    Science.gov (United States)

    Shao, Wenyao; Yan, Mengwen; Chen, Tingting; Chen, Yuqing; Xiao, Zongyuan

    2017-04-01

    This work aims to develop a temperature-controlled continuous solvent emulsification-diffusion process to synthesize all-trans retinoic acid (ATRA)-loaded solid lipid nanoparticles (SLNs) using static mixers. ATRA-loaded SLNs of around 200 nm were obtained when the flow rates of the organic and aqueous phases were 50 ml min-1 and 500 ml min-1, respectively. It was found that the lipid concentration played a dominant role in the size of the obtained SLNs, and higher drug concentration resulted in relatively low entrapment efficiency. The encapsulation of ATRA in the SLNs was effective in improving its stability according to the photo-degradation test. The in vitro release of SLN was slow without an initial burst. This study demonstrates that the solvent emulsification-diffusion technique with static mixing is an effective method of producing SLNs, and could easily be scaled up for industrial applications. Highlights Higher lipid concentration leads to larger SLNs. SLN transformation occurs due to Ostwald ripening. The ATRA-loaded SLNs around 200 nm were successfully produced with static mixers. ATRA-loaded SLNs show better stability towards sunlight. ATRA in SLNs exhibited a relatively slow release rate without a significant initial burst.

  16. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice

    International Nuclear Information System (INIS)

    Ahn, Joong Ho; Kang, Hun Hee; Kim, Young-Jin; Chung, Jong Woo

    2005-01-01

    Exposure to loud noise can induce temporary or permanent hearing loss, and acoustic trauma is the major cause of hearing impairment in industrial nations. However, the mechanisms underlying the death of hair cells after acoustic trauma remain unclear. In addition to its involvement in cellular stress and apoptosis, the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is involved in cell survival, transformation, embryonic morphogenesis, and differentiation. JNK is primarily activated by various environmental stresses including noise, and the phenotypic result appears be to cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A that regulates a wide range of biological processes, including cell proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA in preserving hearing in mice exposed to noise that can induce permanent hearing loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure had a more preserved hearing threshold than mice fed sesame oil or saline. Histological and TUNEL staining of the cochlea showed significantly enhanced preservation of the organ of Corti, including outer hair cells and relatively low apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho-JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to noise

  17. A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomi Hirako

    Full Text Available We recently revealed that myeloid master regulator SPI1/PU.1 directly represses metallothionein (MT 1G through its epigenetic activity of PU.1, but the functions of MT1G in myeloid differentiation remain unknown. To clarify this, we established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE cells, and investigated whether MT1G functionally contributes to all-trans retinoic acid (ATRA-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by ATRA were significantly attenuated in NB4MTOE cells. Morphological examination revealed that the percentages of differentiated cells induced by ATRA were reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we observed a decrease in G1 accumulation, as well as decreases in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue tetrazolium (NBT reduction assays revealed that the proportions of NBT-positive cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray analyses showed that the changes in expression of several myeloid differentiation-related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic factor 2 and oncostatin M induced by ATRA were disturbed in NB4MTOE cells. Collectively, overexpression of MT1G inhibits the proper differentiation of myeloid cells.

  18. Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

    International Nuclear Information System (INIS)

    Sakamoto, K; Imamura, T; Yano, M; Yoshida, H; Fujiki, A; Hirashima, Y; Hosoi, H

    2014-01-01

    All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

  19. HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6.

    Directory of Open Access Journals (Sweden)

    Shuangshuang Li

    Full Text Available All-trans retinoic acid (ATRA induces complete remission in almost all patients with acute promyelocytic leukemia (APL via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117. Western blot analysis and quantitative real-time PCR demonstrated that HA117 causes alternative splicing of regulator of G-protein signaling 6 (RGS6 and down-regulation of the expression of the GGL domain of RGS6, which plays an important role in DNA methyltransferase 1 (DNMT1 degradation. Moreover, DNMT1 expression was increased in multi-drug resistance HL60/ATRA cells. Knockdown of HA117 restored expression of the GGL domain and blocked DNMT1 expression. Moreover, resistant cells displayed a putative stem-like signature with increased expression of cancer steam cell markers CD133 and CD123. The stem cell marker, Nanog, was significantly up-regulated. In conclusion, our study shows that HA117 potentially promotes the stem-like signature of the HL60/ATRA cell line by inhibiting by the ubiquitination and degradation of DNMT1 and by down-regulating the expression of the GGL domain of RGS6. These results throw light on the cellular events associated with the ATRA-induced multi-drug resistance phenotype in acute leukemia.

  20. All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells: ROLE OF NOTCH1 AND TRANSFORMING GROWTH FACTOR (TGFβ).

    Science.gov (United States)

    Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

    2015-07-17

    All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Identification and characterization of an antennae-specific aldehyde oxidase from the navel orangeworm.

    Directory of Open Access Journals (Sweden)

    Young-Moo Choo

    Full Text Available Antennae-specific odorant-degrading enzymes (ODEs are postulated to inactivate odorant molecules after they convey their signal. Different classes of insect ODEs are specific to esters, alcohols, and aldehydes--the major functional groups of female-produced, hydrophobic sex pheromones from moth species. Esterases that rapidly inactive acetate and other esters have been well-studied, but less is known about aldehyde oxidases (AOXs. Here we report cloning of an aldehyde oxidase, AtraAOX2, from the antennae of the navel orangeworm (NOW, Amyelois transitella, and the first activity characterization of a recombinant insect AOX. AtraAOX2 gene spans 3,813 bp and encodes a protein with 1,270 amino acid residues. AtraAOX2 cDNA was expressed in baculovirus-infected insect Sf21 cells as a ≈280 kDa homodimer with 140 kDa subunits. Recombinant AtraAOX2 degraded Z11Z13-16Ald and plant volatile aldehydes as substrates. However, as expected for aldehyde oxidases, recombinant AtraAOX2 did not show specificity for Z11Z13-16Ald, the main constituent of the sex pheromone, but showed high activity for plant volatile aldehydes. Our data suggest AtraAOX2 might be involved in degradation of a diversity of aldehydes including sex pheromones, plant-derived semiochemicals, and chemical cues for oviposition sites. Additionally, AtraAOX2 could protect the insect's olfactory system from xenobiotics, including pesticides that might reach the sensillar lymph surrounding the olfactory receptor neurons.

  2. cAMP-Dependent Protein Kinase A (PKA)-Mediated c-Myc Degradation Is Dependent on the Relative Proportion of PKA-I and PKA-II Isozymes.

    Science.gov (United States)

    Liu, Qingyuan; Nguyen, Eric; Døskeland, Stein; Ségal-Bendirdjian, Évelyne

    2015-09-01

    The transcription factor c-Myc regulates numerous target genes that are important for multiple cellular processes such as cell growth and differentiation. It is commonly deregulated in leukemia. Acute promyelocytic leukemia (APL) is characterized by a blockade of granulocytic differentiation at the promyelocyte stage. Despite the great success of all-trans retinoic acid (ATRA)-based therapy, which results in a clinical remission by inducing promyelocyte maturation, a significant number of patients relapse due to the development of ATRA resistance. A significant role has been ascribed to the cAMP/cAMP-dependent protein kinase A (PKA) signaling pathway in retinoid treatment since PKA activation is able to restore differentiation in some ATRA-resistant cells and eradicate leukemia-initiating cells in vivo. In this study, using NB4 APL cell variants resistant to ATRA-induced differentiation, we reveal distinct functional roles of the two PKA isozymes, PKA type I (PKA-I) and PKA-type II (PKA-II), on the steady-state level of c-Myc protein, providing a likely mechanism by which cAMP-elevating agents can restore differentiation in ATRA maturation-resistant APL cells. Therefore, both the inhibition of c-Myc activity and the PKA-I/PKA-II ratio should be taken into account if cAMP-based therapy is considered in the clinical management of APL. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Apoptotic and anti-proliferative effects of all-trans retinoic acid

    International Nuclear Information System (INIS)

    Zamora, Monica; Ortega, Juan Alberto; Alana, Lide; Vinas, Octavi; Mampel, Teresa

    2006-01-01

    We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy

  4. A Case of AML Characterized by a Novel t(4;15(q31;q22 Translocation That Confers a Growth-Stimulatory Response to Retinoid-Based Therapy

    Directory of Open Access Journals (Sweden)

    Justin M. Watts

    2017-07-01

    Full Text Available Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML who was treated with all-trans retinoic acid (ATRA as part of investigational therapy (NCT02273102. The patient died from rapid disease progression following eight days of continuous treatment with ATRA. Karyotype analysis and RNA-Seq revealed the presence of a novel t(4;15(q31;q22 reciprocal translocation involving the TMEM154 and RASGRF1 genes. Analysis of primary cells from the patient revealed the expression of TMEM154-RASGRF1 mRNA and the resulting fusion protein, but no expression of the reciprocal RASGRF1-TMEM154 fusion. Consistent with the response of the patient to ATRA therapy, we observed a rapid proliferation of t(4;15 primary cells following ATRA treatment ex vivo. Preliminary characterization of the retinoid response of t(4;15 AML revealed that in stark contrast to non-t(4;15 AML, these cells proliferate in response to specific agonists of RARα and RARγ. Furthermore, we observed an increase in the levels of nuclear RARγ upon ATRA treatment. In summary, the identification of the novel t(4;15(q31;q22 reciprocal translocation opens new avenues in the study of retinoid resistance and provides potential for a new biomarker for therapy of AML.

  5. Tissue transglutaminase contributes to the all-trans-retinoic acid-induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia.

    Science.gov (United States)

    Csomós, Krisztián; Német, István; Fésüs, László; Balajthy, Zoltán

    2010-11-11

    Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNA interference-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions, and their silencing lead to reduced adhesive, migratory, and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell-cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, CCL3, CCL22, CCL24, and cytokines IL1B and IL8 involved in the development of differentiation syndrome are expressed at significantly lower level in TG2-KD NB4 than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of differentiation syndrome.

  6. A possible contribution of retinoids to regulation of fetal B lymphopoiesis.

    Science.gov (United States)

    Chen, Xinrong; Welner, Robert S; Kincade, Paul W

    2009-09-01

    We recently found that all trans retinoic acid (ATRA) accelerated B lymphocyte formation. In the current study, we address the question whether retinoids account for the rapid lymphopoiesis that is characteristic of fetal progenitors. Surprisingly, addition of ATRA to fetal liver cultures actually reduced B lymphopoiesis. A pan-retinoid receptor antagonist selectively suppressed lymphocyte formation from fetal and adult progenitors, suggesting some normal contribution of retinoids to this process. Consistent with this role, B lymphopoiesis was compromised in the marrow of mice with prolonged vitamin A deficiency. Recently identified B1 progenitors from adult marrow were similar to adult B2 progenitors in that their differentiation was stimulated by ATRA. The inhibitory response observed with fetal cells was seen when adult progenitors were exposed to high doses in culture or when adult mice were treated with ATRA for 2 wk. In addition to explosive lymphocyte generation, fetal progenitors tend to be less IL-7 dependent than their adult counterparts, but ATRA did not make fetal progenitors IL-7 independent. We conclude that all known categories of B lineage progenitors are responsive to retinoids and probably regulated by these compounds under physiological conditions. Retinoids may account in part for rapid differentiation in fetal life, but not all unique features of fetal progenitors.

  7. Vav promotes differentiation of human tumoral myeloid precursors

    International Nuclear Information System (INIS)

    Bertagnolo, Valeria; Brugnoli, Federica; Mischiati, Carlo; Sereni, Alessia; Bavelloni, Alberto; Carini, Cinzia; Capitani, Silvano

    2005-01-01

    Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders

  8. C/EBPβ contributes to transcriptional activation of long non-coding RNA NEAT1 during APL cell differentiation.

    Science.gov (United States)

    Wang, Yewei; Fu, Lei; Sun, Ailian; Tang, Doudou; Xu, Yunxiao; Li, Zheyuan; Chen, Mingjie; Zhang, Guangsen

    2018-05-05

    Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPβ bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPβ binding sites both around -54 bp and -1453 bp upstream of the transcription start site. Moreover, the expression of C/EBPβ was increased after ATRA treatment, and the binding of C/EBPβ in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBPβ significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBPβ directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBPβ impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBPβ contributes to ATRA-induced activation of NEAT1 during APL cell differentiation. Our results enrich our knowledge on the regulation of lncRNAs and the regulatory role of C/EBPβ in APL cell differentiation. Copyright © 2017. Published by Elsevier Inc.

  9. Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity

    Directory of Open Access Journals (Sweden)

    Paulo Czarnewski

    2017-01-01

    Full Text Available Vitamin A (VA is amongst the most well characterized food-derived nutrients with diverse immune modulatory roles. Deficiency in dietary VA has not only been associated with immune dysfunctions in the gut, but also with several systemic immune disorders. In particular, VA metabolite all-trans retinoic acid (atRA has been shown to be crucial in inducing gut tropism in lymphocytes and modulating T helper differentiation. In addition to the widely recognized role in adaptive immunity, increasing evidence identifies atRA as an important modulator of innate immune cells, such as tolerogenic dendritic cells (DCs and innate lymphoid cells (ILCs. Here, we focus on the role of retinoic acid in differentiation, trafficking and the functions of innate immune cells in health and inflammation associated disorders. Lastly, we discuss the potential involvement of atRA during the plausible crosstalk between DCs and ILCs.

  10. Potential role of nuclear receptor ligand all-trans retinoic acids in the treatment of fungal keratitis

    Directory of Open Access Journals (Sweden)

    Hong-Yan Zhou

    2015-08-01

    Full Text Available Fungal keratitis (FK is a worldwide visual impairment disease. This infectious fungus initiates the primary innate immune response and, later the adaptive immune response. The inflammatory process is related to a variety of immune cells, including macrophages, helper T cells, neutrophils, dendritic cells, and Treg cells, and is associated with proinflammatory, chemotactic and regulatory cytokines. All-trans retinoic acids (ATRA have diverse immunomodulatory actions in a number of inflammatory and autoimmune conditions. These retinoids regulate the transcriptional levels of target genes through the activation of nuclear receptors. Retinoic acid receptor α (RAR α, retinoic acid receptor γ (RAR γ, and retinoid X receptor α (RXR α are expressed in the cornea and immune cells. This paper summarizes new findings regarding ATRA in immune and inflammatory diseases and analyzes the perspective application of ATRA in FK.

  11. Reproduction-associated immunoreactive peptides in the nervous systems of prosobranch gastropods.

    Science.gov (United States)

    Ram, J L; Gallardo, C S; Ram, M L; Croll, R P

    1998-12-01

    Antibodies against reproductive peptides of Aplysia and Lymnaea were used to localize homologous immunoreactive peptides in the nervous systems of three prosobranch species: Busycon canaliculatum, Concholepas concholepas, and Tegula atra. Positive control experiments in L. stagnalis demonstrated the broad species range of the anti-egg-laying hormone (anti-ELH) antibody used in this study, and showed binding of anti-alpha-caudodorsal-cell peptide (anti-alpha-CDCP) to the same cells in cerebral and buccal ganglia. Dot immunoassays with synthetic ELH confirmed the reactivity and sensitivity (concholepas and T atra, ELH-like immunoreactivity was found in cerebral ganglia, and in T. atra in fibers in the cerebral ganglia and cerebral-pedal connectives. Thus, cerebral ganglia are the major locus of the ELH-like immunoreactivity in prosobranchs.

  12. Acute and chronic exposure in mussel (aulacomya ater) and clam (semelle solida) with Cs137

    International Nuclear Information System (INIS)

    Bringas, J.E.

    1996-01-01

    Two of the most common Peruvian benthonic molluscs, have been shown to be effective concentrators of Cesium-137 and have also proven useful as indicators of that radionuclide in their natural environment, according with results in this paper. However the clam is a better indicator, when determining environmental acute release of Cesium-137 due to reactor accidents, nuclear tests, accidents in nuclear ships, submarines and radioactive material transport, and the mussel for a continuous monitoring of environmental radio contaminant levels. (author). 11 refs

  13. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.

    Directory of Open Access Journals (Sweden)

    Lizhi Wu

    Full Text Available UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. In this study, we investigated the effects of UAB30 on gene expression in human organotypic skin raft cultures and mouse epidermis. The results of this study indicate that treatment with UAB30 results in upregulation of genes responsible for the uptake and metabolism of all-trans-retinol to all-trans-retinoic acid (ATRA, the natural agonist of RAR nuclear receptors. Consistent with the increased expression of these genes, the steady-state levels of ATRA are elevated in human skin rafts. In ultraviolet B (UVB irradiated mouse skin, the expression of ATRA target genes is found to be reduced. A reduced expression of ATRA sensitive genes is also observed in epidermis of mouse models of UVB-induced squamous cell carcinoma and basal cell carcinomas. However, treatment of mouse skin with UAB30 prior to UVB irradiation prevents the UVB-induced decrease in expression of some of the ATRA-responsive genes. Considering its positive effects on ATRA signaling in the epidermis and its low toxicity, UAB30 could be used as a chemoprophylactic agent in the treatment of non-melanoma skin cancer, particularly in organ transplant recipients and other high risk populations.

  14. Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    Raza, S.; Ahmed, P.; Khan, B.

    2008-01-01

    To compare survival in Acute Promyelocytic Leukemia (APL) patients treated with or without All-Trans Retinoic Acid (ATRA). Longitudinal, comparative study. All consecutive newly diagnosed patients of acute promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given chemotherapy according to availability of ATRA. Diagnosis was confirmed on morphology/ karyotyping/ molecular analysis. Eligibility criteria included confirmed morphologic diagnosis and/or by demonstration of t(15;17) and/or PML/RAR macro re-arrangement, no prior chemotherapy, normal hepatic and renal function, Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and no contraindications to ATRA (history of sensitivity to Vit. A or other retinoids). All patients having history of cardiac failure (LVEF 150 macro mol/L and pregnancy were excluded from this study. Survival was calculated from the date of chemotherapy to death or last follow-up according to Kaplan-Meier and Cox (Proportional hazard) regression analysis methods. During the 6 years study period, 31 newly diagnosed patients with acute promyelocytic leukemia received treatment at AFBMTC. Seventeen patients received anthracycline-based remission induction and consolidation chemotherapy, while 14 received ATRA-based remission induction, consolidation and by two years maintenance therapy. Overall Survival (OS), Disease Free Survival (DFS) and mortality were 29.4%, 29.4% and 70.6% respectively in 17 patients who received anthracycline based chemotherapy, whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were septicemia and chemotherapy related toxicity. Response to ATRA-based chemotherapy in patient cohort was better as compared with anthracycline based chemotherapy (71.4% vs. 29.4%) in terms of survival and mortality. (author)

  15. All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo.

    Science.gov (United States)

    Ma, Hayley S; Greenblatt, Sarah M; Shirley, Courtney M; Duffield, Amy S; Bruner, J Kyle; Li, Li; Nguyen, Bao; Jung, Eric; Aplan, Peter D; Ghiaur, Gabriel; Jones, Richard J; Small, Donald

    2016-06-09

    FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients. We explored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD)(+) LSCs. Our studies reveal highly synergistic drug activity, preferentially inducing apoptosis in FLT3/ITD(+) cell lines and patient samples. Colony-forming unit assays further demonstrate decreased clonogenicity of FLT3/ITD(+) cells upon treatment with ATRA and TKI. Most importantly, the drug combination depletes FLT3/ITD(+) LSCs in a genetic mouse model of AML, and prolongs survival of leukemic mice. Furthermore, engraftment of primary FLT3/ITD(+) patient samples is reduced in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular differentiation occurring in vivo. Mechanistically, we provide evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein Bcl6, limiting the drug's apoptotic effect. However, cotreatment with ATRA reduces Bcl6 expression to baseline levels through suppression of interleukin-6 receptor signaling. These studies provide evidence of the potential of this drug combination to eliminate FLT3/ITD(+) LSCs and reduce the rate of relapse in AML patients with FLT3 mutations.

  16. Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis: A Human Pilot Study.

    Science.gov (United States)

    Assis, David N; Abdelghany, Osama; Cai, Shi-Ying; Gossard, Andrea A; Eaton, John E; Keach, Jill C; Deng, Yanhong; Setchell, Kenneth D R; Ciarleglio, Maria; Lindor, Keith D; Boyer, James L

    2017-02-01

    To perform an exploratory pilot study of all-trans retinoic acid (ATRA) combined with ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC). PSC is a progressive disorder for which there is no accepted therapy. Studies in human hepatocyte cultures and in animal models of cholestasis indicate that ATRA might have beneficial effects in cholestatic disorders. ATRA (45 mg/m/d, divided and given twice daily) was combined with moderate-dose UDCA in patients with PSC who had incomplete response to UDCA monotherapy. The combination was administered for 12 weeks, followed by a 12-week washout in which patients returned to UDCA monotherapy. We measured alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, cholesterol, bile acids, and the bile acid intermediate 7α-hydroxy-4-cholesten-3-one (C4) at baseline, week 12, and after washout. Fifteen patients completed 12 weeks of therapy. The addition of ATRA to UDCA reduced the median serum ALP levels (277±211 to 243±225 U/L, P=0.09) although this, the primary endpoint, did not reach significance. In contrast, median serum ALT (76±55 to 46±32 U/L, P=0.001) and C4 (9.8±19 to 7.9±11 ng/mL, P=0.03) levels significantly decreased. After washout, ALP and C4 levels nonsignificantly increased, whereas ALT levels significantly increased (46±32 to 74±74, P=0.0006), returning to baseline. In this human pilot study, the combination of ATRA and UDCA did not achieve the primary endpoint (ALP); however, it significantly reduced ALT and the bile acid intermediate C4. ATRA appears to inhibit bile acid synthesis and reduce markers of inflammation, making it a potential candidate for further study in PSC (NCT 01456468).

  17. Polydimethylsiloxane (PDMS) modulates CD38 expression, absorbs retinoic acid and may perturb retinoid signalling.

    Science.gov (United States)

    Futrega, Kathryn; Yu, Jianshi; Jones, Jace W; Kane, Maureen A; Lott, William B; Atkinson, Kerry; Doran, Michael R

    2016-04-21

    Polydimethylsiloxane (PDMS) is the most commonly used material in the manufacture of customized cell culture devices. While there is concern that uncured PDMS oligomers may leach into culture medium and/or hydrophobic molecules may be absorbed into PDMS structures, there is no consensus on how or if PDMS influences cell behaviour. We observed that human umbilical cord blood (CB)-derived CD34(+) cells expanded in standard culture medium on PDMS exhibit reduced CD38 surface expression, relative to cells cultured on tissue culture polystyrene (TCP). All-trans retinoic acid (ATRA) induces CD38 expression, and we reasoned that this hydrophobic molecule might be absorbed by PDMS. Through a series of experiments we demonstrated that ATRA-mediated CD38 expression was attenuated when cultures were maintained on PDMS. Medium pre-incubated on PDMS for extended durations resulted in a time-dependant reduction of ATRA in the medium and increasingly attenuated CD38 expression. This indicated a time-dependent absorption of ATRA into the PDMS. To better understand how PDMS might generally influence cell behaviour, Ingenuity Pathway Analysis (IPA) was used to identify potential upstream regulators. This analysis was performed for differentially expressed genes in primary cells including CD34(+) haematopoietic progenitor cells, mesenchymal stromal cells (MSC), and keratinocytes, and cell lines including prostate cancer epithelial cells (LNCaP), breast cancer epithelial cells (MCF-7), and myeloid leukaemia cells (KG1a). IPA predicted that the most likely common upstream regulator of perturbed pathways was ATRA. We demonstrate here that ATRA is absorbed by PDMS in a time-dependent manner and results in the concomitant reduced expression of CD38 on the cell surface of CB-derived CD34(+) cells.

  18. The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-induced differentiation of colon cancer cells

    International Nuclear Information System (INIS)

    Bengtsson, Astrid M; Jönsson, Gunilla; Magnusson, Cecilia; Salim, Tavga; Axelsson, Cecilia; Sjölander, Anita

    2013-01-01

    Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT 1 R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT 2 R) is lost. Further, our previous data indicate that patients with high CysLT 1 R and low CysLT 2 R expression have a poor prognosis. In this study, we examined whether the balance between CysLT 1 R and CysLT 2 R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA). To determine the effect of ATRA on CysLT 2 R promoter activation, mRNA level, and protein level, we performed luciferase gene reporter assays, real-time polymerase chain reactions, and Western blots in colon cancer cell lines under various conditions. ATRA treatment induces CysLT 2 R mRNA and protein expression without affecting CysLT 1 R levels. Experiments using siRNA and mutant cell lines indicate that the up-regulation is retinoic acid receptor (RAR) dependent. Interestingly, ATRA also up-regulates mRNA expression of leukotriene C 4 synthase, the enzyme responsible for the production of the ligand for CysLT 2 R. Importantly, ATRA-induced differentiation of colorectal cancer cells as shown by increased expression of MUC-2 and production of alkaline phosphatase, both of which could be reduced by a CysLT 2 R-specific inhibitor. This study identifies a novel mechanism of action for ATRA in colorectal cancer cell differentiation and demonstrates that retinoids can have anti-tumorigenic effects through their action on the cysteinyl leukotriene pathway

  19. Azadirachtin interacts with retinoic acid receptors and inhibits retinoic acid-mediated biological responses.

    Science.gov (United States)

    Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B; Sureshkumar, Chitta; Manna, Sunil K

    2011-02-11

    Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor κB (NF-κB) activation, not the DNA binding but the NF-κB-dependent gene expression. It did not inhibit IκBα degradation, IκBα kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-κB-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-κB activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-κB, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies.

  20. Azadirachtin Interacts with Retinoic Acid Receptors and Inhibits Retinoic Acid-mediated Biological Responses*

    Science.gov (United States)

    Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B.; Sureshkumar, Chitta; Manna, Sunil K.

    2011-01-01

    Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor κB (NF-κB) activation, not the DNA binding but the NF-κB-dependent gene expression. It did not inhibit IκBα degradation, IκBα kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-κB-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-κB activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-κB, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies. PMID:21127062

  1. Comparative proteomic analysis of colon cancer cell HCT-15 in response to all-trans retinoic acid treatment.

    Science.gov (United States)

    Zhao, Jie; Wen, Gaotian; Ding, Ming; Pan, Jian-Yi; Yu, Mei-Lan; Zhao, Fukun; Weng, Xia-Lian; Du, Jiang-Li

    2012-12-01

    Colon cancer is one of the most common malignances. In vitro and in vivo study show that retinoic acids inhibit a wide variety of cancer cells but the molecular mechanism of their anti-tumor effects are not yet fully understood. Alltrans retinoic acid (ATRA), an isomer of retinoic acid, can inhibit the proliferation of HCT-15 human colon cancer cell line. A proteomic analysis was performed using HCT-15 treated with ATRA to further elucidate the retinoic acid signaling pathway and its anti-tumor effect mechanism. MTT results showed that the growth of HCT-15 cells were significantly inhibited by ATRA. The alkaline phosphatase activity assay showed that ATRA failed to induce the differentiation of HCT-15. The DNA ladder detection showed that ATRA induced apoptosis in HCT-15. Two-dimensional gel electrophoresis coupled with MALDI-TOF/TOF mass spectrometry identified 13 differentially expressed proteins in HCT-15 cells after all-trans retinoic acid treatment. Among the identified differentially expressed proteins, there were four scaffold proteins (YWHAE, SFN, YWHAB, and YWHAZ), two ubiquitin modification related proteins (ISG-15 and UBE2N), two translational initiation factors (EIF1AX and EIF3K), two cytoskeleton related proteins (EZRI and CNN3), two proteinmodification related proteins (TXNDC17 and PIMT), and one enzyme related to phospholipid metabolism (PSP). Both EZRI and UBE2N were rendered to western-blot validation and the results were consistent with the two-dimension electrophoresis analysis. In this study, the differentially expressed proteins in HCT-15 treated by ATRA were identified, which will assist the further elucidation of the anti-tumor mechanism of retinoic acids.

  2. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  3. Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1 in cancer cell differentiation process

    International Nuclear Information System (INIS)

    Fu Haiyan; Yang Guodong; Lu Fan; Wang Ruihua; Yao Libo; Lu Zifan

    2006-01-01

    RESTIN, a member of the melanoma-associated antigen superfamily, is a nuclear protein induced by atRA (all-trans retinoic acid) in HL60 cells. HeLa cells stably transfected with restin results in G1 cell cycle arrest. How this gene is regulated by atRA in the cell differentiation process is still unclear. In this study, we observed that up-regulation of restin was present during the atRA-induced HL60 cell differentiation process, suggesting the functional relevance between RESTIN and atRA-induced cellular effects. In order to further define the transcriptional regulation of restin by atRA, we analyzed the promoter region of restin. About 2.1 kb 5' flanking sequence of this gene was cloned into vector pGL3 and its core promoter region was identified through systemic deletions. Interestingly, restin promoter containing several potential consensus-binding sites of STAT-1α was activated by atRA in ER + MCF-7 cells but not in ER - MDA-MB-231 cells, over-expression of STAT-1α in latter rescued the activation effect of restin promoter in response to atRA and IFNγ. Our evidence supported that STAT-1α plays an important role in the atRA-induced transcriptional up-regulation of restin, which was associated with the atRA-induced HL60 cell differentiation and potentially mediated the downstream effects of atRA signal pathway via STAT-1α in some cancer cells

  4. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.

    Science.gov (United States)

    Schlenk, Richard F; Lübbert, Michael; Benner, Axel; Lamparter, Alexander; Krauter, Jürgen; Herr, Wolfgang; Martin, Hans; Salih, Helmut R; Kündgen, Andrea; Horst, Heinz-A; Brossart, Peter; Götze, Katharina; Nachbaur, David; Wattad, Mohammed; Köhne, Claus-Henning; Fiedler, Walter; Bentz, Martin; Wulf, Gerald; Held, Gerhard; Hertenstein, Bernd; Salwender, Hans; Gaidzik, Verena I; Schlegelberger, Brigitte; Weber, Daniela; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut

    2016-12-01

    The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m 2 , days 6-8; 15 mg/m 2 , days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).

  5. Ethanol induced hepatic mitochondrial dysfunction is attenuated by all trans retinoic acid supplementation.

    Science.gov (United States)

    Nair, Saritha S; Prathibha, P; Rejitha, S; Indira, M

    2015-08-15

    Alcoholics have reduced vitamin A levels in serum since vitamin A and ethanol share the same metabolic pathway. Vitamin A supplementation has an additive effect on ethanol induced toxicity. Hence in this study, we assessed the impact of supplementation of all trans retinoic acid (ATRA), an active metabolite of vitamin A on ethanol induced disruptive alterations in liver mitochondria. Male Sprague Dawley rats were grouped as follows: I: Control; II: Ethanol (4 g/kg b.wt./day); III: ATRA (100 μg/kg b.wt./day); and IV: Ethanol (4 g/kg b.wt./day)+ATRA (100 μg/kg b.wt./day). Duration of the experiment was 90 days, after which the animals were sacrificed for the study. The key enzymes of energy metabolism, reactive oxygen species, mitochondrial membrane potential and hepatic mRNA expressions of Bax, Bcl-2, c-fos and c-jun were assessed. Ethanol administration increased the reactive oxygen species generation in mitochondria. It also decreased the activities of the enzymes of citric acid cycle and oxidative phosphorylation. ATP content and mitochondrial membrane potential were decreased and cytosolic cytochrome c was increased consequently enhancing apoptosis. All these alterations were altered significantly on ATRA supplementation along with ethanol. These results were reinforced by our histopathological studies. ATRA supplementation to ethanol fed rats, led to reduction in oxidative stress, decreased calcium overload in the matrix and increased mitochondrial membrane potential, which might have altered the mitochondrial energy metabolism and elevated ATP production thereby reducing the apoptotic alterations. Hence ATRA supplementation seemed to be an effective intervention against alcohol induced mitochondrial dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Treatment of refractory undifferentiated acute myelogenous leukemia with all-trans-retinoic acid.

    Science.gov (United States)

    Griggs, J J; Henley, S E; Rowe, J M

    1994-02-01

    A patient is described with undifferentiated acute myeloblastic leukemia refractory to two courses of daunorubicin and cytosine arabinoside. Because some the myeloblasts developed morphologic features of promyelocytes, the patient was treated with all-trans-retinoic acid (ATRA) in an attempt to promote maturation. Cytogenetic studies and sensitive molecular analysis did not reveal any abnormality classically associated with acute promyelocytic leukemia. Serial bone marrow biopsies demonstrated myeloid maturation, and the patient uneventfully went into a sustained complete remission. A review of the literature confirms this to be an apparently hitherto undescribed response to ATRA that may have therapeutic implications in similar patients.

  7. Study of irradiation creep of vanadium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Strain, R.V.; Smith, D.L. [Argonne National Lab., IL (United States)] [and others

    1997-08-01

    Thin-wall tubing was produced from the 832665 (500 kg) heat of V-4 wt.% Cr-4 wt.% Ti to study its irradiation creep behavior. The specimens, in the form of pressurized capsules, were irradiated in Advanced Test Reactor and High Flux Isotope Reactor experiments (ATR-A1 and HFIR RB-12J, respectively). The ATR-A1 irradiation has been completed and specimens from it will soon be available for postirradiation examination. The RB-12J irradiation is not yet complete.

  8. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells.

    Directory of Open Access Journals (Sweden)

    Zhenya Gao

    Full Text Available All-trans retinoic acid (ATRA plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2 and matrix metalloproteinase 2 (MMP-2 and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19 cells.The effects of ATRA (concentrations from 10-9 to 10-5 mol/l on the expression of retinoic acid receptors (RARs in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10-9 to 10-5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR and enzyme-linked immunosorbent assay (ELISA. The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ.RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10-9 to 10-5 mol/l with a maximum effect observed at 10-6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10-6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135.ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated these cells to secrete BMP-2 and MMP-2.

  9. All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available It has been documented all-trans retinoic acid (atRA promotes the development of TGF-β-induced CD4(+Foxp3(+ regulatory T cells (iTreg that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs.Addition of atRA to naïve CD4(+CD25(- cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered.We have identified the cellular and molecular mechanism(s by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

  10. PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

    OpenAIRE

    Ozpolat, Bulent; Akar, Ugur; Tekedereli, Ibrahim; Alpay, S. Neslihan; Barria, Magaly; Gezgen, Baki; Zhang, Nianxiang; Coombes, Kevin; Kornblau, Steve; Lopez-Berestein, Gabriel

    2012-01-01

    Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2 α ), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2 α in acute promyelocytic (APL) and acute myeloid leukemia (AML) cells in response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation) of eIF2 α , through the induct...

  11. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    International Nuclear Information System (INIS)

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-01

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  12. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Orfali, Nina [Cork Cancer Research Center, University College Cork, Cork (Ireland); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); McKenna, Sharon L. [Cork Cancer Research Center, University College Cork, Cork (Ireland); Cahill, Mary R. [Department of Hematology, Cork University Hospital, Cork (Ireland); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); Mongan, Nigel P., E-mail: nigel.mongan@nottingham.ac.uk [Faculty of Medicine and Health Science, School of Veterinary Medicine and Science, University of Nottingham, LE12 5RD (United Kingdom); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States)

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  13. Population structure, growth and production of a recent brachiopod from the Chilean fjord region

    KAUST Repository

    Baumgarten, Sebastian; Laudien, Jü rgen; Jantzen, Carin; Hä ussermann, Verena; Fö rsterra, Gü nter

    2013-01-01

    -57% of that of A. atra in the respective fjords). The high shell growth rate of M. venosa, together with its high overall growth performance may explain the locally high population density of this brachiopod in Comau Fjord. However, the production per biomass

  14. Analysis of the interplay between all-trans retinoic acid and histone deacetylase inhibitors in leukemic cells

    DEFF Research Database (Denmark)

    Noack, Katrin; Mahendrarajah, Nisintha; Hennig, Dorle

    2017-01-01

    The treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) induces granulocytic differentiation. This process renders APL cells resistant to cytotoxic chemotherapies. Epigenetic regulators of the histone deacetylases (HDACs) family, which comprise four classes (I–IV),...

  15. Feeding, social behaviour and temperature preferences in Agama ...

    African Journals Online (AJOL)

    Agama atra is mainly insectivorous, ants being the main food of juveniles, and larger insects that of adults. The lizards are territorial and hierarchical and perform elaborate aggressive and courtship displays on prominent rocks. In the field, routine activities commence at an air temperature of about 19°C and reach a peak at ...

  16. Growth increments of the recent brachiopod Magellania venosa mechanically marked in Paso Comau and Comau Fjord, Chile, 2011/2012, supplement to: Baumgarten, Sebastian; Laudien, Jürgen; Jantzen, Carin; Häussermann, Verena; Försterra, Günter (2013): Population structure, growth and production of a recent brachiopod from the Chilean fjord region. Marine Ecology, 35(4), 401-413

    KAUST Repository

    Baumgarten, Sebastian; Laudien, Jü rgen; Jantzen, Carin; Hä ussermann, Verena; Fö rsterra, Gü nter

    2015-01-01

    and in the range of that for Mytilus chilensis (4.8-5.27), but lower than that of A. atra (5.74). The maximal individual production (PInd) is 0.29 g AFDM/ind/year at 42 mm shell length and annual production ranges from 1.28 to 89.25 g AFDM/year/m**2 (1

  17. Allergen-Induced Dermatitis Causes Alterations in Cutaneous Retinoid-Mediated Signaling in Mice

    Science.gov (United States)

    Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

    2013-01-01

    Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases. PMID:23977003

  18. to view fulltext PDF

    Indian Academy of Sciences (India)

    Unknown

    all died either in fetal life or shortly after birth, with a variety of ... ATRA-induced genes, the dominant negative effect of. PML-RARα on PML .... and our own work, a picture of well-coordinated gene expression ... The restoration of the balance.

  19. Anticancer Activity from Active Fraction of Sea Cucumber

    Directory of Open Access Journals (Sweden)

    Nurul Mutia Putram

    2017-05-01

    Full Text Available Sea Cucumber Holothuria atra is one of marine organisms has been used as a new source of novel bioactive compounds. Many of them have been used as the lead compounds in discovery of new anticancer drugs. The objective of this study was to determine the active fractions of sea cucumber (H. atra which have anticancer activity. H. atra was macerated using ethanol and the extract was freezedried using a freeze dryer. The crude extract was partitioned using n-hexane, ethyl acetate, and methanol-water (3:1:1:1. Cytotoxicity test was performed using HeLa (cervic cancer cell line and MCF-7 (breast cancer cell line based on the MTT assay. The crude extract of H. atra showed the best cytotoxic activity against HeLa cells (IC50 = 12.48 µg/mL and MCF-7 cells (IC50 = 17.90 µg/mL. The toxicity tests showed the IC50 value of the n-hexane fraction, ethyl acetate fraction, and methanol-water fraction against HeLa cells HeLa (IC50 = 76.45 µg/mL; 77.95 µg/mL;  14.27 µg/mL and MCF-7 cells (IC50 = 58.50 µg/mL; 59.59 µg/mL; 14.33 µg/mL.

  20. Functional responses of human hunters to their prey - why harvest statistics may not always reflect changes in prey population abundance

    DEFF Research Database (Denmark)

    Kahlert, Johnny Abildgaard; Fox, Anthony David; Heldbjerg, Henning

    pigeon Columba palumbus, coot Fulica atra, grey partridge Perdix perdix, roe deer Capreolus capreolus and brown hare Lepus europaeus in Denmark. If we consider hunting a form of predator-prey interaction, the annual kill can be viewed as a predator functional response to prey population size. Convergence...

  1. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.

    2018-01-01

    the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell

  2. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    Orfali, Nina; McKenna, Sharon L.; Cahill, Mary R.; Gudas, Lorraine J.; Mongan, Nigel P.

    2014-01-01

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects

  3. A Study on the Factors Influencing the Growth and Survival of ...

    African Journals Online (AJOL)

    Nafiisah

    salinity and temperature and biological factors such as stocking density and feed type on the .... vary, as well as ingested sand in the gut and depend on stress condition. All the ..... As compared to H. atra, it has not evolved such mechanism to.

  4. Lutzomyia gasparviannai Martins, Godoy & Silva, 1962, probable vector of Leishmania mexicana ssp. in Viana municipality, Espírito Santo State, Brazil

    OpenAIRE

    Falqueto,Aloísio; Grimaldi Júnior,Gabriel; Sessa,Paulo Augusto; Varejão,José Benedito Malta; Deane,Leonidas M.

    1985-01-01

    Dos flebótomos atraídos pelo Proechimys iheringi numa área onde esse roedor foi achado naturalmente infectado por Leishmania mexicana ssp., 98,1% foram Lutzomyia gasparviannai, o que sugere que essa espécie não antropofílica seja o transmissor entre os roedores mas não habitualmente ao homem.

  5. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Directory of Open Access Journals (Sweden)

    Yifei Zhong

    Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  6. The common coot as sentinel species for the presence of West Nile and Usutu flaviviruses in Central Europe

    Czech Academy of Sciences Publication Activity Database

    Straková, Petra; Šikutová, Silvie; Jedličková, Petra; Sitko, J.; Rudolf, Ivo; Hubálek, Zdeněk

    2015-01-01

    Roč. 102, October (2015), s. 159-161 ISSN 0034-5288 EU Projects: European Commission(XE) 261504 Institutional support: RVO:68081766 Keywords : West Nile virus * Usutu virus * Common coot * Fulica atra * Surveillance * Mosquito -borne viruses * Culex spp. Subject RIV: EG - Zoology Impact factor: 1.504, year: 2015

  7. Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

    Science.gov (United States)

    Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

    2016-11-04

    In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Piao; Yang Shi; Pu-Jun Gao

    2003-01-01

    AIM: To study the inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell line SMMC-7721and to explore the mechanism of its effect.METHODS: SMMC-7721 cells were divided into two groups, one treated with all-trans retinoic acid (ATRA) for 5 days and the other as a control group. Light microscope and electron microscope were used to observe the morphological changes. Telomerase activity was analyzed with silver-stained telomere repeated assay protocal (TRAP). Expression of Caspase-3 was demonstrated with western blot.RESULTS: ATRA-treated cells showed differentiation features including small and pyknotic nuclei, densely stained chromatin and fewer microvilli. Besides, ATRA could inhibit the activity of telomerase, promote the expression of Caspase-3 and its activation.CONCLUSION: Telomerase activity and Caspase-3expression are changed in human hepatocellular carcinoma cell line SMMC-7721 treated with all-trans retinioc acid.The inhibition of telomerase activity and the activation of Caspase-3 may be the key steps through which ATRA inhibits the proliferation of SMMC-7721 cell line.

  9. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char-

  10. Pathogenesis and treatment of leukemia: an Asian perspective.

    Science.gov (United States)

    Kwong, Yok-Lam

    2012-03-01

    Leukemias occur worldwide, but there are important geographic differences in incidences. Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK-cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome.

  11. All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells

    International Nuclear Information System (INIS)

    Ohno, Marumi; Ikenaka, Yoshinori; Ishizuka, Mayumi

    2012-01-01

    Highlights: ► AHR and ARNT transcriptionally regulate genes related to metabolisms such as CYP1A1. ► We investigated the effect of retinoic acid (RA) on the function of AHR/ARNT. ► RA inhibited the recruitment of ARNT, not AHR, to the regulatory region of CYP1A1. ► It resulted in a reduction of constitutive expression of CYP1A1 to less than half. -- Abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RARα. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1–100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.

  12. Frequent antibody production against RARalpha in both APL mice and patients.

    Science.gov (United States)

    Robin, Marie; Andreu-Gallien, Juliette; Schlageter, Marie-Helene; Bengoufa, Djaouida; Guillemot, Isabelle; Pokorna, Katerina; Robert, Carine; Larghero, Jerome; Rousselot, Philippe; Raffoux, Emmanuel; Dombret, Herve; Fenaux, Pierre; Pla, Marika; Charron, Dominique; Padua, Rose-Ann; Chomienne, Christine

    2006-09-15

    In an acute promyelocytic leukemia (APL)-transplantable mouse model, we previously reported the presence of antibodies recognizing PML-RARalpha and RARalpha in the sera of ATRA-treated mice. To evaluate this immune response, we determined the prevalence of anti-RARalpha antibodies in a cohort of 48 APL mice, treated by ATRA (n = 24) or by placebo pellets (n = 24), and in a preliminary subset of 9 patients with APL using a specific enzyme-linked immunosorbent assay (ELISA). In APL mice, significantly higher antibody levels were observed at the latest time points (day 48 to 58 levels superior to day 15 to 18 or day 28 to 38 levels). Antibody levels were higher in ATRA-treated mice than in placebo-treated mice and were also predictive of better survival. In the patients with APL, anti-RARalpha antibodies were detected at diagnosis and after maintenance therapy, reminiscent of the ATRA-treated APL mice. Antinuclear or antineutrophil cytoplasmic autoantibodies were also detected. These data reveal for the first time that in patients with APL an immune response may be detected at diagnosis and enhanced after maintenance therapy.

  13. BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation

    Directory of Open Access Journals (Sweden)

    Belinda J Goldie

    2014-10-01

    Full Text Available The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialised features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterise the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas and colleagues (2010 using integrative whole-genome gene and microRNA (miRNA expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modelled.

  14. BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation.

    Science.gov (United States)

    Goldie, Belinda J; Barnett, Michelle M; Cairns, Murray J

    2014-01-01

    The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialized features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterize the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas et al. (2000) using integrative whole-genome gene and microRNA (miRNA) expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modeled.

  15. 78 FR 7387 - Continuation of Farm Service Agency 2008 Farm Bill Programs

    Science.gov (United States)

    2013-02-01

    ..., if effective prices are greater than specified target prices during the 2013 marketing year, there... the USDA Target Center at (202) 720-2600 (voice and TDD). SUPPLEMENTARY INFORMATION: ATRA (Pub. L. 112... Program (DPPSP), Dairy Indemnity Payment Program (DIPP), Marketing Assistance Loans (MAL), Loan Deficiency...

  16. Studies of antifungal activity of forsskalea tenacissima

    International Nuclear Information System (INIS)

    Qaisar, M.; Ahmad, V.U.; Nisar, M.; Gilani, S.N.; Pervez, S.

    2011-01-01

    Antifungal activity of different extracts from Forsskalea tenacissima prepared by solvent-solvent extraction and vacuum liquid chromatography (VLC) was determined. Extracts were found to be active against Candida albicans, Trichophyton mentagrophyte, Allescheria boydii, Microsporum canis, Aspergillus niger, Drechslera rostrata, Nigrospora oryzae, Stachybotrys atra, Curvularia lunata, Trichophyton semii and Trichophyton schoenleinii. (author)

  17. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague–Dawley rats

    International Nuclear Information System (INIS)

    Chatterjee, A.; Chatterji, U.

    2011-01-01

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin–eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ERα), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ERα, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: ► Arsenic disrupts the uterine histology and

  18. High-dose dexamethasone or all-trans-retinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia.

    Science.gov (United States)

    Feng, Q; Xu, M; Yu, Y Y; Hou, Y; Mi, X; Sun, Y X; Ma, S; Zuo, X Y; Shao, L L; Hou, M; Zhang, X H; Peng, J

    2017-09-01

    Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients. Background Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and have diverse immunologic functions. Objectives To investigate the M1/M2 imbalance in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans-retinoic acid (ATRA) could restore this imbalance. Methods The numbers of M1 and M2 macrophages in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence. Monocyte-derived macrophages were cultured and induced with cytokines and drugs. The expression of M1 and M2 markers and functions of M1 and M2 macrophages before and after modulation by HD-DXM or ATRA were evaluated with flow cytometry and ELISA. Results There was preferred M1 polarization in ITP spleens as compared with healthy controls. Monocyte-derived macrophages from ITP patients had increased expression of M1 markers and impaired immunosuppressive functions. Either HD-DXM or ATRA corrected this imbalance by decreasing the expression of M1 markers and increasing the expression of M2 markers. Moreover, HD-DXM-modulated or ATRA-modulated macrophages suppressed both CD4 + and CD8 + T-cell proliferation and expanded CD4 + CD49 + LAG3 + type 1 T-regulatory cells. HD-DXM or ATRA modulated macrophages to shift the T-cell cytokine profile towards Th2. Treating patients with HD-DXM or ATRA

  19. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  20. Natural and synthetic retinoids afford therapeutic effects on intracerebral hemorrhage in mice.

    Science.gov (United States)

    Matsushita, Hideaki; Hijioka, Masanori; Hisatsune, Akinori; Isohama, Yoichiro; Shudo, Koichi; Katsuki, Hiroshi

    2012-05-15

    We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we further addressed the effects of retinoids as potential therapeutic drugs, using a collagenase-induced model of intracerebral hemorrhage. Daily oral administration of all-trans retinoic acid (ATRA; 5 and 15 mg/kg), a naturally occurring NR1B agonist, from 1 day before collagenase injection significantly inhibited loss of neurons within the hematoma. ATRA in the same treatment regimen also decreased the number of activated microglia/macrophages around the hematoma but did not affect the hematoma volume. ATRA (15 mg/kg) as well as Am80 (5mg/kg) rescued neurons in the central region of hematoma, even when drug administration was started from 6h after induction of intracerebral hemorrhage. However, in this post-treatment regimen, only Am80 significantly decreased the number of activated microglia/macrophages. With regard to neurological deficits, both ATRA (15 mg/kg) and Am80 (5mg/kg) given in the post-treatment regimen improved performance of mice in the beam-walking test and the modified limb-placing test. ATRA and Am80 also significantly attenuated damage of axon tracts as revealed by amyloid precursor protein immunohistochemistry. These results underscore potential therapeutic values of NR1B agonists for intracerebral hemorrhage. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Development of a global aerosol model using a two-dimensional sectional method: 1. Model design

    Science.gov (United States)

    Matsui, H.

    2017-08-01

    This study develops an aerosol module, the Aerosol Two-dimensional bin module for foRmation and Aging Simulation version 2 (ATRAS2), and implements the module into a global climate model, Community Atmosphere Model. The ATRAS2 module uses a two-dimensional (2-D) sectional representation with 12 size bins for particles from 1 nm to 10 μm in dry diameter and 8 black carbon (BC) mixing state bins. The module can explicitly calculate the enhancement of absorption and cloud condensation nuclei activity of BC-containing particles by aging processes. The ATRAS2 module is an extension of a 2-D sectional aerosol module ATRAS used in our previous studies within a framework of a regional three-dimensional model. Compared with ATRAS, the computational cost of the aerosol module is reduced by more than a factor of 10 by simplifying the treatment of aerosol processes and 2-D sectional representation, while maintaining good accuracy of aerosol parameters in the simulations. Aerosol processes are simplified for condensation of sulfate, ammonium, and nitrate, organic aerosol formation, coagulation, and new particle formation processes, and box model simulations show that these simplifications do not substantially change the predicted aerosol number and mass concentrations and their mixing states. The 2-D sectional representation is simplified (the number of advected species is reduced) primarily by the treatment of chemical compositions using two interactive bin representations. The simplifications do not change the accuracy of global aerosol simulations. In part 2, comparisons with measurements and the results focused on aerosol processes such as BC aging processes are shown.

  2. Tamibarotene as maintenance therapy for acute promyelocytic leukemia: results from a randomized controlled trial.

    Science.gov (United States)

    Shinagawa, Katsuji; Yanada, Masamitsu; Sakura, Toru; Ueda, Yasunori; Sawa, Masashi; Miyatake, Junichi; Dobashi, Nobuaki; Kojima, Minoru; Hatta, Yoshihiro; Emi, Nobuhiko; Tamaki, Shigehisa; Gomyo, Hiroshi; Yamazaki, Etsuko; Fujimaki, Katsumichi; Asou, Norio; Matsuo, Keitaro; Ohtake, Shigeki; Miyazaki, Yasushi; Ohnishi, Kazunori; Kobayashi, Yukio; Naoe, Tomoki

    2014-11-20

    The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL. Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study. © 2014 by American Society of Clinical Oncology.

  3. Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-03-26

    Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  4. Effect of all-trans retinoic acid combined with trichostatin A on the nude mice bearing human follicular thyroid carcinoma

    International Nuclear Information System (INIS)

    Yu Libo; Yuan Gengbiao

    2011-01-01

    Objective: To study the changes of iodine uptake of the follicular thyroid carcinoma cell line (FTC-133) and nude mice bearing human follicular thyroid carcinoma after the induction with all-trans retinoic acid (ATRA), trichostatin A (TSA) or ATRA combined with TSA. Methods: After the induction with ATRA, TSA, or ATRA combined with TSA in different concentrations for 96 h, the iodine uptake of FTC-133 cells was observed. The concentrations for different groups were as follows: ATRA 1.0 ×10 -6 mol/L(A low group), ATRA 1.0 × 10 -4 mol/L (A high group), TSA 1.65 ×10 -7 mol/L (T group), A low + T group, A high + T group and ethanol (control group). Cell quantities and morphology were observed by HE staining. FTC-133 cells were subcutaneously injected into nude mice. Twelve nude mice were randomly divided into 4 groups after tumor formation: ATRA group (2 mg/kg, intragastric administration), TSA group (10 mg/kg, intraperitoneal injection), combined therapy group (ATRA + TSA, the same doses as above) and saline control group (10 ml/kg, intragastric and intraperitoneal administration, respectively). Drugs were administered to the tumor-bearing mice according to the mouse body mass daily. At the 22nd day, the tumor-bearing mice were injected with 37 MBq 131 I intraperitoneally. The biodistribution of 131 I and gamma imaging were performed at 4, 6, 12 and 24 h after the injection respectively. Histopathological examinations of the tumor samples were taken after imaging completion. The results were analyzed by analysis of variance (ANOVA) with SPSS 13.0. Results: The cellular iodine uptake were (23 885 ± 616.0) and (13 849 ±728.2) counts · min -1 · 10 -6 cells in the A low + T group and A high + T group respectively, and the data were (985 ± 84.2) - (17 600 ± 782.7) counts · min -1 · 10 -6 in the other groups (F=600.879, P<0.001). The % ID/g of tumor at 6 h was 6.17 ±0.46 in the combined group and it increased to 9.34 ±0.61 at 12 h and 11.19 ± 0.98 at 24 h. The

  5. Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats.

    Science.gov (United States)

    Kumar, Manoj; Sharma, Gaurav; Singla, Dinesh; Singh, Sukhjeet; Sahwney, Sudhir; Chauhan, Anurag S; Singh, Gagandeep; Kaur, Indu Pal

    2014-03-01

    A sensitive ultra-performance liquid chromatography (UPLC) method was developed for simultaneous estimation of all-trans retinoic acid (ATRA) and cholecalciferol (vitamin D3) in rat plasma. The method was validated over the linear range of 1.0-5000ng/ml (r(2)=0.999) for both vitamins with a limit of detection of 0.5ng/ml. Chromatographic separation was achieved using liquid-liquid extraction (LLE) on an Acquity BEH RP 18 column (2.1mm×50mm, I.D. 1.7μm), with mobile phase comprising of acetonitrile:methanol:water (90:8:2, v/v/v), at a flow rate of 0.20ml/min and a total run time of 5min. Intra and inter-day variability (RSD) was ≤3.1%, and the accuracy varied between 95.4-99.9% and 95.3-101.1% respectively, for ATRA and 98.5-100.8% and 99.3-101.7%, respectively for vitamin D3. High recovery of ≥96.0% for ATRA and ≥87.80% for vitamin D3 was achieved. ATRA and vitamin D3 were stable in plasma under different storage and processing conditions. The method was applied to estimate the total drug content and entrapment efficiency of ATRA and vitamin D3 loaded solid lipid nanoparticles (SLNs). Concentration of these two agents was determined in rat plasma after simultaneous subcutaneous administration in free form or when loaded into SLNs thus establishing pharmacokinetic application of the developed procedure. Results indicated an improvement in AUC0-∞ by 5.4 times and 29.4 times for ATRA and vitamin D3, respectively, upon their incorporation into SLNs. Simultaneous administration of these two vitamins and their improved and prolonged bioavailability has scope for their use in treatment and control of tuberculosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. [Acute renal failure in the transretinoic syndrome].

    Science.gov (United States)

    Sastre, A; Gago, E; Baños, M; Gómez, E

    2007-01-01

    The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment

  7. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  8. Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line.

    Science.gov (United States)

    Shiohira, Hideo; Kitaoka, Akira; Enjoji, Munechika; Uno, Tsukasa; Nakashima, Manabu

    2012-01-01

    Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.

  9. Acute Promyelocytic Leukemia Presenting as Focal Neurologic Findings and Deteriorating Mental Status.

    Science.gov (United States)

    Dolan, Matthew; Ngaruiya, Christine

    2017-01-01

    Acute promyelocytic leukemia (APL) is a rare but particularly malignant form of acute leukemia that is characterized by a rapid progression to fatal hemorrhage. Survival rates of patients with APL have increased with the introduction of all-trans retinoic acid (ATRA), but early deaths caused by hemorrhage still persist. A man with undiagnosed APL presenting with focal neurologic findings and deteriorating altered mental status caused by an intracranial hemorrhage is discussed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to consider APL when diagnosing etiologies for intracranial hemorrhage. In addition to standard care, early administration of ATRA is recommended upon clinical suspicion of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Gluteoplastia de aumento: experiência do Serviço de Cirurgia Plástica Dr. Ewaldo Bolivar de Souza Pinto

    OpenAIRE

    Azevedo, Daniel Melo de; Gonçalves Junior, Paulo; Pereira, Juliano; Amoedo, Tiago Boulhosa; Kuroyanagi, Fábio Massaru; Cotes, Emmanuel Francis Mallol; Pinto, Ewaldo Bolivar de Souza; Saldanha, Osvaldo Ribeiro

    2012-01-01

    INTRODUÇÃO: As nádegas são constituídas por músculos responsáveis pelos movimentos das pernas, assumindo o músculo glúteo máximo o volume principal. Possuem uma função secundária, de cunho sexual, como zona erógena, símbolo de fertilidade, cujo poder de atração é um forte apelo usado pela publicidade de artigos de consumo masculino. Mulheres com maior volume de nádegas despertam maior atração e desejo sexual, o que tem levado ao aumento da procura pela gluteoplastia de aumento com utilização ...

  11. Differentiation of stem cells upon deprivation of exogenous FGF2

    DEFF Research Database (Denmark)

    Kjartansdóttir, Kristín Rós; Gabrielsen, Anette; Reda, Ahmed

    2012-01-01

    Establishing a model for in vitro differentiation of human embryonic stem cells (hESCs) towards the germ cell lineage could be used to identify molecular mechanisms behind germ cell differentiation that may help in understanding human infertility. Here, we evaluate whether a lack of exogenous...... fibroblast growth factor 2 (FGF2) is supporting spontaneous differentiation of hESCs cultured on human foreskin fibroblast (hFF) monolayers towards germ cell lineage. Additionally to depriving the hESCs of exogenous FGF2, cells were stimulated with all-trans retinoic acid (ATRA). To get a more comprehensive...... impression on effects of removal of FGF2 and stimulation with ATRA, we combined the results of three cell lines for each experimental setting. When combining gene expression profiles of three cell lines for 96 genes, only 6 genes showed a significant up-regulation in all cell lines, when no FGF2 was added...

  12. Effect of all-trans retinoic acid treatment on prohibitin and renin-angiotensin-aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury.

    Science.gov (United States)

    Zhou, Tian-Biao; Ou, Chao; Rong, Liang; Drummen, Gregor P C

    2014-09-01

    All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p system under hypoxia/reoxygenation conditions. © The Author(s) 2014.

  13. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  14. Retinoic acid induces signal transducer and activator of transcription (STAT) 1, STAT2, and p48 expression in myeloid leukemia cells and enhances their responsiveness to interferons.

    Science.gov (United States)

    Matikainen, S; Ronni, T; Lehtonen, A; Sareneva, T; Melén, K; Nordling, S; Levy, D E; Julkunen, I

    1997-06-01

    IFNs are antiproliferative cytokines that have growth-inhibitory effects on various normal and malignant cells. Therefore, they have been used in the treatment of certain forms of cancer, such as chronic myelogenous leukemia and hairy cell leukemia. However, there is little evidence that IFNs would be effective in the treatment of acute myelogenous leukemia, and molecular mechanisms underlying IFN unresponsiveness have not been clarified. Here we have studied the activation and induction of IFN-specific transcription factors signal transducer and activator of transcription (STAT) 1, STAT2, and p48 in all-trans-retinoic acid (ATRA)-differentiated myeloid leukemia cells using promyelocytic NB4, myeloblastic HL-60, and monoblastic U937 cells as model systems. These cells respond to ATRA by growth inhibition and differentiation. We show that in undifferentiated NB4 cells, 2',5'-oligoadenylate synthetase and MxB gene expression is not activated by IFN-alpha, possibly due to a relative lack of signaling molecules, especially p48 protein. However, during ATRA-induced differentiation, steady-state STAT1, STAT2, and especially p48 mRNA and corresponding protein levels were elevated both in NB4 and U937 cells, apparently correlating to an enhanced responsiveness of these cells to IFNs. ATRA treatment of NB4 cells sensitized them to IFN action as seen by increased IFN-gamma activation site DNA-binding activity or by efficient formation of IFN-alpha-specific ISGF3 complex and subsequent oligoadenylate synthetase and MxB gene expression. Lack of p48 expression could be one of the mechanisms of promyelocytic leukemia cell escape from growth-inhibitory effects of IFN-alpha.

  15. Alterations of Intercellular Junctions in Peritoneal Mesothelial Cells from Patients Undergoing Dialysis: Effect of Retinoic Acid

    Science.gov (United States)

    Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L.

    2015-01-01

    ♦ Background: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. ♦ Methods: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. ♦ Results: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. ♦ Conclusions: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. PMID:24584604

  16. Propuesta de un proceso de selección del talento humano por competencias para petroindustrial.

    OpenAIRE

    Hormaza Valencia, Sandra Bethzabe

    2007-01-01

    La Selección por Competencias, es el procedimiento por el cual se atrae, contrata e incorpora talento humano que se ajuste lo más rigurosamente al perfil de competencias requerido para determinado cargo. Este es un paso de suma importancia ya que deben encontrarse candidatos adecuados que reúnan características afines al puesto. Frecuentemente la contratación y retención de candidatos resulta insatisfactoria y sumamente costosa para las empresas.

  17. Inorganic Carbon Turnover caused by Digestion of Carbonate Sands and Metabolic Activity of Holothurians

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Kenneth; Silverman, Jacob; Kravitz, Benjamin S.; Rivlin, Tanya; Schneider-Mor, Aya; Barbosa, Sergio; Byrne, Maria; Caldeira, Ken

    2013-11-20

    Recent measurements have shown that holothurians (sea cucumbers) play an important role in the cycling of CaCO3 in tropical coral reef systems through ingestion and processing of carbonate sediment. In this study inorganic additional aspects of carbon turnover were determined in laboratory incubations of Holothuria atra, H. leucospilota and Stichopus herrmanni from One Tree Reef, Great Barrier Reef. The pH values of the gut lumen ranged from 6.1 to 6.7 in animals with empty digestive tracts as opposed to 7.0 to 7.6 when digestive tracts were filled with sediment. Empty gut volume estimates for H. atra and S. herrmanni were 36 ± 4 mL and 151 ± 14 mL, respectively. Based on these measurements it is estimated that these species process 19 ± 2kg and 80 ± 7kg CaCO3 sand yr-1 per individual, respectively. The annual dissolution rates of H. atra and S. herrmanni of 6.5±1.9g and 9.6±1.4g, respectively, suggest that 0.05±0.02% and 0.1±0.02% of the CaCO3 processed through their gut annually is dissolved. During the incubations the CaCO3 dissolution was 0.07±0.01%, 0.04±0.01% and 0.21±0.05% of the fecal casts for H. atra, H. leucospilota and S. herrmanni, respectively. The CaCO3 saturation state for both aragonite and calcite minerals during laboratory incubations decreased markedly due to a greater increase in dissolved inorganic carbon (DIC) relative to total alkalinity (AT) as a result of respiration by the animals. Our results support the hypothesis that deposit feeders such as sea cucumbers play an important ecological role in the coral reef CaCO3 cycle.

  18. Crotoxin: Structural Studies, Mechanism of Action and Cloning of Its Gene

    Science.gov (United States)

    1987-03-01

    with these same antisera, while cross-reactivity with B3-bungarotoxin was very slight. Neurophysin and phospholipase A2 from N. n. atra and honey bee ...toxin from Cror alus viridis concolor, and monoclonal antibodies to czotoxin. We have used these to search for cross-reactive, homologoiis proteins in...concolor, and monoclonal antibodies to crotoxin. We have used these to search for cross-reactive, homclogous proteins in other venoms and examine their

  19. Inorganic carbon turnover caused by digestion of carbonate sands and metabolic activity of holothurians

    Science.gov (United States)

    Schneider, Kenneth; Silverman, Jacob; Kravitz, Ben; Rivlin, Tanya; Schneider-Mor, Aya; Barbosa, Sergio; Byrne, Maria; Caldeira, Ken

    2013-11-01

    Recent measurements have shown that holothurians (sea cucumbers) may play an important role in the cycling of CaCO3 in tropical coral reef systems through ingestion and processing of carbonate sediment. In this report, we present estimates of inorganic carbon turnover rates determined from laboratory incubations of Holothuria atra, Holothuria leucospilota and Stichopus herrmanni. The pH values of the gut lumen ranged from 7.0 to 7.6 when digestive tracts were filled with sediment compared with 6.1-6.7 in animals with empty digestive tracts. Empty gut volume estimates for H. atra and S. herrmanni were 36 ± 4 mL and 151 ± 14 mL, respectively. Based on these measurements and the density and porosity of carbonate sediments of coral reefs, it is estimated that these species process 19 ± 2 kg and 80 ± 7 kg CaCO3 sand yr-1 per individual, respectively. The annual CaCO3 dissolution rates per H. atra and S. herrmanni individual are estimated to be 6.5 ± 1.9 g and 9.6 ± 1.4 g, respectively, suggesting that 0.05 ± 0.02% and 0.1 ± 0.02% of the CaCO3 processed through their gut annually is dissolved. During incubations the CaCO3 dissolution of the fecal casts was 0.07 ± 0.01%, 0.04 ± 0.01% and 0.21 ± 0.05% for H. atra, H. leucospilota and S. herrmanni, respectively. The CaCO3 saturation state in the incubation seawater decreased markedly due to a greater increase in dissolved inorganic carbon (DIC) relative to total alkalinity (AT) as a result of respiration by the animals. Our results support the hypothesis that deposit feeders such as sea cucumbers play an important ecological role in the coral reef CaCO3 cycle.

  20. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

    Directory of Open Access Journals (Sweden)

    B.C. de-Medeiros

    1998-12-01

    Full Text Available Thirty-seven patients with acute promyelocytic leukemia (APL were treated with all-trans retinoic acid (ATRA. Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR was achieved, defined as: a presence of less than 5% blasts in the bone marrow, with b white blood cells >103/mm3, c platelets >105/mm3 and d hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7% patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days, was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS were observed in 7 (19%, 6 (16% and 4 (11% patients, respectively. Thirteen (35% patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3 and six of these presented with new signs of coagulopathy after chemotherapy. Four (11% patients died secondarily to intracerebral hemorrhage (IH and two (5.4% dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity. RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

  1. Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

    Directory of Open Access Journals (Sweden)

    Jing-Bo Peng

    2014-01-01

    Full Text Available A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA in human plasma. Acitretin was used as the internal standard (IS. After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE, ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE–methanol–acetic acid, 50:50:0.5, v/v and 60% phase B (water–methanol–acetic acid, 50:50:0.5, v/v with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45–217.00 ng/mL (r ≥ 0.999 with a lower limit of quantitation (LLOQ of 0.45 ng/mL. The intra- and inter-day precisions values were below 8% relative standard deviation and the accuracy was from 98.98% to 106.19% in terms of relative error. The validated method was successfully applied in a bioequivalence study of ATRA in Chinese healthy volunteers.

  2. Occurrence, diversity and community structure of culturable atrazine degraders in industrial and agricultural soils exposed to the herbicide in Shandong Province, P.R. China

    OpenAIRE

    Bazhanov, Dmitry P.; Li, Chengyun; Li, Hongmei; Li, Jishun; Zhang, Xinjian; Chen, Xiangfeng; Yang, Hetong

    2016-01-01

    Background Soil populations of bacteria rapidly degrading atrazine are critical to the environmental fate of the herbicide. An enrichment bias from the routine isolation procedure prevents studying the diversity of atrazine degraders. In the present work, we analyzed the occurrence, diversity and community structure of soil atrazine-degrading bacteria based on their direct isolation. Methods Atrazine-degrading bacteria were isolated by direct plating on a specially developed SM agar. The atra...

  3. Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes

    Directory of Open Access Journals (Sweden)

    Deep-Dixit Vishwa

    2006-11-01

    Full Text Available Abstract Background Vitamin A (VA deficiency induces a type 1 cytokine response and exogenously provided retinoids can induce a type 2 cytokine response both in vitro and in vivo. The precise mechanism(s involved in this phenotypic switch are inconsistent and have been poorly characterized in humans. In an effort to determine if retinoids are capable of inducing Th2 cytokine responses in human T cell cultures, we stimulated human PBMCs with immobilized anti-CD3 mAb in the presence or absence of all-trans retinoic acid (ATRA or 9-cis-RA. Results Stimulation of human PBMCs and purified T cells with ATRA and 9-cis-RA increased mRNA and protein levels of IL-4, IL-5, and IL-13 and decreased levels of IFN-γ, IL-2, IL-12p70 and TNF-α upon activation with anti-CD3 and/or anti-CD28 mAbs. These effects were dose-dependent and evident as early as 12 hr post stimulation. Real time RT-PCR analysis revealed a dampened expression of the Th1-associated gene, T-bet, and a time-dependent increase in the mRNA for the Th2-associated genes, GATA-3, c-MAF and STAT6, upon treatment with ATRA. Besides Th1 and Th2 cytokines, a number of additional proinflammatory and regulatory cytokines including several chemokines were also differentially regulated by ATRA treatment. Conclusion These data provide strong evidence for multiple inductive roles for retinoids in the development of human type-2 cytokine responses.

  4. Dicty_cDB: Contig-U15350-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available all GTP-binding protein mRNA, ... 90 1e-16 AB241248_1( AB241248 |pid:none) Symbiotic.... 87 1e-15 AB241247_1( AB241247 |pid:none) Symbiotic protist of Reticuliterme... 87 1e-15 ( P51159 ) RecName...rabidopsis thaliana mRNA for AtRa... 75 3e-12 AB241251_1( AB241251 |pid:none) Symbiotic protist of Reticulit

  5. Lutzomyia gasparviannai Martins, Godoy & Silva, 1962, probable vector of Leishmania mexicana ssp. in Viana municipality, Espírito Santo State, Brazil

    Directory of Open Access Journals (Sweden)

    Aloísio Falqueto

    1985-12-01

    Full Text Available Dos flebótomos atraídos pelo Proechimys iheringi numa área onde esse roedor foi achado naturalmente infectado por Leishmania mexicana ssp., 98,1% foram Lutzomyia gasparviannai, o que sugere que essa espécie não antropofílica seja o transmissor entre os roedores mas não habitualmente ao homem.

  6. All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Marumi; Ikenaka, Yoshinori [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan); Ishizuka, Mayumi, E-mail: ishizum@vetmed.hokudai.ac.jp [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer AHR and ARNT transcriptionally regulate genes related to metabolisms such as CYP1A1. Black-Right-Pointing-Pointer We investigated the effect of retinoic acid (RA) on the function of AHR/ARNT. Black-Right-Pointing-Pointer RA inhibited the recruitment of ARNT, not AHR, to the regulatory region of CYP1A1. Black-Right-Pointing-Pointer It resulted in a reduction of constitutive expression of CYP1A1 to less than half. -- Abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RAR{alpha}. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1-100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.

  7. Comité Scientifique de la Revue des Sciences et de la Technologie ...

    African Journals Online (AJOL)

    MICROSIM

    berges ou dans l'eau libre, soit par basculement du corps, ou par immersion du bec ou de la tête de l'oiseau. Mots clés : Fulica atra - El-Kala .... de l'avant du corps dans l'eau et alimentation à pied dans les vasières et les berges. .... moyens matériels et humains nécessaires à la réalisation de ce travail sur le terrain.

  8. Lower concentrations of receptor for advanced glycation end products and epiregulin in amniotic fluid correlate to chemically induced cleft palate in mice.

    Science.gov (United States)

    Wang, Xinhuan; Zhu, Jingjing; Fang, Yanjun; Bian, Zhuan; Meng, Liuyan

    2017-04-01

    This study investigated the correlation between differentially expressed proteins in amniotic fluid (AF) and cleft palate induced by all-trans retinoic acid (atRA), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. Seven proteins were differentially expressed at embryonic day (E) 16.5 in atRA and control groups as revealed by label-based mouse antibody array. Enzyme-linked immunosorbent assay was further used to detect the expression levels of these proteins in AF from E13.5 to E16.5 in atRA, TCDD, and control groups. The cleft palate groups showed lower concentrations of receptor for advanced glycation end products (RAGE) and epiregulin at E16.5. RAGE immunostaining obviously decreased in palatal tissue sections obtained from E14.5 to E16.5 in the cleft palate groups as revealed by immunohistochemistry. These findings indicate that reduced levels of RAGE and epiregulin in AF are correlated to chemically induced cleft palate in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Sook-Kyoung Heo

    Full Text Available Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI, is approved for the second-line treatment of chronic myeloid leukemia (CML in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP-1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi-1 cells either in presence or absence of all trans-retinoic acid (ATRA. We found that radotinib promoted differentiation and induced CD11b expression in AML cells by downregulating LYN. However, CD11b expression induced by ATRA in HL60 cells was decreased by radotinib through upregulation of LYN. Furthermore, radotinib mainly induced apoptosis of CD11b+ cells in the total population of AML cells. Radotinib also increased apoptosis of CD11b+ HL60 cells when they were differentiated by ATRA/dasatinib treatment. We show that radotinib induced apoptosis via caspase-3 activation and the loss of mitochondrial membrane potential (ΔΨm in CD11b+ cells differentiated from AML cells. Our results suggest that radotinib may be used as a candidate drug in AML or a chemosensitizer for treatment of AML by other therapeutics.

  10. Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yue; Li, Ge; Wang, Ke; Xie, Ya-Ya; Zhou, Ren-Peng; Meng, Yao; Ding, Ran; Ge, Jin-Fang; Chen, Fei-Hu, E-mail: cfhchina@sohu.com

    2017-03-15

    As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ATPR on APL cells was accompanied with autophagy induction and PML-RARα degradation via activating Notch1 signaling pathway. Moreover, inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNA (siRNA) that targets essential autophagy gene ATG5 abrogated the ATPR-induced cell differentiation. Furthermore, when pretreated with DAPT, a γ-secretase inhibitor, the Notch1 signaling pathway was blocked in APL cells, followed by the reduction of ATPR-induced autophagy and differentiation. Taken together, these results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients. - Highlights: • ATPR induces autophagy in APL cell line NB4 cells. • Autophagy induction is essential for cell differentiation in NB4 cells. • Notch1 signaling is involved in ATPR-induced autophagy and differentiation in NB4 cells.

  11. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

    Directory of Open Access Journals (Sweden)

    Yoshihiro Akimoto

    2014-06-01

    Full Text Available Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488. However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

  12. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.

    Science.gov (United States)

    Takahashi, Hiroyuki; Watanabe, Tomoyuki; Kinoshita, Akitoshi; Yuza, Yuki; Moritake, Hiroshi; Terui, Kiminori; Iwamoto, Shotaro; Nakayama, Hideki; Shimada, Akira; Kudo, Kazuko; Taki, Tomohiko; Yabe, Miharu; Matsushita, Hiromichi; Yamashita, Yuka; Koike, Kazutoshi; Ogawa, Atsushi; Kosaka, Yoshiyuki; Tomizawa, Daisuke; Taga, Takashi; Saito, Akiko M; Horibe, Keizo; Nakahata, Tatsutoshi; Miyachi, Hayato; Tawa, Akio; Adachi, Souichi

    2016-08-01

    We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered. © 2016 John Wiley & Sons Ltd.

  13. RETINOID RECEPTORS IN BONE AND THEIR ROLE IN BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Petra eHenning

    2015-03-01

    Full Text Available Vitamin A (retinol is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA, which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RAR, RAR, RAR. RARs and closely related retinoid X receptors (RXR, RXR, RXR form heterodimers which bind to DNA and function as ligand activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver and processed to ATRA. ATRA’s effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

  14. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia.

    Science.gov (United States)

    Padua, Rose Ann; Larghero, Jerome; Robin, Marie; le Pogam, Carol; Schlageter, Marie-Helene; Muszlak, Sacha; Fric, Jan; West, Robert; Rousselot, Philippe; Phan, Thi Hai; Mudde, Liesbeth; Teisserenc, Helene; Carpentier, Antoine F; Kogan, Scott; Degos, Laurent; Pla, Marika; Bishop, J Michael; Stevenson, Freda; Charron, Dominique; Chomienne, Christine

    2003-11-01

    Despite improved molecular characterization of malignancies and development of targeted therapies, acute leukemia is not curable and few patients survive more than 10 years after diagnosis. Recently, combinations of different therapeutic strategies (based on mechanisms of apoptosis, differentiation and cytotoxicity) have significantly increased survival. To further improve outcome, we studied the potential efficacy of boosting the patient's immune response using specific immunotherapy. In an animal model of acute promyelocytic leukemia, we developed a DNA-based vaccine by fusing the human promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) oncogene to tetanus fragment C (FrC) sequences. We show for the first time that a DNA vaccine specifically targeted to an oncoprotein can have a pronounced effect on survival, both alone and when combined with all-trans retinoic acid (ATRA). The survival advantage is concomitant with time-dependent antibody production and an increase in interferon-gamma (IFN-gamma). We also show that ATRA therapy on its own triggers an immune response in this model. When DNA vaccination and conventional ATRA therapy are combined, they induce protective immune responses against leukemia progression in mice and may provide a new approach to improve clinical outcome in human leukemia.

  15. All trans retinoic acid abrogates spontaneous monocytic growth in juvenile chronic myelomonocytic leukaemia.

    Science.gov (United States)

    Cambier, N; Menot, M L; Schlageter, M H; Balitrand, N; Leblanc, T; Bordigoni, P; Rohrlich, P; Lamagnère, J P; Donadieu, J; Herbelin, C; Puissant, C; Gourand, F; Baruchel, A; Chomienne, C

    2001-01-01

    All trans retinoic acid, the active metabolite of vitamin A, exerts profound effects on cell differentiation. On normal myeloid progenitors, retinoids switch the differentiation program of granulo-macrophagic progenitors towards the granulocytic lineage and consequently reduce CFU-M colony formation. Bone marrow and peripheral blood mononuclear cells from children with Juvenile Chronic Myelomonocytic Leukaemia show typical spontaneous monocytic growth. We questioned whether in this disease, retinoids could switch myelomonocytic growth and inhibit the abnormal CFU-M colony proliferation. Ten JCML samples were studied in the presence of ATRA in methyl cellulose colony assay, before (CFU-C) or after (pre-CFU) liquid suspension culture. In vitro characteristics of JCML such as spontaneous monocytic growth in the absence of growth factor was noted in all patients. In the presence of leucocyte-conditioned medium, nine samples showed only CFU-M growth and one sample CFU-GM growth. Incubation with ATRA inhibited CFU-M colony formation in nine cases. Enhancement of granulocytic differentiation (CFU-G) was noted in nine cases. ATRA also inhibited CD34+ JCML monocytic growth and GM-CSF hypersensitivity. These data suggest that, in JCML progenitors, retinoid pathways are functional and inhibition of immature monocytic progenitors cells may be achieved with retinoids, without impeding granulocytic cell growth.

  16. ORNITHOLOGICAL OBSERVATIONS ON THE VÂLCELE BASIN DURING FEBRUARY 2013 – JANUARY 2014

    Directory of Open Access Journals (Sweden)

    Adrian Mestecăneanu

    2014-06-01

    Full Text Available In this paper are showed the results of the researches performed during February 2013 – January 2014 on the avifauna from the Vâlcele Basin. The 65 observed species belong to 13 orders, Passeriformes being the richest (33 species. Anseriformes and Charadriiformes (each with 7 species were the best represented among the wetland birds. 5 species (Podiceps cristatus, Phalacrocorax carbo, Anas platyrhynchos, Fulica atra, and Larus argentatus cachinnans/michahellis were euconstant and 2 species (Anas platyrhynchos and Fulica atra were eudominant. Anas platyrhynchos counted most individuals in a month in December; in July were no individuals. Fulica atra had the most number in September; it was absent in May. For the Vâlcele Basin avicoenose, Anseriformes and Gruiformes were the overdominat orders and, inside the Anseriformes order, Anas platyrhynchos was overdominant species. 7 species (Egretta alba, Nycticorax nycticorax, Ciconia ciconia, Chlidonias hybridus, Alcedo atthis, Picus canus, and Lanius collurio are in the Annex I of the Birds Directive.

  17. TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA WITH HIGH WHITE CELL BLOOD COUNTS.

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    Charicleia Kelaidi

    2011-09-01

    Full Text Available Acute promyelocytic leukemia (APL with WBC above 10 G/L has long been considered, even in the all-trans retinoic acid (ATRA era, to carry a relatively poor prognosis (compared to  APL with WBC below 10 G/L, due to increased early mortality and relapse. However, early deaths can to a large extent be avoided if specific measures are rapidly instigated, including prompt referral to a specialized center, immediate onset of ATRA and chemotherapy, treatment of coagulopathy with adequate platelet transfusional support, and prevention and management of differentiation syndrome. Strategies to reduce relapse rate include chemotherapy reinforcement with cytarabine and/or arsenic trioxide during consolidation, prolonged maintenance treatment, especially with ATRA and low dose chemotherapy, and possibly, although this is debated, intrathecal prophylaxis to prevent central nervous system relapse. By applying those measures, outcomes of patients with high risk APL have considerably improved, and have become in many studies almost similar to those of standard risk APL patients.

  18. Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ai-Guo, E-mail: wangaiguotl@hotmail.com; Song, Ya-Nan; Chen, Jun; Li, Hui-Ling; Dong, Jian-Yi; Cui, Hai-Peng; Yao, Liang; Li, Xue-Feng; Gao, Wen-Ting; Qiu, Ze-Wen; Wang, Fu-Jin; Wang, Jing-Yu, E-mail: wangjingyus@163.com

    2014-09-26

    Highlights: • The activation of RAS/ERK is insufficient to inhibit RXRα function and deplete RA. • The retinoid metabolism-related genes are down-regulated by ras oncogene. • The atRA has no effect on preventing hepatic tumorigenesis or curing the developed hepatic nodules. - Abstract: Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week

  19. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    International Nuclear Information System (INIS)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-01-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H 4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H 4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H 4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H 4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60

  20. Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

    2016-09-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

  1. Hermit crab (Decapoda, Anomura attraction to dead gastropod baits in an infralittoral algae bank

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    Juarez C. B. Pezzuti

    2002-06-01

    Full Text Available Hermit crabs use gastropod shells as shelter and are adapted to follow chemical cues released from tissues of dead or injured gastropods as a way to find new and more adequate shells. The species composition, crab size, shell types adequacy and physical condition were compared between attracted individuals and crabs collected in previous samples. The previous sampling was carried out in five areas before each experiment. Then, five baits of crushed gastropods in nylon net bags were installed in these areas. Three samples were taken at 30min intervals, capturing all crabs within a circle of 60cm diameter. Attraction of hermit crabs was tested for four different gastropod baits to verify specificity of the chemical cues. Clibanarius antillensis, Pagurus brevidactylus and Paguristes tortugae were collected in the study area. Pagurus brevidactylus, the smallest species, turned out to be more attracted than the 2 other species. The results showed that attracted crabs utilized more gastropod shell types than that collected in previous samples, however shell utilization pattern did not differ between them. Attracted animals were slightly smaller (shield length than those collected in the previous samples but did not present significant differences in shell adequacy and condition. The four experimental baits attracted the crabs in similar ways not indicating a specific response from the crabs. The fact that attracted animals were smaller suggested that the attraction to dead gastropods might enable the acquisition of a new and larger shell and, consequently, chains of shell exchange between the attracted crabs.Ermitões utilizam conchas de gastrópodes para abrigo. Conchas novas e mais adequadas podem ser encontradas pelos ermitões pois estes são atraídos por substâncias químicas liberadas pelos tecidos de gastrópodes feridos ou mortos. A adequação, condição e tipo das conchas e a composição de espécies e o tamanho dos ermitões foram

  2. Effects of all-trans retinoic acid on tumor recurrence and metastasis Efecto del ácido trans-retinoico sobre la recidiva tumoral y el desarrollo metastásico

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    I. García-Alonso

    2005-04-01

    Full Text Available Objective: all-trans-retinoic acid (ATRA promotes cell differentiation. We have studied its effect on the local recurrence and metastatic spreading of an experimental rhabdomyosarcoma in rats. Design: syngenic rhabdomyosarcoma cells (S4MH were inoculated s.c. in male WAG/RijCrl rats. After 25 days tumors were excised and a 40% hepatectomy was performed for all animals. Ten days later the rats were sacrificed and a thorough necropsy was performed. The animals were randomly allocated to receive daily doses of ATRA (5 mg/kg, i.p. or its solvent (Clinoleic®/ethanol 90/10, starting three days before surgery until the end of the experiment. Results: ATRA reduced the incidence of local recurrence from 70 to 33% (p Objetivo: el ácido trans-retinoico (ATRA, "all-trans retinoic acid" es un agente inductor de la diferenciación celular. Se estudia su efecto sobre la recidiva local y la diseminación metastásica de los tumores sólidos. Diseño experimental: mediante inoculación subcutánea de células de rabdomiosarcoma (S4MH se ha inducido un tumor en ratas WAG/RijCrl. Tras 25 días, se practicó una tumorectomía y simultáneamente hepatectomía del 40%. Los animales se sacrificaron el día 35, y fueron sometidos a estudio necrópsico. La mitad de los animales fueron tratados con ATRA (5 mg/kg, i.p. desde el día 22 al 35, mientras que los controles recibieron el excipiente (Clinoleico®/etanol 90/10. Resultados: el tratamiento redujo la tasa de recidiva local del 70 al 33% (p < 0,05, aunque no afectó a su tamaño (1,8 vs. 2,0 cc. El volumen medio de las metástasis inguinales se redujo a la sexta parte (0,2 vs. 1,2 cc; p < 0,05, si bien su frecuencia aumentó con el ATRA (86 vs. 29%; p < 0,05. La extensión retroperitoneal del rabdomisoarcoma también se redujo (0,7 vs. 5,1 cc; p < 0,05, aunque no hubo variación en la incidencia (71 vs. 67%. La incidencia de afectación pulmonar (100% en controles se redujo hasta el 33% (p < 0,05, a la vez que el

  3. [Basic and clinical studies of the gene product-targeting therapy based on leukemogenesis--editorial].

    Science.gov (United States)

    Chen, Sai-Juan; Chen, Li-Juan; Zhou, Guang-Biao

    2005-02-01

    In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival

  4. Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

    Science.gov (United States)

    Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

    2016-02-01

    The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells.

  5. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

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    Anna Falanga

    2011-12-01

    Full Text Available Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  6. Moth sex pheromone receptors and deceitful parapheromones.

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    Pingxi Xu

    Full Text Available The insect's olfactory system is so selective that male moths, for example, can discriminate female-produced sex pheromones from compounds with minimal structural modifications. Yet, there is an exception for this "lock-and-key" tight selectivity. Formate analogs can be used as replacement for less chemically stable, long-chain aldehyde pheromones, because male moths respond physiologically and behaviorally to these parapheromones. However, it remained hitherto unknown how formate analogs interact with aldehyde-sensitive odorant receptors (ORs. Neuronal responses to semiochemicals were investigated with single sensillum recordings. Odorant receptors (ORs were cloned using degenerate primers, and tested with the Xenopus oocyte expression system. Quality, relative quantity, and purity of samples were evaluated by gas chromatography and gas chromatography-mass spectrometry. We identified olfactory receptor neurons (ORNs housed in trichoid sensilla on the antennae of male navel orangeworm that responded equally to the main constituent of the sex pheromone, (11Z,13Z-hexadecadienal (Z11Z13-16Ald, and its formate analog, (9Z,11Z-tetradecen-1-yl formate (Z9Z11-14OFor. We cloned an odorant receptor co-receptor (Orco and aldehyde-sensitive ORs from the navel orangeworm, one of which (AtraOR1 was expressed specifically in male antennae. AtraOR1•AtraOrco-expressing oocytes responded mainly to Z11Z13-16Ald, with moderate sensitivity to another component of the sex pheromone, (11Z,13Z-hexadecadien-1-ol. Surprisingly, this receptor was more sensitive to the related formate than to the natural sex pheromone. A pheromone receptor from Heliothis virescens, HR13 ( = HvirOR13 showed a similar profile, with stronger responses elicited by a formate analog than to the natural sex pheromone, (11Z-hexadecenal thus suggesting this might be a common feature of moth pheromone receptors.

  7. Inhibition of the nicotinic acetylcholine receptors by cobra venom α-neurotoxins: is there a perspective in lung cancer treatment?

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    Angela Alama

    Full Text Available Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated.We determined the activity of α-neurotoxins from Naja atra (short-chain neurotoxin, α-cobrotoxin and Naja kaouthia (long-chain neurotoxin, α-cobratoxin in vitro by cytotoxicity measurements in 5 lung cancer cell lines, by colony formation assay with α7nAChRs expressing and non-expressing cell lines and in vivo by assessing tumor growth in an orthotopic Non-Obese Diabetic/Severe Combined Immunodeficient (NOD/SCID mouse model system utilizing different treatment schedules and dosages.No statistically significant reduction in tumor growth was observed in the treatment arms in comparison to the control for both toxins. Paradoxically α-cobrotoxin from Naja atra showed the tendency to enhance tumor growth although, even in this case, the statistical significance was not reached.In conclusion our results show that, in contrast with other reports, the nAChR inhibitors α-cobratoxin from N. kaouthia and α-cobrotoxin from N. atra neither suppressed tumor growth nor prolonged the survival of the treated animals.

  8. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    International Nuclear Information System (INIS)

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min; Wang, Jianxiang

    2012-01-01

    Highlights: ► Metformin induces differentiation in NB4 and primary APL cells. ► Metformin induces activation of the MEK/ERK signaling pathway in APL cells. ► Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. ► Metformin induces the relocalization and degradation of the PML-RARα fusion protein. ► The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  9. Escolha de ginecologia e obstetrícia por graduandos da Universidade de Brasília: um estudo de influências numa série histórica

    Directory of Open Access Journals (Sweden)

    Dejano T. Sobral

    Full Text Available Analisa-se a escolha de residência médica em Ginecologia e Obstetrícia (GO em função de características pessoais dos graduandos, eventos curriculares e contexto temporal da instituição. O estudo incluiu 792 egressos do curso de Medicina da Universidade de Brasília, formados no período 1994-2006. Os dados abrangeram descritores demográficos e de aprendizagem, preferência inicial por carreira, monitorias, rendimento acadêmico, estágio seletivo no internato e inscrição para residência médica ao término do curso. Análises de contingência e de regressão logística foram realizadas com os egressos agrupados segundo a escolha ou não de GO. No conjunto, 8% dos egressos escolheram GO, dentre os quais 33% manifestaram atração inicial pela área. Não houve tendência temporal consistente na escolha ou na atração inicial, mas no qüinqüênio 1997-2001 a proporção de escolha foi menor do que a de atração inicial, em correspondência a mudanças na ambiência do curso. A análise de regressão logística identificou seis fatores preditivos da escolha: estágio seletivo, monitoria e incremento de rendimento em GO, preferência inicial, sexo feminino e época de graduação. Em conclusão, fatores associados à escolha de GO numa série histórica de 13 anos incluíram características pessoais, eventos curriculares e fase da conjuntura institucional.

  10. Collective Dynamics of Specific Gene Ensembles Crucial for Neutrophil Differentiation: The Existence of Genome Vehicles Revealed

    Science.gov (United States)

    Giuliani, Alessandro; Tomita, Masaru

    2010-01-01

    Cell fate decision remarkably generates specific cell differentiation path among the multiple possibilities that can arise through the complex interplay of high-dimensional genome activities. The coordinated action of thousands of genes to switch cell fate decision has indicated the existence of stable attractors guiding the process. However, origins of the intracellular mechanisms that create “cellular attractor” still remain unknown. Here, we examined the collective behavior of genome-wide expressions for neutrophil differentiation through two different stimuli, dimethyl sulfoxide (DMSO) and all-trans-retinoic acid (atRA). To overcome the difficulties of dealing with single gene expression noises, we grouped genes into ensembles and analyzed their expression dynamics in correlation space defined by Pearson correlation and mutual information. The standard deviation of correlation distributions of gene ensembles reduces when the ensemble size is increased following the inverse square root law, for both ensembles chosen randomly from whole genome and ranked according to expression variances across time. Choosing the ensemble size of 200 genes, we show the two probability distributions of correlations of randomly selected genes for atRA and DMSO responses overlapped after 48 hours, defining the neutrophil attractor. Next, tracking the ranked ensembles' trajectories, we noticed that only certain, not all, fall into the attractor in a fractal-like manner. The removal of these genome elements from the whole genomes, for both atRA and DMSO responses, destroys the attractor providing evidence for the existence of specific genome elements (named “genome vehicle”) responsible for the neutrophil attractor. Notably, within the genome vehicles, genes with low or moderate expression changes, which are often considered noisy and insignificant, are essential components for the creation of the neutrophil attractor. Further investigations along with our findings might

  11. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  12. Italian municipalities' NPFM reforms: an institutional theory perspective

    OpenAIRE

    Elisabetta Reginato; Isabella Fadda; Aldo Pavan

    2010-01-01

    Entender las razones del fracaso o el éxito de las reformas impulsada por el NPFM es un tema que ha atraído recientemente la atención de la literatura sobre la gestión del sector público. Sobre la base de un estudio de caso realizado en el gobierno local italiano, la investigación analiza el estado de real aplicación de las reformas mencionadas anteriormente, y contribuye al debate teórico sobre las razones que explican las diferencias entre los cambios formales y sustanciales en la administr...

  13. Resistance of the Opossum (Didelphis Virginiana) to Envenomation by Snakes of the Crotalidae Family.

    Science.gov (United States)

    1976-12-01

    ni., .d in Eiock 20. If dtli.r., ( ha. R.p.f ) IS S UPPL€ MEN TA RY NOTES Animal studies in relation to chemical agents 5 I E Y WO RDS (Co&Mu. ., r...cobra 1 .07 mg/kg, iv Died in 30 mm Na/a na/a atra 0 Snakebite Died in 45 min Chinese cobra Na/a nivea 03 1.38 mg/kg, iv Died in 1 hr Cape cobra Micn

  14. Influencia del ajedrez en la comprensión lectora y los movimientos sacádicos en niños

    OpenAIRE

    Dapica-Tejada, Rubén

    2016-01-01

    La inclusión del ajedrez como asignatura optativa en determinadas fases de la educación primaria y secundaria es una opción que atrae cada vez más la atención de las instituciones. Sin embargo, las posibles transferencias entre la práctica del ajedrez y el rendimiento académico continúan siendo difusas. El objetivo de este estudio es comprobar si existen diferencias significativas en la comprensión lectora y los movimientos sacádicos entre niños que practican ajedrez habitualmente y los que n...

  15. TURISMO DE SOL Y PLAYA. ANÁLISIS DE LA DEMANDA EN BOAVISTA (CABO VERDE)

    OpenAIRE

    Castillo-Canalejonio, Ana María; Sánchez Cañizares, Sandra Mª

    2015-01-01

    El turismo de sol y playa ha jugado un papel destacado en el desarrollo socioeconómico de muchos países y las islas siempre han atraído a un gran número de visitantes seducidos por lo exótico. Paralelamente, la demanda de los turistas desde hace unos años, manifiesta una tendencia a buscar nuevas satisfacciones y así aparecen nuevos destinos turísticos. En esta línea el objetivo de este artículo es explorar las posibilidades de desarrollar un turismo sostenible en la isla de Boavista (Cabo Ve...

  16. Sea Cucumber Resources At Tanjung Pai Waters Padaido Biak Numfor Papua

    Directory of Open Access Journals (Sweden)

    Eddy Yusron

    2004-12-01

    Full Text Available Observation on sea cucumber diversity was carried out at coastal waters of Pai and Imbeyomi Islands in the Padaido Island Biak Numfor. Sampling was done by using a transect quadrant of 1 m x 1 m. This sampling and observation on its microhabitat were conducted by snorkling. Analyses on the sea cucumber community structure were based on its frequency of occurance, diversity, and density. The results showed that at both locations 10 species of sea cucumber were found where Holothuria edulis, H. atra, and H. nobilis were predominant common and more evenly distributed than the other species.

  17. Síntesis y caracterización de copolicarbonatos de Bisfenol A y Gludioxol

    OpenAIRE

    Sánchez Claveria, Laura

    2013-01-01

    El uso de derivados de hidratos de carbono para la síntesis de polímeros ha atraído mucho la atención últimamente no sólo debido a la gran abundancia y carácter renovable de los mismos, sino también debido al comportamiento degradable y biocompatible que se puede esperar de tales polímeros. El desarrollo de polímeros sintéticos utilizando monómeros procedentes de fuentes naturales constituye un nuevo rumbo para desarrollar polímeros sostenibles. En este trabajo se pretende s...

  18. The Influence of Genetic Stability on Aspergillus fumigatus Virulence and Azole Resistance

    Directory of Open Access Journals (Sweden)

    Thaila Fernanda dos Reis

    2018-01-01

    Full Text Available Genetic stability is extremely important for the survival of every living organism, and a very complex set of genes has evolved to cope with DNA repair upon DNA damage. Here, we investigated the Aspergillus fumigatus AtmA (Ataxia-telangiectasia mutated, ATM and AtrA kinases, and how they impact virulence and the evolution of azole resistance. We demonstrated that A. fumigatus atmA and atrA null mutants are haploid and have a discrete chromosomal polymorphism. The ΔatmA and ΔatrA strains are sensitive to several DNA-damaging agents, but surprisingly both strains were more resistant than the wild-type strain to paraquat, menadione, and hydrogen peroxide. The atmA and atrA genes showed synthetic lethality emphasizing the cooperation between both enzymes and their consequent redundancy. The lack of atmA and atrA does not cause any significant virulence reduction in A. fumigatus in a neutropenic murine model of invasive pulmonary aspergillosis and in the invertebrate alternative model Galleria mellonela. Wild-type, ΔatmA, and ΔatrA populations that were previously transferred 10 times in minimal medium (MM in the absence of voriconazole have not shown any significant changes in drug resistance acquisition. In contrast, ΔatmA and ΔatrA populations that similarly evolved in the presence of a subinhibitory concentration of voriconazole showed an ∼5–10-fold increase when compared to the original minimal inhibitory concentration (MIC values. There are discrete alterations in the voriconazole target Cyp51A/Erg11A or cyp51/erg11 and/or Cdr1B efflux transporter overexpression that do not seem to be the main mechanisms to explain voriconazole resistance in these evolved populations. Taken together, these results suggest that genetic instability caused by ΔatmA and ΔatrA mutations can confer an adaptive advantage, mainly in the intensity of voriconazole resistance acquisition.

  19. Inhibition of fat cell differentiation in 3T3-L1 pre-adipocytes by all-trans retinoic acid: Integrative analysis of transcriptomic and phenotypic data

    Directory of Open Access Journals (Sweden)

    Katharina Stoecker

    2017-03-01

    Full Text Available The process of adipogenesis is controlled in a highly orchestrated manner, including transcriptional and post-transcriptional events. In developing 3T3-L1 pre-adipocytes, this program can be interrupted by all-trans retinoic acid (ATRA. To examine this inhibiting impact by ATRA, we generated large-scale transcriptomic data on the microRNA and mRNA level. Non-coding RNAs such as microRNAs represent a field in RNA turnover, which is very important for understanding the regulation of mRNA gene expression. High throughput mRNA and microRNA expression profiling was performed using mRNA hybridisation microarray technology and multiplexed expression assay for microRNA quantification. After quantitative measurements we merged expression data sets, integrated the results and analysed the molecular regulation of in vitro adipogenesis. For this purpose, we applied local enrichment analysis on the integrative microRNA-mRNA network determined by a linear regression approach. This approach includes the target predictions of TargetScan Mouse 5.2 and 23 pre-selected, significantly regulated microRNAs as well as Affymetrix microarray mRNA data. We found that the cellular lipid metabolism is negatively affected by ATRA. Furthermore, we were able to show that microRNA 27a and/or microRNA 96 are important regulators of gap junction signalling, the rearrangement of the actin cytoskeleton as well as the citric acid cycle, which represent the most affected pathways with regard to inhibitory effects of ATRA in 3T3-L1 preadipocytes. In conclusion, the experimental workflow and the integrative microRNA–mRNA data analysis shown in this study represent a possibility for illustrating interactions in highly orchestrated biological processes. Further the applied global microRNA–mRNA interaction network may also be used for the pre-selection of potential new biomarkers with regard to obesity or for the identification of new pharmaceutical targets.

  20. Reglas claras o presunciones: el derecho de reserva a razón de la franquicia

    OpenAIRE

    Cornejo Sota, Lourdes Pamela

    2015-01-01

    Cuando uno habla de franquicia se viene a la mente negocios con reconocido nombre, ya sea a nivel nacional como internacional, y es así que muchos se sienten atraídos por incursionar en este mundo y obtener un contrato de franquicia que tenga prestigio para poder operarlo de igual manera. Si bien las franquicias han sido utilizadas a nivel internacional desde hace mucho tiempo atrás, las franquicias nacionales datan recién desde el año 1992, las cuales tienden a crecer dados...

  1. HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.

    Science.gov (United States)

    Scott, A A; Head, D R; Kopecky, K J; Appelbaum, F R; Theil, K S; Grever, M R; Chen, I M; Whittaker, M H; Griffith, B B; Licht, J D

    1994-07-01

    We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and

  2. Oxidação eletrocatalítica de NADH empregando um novo sensor à base de um complexo macrocíclico n4 sobre grafeno e DNA

    OpenAIRE

    Ribeiro, Izabela Aparecida Luiz

    2015-01-01

    Área de concentração: Química Analítica. β-Nicotinamida adenina dinucleotídeo (NADH) e sua forma oxidada correspondente (NAD+) representam uma coenzima de grande importância em centenas de reações naturais catalisadas por enzimas desidrogenase, sendo vitais no metabolismo respiratório mitocondrial por estimular a produção de energia e atuam como principais transportadoras de cargas centrais em células vivas. Por estes motivos, a determinação eletroquímica de NADH tem atraído considerável a...

  3. El camino del ‘desarrollo armonioso’ de China

    OpenAIRE

    Zhou, Hang

    2013-01-01

    Las dos cuestiones esenciales que se plantean en este programa, tanto el crecimiento de la economía como la armonía interna en la sociedad necesaria para conseguirlo, se han convertido en el foco del futuro desarrollo social chino. La aparición de la ‘armonía’ como condición previa por primera vez en el diseño de camino de este país socialista atraído la atención de los estudiosos.

  4. Trapecio amazónico: turismo e imaginarios sociales sobre un territorio exotizado

    OpenAIRE

    Vélez Rivas, Martha Lucía

    2017-01-01

    Resumen El objetivo del artículo es comprender los imaginarios sociales construidos sobre el Trapecio Amazónico colombiano y su influencia en la experiencia turística. De manera creciente, se observa un aumento en el flujo de turistas atraídos por ofertas hacia este territorio selvático, el cual está habitado principalmente por comunidades indígenas que son, al mismo tiempo, objeto y sujetos del turismo. La experiencia turística está permeada por imaginarios construidos a través de relatos, n...

  5. Uso de imagens de satélite como suporte à estimativa da demanda hídrica na sub-bacia do Rio Urucuia, MG

    OpenAIRE

    Silva, Lorena Santos Cordeiro da

    2014-01-01

    O objetivo deste trabalho foi estimar a demanda hídrica destinada à irrigação na sub-bacia Urucuia, MG, utilizando dados de sensoriamento remoto e comparar os resultados obtidos com a disponibilidade hídrica da sub-bacia. Para estimativa da demanda hídrica foi calculada a evapotranspiração de referência a partir dos dados coletados da Plataforma de Coleta de Dados (PCD) do município de Santa Fé de Minas e, posteriormente, foi calculada a evapotranspiração das culturas existentes na área. Atra...

  6. El síndrome del niño sacudido

    OpenAIRE

    Alvarado Guevara, AnaTeresa; Garro Vargas, Karen

    2008-01-01

    Dentro de las múltiples manifestaciones de la violencia intrafamiliar, una de las que mas atención atrae es aquella dirigida hacia los niños y uno de los cuadros mas estudiados ampliamente es el Síndrome del Niño Sacudido, causado cuando un niño pequeño es tomado por un adulto del tórax y sacudido hacia atrás y adelante. El mismo es una entidad clínica reconocida por la medicina actual, con factores predisponentes y cuadro clínico identificable por el personal medico y de salud en contacto co...

  7. Produtos farmacêuticos e de higiene pessoal no rio Iguaçu e seus afluentes

    OpenAIRE

    Ide, Alessandra Honjo

    2014-01-01

    A qualidade das águas é atualmente um assunto que tem atraído a atenção de pessoas de todas as áreas, especialmente quanto à contaminação dos ambientes aquáticos pelos chamados poluentes emergentes. Esses contaminantes constituem compostos orgânicos ou inorgânicos, sintéticos ou naturais, contidos nos bens de consumo utilizados por toda população e que tem como destino final os corpos aquáticos. O objetivo deste trabalho foi verificar a presença de produtos farmacêuticos e de higiene pessoal ...

  8. Nav2 is necessary for cranial nerve development and blood pressure regulation

    OpenAIRE

    McNeill, Elizabeth M; Roos, Kenneth P; Moechars, Dieder; Clagett-Dame, Margaret

    2010-01-01

    Abstract Background All-trans retinoic acid (atRA) is required for nervous system development, including the developing hindbrain region. Neuron navigator 2 (Nav2) was first identified as an atRA-responsive gene in human neuroblastoma cells (retinoic acid-induced in neuroblastoma 1, Rainb1), and is required for atRA-mediated neurite outgrowth. In this paper, we explore the importance of Nav2 in nervous system development and function in vivo. Results Nav2 hypomorphic homozygous mutants show d...

  9. Impactos da adoção de um modelo para gestão da cadeia de suprimentos : um estudo de caso em uma empresa de alimentos

    OpenAIRE

    Alves, Pedro Henrique Bortolotto Fagundes

    2015-01-01

    A Gestão da Cadeia de Suprimentos, também conhecida pelo seu termo em inglês (Supply Chain Management - SCM), tem atraído cada vez mais a atenção de pesquisadores e executivos, na medida em que seus benefícios vêm sendo obtidos em empresas de diversos segmentos e portes. O presente trabalho tem o objetivo de apresentar os impactos da adoção de um modelo proposto à SCM em uma empresa do ramo de alimentos, mais especificamente em suas cadeias de lácteos e frangos. Foi verificada na literat...

  10. Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída

    Directory of Open Access Journals (Sweden)

    A. Sanz Miguel

    2006-04-01

    Full Text Available Hasta la demostración de la actividad sobresaliente del trióxido de arsénico (ATO en recaídas de pacientes con leucemia promielocítica (LPA, el tratamiento de rescate en esta enfermedad consistía en la readministración de ácido holo-trans retinóico (ATRA y quimioterapia para inducir la remisión, generalmente conteniendo citarabina a altas dosis, seguido de consolidación y/o trasplante de progenitores hematopoyéticos (TPH.

  11. Skate na cidade, imagens da cidade

    OpenAIRE

    Machado, Giancarlo Marques Carraro

    2014-01-01

    Apesar da existência de dezenas de pistas de skate na cidade de São Paulo – espaços considerados “próprios” para o skate -, a maioria dos skatistas da modalidade street skate confere maior importância à prática feita nas ruas, onde, para muitos, se “anda de skate de verdade”. A atração que elas exercem é a possibilidade de encontrar diferentes tipos de picos, ou seja, equipamentos urbanos (bancos, corrimãos, escadas, canteiros) obstáculos onde se realizam as manobras. Este artigo busca analis...

  12. Ondas de spin em redes decoradas

    OpenAIRE

    WanÃssa FaÃanha da Silva

    2014-01-01

    Sistema de baixa dimensionalidade tÃm atraÃdo uma grande atenÃÃo ultimamente devido a sistemas como grafeno e nanotubos de carbono. Tais sistemas tÃm grandes possibilidades de aplicaÃÃes tecnolÃgicas, em particular na criaÃÃo de dispositivos eletrÃnicos, devido Ãs suas propriedades eletrÃnicas especÃficas. Nesse sentido, o estudos de outros sistemas em baixa dimensÃo se torna urgente. Mais especificamente, o estudo de propriedades magnÃticas de materiais de materiais em baixa dimensionalidade...

  13. Sistema de innovación basado en la red de valor. Diseño orientado a Ia gestión del patrimonio territorial como activo para al desarrollo económico de las Micro y Pequeñas Empresas

    Directory of Open Access Journals (Sweden)

    Katherine Mollenhauer

    2016-08-01

    Full Text Available El presente documento enuncia aspectos básicos conceptuales en torno a la ciencia, tecnología e innovación, como complemento al modelo de Sistema Nacional de Innovación aplicado actualmente en Chile y la derivación de éste hacia un nivel regional en el Sistema de Innovación Regional. En este contexto se exponen los fundamentos y aplicaciones del SID_d, atrasé de los cuatro elementos que lo componen: modelo para la innovación, actores, actuaciones y proyectos como buenas prácticas para la innovación.

  14. Exhibit of ADS transmutation system to-Handle MA contained in Highly Radioactive Waste

    International Nuclear Information System (INIS)

    Marsodi; Lasman, A.N.; Nishihara, K.; Marsongkohadi; Su'ud, Z.

    2002-01-01

    This ADS transmutation system consists of a high intensity proton beam accelerator, spallation target, and sub-critical reactor core. The general approach was conducted using N-15 fuel to choose a strategy for destroying or minimizing the dangerously radioactive waste using a fast neutron spectrum. The fuel of this system was put surrounding the target with the some composition, i.e. the composition of MOX from PWR reactor spent-fuel with 5 year cooling time. Basic characteristics of this system have been conducted based on analysis of neutronics calculation results using ATRAS codes system

  15. El vínculo entre sexualidad y violencia en el teatro de Angélica Liddell

    OpenAIRE

    Topolska, Ewelina Maria

    2014-01-01

    Angélica Liddell’s surge to (relative) fame in recent years (a process which began in 2000, peaking around 2008/09) resulted in an increasing number of articles being published about her theatre, not to mention a significant number of interviews she gave for the Spanish and international press. There is also a doctoral thesis by Ana Vidal Egea concerning Atra Bilis’ (the name of Liddell’s group) work. However, no existing study engaged in detailed analysis of the artist’s theatrical productio...

  16. Documental sobre las formas comunicacionales y la construcción de cultura e identidades colectivas. Estudio comparativo entre: Sociedad Deportiva Aucas y Liga Deportiva Universitaria de Quito con retrospectiva histórica

    OpenAIRE

    Barreno Paredes, Ana María; Zaruma Silva, Juan José; Viinueza Guerrero, Franklin Roberto

    2012-01-01

    Al ser el fútbol, el deporte más practicado y seguido a nivel mundial, se convierte en un fenómeno social y cultural, que atrae a millones de personas a sus escenarios deportivos cada semana. El Ecuador se encuentra inmerso en la fiebre del fútbol, siendo Quito el espacio donde se expresan estas pasiones. Aucas y Liga, dos clubes de enorme valía histórica, cultural, social y deportiva han abierto sus puertas, dando la oportunidad de estudiar a fondo sus hichadas, sus instituciones y todo alre...

  17. SÃntese e caracterizaÃÃo dos Ãxidos TiO2 , SnO2 e In2O3 dopados com Fe sintetizados por moagem mecÃnica: influÃncia das ferramentas de moagem

    OpenAIRE

    GislÃnia Maria de Souza Lima Mendes

    2013-01-01

    Os semicondutores magnÃticos atraÃram a atenÃÃo de muitos cientistas nos Ãltimos anos devido, principalmente, a aplicaÃÃes tecnolÃgicas no ramo da spintrÃnica. Esses semicondutores podem ser desenvolvidos por meio de um processo chamado dopagem, onde alguns Ãtomos da matriz semicondutora sÃo substituÃdos aleatoriamente por Ãtomos magnÃticos. Esta propriedade possibilita a fabricaÃÃo de uma variedade de dispositivos eletrÃnicos a partir do mesmo material semicondutor. Neste trabalho utilizou-s...

  18. Mulheres com H: estereótipos ambivalentes, representações tensionadas e identidades queer no programa de TV Papeiro da Cinderela

    OpenAIRE

    DOURADO, Rodrigo Carvalho Marques

    2009-01-01

    Este trabalho analisa o programa de televisão Papeiro da Cinderela, produzido e veiculado pela TV Jornal do Commercio de Pernambuco, tendo como apresentador o ator-transformista Jeison Wallace, intérprete da personagem Cinderela . Essa personagem surgiu no cenário teatral pernambucano em 1991 e, desde então, estabeleceu um permanente diálogo com os veículos de comunicação do estado, passando a comandar uma atração diária na programação daquela emissora a partir de 2005. O o...

  19. Monitoreo de Dinoflagelados Causantes de Ciguatera en las Aguas de Punta Galeta, Colón, Panamá

    OpenAIRE

    González, Alexander; Fábrega, José; Broce, Kathia

    2018-01-01

    Los océanos son la clave para la conservación de la vida y son la conexión para los ecosistemas y el mercado mundial. Los seres humanos somos atraídos a las zonas costeras por los múltiples beneficios que nos brinda, siendo el principal la pesca. A través de los productos del mar que consumimos, podemos resultar contaminados con toxinas que producen unos microorganismos acuáticos llamados  dinoflagelados que a su vez pueden causar la enfermedad ciguatera. En Panamá dentro el Paisaje Protegido...

  20. Combination Superficial Peels With Salicylic Acid and Post-Peel Retinoids.

    Science.gov (United States)

    Kligman, Douglas E; Draelos, Zoe D

    2016-04-01

    Salicylic acid (SA) and retinoids, tretinoin (all-trans retinoic acid [ATRA]), and retinol (all-trans retinol) are widely used as topical agents for the improvement of photodamage and acne vulgaris. They can be used in daily take-home products or as part of an in-office procedure, combining the benefits of a keratolytic (SA) and a retinoid. The objective of this research was to compare the efficacy for ameliorating photodamage of topical tretinoin (0.25%) and retinol (0.25%) to baseline and with each other when applied after a 30% salicylic acid peel on human facial skin. Twenty female subjects received a full face 30% SA peel followed by the overnight application of tretinoin to a 1 randomized half-face and retinol to the opposite side (split-face study). The identical procedure was repeated at week 2. Double-blinded subject and investigator assessments of the results were captured at weeks 2 and 4. By investigator evaluation, both peeling regimens were effective in improving photodamage parameters compared to baseline. (ATRA P-values at week 4 were: P=.00008 texture, P=.00013 roughness, P=.00221 pores, P=.00098 dryness, P=.02770 erythema, and P=.00008 overall appearance. Retinol P-values at week 4 were: P=.00019 texture, P=.00053 roughness, P=.00221 pores, P=.00147 dryness, P=.02770 erythema, and P=.0043 overall appearance.) By subject self-assessment compared with baseline, both tretinoin and retinol were effective in improving overall appearance (ATRA P=.0229 and retinol P=.0190). By investigator evaluation comparing tretinoin with retinol, tretinoin was slightly better than retinol at week 4 in improving texture P=.00506, roughness P=.01171, and overall appearance P=.00506. By subject self-assessment comparing tretinoin with retinol, there was no difference in overall appearance (ATRA P=.2367 and retinol P=.3613). Either topical tretinoin (0.25%) or retinol (0.25%) can be used safely and effectively when applied in office immediately after SA peeling to

  1. PROTEINA BLANCO DE LOS AUTO-ANTICUERPOS ANTI-P ASOCIADOS A LUPUS NEUROPSIQUATRICO: FUNCION Y MECANISMOS PATOGENICOS

    OpenAIRE

    segovia miranda, fabian josue

    2012-01-01

    El potencial patogénico de los auto-anticuerpos en las disfunciones del sistema nervioso central ha atraído gran interés en los últimos años. La identificación de autoanticuerpos neuropatogénicos dirigidos contra componentes de la superficie neuronal ayuda a entender la influencia que el sistema inmune puede ejercer sobre procesos que involucran memoria, cognición y comportamiento. También provee herramientas para entender mejor la función de componentes ya conocidos, o de nuevos com...

  2. Estudo do uso de corantes artificiais em alimentos e estimativa de ingestão de tartrazina pela população brasileira

    OpenAIRE

    Patrícia da Silva Rodrigues

    2015-01-01

    A atração dos seres humanos pelas cores é um fenômeno instintivo. Cores agradáveis em alimentos geram no consumidor a sensação de um produto com características sensoriais mais prazerosas e fornecem a sensação de maior qualidade global. Os objetivos deste trabalho foram verificar quais os alimentos comercializados por uma das maiores redes de supermercados do país que continham corantes na sua formulação, selecionar aqueles que continham o corante artificial tartrazina, estimar a Ingestão Diá...

  3. Biologia floral e sistema reprodutivo de Cattleya granulosa Lindl., uma orchidaceae ameaçada e endêmica do Nordeste do Brasil

    OpenAIRE

    de Araújo Costa, Rosaly

    2010-01-01

    Cattleya granulosa Lindl. é uma orquídea endêmica e ameaçada de extinção restrita a fragmentos de Floresta Atlântica do Nordeste do Brasil. A biologia floral e os sistemas reprodutivos de C. granulosa no Parque das Dunas e Barreira do Inferno no Rio Grande do Norte foram investigados, e ainda, foram realizadas coletas de machos de abelhas Euglossini atraídos por iscas odores para verificar a ocorrência de políneas aderidas ao corpo. As flores apresentam cores que variam ent...

  4. Os acordos para evitar a dupla tributação assinados pelo Brasil e as negociações com os Estados Unidos : históricos e desafios

    OpenAIRE

    Carvalho, Marcela Santos de

    2013-01-01

    O presente trabalho é o resultado de um estudo minucioso sobre os Acordos para Evitar a Dupla Tributação Internacional (ADTs) celebrados pelo Brasil e a relação desses Acordos com a atração de investimentos ao País. Para um melhor entendimento do tema da dupla tributação internacional e dos aspectos técnicos que o norteiam, fez-se necessário estudar os diferentes modelos internacionalmente aceitos de Acordo, como o Modelo da Liga das Nações (1928), o Modelo da Organização das Naçõ...

  5. Gipuzkoan hegazti habigile batzuen lehen aipamenak eta beste aipamen interesgarri batzuk

    Directory of Open Access Journals (Sweden)

    OLANO, M., VAZQUEZ, J., AIERBE, T.

    1998-01-01

    Full Text Available Como resultado del trabajo de campo realizado estos últimos años, se da cuenta por primera vez de la presencia como aves nidificantes en Gipuzkoa de Fulica atra, Policeps cristatus, Tachybaptus ruficollis, Riparia riparia, Falco subbuteo, Asio otus, Aquila chysaëtos, Circaetus Gallicus y Drycopus martius. Además, se recogen datos de unas cuantas especies muy poco conocidas en esta provincia : Accipiter gentilis, Hieraëtus pennatus, Milvus migrans, Bubo bubo, Motacilla flava, Monticola solitarius and Certthia familiaris.

  6. Deslocamento de empresas para os estados do Ceará e da Bahia: o caso da indústria calçadista

    OpenAIRE

    Santos, Angela Maria Medeiros Martins; Correa, Abidack Raposo; Alexim, Flavia Menna Barreto; Peixoto, Gabriel Barros Tavares

    2002-01-01

    Este artigo objetiva apresentar o deslocamento do setor calçadista brasileiro das regiões Sul e Sudeste para o Nordeste, especialmente para os Estados do Ceará e da Bahia. Nesse sentido, procura-se mostrar as políticas de atração de novos investimentos do setor nesses estados, assim como suas perspectivas e seus principais problemas. Serão apresentadas as características gerais do setor no Ceará e na Bahia, os fatores que determinaram a migração de empresas calçadistas, a logística de suprime...

  7. El turismo oscuro: análisis de sitios web como herramienta de marketing

    OpenAIRE

    Barón Mosquera, José Luis

    2017-01-01

    El turismo es un sector cuya evolución ha provocado cambios en el modo en que los viajeros disfrutan su tiempo libre, dando lugar a nuevas formas de turismo. Una de estas nuevas ramas del turismo que está adquiriendo gran importancia es el “Dark tourism”, o turismo oscuro en español, en el que los turistas se sienten atraídos por lugares relacionados con la muerte, desmontando la idea clási ca que asocia la atracción turística a lo bello y a lo placentero(...

  8. Nuestro único problema

    Directory of Open Access Journals (Sweden)

    Héctor Rojas Herazo

    1967-12-01

    Full Text Available Toda vida humana por ser, en profundidad y superficie, una batalla contra la muerte, es un fenómeno epopéyico. Más admirable cuanto más secreta y personal sea esa batalla. Pues no nos enfrentamos a este o aquel obstáculo ni somos atraídos por este o aquel señuelo. Nuestra íntima preocupación, nuestro único problema, nuestro máximo terror es sabernos materia de disolución, míseras astillas para alimentar el insaciable fuego de la muerte.

  9. Evidência de transmissão de leishmaniose visceral por Lutzomyia cruzi no município de Jaciara, Estado de Mato Grosso, Brasil

    OpenAIRE

    Missawa, Nanci Akemi; Veloso, Márcia Aurélia Esser; Maciel, Giovana Belem Moreira Lima; Michalsky, Érika Monteiro; Dias, Edelberto Santos

    2011-01-01

    INTRODUÇÃO: O município de Jaciara foi classificado em 2003, como área de transmissão de leishmaniose visceral em situação de surto. O trabalho objetivou determinar evidência de transmissão de Leishmania (Leishmania) infantum chagasi por Lutzomyia cruzi no município de Jaciara, Estado de Mato Grosso, Brasil. MÉTODOS: O município situa-se a 127km da capital Cuiabá e é um importante ponto de atração para os praticantes de eco-turismo. Fêmeas de Lutzomyia cruzi, capturadas com armadilha de CDC, ...

  10. Los estudios sobre el socialismo temprano en Colombia: una versión de la izquierda

    Directory of Open Access Journals (Sweden)

    Isidro Vanegas

    2000-01-01

    Full Text Available Este ensayo indaga sobre los estudios acerca del socialismo en Colombia antes de 1930. Un tema que ha atraído a considerable número de investigadores y ha dado frutos en un amplia cantidad de trabajos. Al ser la izquierda un campo político fuertemente apegado a los debates doctrinarios, hila esta panorámica el supuesto de que existe una fuerte relación entre los avatares de la izquierda y la forma como ha reconstruido discursivamente sus propios orígenes, su desarrollo y sus vinculaciones con la sociedad colombiana.

  11. “¿Mi novio sería capaz de matarme?” Violencia en el noviazgo entre adolescentes de la Universidad Autónoma Chapingo, México

    OpenAIRE

    Verónica Vázquez García; Roberto Castro

    2008-01-01

    En este artículo analizamos la violencia en las relaciones de noviazgo en la Universidad Autónoma Chapingo (Uach), una institución mexicana dedicada a formar recursos humanos en ciencias agronómicas. La Uach posee tres características: atrae estudiantes de medios desfavorecidos de todo el país; recibe más hombres que mujeres debido a la construcción de la Agronomía como una ocupación masculina; y, funciona como una institución total en el sentido de que sus estudiantes dejan la casa paterna a...

  12. Hypercalcemia and acute pancreatitis in a male patient with acute promyelocytic leukemia and pulmonary tuberculosis.

    Science.gov (United States)

    Abdullah, Ali S; Adel, Ahmad M; Hussein, Radwa M; Abdullah, Mohammed Aj; Yousaf, Anil; Mudawi, Deena; Mohamed, Shehab F; Nashwan, Abdulqadir J; Soliman, Dina; Ibrahim, Feryal; Yassin, Mohamed A

    2018-04-03

    We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

  13. El perfil del consumidor de hostel en Brasil y sus motivaciones

    OpenAIRE

    Mané, Alexandra; Ferreira, Lissa

    2017-01-01

    El creciente número de hostels en Brasil ha atraído cada vez más brasileños que buscan este tipo de establecimiento para hospedarse. No obstante, vale destacar que deben realizarse más estudios que aborden la importancia de los hostels y sus consumidores en el mercado de turismo. Podrán contribuir al conocimiento teórico y práctico posibilitando un mejor entendimiento sobre este segmento. El objetivo de este artículo es identificar y describir el perfil del consumidor de hostel, sus motivacio...

  14. Primeiro registro de Eufriesea laniventris (Ducke, 1902 (Hymenoptera, Apidae, Euglossini no Amazonas, Brasil First record of Eufriesea laniventris (Ducke, 1902 (Hymenoptera, Apidae, Euglossini in the state of Amazonas, Brazil

    Directory of Open Access Journals (Sweden)

    Eliana Fernandez Storti

    2004-01-01

    Full Text Available É registrada pela primeira vez a ocorrência de Eufriesea laniventris no Amazonas. No ano 2000, foram coletados seis exemplares na região de Manaus (2º 36' S e 60º 02' W atraídos pelas substâncias odoríferas 1,8 cineol e salicilato de metila.The first record of Eufriesea laniventris in the state of Amazonas is here reported. Attracted to 1.8 cineole and methyl salicylate fragrances, six specimens were colected in the region of Manaus (2º 36' S 60º 02' W during the year 2000.

  15. BCL-x{sub L}/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Perri, Mariarita; Yap, Jeremy L.; Yu, Jianshi [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Cione, Erika [Department of Pharmacy, Health and Nutritional Sciences, Ed. Polifunzionale, University of Calabria, 87036 Rende, CS (Italy); Fletcher, Steven [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Kane, Maureen A., E-mail: mkane@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States)

    2014-10-01

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As{sub 2}O{sub 3} has increased survival further, patients that experience relapse and are refractory to atRA and/or As{sub 2}O{sub 3} is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-x{sub L}) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-x{sub L}/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-x{sub L}/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis.

  16. Description of rainfall variability in Br hat -samhita of Varâha-mihira

    OpenAIRE

    Iyengar, RN

    2004-01-01

    Br hat -samhita of Varâha-mihira (5–6th century AD) provides valuable information on the approach in ancient India towards monsoon rainfall, including its measurement and forecasting. In this context, we come across a description of the expected amount of total seasonal rainfall depending on the first rains under the 27 naks atras of Indian astronomy. This provides a rough statistical picture of what might have been the rainfall and its variability in the region around Ujjain, where Varâha-mi...

  17. Differentiation Therapy of Acute Myeloid Leukemia

    International Nuclear Information System (INIS)

    Gocek, Elzbieta; Marcinkowska, Ewa

    2011-01-01

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D 3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML

  18. A designated centre for people with disabilities operated by Ability West, Galway

    LENUS (Irish Health Repository)

    Orfali, Nina

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

  19. Coiled-coil domain of PML is essential for the aberrant dynamics of PML-RARα, resulting in sequestration and decreased mobility of SMRT

    International Nuclear Information System (INIS)

    Huang Ying; Qiu Jihui; Chen Guoqiang; Dong Shuo

    2008-01-01

    Promyelocytic leukemia-retinoic acid receptor α (PML-RARα) is the most frequent RARα fusion protein in acute promyelocytic leukemia (APL). Our previous study has demonstrated that, compared with RARα, PML-RARα had reduced intranuclear mobility accompanied with mislocalization. To understand the molecular basis for the altered dynamics of PML-RARα fusion protein, we performed FRAP analysis at a single cell level. Results indicated that three known sumoylation site mutated PML-RARα had same intracellular localization and reduced mobility as wild-type counterpart. The coiled-coil domain of PML is responsible for the aberrant dynamics of PML-RARα. In addition, we revealed that co-repressor SMRT co-localized with PML-RARα, resulting in the immobilization of SMRT while ATRA treatment eliminated their association and reversed the immobile effect of SMRT. Furthermore, co-activator CBP, co-localized with PML-RARα in an ATRA-independent way, was demonstrated as a high dynamic intranuclear molecule. These results would shed new insights for the molecular mechanisms of PML-RARα-associated leukemogenesis

  20. Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji.

    Science.gov (United States)

    Eastwood, Erin K; López, Elora H; Drew, Joshua A

    2016-01-25

    Coral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures, and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae), and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical.

  1. Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.

    Science.gov (United States)

    Maniwa, Yasuhisa; Kasukabe, Takashi; Kumakura, Shunichi

    2015-08-01

    Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NBT-reducing activity and non-specific esterase-positive cells as well as morphological changes to monocyte/macrophage-like cells. Vitamin K2 and cotylenin A cooperatively inhibited the proliferation of HL-60 cells in short-term and long-term cultures. This treatment also induced growth arrest at the G1 phase. Although 5 µg/ml cotylenin A or 5 µM vitamin K2 alone reduced c-MYC gene expression in HL-60 cells to approximately 45% or 80% that of control cells, respectively, the combined treatment almost completely suppressed c-MYC gene expression. We also demonstrated that the combined treatment of vitamin K2 and cotylenin A synergistically induced the expression of cyclin G2, which had a positive effect on the promotion and maintenance of cell cycle arrest. These results suggest that the combination of vitamin K2 and cotylenin A has therapeutic value in the treatment of acute myeloid leukemia.

  2. Centralidade basada em deslocamentos e seus reflexos sobre a estrutura monopolicentrica da região metropolitana do Rio de Janeiro

    Directory of Open Access Journals (Sweden)

    José André Villas Bôas Mello

    2016-03-01

    Full Text Available Este artigo tem o objetivo de propor uma categoría de centralidade baseada nos deslocamentos de viagem atraídos por uma região, classificando-os em função dos motivos de viagem e avaliando os reflexos sobre a estrutura monopolicentrica da Região Metropolitana do Estado do Rio de Janeiro (RMRJ. A análise teve como base os dados de origem e destino (OD disponibilizados pela secretaria estadual de transportes, contidos no PDTU, Plano Diretor de Transporte Urbano. Para se definir os limites inferior e superior das classes intituladas eixos de centralidade se utilizou de um modelo de otimização que classifica os dados utilizando “quebras naturais”. A análise permitiu reconhecer a concentração de deslocamentos totais atraídos pelo municipio do Rio de Janeiro, principalmente devido aos volumes originados e mantidos entre as zonas da própria cidade. Também foi possível verificar que o centro é o principal, mas não o único eixo de centralidades, enfatizando que os motivos de viagem podem contribuir para a materialização da monopolicentralidade na região.

  3. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.

    LENUS (Irish Health Repository)

    Orfali, Nina

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

  4. Microbial modification of host long-distance dispersal capacity

    Directory of Open Access Journals (Sweden)

    Hutchings Linda

    2009-06-01

    Full Text Available Abstract Background Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider, Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'. Results We show that there is spatial heterogeneity in the prevalence of two maternally acquired endosymbiont infections within the wider E. atra meta-population and we demonstrate through several independent approaches a link between the presence of one of these endosymbionts, Rickettsia, and the tendency for long-distance movement. Conclusion This novel finding that particular endosymbionts can influence host dispersal is of broad importance given the extremely widespread occurrence of similar bacteria within arthropod communities. A bacterial phenotype that limits dispersal has the potential not only to reduce gene flow and thus contribute to degrees of reproductive isolation within species, but also to influence species distribution and thus overall community composition.

  5. Marketing vivencial: o caso de eventos musicais no shopping.

    Directory of Open Access Journals (Sweden)

    Ana Akemi Ikeda

    2005-12-01

    Full Text Available À medida que o mercado de shopping centers vem crescendo no Brasil e tornando-se cada vez mais competitivo, gerar fluxo de freqüentadores torna-se uma tarefa, cada vez mais, desafiadora. Diante deste cenário, o objetivo neste artigo é estudar a experiência proporcionada por eventos musicais em shopping. Para isso, além de pesquisa bibliográfica sobre o assunto, foi analisado um projeto de shows musicais realizado pelo Shopping Anália Franco, em São Paulo, que visava a melhorar a atração de visitantes, permanência do público no local e impacto nas vendas. O trabalho foi complementado com uma pesquisa de campo com os freqüentadores dos shows musicais. Os resultados mostraram que esse tipo de experiência pode beneficiar o estabelecimento em termos de maior simpatia e satisfação do público, melhoria de imagem, atração de novos consumidores, aumento do fluxo de visitantes e do volume de vendas.

  6. Resposta de fêmeas de Encarsia formosa Gahan (Hymenoptera: Aphelinidae aos odores do hospedeiro e da planta-hospedeira em olfatômetro de quatro vias Response of female Encarsia formosa Gahan (Hymenoptera: Aphelinidae to host and plant-host odors

    Directory of Open Access Journals (Sweden)

    Kátia Maria Medeiros de Siqueira

    2003-01-01

    Full Text Available A crescente importância da mosca-branca Bemisia tabaci raça B (Hemiptera: Aleyrodidae como praga agrícola tem incentivado a busca de inimigos naturais que possam ser utilizados em programas de controle biológico. Estudou-se a atração de fêmeas de Encarsia formosa (Hymenoptera: Aphelinidae aos odores emanados pelo seu hospedeiro - a mosca-branca B. tabaci raça B - em plantas de tomate, em olfatômetro de quatro vias. O parasitóide não apresentou atração aos odores da planta de tomate nem ao complexo planta de tomate-ninfas de B. tabaci.The increasing importance of the whitefly Bemisia tabaci race B (Hemiptera: Aleyrodidae as one of the major agricultural pest of this century, has resulted in a search for natural enemies that can be used in biological control programs. The response of naive females of Encarsia formosa (Hymenoptera: Aphelinidaeto volatiles from its hostspecies: insect (B. tabacci race B and plant (Lycopersicom esculentum Mill. were tested using 4-nose olfactometre. Parasitoid was not attracted by neither or insect hostspecies volatile.

  7. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    Science.gov (United States)

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Parasitism of Trombidium brevimanum larvae on agrobiont linyphiid spiders from Germany.

    Science.gov (United States)

    Tomić, Vladimir; Mąkol, Joanna; Stamenković, Srdjan; Büchs, Wolfgang; Prescher, Sabine; Sivčev, Ivan; Graora, Draga; Sivčev, Lazar; Gotlin-Čuljak, Tatjana; Dudić, Boris

    2015-08-01

    An experiment on three differently-managed agricultural fields in Ahlum, Germany, which aimed at establishing the impact of different management systems on the biodiversity of predators and decomposers, yielded a significant number of spiders parasitized by larvae of Trombidium brevimanum (Actinotrichida, Parasitengona, Trombidiidae). Spider data from the whole sampling period (September 2010-July 2012), indicated that ectoparasitic larvae were recorded only on spiders in pitfall traps in the period of June-July 2011. In this period, only eight species of Linyphiidae--out of 42 species assigned to nine spider families recorded from the study area--were parasitized by mites; considerable levels of parasitism were recorded on Erigone atra, E. dentipalpis, and Oedothorax apicatus. The highest prevalence of parasitism was recorded on the organic field for E. atra (29%), while on the integrated and conventional fields significantly fewer parasitized spiders were observed. The preferred attachment sites on the spider host were regions with softer cuticle, especially regions on the carapace and on the abdomen, adjacent to the pedicel.

  9. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

    2011-05-16

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  10. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells.

    Science.gov (United States)

    Zagani, Rachid; El-Assaad, Wissal; Gamache, Isabelle; Teodoro, Jose G

    2015-09-29

    The G0/G1 switch gene 2 (G0S2) is methylated and silenced in a wide range of human cancers. The protein encoded by G0S2 is an endogenous inhibitor of lipid catabolism that directly binds adipose triglyceride lipase (ATGL). ATGL is the rate-limiting step in triglyceride metabolism. Although the G0S2 gene is silenced in cancer, the impact of ATGL in the growth and survival of cancer cells has never been addressed. Here we show that ectopic expression of G0S2 in non-small cell lung carcinomas (NSCL) inhibits triglyceride catabolism and results in lower cell growth. Similarly, knockdown of ATGL increased triglyceride levels, attenuated cell growth and promoted apoptosis. Conversely, knockdown of endogenous G0S2 enhanced the growth and invasiveness of cancer cells. G0S2 is strongly induced in acute promyelocytic leukemia (APL) cells in response to all trans retinoic acid (ATRA) and we show that inhibition of ATGL in these cells by G0S2 is required for efficacy of ATRA treatment. Our data uncover a novel tumor suppressor mechanism by which G0S2 directly inhibits activity of a key intracellular lipase. Our results suggest that elevated ATGL activity may be a general property of many cancer types and potentially represents a novel target for chemotherapy.

  11. NLS-RARα promotes proliferation and inhibits differentiation in HL-60 cells.

    Science.gov (United States)

    Hu, Xiu-Xiu; Zhong, Liang; Zhang, Xi; Gao, Yuan-Mei; Liu, Bei-Zhong

    2014-01-01

    A unique mRNA produced in leukemic cells from a t(15;17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor α (RARα) and a myeloid gene product called PML. Studies have reported that neutrophil elastase (NE) cleaves bcr-1-derived PML-RARα in early myeloid cells, leaving only the nuclear localization signal (NLS) of PML attached to RARα. The resultant NLS-RARα fusion protein mainly localizes to, and functions within, the cell nucleus. It is speculated that NLS-RARα may act in different ways from the wild-type RARα, but its biological characteristics have not been reported. This study takes two approaches. Firstly, the NLS-RARα was silenced with pNLS-RARα-shRNA. The mRNA and protein expression of NLS-RARα were detected by RT-PCR and Western blot respectively. Cell proliferation in vitro was assessed by MTT assay. Flow cytometry (FCM) was used to detect the differentiation of cells. Secondly, the NLS-RARα was over-expressed by preparation of recombinant adenovirus HL-60/pAd-NLS-RARα. The assays of mRNA and protein expression of NLS-RARα, and cell proliferation, were as above. By contrast, cell differentiation was stimulated by all trans retinoic acid (ATRA) (2.5µmol/L) at 24h after virus infection of pAd-NLS-RARα, and then detected by CD11b labeling two days later. The transcription and translation of C-MYC was detected in HL-60/pAd-NLS-RARα cells which treated by ATRA. Our results showed that compared to the control groups, the expression of NLS-RARα was significantly reduced in the HL-60/pNLS-RARα-shRNA cells, and increased dramatically in the HL-60/pAd-NLS-RARα cells. The proliferation was remarkably inhibited in the HL-60/pNLS-RARα-shRNA cells in a time-dependent manner, but markedly promoted in the HL-60/pAd-NLS-RARα cells. FCM outcome revealed the differentiation increased in HL-60/pNLS-RARα-shRNA cells, and decreased in the HL-60/pAd-NLS-RARα cells treated with 2.5µmol/L ATRA. The

  12. Inactivation of Vibrio cholerae O1 El Tor inoculated into Peruvian ''choro'' mussels (Aulacomya ater) and two species of clams (Argopecten purpuratus and Gari solida) using medium-dose irradiation

    International Nuclear Information System (INIS)

    Torres, Z.; Bernuy, B.; Kahn, G.; Zapata, G.; Vivanco, M.; Guzman, E.; Leon, R.

    2001-01-01

    The radiation decimal reduction dose (D 10 ) for Vibrio cholerae O1 biotype El Tor inoculated through the natural feeding system into three species of bivalve mollusks from the Peruvian Pacific coast: ''choro'' mussels (Aulacome ater), ''abanico'' clams (Argopecten purpuratus), and common clams (Gari solida), was determined in vivo. The D 10 value obtained in vivo was 0.14 kGy in all mollusks tested. Concurrent studies conducted to determine the potential use of irradiation to extend the microbiological shelf-life of the mollusks during post-irradiation storage at 0-1 deg. C indicated that a dose of 1.0 kGy was optimal for choro mussels and abanico clams, whereas 2.0 kGy produced the best results when treating common clams. Shelf-life extension thus achieved was 31 days for choro mussels, 16 days for abanico clams, and 21 days for common clams. Non-irradiated control samples of all mollusks spoiled after 17 days of refrigerated storage. There were no significant (p<.05) adverse effects from the application of the optimal radiation treatments on the sensory characteristics (i.e. appearance, odor, flavor, and texture) of the mollusks. Total volatile basic nitrogen (VBN) and pH values were examined for use as indexes of seafood freshness. (author)

  13. CaCO3 dissolution by holothurians (sea cucumber): a case study from One Tree Reef, Great Barrier Reef

    Science.gov (United States)

    Schneider, K.; Silverman, J.; Kravitz, B.; Woolsey, E.; Eriksson, H.; Schneider-Mor, A.; Barbosa, S.; Rivlin, T.; Byrne, M.; Caldeira, K.

    2012-12-01

    Holothurians (sea cucumbers) are among the largest and most important deposit feeder in coral reefs. They play a role in nutrient and CaCO3 cycling within the reef structure. As a result of their digestive process they secrete alkalinity due to CaCO3 dissolution and organic matter degradation forming CO2 and ammonium. In a survey at station DK13 on One Three Reef we found that the population density of holothurians was > 1 individual m-2. The dominant sea cucumber species Holothuria leucospilota was collected from DK13. The increase in alkalinity due to CaCO3 dissolution in aquaria incubations was measured to be 47±7 μmol kg-1 in average per individual. Combining this dissolution rate with the sea cucumbers concentrations at DK13 suggest that they may account for a dissolution rate of 34.9±17.8 mmol m-2 day-1, which is equivalent to about half of night time community dissolution measured in DK13. This indicates that in reefs where the sea cucumber population is healthy and protected from fishing they can be locally important in the CaCO3 cycle. Preliminary result suggests that the CaCO3 dissolution rates are not affected by the chemistry of the sea water they are incubated in. Measurements of the empty digestive track volume of two sea cucumbers H. atra and Stichopus herrmanni were 36 ± 4 ml and 151 ± 14 ml, respectively. Based on these measurements it is estimated that these species process 19 ± 2kg and 80 ± 7kg CaCO3 sand yr-1 per individual, respectively. The annual dissolution rates of H. atra and S. herrmanni are 6.5±1.9g and 9.6±1.4g, respectively, suggest that 0.05±0.02% and 0.1±0.02% of the CaCO3 processed through their gut annually is dissolved. During the incubations the CaCO3 dissolution was 0.07±0.01%, 0.04±0.01% and 0.21±0.05% of the fecal casts for H. atra, H. leucospilota and S. herrmanni, respectively. Our result that the primary parameter determining the CaCO3 dissolution by sea cucumber is the amount of carbonate send in their gut

  14. A complex RARE is required for the majority of Nedd9 embryonic expression.

    Science.gov (United States)

    Knutson, Danielle C; Clagett-Dame, Margaret

    2015-02-01

    Neural precursor cell expressed, developmentally down-regulated 9 (Nedd9, Casl, Hef1, p105cas, Ef1) is a scaffolding protein that assembles complexes involved in regulating cell adhesion, migration, division, and survival. Nedd9 is found very early in the developing embryonic nervous system. A highly conserved complex retinoic acid response element (RARE) is located 485 base pairs (bp) upstream of exon 2B in the promoter of the Nedd9 gene. Mice transgenic for a 5.2 kilobase (kb) region of the 2B Nedd9 promoter containing the RARE upstream of a lacZ reporter gene [Nedd9(RARE)-lacZ] show a large subset of the normal endogenous Nedd9 expression including that in the caudal hindbrain neuroepithelium, spinal cord, dorsal root ganglia (drg) and migrating neural crest (ncc). However, the transgenic mice do not recapitulate the native Nedd9 expression pattern in presumptive rhombomeres (pr) 3 and 5 of the early hindbrain, the base of the neuroepithelium in the midbrain, nor the forebrain telencephalon. Thus, the 5.2 kb region containing the intact RARE drives a large subset of Nedd9 expression, with additional sequences outside of this region needed to define the full complement of expression. When the 5.2 kb construct is modified (eight point mutations) to eliminate responsiveness of the RARE to all-trans retinoic acid (atRA) [Nedd9(mutRARE)-lacZ], virtually all β-galactosidase (β-gal, lacZ) expression is lost. Exposure of Nedd9(RARE)-lacZ transgenic embryos to excess atRA at embryonic day 8.0 (E8.0) leads to rostral ectopic transgene expression within 6 h whereas the Nedd9(mutRARE)-lacZ mutant does not show this effect. Thus the RARE upstream of the Nedd9 2B promoter is necessary for much of the endogenous gene expression during early development as well as ectopic expression in response to atRA.

  15. Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kısım Aslı

    2010-07-01

    Full Text Available Abstract Background Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR, myeloid cell leukemia-1 (MCL-1, tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A, TNFRSF1A-associated death domain protein (TRADD. Results We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF, TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions These are the preliminary molecular results of a novel combination treatment of

  16. {alpha}{sub v}{beta}{sub 3} imaging can accurately distinguish between mature teratoma and necrosis in {sup 18}F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

    Energy Technology Data Exchange (ETDEWEB)

    Aide, Nicolas [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen (France); Briand, Melanie; Dutoit, Soizic; Deslandes, Edwiges; Poulain, Laurent [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Bohn, Pierre; Rouvet, Jean; Modzelewski, Romain; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Department of Nuclear Medicine, Rouen (France); Lasnon, Charline [Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Chasle, Jacques [Francois Baclesse Cancer Centre and Caen University, Pathology Department, Caen (France); Vela, Antony [Francois Baclesse Cancer Centre and Caen University, Radiophysics Unit, Caen (France); Carreiras, Franck [Universite de Cergy Pontoise, UFR Sciences et Techniques, ERRMECe, EA 1391, Institut des materiaux, Cergy-Pontoise (France)

    2011-02-15

    We assessed whether imaging {alpha}{sub v}{beta}{sub 3} integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).{sup 18}F-Fluorodeoxyglucose ({sup 18}F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of {alpha}{sub v}{beta}{sub 3} expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [{sup 99m}Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse {alpha}{sub v}{beta}{sub 3} expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for {sup 18}F-FDG [mean standardised uptake value (SUV{sub mean}) = 0.48 {+-} 0.05] compared to untreated embryonal carcinoma (SUV{sub mean} = 0.92 {+-} 0.13) (p = 0.005). {alpha}{sub v}{beta}{sub 3} imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 {+-} 1.57) from necrosis (tumour to muscle ratio = 1.3 {+-} 0.26) (p = 0.0002). Immunohistochemistry studies showed that {alpha}{sub v}{beta}{sub 3} integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging {alpha}{sub v}{beta}{sub 3} integrin accurately distinguished mature teratoma from

  17. MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid

    International Nuclear Information System (INIS)

    Khan, Sonja; Wall, Deirdre; Curran, Catherine; Newell, John; Kerin, Michael J; Dwyer, Roisin M

    2015-01-01

    MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a. Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T 4 ) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3. The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log 10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log 10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log 10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T 4 alone did not stimulate miR-10a expression, the combination of T 4 and ATRA was found to have a positive synergistic effect. The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the

  18. Avaliação do Plano Operacional de Comercialização do Turismo: o caso de Bonito, município de Mato Grosso do Sul-Brasil

    Directory of Open Access Journals (Sweden)

    Milton Augusto Pasquotto Mariani

    2011-09-01

    Full Text Available

    O presente estudo tem como objetivo geral analisar as percepções do trade turístico de Bonito acerca do plano de comercialização desenvolvido para o município, buscando a compreensão da interface marketing-turismo. Tratando-se o marketing turístico como uma ferramenta para a conquista e manutenção de clientes, a fim de que a experiência vivenciada pelo turista seja única e inesquecível, o presente estudo justifica-se na busca de contribuições para a gestão pública do destino turístico analisado, com vistas a sua consolidação como pólo na atração de visitantes. Trata-se de um estudo qualitativo, de natureza exploratória, descritiva e explicativa, cujo procedimento de coleta, análise e interpretação dos dados resumiu-se em entrevistas com os atores locais. Os resultados apontam que aproximadamente 89% dos sujeitos consideram o plano importante para o desenvolvimento da atividade turística local, sendo que 44% o consideram importante para “vender” o destino como ícone brasileiro no ecoturismo; 33% o consideram importante por propiciar o direcionamento da região rumo à atração de turistas do mundo todo e 11% o consideram importante como ação estratégica para superar as dificuldades existentes e construir um novo posicionamento estratégico no mercado turístico. Sendo assim, referindo-se ao turismo como um dos principais setores empregatícios e gerador de renda para o município, o plano de comercialização se apresenta como uma ferramenta importante para a consolidação do destino como um verdadeiro pólo na atração de turistas.

  19. Alinhamento entre gestão do conhecimento e estratégia competitiva: um estudo de caso numa empresa de telecomunicações

    OpenAIRE

    Vilaça, Débora Barbosa Guedes de Oliveira

    2011-01-01

    As organizações da atualidade têm se deparado cada vez mais com um ambiente altamente competitivo, globalizante, onde o processo de inovação constante tem cobrado delas um comportamento proativo e dinâmico, em que muitas vezes elas se vêem forçadas a se anteciparem às necessidades e desejos de seus clientes e em muitos casos até mesmos criar e alimentar essas necessidades e desejos. É dentro deste contexto que as práticas de gestão do conhecimento têm atraído a atenção de vário...

  20. Cryptic PML-RARα positive acute promyelocytic leukemia with unusual morphology and cytogenetics

    Directory of Open Access Journals (Sweden)

    Goyal Manu

    2010-10-01

    Full Text Available Acute Promyelocytic Leukemia (APL is different from other forms of acute myeloid leukemia (AML, to the reason being the potential devastating coagulopathy and the sensitivity to all-trans retinoic acid (ATRA and arsenic trioxide (As 2 O 3 . We hereby present a case of APL, morphologically distinct from the hypergranular APL; however, the flow cytometry revealed a characteristic phenotype showing dim CD45, bright CD13, bright CD33 and dim CD117 positivity. These were negative for CD34, HLA-DR, B-lymphoid and T-lymphoid lineage markers. Conventional cytogenetics revealed a distinct karyotype of a male with translocation t(4;15(q34.2:q26.3. However, interphase florescence-in-situ hybridization (FISH revealed PML/RARA fusion signal on chromosome 15 in 90% cells. The cryptic translocations may be missed on conventional cytogenetics, however, need to be picked by other techniques as FISH.

  1. Simulação do efeito de palhada e adubação nitrogenada na produtividade de cana-de-açúcar

    OpenAIRE

    Leandro Garcia da Costa

    2012-01-01

    A demanda crescente por fontes energéticas alternativas, em detrimento dos combustiveis fósseis, tem dado destaque ao Brasil no cenário inernacional como modelo de produção de energia renovável e atraído investimentos massivos ao setor sucroenergético brasileiro nacional. Para garantir a segurança financeira do negócio, é necessário que a produção de cana-de-açúcar supra as necessidades socioeconômicas e agroambientais, com ênfase na relação entre a produção de energia elétrica, a partir da q...

  2. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

    Directory of Open Access Journals (Sweden)

    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  3. Graphene samples preparation and some possible uses in developing optical communication devices

    Directory of Open Access Journals (Sweden)

    Juan Diego Zapata-Caro

    2015-01-01

    Full Text Available El grafeno es un material bidimensional que ha atraído la atención de toda la comunidad científica alrededor del mundo; este interés es motivado por sus propiedades ópticas y electrónicas. Existen diferentes métodos para obtener grafeno, sin embargo el proceso más simple para su obtención es exfoliación micro mecánica, este proceso permite muestras con alta calidad. En este artículo, se muestra el proceso de preparación de muestras de grafeno por exfoliación micro mecánica y se usa la espectroscopia Raman para su caracterización. También se describen algunos posibles usos del grafeno en el desarrollo de dispositivos de comunicaciones ópticas de alta velocidad.

  4. HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis

    Science.gov (United States)

    Antignano, Frann; Korinek, Vladimir; Underhill, T. Michael

    2018-01-01

    The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been implicated in the regulation of this balance, partially by regulating innate lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we define a role for the transcriptional repressor Hypermethylated in cancer 1 (HIC1, ZBTB29) in the regulation of ILC responses in the intestine. Intestinal ILCs express HIC1 in a vitamin A-dependent manner. In the absence of HIC1, group 3 ILCs (ILC3s) that produce IL-22 are lost, resulting in increased susceptibility to infection with the bacterial pathogen Citrobacter rodentium. Thus, atRA-dependent expression of HIC1 in ILC3s regulates intestinal homeostasis and protective immunity. PMID:29470558

  5. La Universidad como espacio de mediación cultural

    Directory of Open Access Journals (Sweden)

    Willem FRIJHOFF

    2010-03-01

    Full Text Available RESUMEN: Los organizadores de este congreso me han concedido el tremendo honor de situar mi conferencia al final de nuestros trabajos, incluso recortando el tiempo disponible hasta un punto extremo. Me atrae la tentación de entregar un breve resumen de lo que se ha dicho y tratado, y ello porque algunas de las contribuciones que aquí se han presentado cosquillean, incluso provocan hasta un grado difícil de aguantar la conciencia profesional del historiador que soy. No se me ha pedido preparar una síntesis o una réplica. Por eso no lo haré. Al menos en la forma debida, porque tampoco puedo escabullirme del todo. ¿No es acaso la historia, como decía mi compatriota, el eminente historiador de la cultura que era Johan Huizinga, «una perpétua discusión»?

  6. Proyectos de desarrollo rural en zonas marginadas de Mexico usando ingenieria concurrente

    OpenAIRE

    González Almaguer, Carlos Alberto; Montejano, Gerardo; Vázquez Feijoo, Horacio; Nieto Barrera, Jorge; Lloveras Macià, Joaquín

    2012-01-01

    La Ingeniería concurrente (CE) ha atraído más atención en los últimos años debido a que su aplicación reduce el tiempo de diseño de productos desde su concepción hasta su manufactura masiva, mejorando la calidad y el desempeño de los equipos de trabajo en la organización rompiendo las barreras de la ingeniería secuencial. El presente documento muestra una metodología para la realización de proyectos rurales con nuevos productos agroindustriales o su innovación en zonas marginad...

  7. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

    Directory of Open Access Journals (Sweden)

    Harsh Shah

    2015-01-01

    Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  8. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis.

    Science.gov (United States)

    Shah, Harsh; Bradford, Carol; Sayar, Hamid

    2015-01-01

    We report a case of acute promyelocytic leukemia (APL) presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA-) containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  9. Praça da Matemática: as faces da história na construção de um monumento

    OpenAIRE

    Pimentel, Augusto Cesar Aguiar

    2008-01-01

    O presente trabalho consiste na investigação histórico-cultural da construção de uma praça, com um monumento em homenagem à Matemática, idealizado por um prefeito visionário, de 29 anos, na cidade de Itaocara, interior do Estado do Rio de Janeiro, no ano de 1943. O que é hoje uma atração turística, surgiu da criatividade do jovem político que apesar de advogado, via na matemática sua fonte de prazer. Para essa pesquisa, realizou-se entrevistas com o próprio prefeito da época...

  10. A new synonym of the Neotropical parasitoid wasp genus Notiospathius (Braconidae, Doryctinae), with redescription of two species and description of five new species from Brazil

    Science.gov (United States)

    De Jesús-Bonilla, Vladimir Salvador; Nunes, Juliano F.; Penteado-Dias, Angélica M.; Csösz, Sándor; Zaldívar-Riverón, Alejandro

    2011-01-01

    Abstract A junior synonym of the parasitoid wasp genus Notiospathius Matthews and Marsh, Hansonorum syn. n., with two new combinations, Notiospathius carolinae (Marsh) comb. n. and Notiospathius pauli (Marsh) comb. n., are proposed. Two species of Notiospathius from Brazil originally described in early twentieth century are redescribed, Notiospathius caudatus (Szépligeti) and Notiospathius diversus (Szépligeti). Five new species of Notiospathius from southern Brazil are also described: Notiospathius atra sp. n., Notiospathius johnlennoni sp. n., Notiospathius novateutoniae sp. n., Notiospathius sulcatus sp. n., and Notiospathius xanthofasciatus sp. n. Most of the type specimens of the above new species were collected in the mid twentieth century in the Nova Teutonia region, which is now part of the municipality of Seara in the state of Santa Catarina. PMID:21998528

  11. Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report.

    Science.gov (United States)

    He, Haiyan; An, Ran; Hou, Jian; Fu, Weijun

    2017-06-01

    Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.

  12. Turismo e sustentabilidade

    OpenAIRE

    Melo Filho, Benicio de

    2013-01-01

    Este trabalho trata da caracterização estrutural de uma área localizada no município de Tijucas do Sul, Estado do Paraná, para fins do desenvolvimento de turismo de base local, como também propõe uma estratégia de avaliação desse potencial. Como base metodológica realizou-se um inventario para observar as variáveis e os indicadores: índice de atração, histórica cultural, física ambiental, socioeconômica, política administrativa, índice populacional de desenvolvimento humano e infra-estrutura,...

  13. Incidencia del síndrome de Burnout en sacerdotes católicos lationamericanos y su relación con la inteligencia emocional

    OpenAIRE

    López Herrera, Helena

    2011-01-01

    [ES]Burnout es una palabra en inglés que significa “Quemado” o “Desgastado”. Este concepto se ha utilizado cuando una persona se siente agotada de su profesión u ocupación. Es un problema que alcanza tales magnitudes, que ha atraído la atención de los científicos de la conducta humana, quienes han identificado síntomas típicos de esta condición: dificultad para dormir, malestares somáticos (pérdida de peso, dolores de cabeza, perturbaciones gastrointestinales, fatiga crónica, depresión, entre...

  14. Bioactive Compounds from Omani Sea Cucumbers

    Directory of Open Access Journals (Sweden)

    Sergey Dobretsov

    2009-01-01

    Full Text Available Antimicrobial, anti-diatom and anti-larval activities of both water soluble (water  extracts and non-water soluble metabolites (methanol: chlorophorm, 1:1 extracts of the sea cucumbers Holothuria atra and Holothuria edulis  from Bander AL-Khiran region, Oman were tested in this study. There was no significant effect of  the extracts from sea cucumbers on bacterial (3 reference bacteria from seawater and pathogens  Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa,  Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus epidermidis and the diatom  Chaetoceros sp. growth. Both water extracts and methanol: chlorophorm extracts caused significant mortality of Artemia salina nauplia. This study suggests that Omani sea cucumbers might be a good  source of toxic anti-larval compounds.

  15. Structure-Activity Relationship Study of N(6)-Benzoyladenine-Type BRD4 Inhibitors and Their Effects on Cell Differentiation and TNF-α Production.

    Science.gov (United States)

    Amemiya, Seika; Yamaguchi, Takao; Sakai, Taki; Hashimoto, Yuichi; Noguchi-Yachide, Tomomi

    2016-01-01

    Bromodomains are epigenetic 'readers' of histone acetylation. The first potent bromodomain and extra-terminal domain (BET) inhibitors, (+)-JQ1 and I-BET762 (also known as GSK525762), were reported in 2010. Some BET inhibitors are already under clinical trial for the treatment of cancers, but so far, only a few chemical scaffolds are available. We have reported potent N(6)-benzoyladenine-based inhibitors of BRD4, a BET family member that serves as a key mediator of transcriptional elongation. Here we present an analysis of the structure-activity relationships of these inhibitors. Among the compounds examined, 20, 28 and 29 enhanced all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation and inhibited tumor necrosis factor (TNF)-α production by THP-1 cells.

  16. Reacciones de formación de enlaces C-C catalizadas por metales de transición y factores que les afectan

    OpenAIRE

    Noverges Pedro, Bárbara

    2015-01-01

    La síntesis y funcionalización de compuestos carbonílicos ha atraído la atención de los químicos a lo largo del tiempo ya que el grupo carbonilo es una función muy versátil en química orgánica y está presente en numerosos compuestos con actividad biológica. Por su parte, las reacciones de acoplamiento cruzado de dos y tres componentes son metodologías que actualmente se aplican a nivel tanto académico como industrial debido a que requieren condiciones suaves de reacción, la extracción de los ...

  17. Efeito do ácido fórmico na eletrodeposição de ligas Zn-Ni em substrato de aço

    OpenAIRE

    Pedroza, Graziella Aguiar Gomes

    2013-01-01

    A utilização dos depósitos de Zn-Ni eletrodepositados para melhorar a resistência à corrosão de chapas de aço revestidas tem atraído um interesse crescente porque oferece uma alternativa particularmente promissora para o Zn puro, devido às suas melhores propriedades mecânicas e de resistência à corrosão. Portanto, os estudos sobre os fatores que aumentam a eficiência de deposição e resistência à corrosão de eletrodepósitos das ligas Zn-Ni são altamente relevantes. Este trabalho descreve uma i...

  18. Engenharia da máquina de Stirling em armadilhas iônicas e protocolo de medida da função de distribuição de trabalho

    OpenAIRE

    Victor Fernandes Teizen

    2014-01-01

    As ligações entre a termodinâmica e a mecânica quântica mostram-se interessantes tópicos de pesquisa desde os anos 50 e tem atraído cada vez mais atenção nos últimos anos, tanto por suas possíveis aplicações tecnológicas, quanto pelo aspecto teórico - como, por exemplo, as relações de sistemas quânticos com a segunda lei da termodinâmica. Para sistemas quânticos mesoscópicos, restritos apenas a um número relativamente pequeno de estados energéticos, torna-se necessária uma generalização da te...

  19. Synthetic sex pheromone use for field trapping of diamondback moth males

    OpenAIRE

    MICHEREFF, MIRIAN FERNANDES FURTADO; VILELA, EVALDO FERREIRA; MICHEREFF FILHO, MIGUEL; MAFRA-NETO, AGENOR

    2000-01-01

    Este trabalho teve como objetivo estudar a atração dos machos da traça-das-crucíferas (Plutella xylostella L., Lepidoptera: Yponomeutidae) por diferentes formulações do feromônio sexual sintético. Os tratamentos consistiram em: 1) formulação comercial; 2) Z11,16:Ald; 3) Z11,16:Ac; 4) mistura 7:3 de 2+3; 5) mistura 5:5 de 2+3; 6) septos de borracha com hexano (testemunha); e 7) cinco fêmeas virgens. A formulação comercial do feromônio sexual sintético propiciou maior captura de machos, não dif...

  20. Trisomy 11 as an Additional Chromosome Alteration in a Child with Acute Promyelocytic Leukemia with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Elenice Ferreira Bastos

    2012-01-01

    Full Text Available The prognostic significance of the additional abnormalities to the t(15; 17 remains controversial. We report a case of promyelocytic leukemia (APL in a ten-year-old boy. Classical and molecular cytogenetic (FISH studies of a bone marrow sample obtained at diagnosis revealed the presence of trisomy of chromosome 11 as an additional chromosomal abnormality to the t(15; 17. The presence of the translocation t(15; 17, the cytogenetic marker of APL, is usually associated with good response to treatment with ATRA. In this case, although the patient had risk factors associated with good prognosis, he evolved and died quickly. So it seems that the presence of the trisomy 11 may be associated with disease progression and the poor outcome. To our knowledge, this is the first reported case of t(15; 17 associated with trisomy of chromosome 11 in a child with APL.

  1. Lichensphere: a protected natural microhabitat of the non-lichenised fungal communities living in extreme environments of Antarctica.

    Science.gov (United States)

    Santiago, Iara F; Soares, Marco Aurélio; Rosa, Carlos A; Rosa, Luiz H

    2015-11-01

    We surveyed the diversity, distribution and ecology of non-lichenised fungal communities associated with the Antarctic lichens Usnea antarctica and Usnea aurantiaco-atra across Antarctica. The phylogenetic study of the 438 fungi isolates identified 74 taxa from 21 genera of Ascomycota, Basidiomycota and Zygomycota. The most abundant taxa were Pseudogymnoascus sp., Thelebolus sp., Antarctomyces psychrotrophicus and Cryptococcus victoriae, which are considered endemic and/or highly adapted to Antarctica. Thirty-five fungi may represent new and/or endemic species. The fungal communities displayed high diversity, richness and dominance indices; however, the similarity among the communities was variable. After discovering rich and diverse fungal communities composed of symbionts, decomposers, parasites and endemic and cold-adapted cosmopolitan taxa, we introduced the term "lichensphere". We hypothesised that the lichensphere may represent a protected natural microhabitat with favourable conditions able to help non-lichenised fungi and other Antarctic life forms survive and disperse in the extreme environments of Antarctica.

  2. El escrito, la palabra y el gesto en las tomas de posesión señoriales

    Directory of Open Access Journals (Sweden)

    Isabel BECEIRO PITA

    2009-12-01

    Full Text Available Las tomas de posesión han atraído el interés de los historiadores en cuanto actos rituales que expresan la naturaleza del poder de una forma simbólica, que guarda similitudes con el vasallaje y la investidura feuda1. Con todo, a mi entender, los elementos de esta construcción imaginaria no pueden ser comprendidos cabalmente si no se efectúa, además, el análisis de los canales utilizados para transmitirla a sus destinatarios. Estos canales se pueden sintetizar en la suma de los tres sistemas de comunicación de todo mensaje: la escritura, la oralidad y el gesto, entendiendo este último como una totalidad de expresiones y movimientos que poseen un valor connotativo.

  3. Prácticas socioculturales, turismo e identidad entre los hijos de migrantes yucatecos en Cancún

    Directory of Open Access Journals (Sweden)

    Pedro Antonio Be Ramírez

    2017-06-01

    Full Text Available El centro turístico de Cancún en el sur de México atrae a muchas familias migrantes mayas originarias de la región maicera de la península yucateca, donde las tradiciones ceremoniales y rituales se conservan. En el nuevo escenario, la transmisión de prácticas y valores indígenas a las nuevas generaciones está en tensión constante con el contexto turístico de la ciudad. Desde la perspectiva de los hijos de las familias migrantes, nos enfocamos en el rol de la cultura maya para dar significado a las prácticas y construcciones sociales que ofrecen un sentido de congruencia a las vidas.

  4. El México abismal de Roberto Bolaño

    Directory of Open Access Journals (Sweden)

    Felipe Adrián Ríos Baeza

    2016-07-01

    Full Text Available Este trabajo de análisis no solo resalta la presencia de México, en cuanto motivo literario y espacio refractado estéticamente, en la literatura de Roberto Bolaño, cuestión que ha atraído a la mayoría de la crítica especializada, sino analiza su comportamiento y su influjo en diversos personajes, con el propósito de demostrar la hipótesis de que dicho país deviene algo más que una referencia. En su obra, México resulta un acontecimiento, como se entiende en la crítica posestructuralista, capaz de alterar la percepción de quienes allí habitan o arriban, posibilitando la invención de un territorio altamente caótico y cambiante.

  5. El México abismal de Roberto Bolaño

    OpenAIRE

    Felipe Adrián Ríos Baeza

    2016-01-01

    Este trabajo de análisis no solo resalta la presencia de México, en cuanto motivo literario y espacio refractado estéticamente, en la literatura de Roberto Bolaño, cuestión que ha atraído a la mayoría de la crítica especializada, sino analiza su comportamiento y su influjo en diversos personajes, con el propósito de demostrar la hipótesis de que dicho país deviene algo más que una referencia. En su obra, México resulta un acontecimiento, como se entiende en la crítica posestructuralista, capa...

  6. Trends of some wintering waterbirds in Lazio (1993-2006

    Directory of Open Access Journals (Sweden)

    Massimo Brunelli

    2012-09-01

    Full Text Available Since the 90s, censuses of wintering waterfowl have been carried out in the main wetlands of Lazio. We analysed the trends of 31 species in the 1993-2006 period (base year 1993 by means of TRIM (Trends and Indices Monitoring data software (Model 3. Among the species regularly recorded in the region, Ardea alba, Ardea cinerea, Bubulcus ibis and Anser anser showed a strong increase; Podiceps cristatus, Nycticorax nycticorax, Egretta garzetta, Phoenicopterus ruber, Anas penelope, Anas strepera, Anas crecca, Anas platyrhynchos, Anas clypeata, Netta rufina, Aythya ferina, Aythya nyroca, Circus aeruginosus, Fulica atra, Pluvialis apricaria and Vanellus vanellus showed a moderate increase; Gavia arctica, Tachybaptus ruficollis, Podiceps nigricollis, Phalacrocorax carbo, Aythya fuligula and Numenius arquata resulted “stable”; Botaurus stellaris, Tadorna tadorna, Anas acuta, Pluvialis squatarola and Calidris alpina showed an uncertain trend. The trends for most species are similar to those recorded at a national level.

  7. The Importance of Landscape Structure for the Long-Term Conservation of Species

    DEFF Research Database (Denmark)

    Nabe-Nielsen, Jacob; Sibly, Richard M; Forchhammer, Mads C.

    population recovery was affected by landscape structure for four species in an agricultural landscape: skylark (Alauda arvensis), vole (Microtus agrestis), a ground beetle (Bembidion lampros) and a linyphiid spider (Erigone atra). We characterized population persistence based on equilibrium population sizes...... (K) and the time it took populations to recover from perturbations. We separated the effects of corridors and patch arrangement by comparing results from a real landscape with results from two virtual landscapes: One where linear corridors were removed by homogenizing patch shapes, while leaving...... the spatial arrangement of the patches unaltered, and one where patches were shuffled around, while still leaving the landscape composition unaltered. Patch arrangement and the presence of corridors had a large effect on population dynamics for species whose local success depended on the identity...

  8. América Latina marginada

    Directory of Open Access Journals (Sweden)

    Tito Drago

    2015-01-01

    Full Text Available La renovación en los países comunistas atrae la atención, el comercio, las inversiones y la ayuda de Estados Unidos, Japón y Europa Occidental. En una primera etapa, ello incidirá negativamente en las relaciones de ese continente con América Latina, es creciente y está en pleno proceso acelerado, la marginación del comercio exterior de la Comunidad Europea. Las inversiones directas no presentan perspectivas. Asegura que a esto se suma la invasión a Panamá, que fue interpretada como que las potencias llegaron a acuerdos en Malta para el reparto del mundo.Con la perestroika la situación de América Latina desmejoró notablemente.

  9. La nueva crisis de los refugiados en Europa: una revisita del modelo de repulsión-atracción y los desafíos de las nuevas políticas migratorias

    OpenAIRE

    Oliveira, Catarina Reis; Peixoto, João; Góis, Pedro

    2017-01-01

    Resumo O objetivo deste artigo é refletir sobre os desafios que se colocam perante os novos fluxos de refugiados dirigidos à Europa desde o início da segunda década do século XXI. Com o intuito de explicar a nova crise dos refugiados, revisita-se o modelo de repulsão-atração e confronta-se o desígnio da agência – motivos individuais que induzem à migração – com a interferência da estrutura – fatores económicos, sociais e políticos que explicam o aumento dos fluxos, atendendo também à dinâmica...

  10. Immunomodulatory effects of honey cannot be distinguished from endotoxin

    DEFF Research Database (Denmark)

    Timm, Michael; Bartelt, Stine; Hansen, Erik Wind

    2008-01-01

    in vitro effects of honey. Our results show that natural honeys induce interleukin-6 release from Mono Mac 6 cells as well as release of reactive oxygen species from all-trans retinoic acid (ATRA) differentiated HL-60 cells. The natural honeys contained substantial amounts of endotoxin, and the responses...... observed in the cell based assays were similar to the responses induced by endotoxin alone. In addition, we determined that the immunomodulatory component present in the natural honeys was retained in the ultra filtrated fraction with a molecular weight greater than 20 kDa. The component was resistant...... to boiling and its immunomodulatory activity could be abrogated by the addition of polymyxin B. We speculate that the observed in vitro immunomodulatory effects of honey might solely be explained by the endotoxin content in the natural honeys....

  11. Ajuste de particiones planas mediante diagramas de Voronoi discretos

    OpenAIRE

    García Bernal, Daniel

    2017-01-01

    La geometría computacional se centra en el diseño y análisis de algoritmos para problemas geométricos. En la última decada, esta disciplina ha atraído un enorme interés. Pero ha sido en los últimos a~nos cuando se ha incrementado el interés en una estructura geométrica, concretamente los diagramas de Voronoi. No solo por sus características y propiedades matemáticas, sino también por aparecer ampliamente relacionados con fenómenos y procesos físicos que se dan en la naturale...

  12. Estratégias de desenvolvimento do Brasil e da China

    OpenAIRE

    Oliveira Júnior, Alcides Mário Amaral de

    2011-01-01

    Resumo: Este trabalho visa analisar as estratégias de desenvolvimento econômico de longo prazo, observando as experiências do Brasil e da China. O mundo era diferente três décadas atras. A economia do Brasil era maior do que a da China. Os anos de 1980 marcaram uma trajetória diferente entre estes dois países. A China cresceu nas últimas três décadas a taxas médias de 8% enquanto o Brasil ficou com uma média de 3% no mesmo período. O objetivo do presente trabalho é analisar quais os motivos d...

  13. Aportaciones coloniales a las creencias funerarias ibéricas

    Directory of Open Access Journals (Sweden)

    Joaquín García Raya

    1999-01-01

    Full Text Available La «mediterraneidad» de la península ibérica ha producido una serie de contactos con otros pueblos de esta cuenca, atraídos por su riqueza minera o como recurso a la colmatación de sus territorios de origen, lo cual produjo una traslación de ritos funerarios, cuya lectura arqueológica ha significado interpretaciones erróneas básicas.The "Mediterranean style» of the Iberian Península has given way to a series of contacts wth otherpeoples fron this valley, attracted by its mining richness and as an option tgo the overcrowding of their native territories. This brought about the implantation of funeral ceremonies, who archaelogical reading has meant false interpretations.

  14. Avaliação do desempenho ambiental e racionalização do consumo de água no segmento industrial de produção de bebidas

    OpenAIRE

    Cavalcante,Luciana Miranda; Machado,Luíza Carla Girad Teixeira; Lima,Aline Maria Meiguins de

    2013-01-01

    A região Amazônica, detentora de grande potencial hídrico, tem atraído indústrias que promovem uso intensivo de água, por isso, existe uma emergência por instrumentos que administrem essa tendência. Neste trabalho foi diagnosticado o nível de racionalização do uso da água pelo setor industrial de produção de bebidas no estado do Pará, assim como as causas do comportamento do setor. As variáveis dependentes (de comportamento) foram classificadas de acordo com quatro dimensões (gestão ambiental...

  15. Evaluation of the environmental performance and rationing of water consumption in industrial production of beverages

    OpenAIRE

    Cavalcante, Luciana Miranda; Machado, Luíza Carla Girad Teixeira; Lima, Aline Maria Meiguins de

    2013-01-01

    A região Amazônica, detentora de grande potencial hídrico, tem atraído indústrias que promovem uso intensivo de água, por isso, existe uma emergência por instrumentos que administrem essa tendência. Neste trabalho foi diagnosticado o nível de racionalização do uso da água pelo setor industrial de produção de bebidas no estado do Pará, assim como as causas do comportamento do setor. As variáveis dependentes (de comportamento) foram classificadas de acordo com quatro dimensões (gestão ambiental...

  16. Perspectivas Futuras do Aquecimento Residencial de Água no Brasil: uma Análise a Partir da Construção de Cenários

    OpenAIRE

    Sgarbi, Felipe de Albuquerque; Guilherme, Danielle Johann; Croso, Taluia; Fossa, Alberto; dos Santos, Edmilson Moutinho; Fagá, Murilo Tadeu Werneck

    2014-01-01

    Eletricidade é a principal forma de energia utilizada no aquecimento de água para banho no Brasil. O elevado consumo elétrico decorrente desse uso final, entretanto, tem atraído a atenção daqueles envolvidos no planejamento energético do país na medida em que análises indicam que a expansão da capacidade de geração elétrica deve ocorrer a partir da maior participação de fontes de energia não renováveis em detrimento da hidroeletricidade. Além disso, a utilização maciça de chuveiros elétricos ...

  17. Avaliação do perfil do consumidor que escolhe produtos de beleza através das Tecnologias de Informação e Comunicação (TICs) sob a ótica da Etnografia Digital.

    OpenAIRE

    FERREIRA, Juliana da Cunha

    2014-01-01

    Diante da expansão de ferramentas tecnológicas e plataformas digitais como as mídias sociais, as empresas estão atentas ao desenvolvimento, aceitação e poder de penetração dessas tecnologias de comunicação. Tal desenvolvimento tem chamado a atenção e convidado empresas de todos os ramos comerciais, a estreitar laços e conhecer o perfil de uma parcela da população (internautas), que em constante expansão, é intimamente influenciada por opiniões e atraída pelo dinamismo que as Tecnologias de In...

  18. Metodologías Sintéticas para la Obtención de Compuestos de Coordinación Metal-Orgánicos

    OpenAIRE

    Bazán Blau, Begoña del Pilar; Barandika Argoitia, Miren Gotzone; Calderón Casado, Ainhoa; Fidalgo Marijuan, Arkaitz; Llano Tomé, Francisco; Urtiaga Greaves, Miren Karmele; Arriortua Marcaida, María Isabel

    2016-01-01

    Comunicación a congreso (póster): Reunión conjunta de la Sociedad Española de Mineralogía y la Sociedad Española de Arcillas (SEM-SEA 2012), Bilbao 27-30 de junio 2012. La síntesis de compuestos híbridos orgánicos-inorgánicos o metal-organic framework (MOF) ha atraído un interés especial durante las últimas dos décadas, debido a la posibilidad de obtener una gran variedad de estructuras de interés para su empleo en aplicaciones relacionadas con los materiales porosos, como las zeolitas o e...

  19. Desenvolvimento de mix de sais com reduzido teor de sódio: otimização e caracterização sensorial temporal (TDS e TI)

    OpenAIRE

    Gonçalves, Carla Saraiva

    2013-01-01

    A redução de sódio em alimentos tem atraído muita atenção, uma vez que os estudos indicam uma correlação entre a ingestão de sal na dieta e algumas doenças. Métodos de otimização são úteis dentro da ciência sensorial como uma maneira de obter um resultado sob um conjunto específico de condições para que seja possível compreender questões que proporcione potenciais fórmulas. Neste estudo, avaliou-se a concentração ótima do cloreto de sódio na sopa de batata, usando a escala ideal, e a magnitud...

  20. CONFLITOS TERRITORIAIS ENTRE FAMÍLIAS QUE MOTIVARAM A MIGRAÇÃO INTERNA NOS SERTÕES DOS INHAMUNS – CEARÁ

    OpenAIRE

    Melo, Cristiane Castro Feitosa; Universidade Estadual do Ceará; Cruz, Maria Lucia Brito; Universidade Estadual do Ceará

    2015-01-01

    Este artigo analisa os conflitos territoriais entre duas famílias, no início do século XVIII, que motivaram a migração interna nos Sertões dos Inhamuns, no Estado do Ceará, região semiárida do Nordeste do Brasil. A implantação das sesmarias estabeleceu reestruturações espaciais, constituindo novos padrões de organização social, econômica e cultural. Nessa área o fluxo populacional se deu mediante dois processos: o de atração e o de deslocamento. A metodologia consiste em análise espaço-tempor...

  1. Desenvolvimento e implantação de unidade piloto de precipitação de partículas usando antissolvente supercrítico (SAS)

    OpenAIRE

    Rossa, Guilherme Evaldt

    2015-01-01

    O interesse em micro e nanopartículas tem crescido nos últimos anos, uma vez que o avanço tecnológico ampliou as possibilidades de produção e manipulação dessas partículas. Por ter aplicações em diferentes setores, tais como os de pigmentos, explosivos, polímeros, fármacos e supercondutores, a nanotecnologia tem atraído cada vez mais o interesse de governos, pesquisadores acadêmicos e indústrias. Dentre as tecnologias para obtenção de micro e nanopartículas, destacam-se as que fazem uso de an...

  2. Graphene samples preparation and some possible uses in developing optical communication devices

    OpenAIRE

    Juan Diego Zapata-Caro; Ana María Cárdenas-Soto; Rodrigo Henao-Henao; Eunezio Antonio Thoroh de Souza

    2015-01-01

    El grafeno es un material bidimensional que ha atraído la atención de toda la comunidad científica alrededor del mundo; este interés es motivado por sus propiedades ópticas y electrónicas. Existen diferentes métodos para obtener grafeno, sin embargo el proceso más simple para su obtención es exfoliación micro mecánica, este proceso permite muestras con alta calidad. En este artículo, se muestra el proceso de preparación de muestras de grafeno por exfoliación micro mecánica y se ...

  3. IDENTIFICACIÓN DE ALGUNAS ESPECIES DE MICROORGANISMOS BENÉFICOS EN LA RIZOSFERA DE GERBERA Y SU EFECTO EN LA PRODUCTIVIDAD

    Directory of Open Access Journals (Sweden)

    M. R. Soroa-Bell

    2009-01-01

    Full Text Available Se identificaron las especies de hongos micorrízicos arbusculares y los géneros de bacterias promotoras del crecimiento vegetal atraídos por los exudados radicales de Gerbera jamesonii cv. Bolus. Para el aislamiento de las bacterias promotoras del crecimiento vegetal, se utilizó el modelo espermosférico, los tubos colectores y la cámara de quimioatracción modificada. Para la caracterización de las cepas, se realizaron determinaciones micromorfológicas (movilidad, presencia de endosporas, entre otras y culturales (forma, tamaño, opacidad, entre otras en los medios estudiados. Se realizaron cinco repeticiones por tratamiento y se replicaron estas determinaciones tres veces. Se encontraron cinco especies de hongos micorrízicos arbusculares y cuatro géneros de bacterias promotoras del crecimiento vegetal atraídos por los exudados de gerbera. La especie Glomus hoi like, tuvo 10 esporas·g-1, mientras que por las bacterias promotoras del crecimiento vegetal. el género Pseudomonas representó el 30 % de los microorganismos presentes en la rizosfera. A partir de lo obtenido se inocularon plantas adultas establecidas en recipientes de cinco litros de capacidad de suelo ferralítico rojo más estiércol vacuno a una proporción de 2:1. Se evaluó el rendimiento y diámetro del capítulo floral, encontrándose que las plantas inoculadas con Glomus hoi like obtuvieron mayor ocupación fúngica en la raíz (1.91 %, mayores poblaciones de hongos (5.6 esporas·ml-1 y bacterias (8.2 log UFC·ml-1 y mayor número de flores (35.

  4. Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema.

    Science.gov (United States)

    Ozawa, Chihiro; Horiguchi, Michiko; Akita, Tomomi; Oiso, Yuki; Abe, Kaori; Motomura, Tomoki; Yamashita, Chikamasa

    2016-01-01

    Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair. Here, we demonstrate that treatment using a high-affinity PPARβ/δ agonist, GW0742, reverses the lung tissue damage induced by elastase in emphysema-model mice and improves respiratory function. Mice treated with elastase, which collapsed their alveoli, were then treated with either 10% dimethyl sulfoxide (DMSO) in saline (control group) or GW0742 (1.0 mg/kg twice a week) by pulmonary administration. Treatment with GW0742 for 2 weeks increased the in vivo expression of surfactant proteins A and D, which are known alveolar type II epithelial cell markers. GW0742 treatment also shortened the average distance between alveolar walls in the lungs of emphysema model mice, compared with a control group treated with 10% DMSO in saline. Treatment with GW0742 for 3 weeks also improved tissue elastance (cm H2O/mL), as well as the ratio of the forced expiratory volume in the first 0.05 s to the forced vital capacity (FEV 0.05/FVC). In each of these experiments, GW0742 treatment reversed the damage caused by elastase. In conclusion, PPARβ/δ agonists are potential therapeutic agents for pulmonary emphysema.

  5. Bebês: o irresistível poder da graciosidade. Um estudo sobre o significado evolutivo dos traços infantis Babies: the irresistible power of cuteness. A study concerning the evolutionary function of infantile traits

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    Monique Leitão

    2010-04-01

    Full Text Available Os bebês, em geral, despertam ternura e comportamentos de cuidado nas pessoas. O objetivo deste trabalho foi discutir a atração provocada pelos traços infantis, tendo como referencial teórico os quatro níveis de explicação de Tinbergen. Do ponto de vista dos mecanismos que desencadeiam essa atração neonatal, avaliamos a importância da aparência do infante para eliciar as respostas de cuidado parental. Considerando a função adaptativa desta característica, discutimos os processos evolutivos que moldaram as preferências pelos atributos infantis, além da história filogenética do favoritismo pelos sinais morfológicos de filhotes. Apresentamos, ainda, dados sobre o desenvolvimento deste traço comportamental ao longo da vida. Tomadas em conjunto, estas informações provêem uma análise de por que achamos os bebês tão irresistíveis.Babies generally elicit tenderness and caretaking behaviors on people. The aim of this study is to discuss the attraction towards babyish features, taking Tinbergen's four questions as a theoretical benchmark. Concerning the mechanisms implicated in this neonatal attraction, we evaluated the importance of children´s morphology on eliciting parental responses. Considering the adaptive function of this characteristic, we discuss the evolutionary process that shaped the preferences towards infantile traits as well as the phylogeny of the preference towards infant´s morphological traits. It was also presented data about the development of this behavioral trait across life span. The information provided here suggests a reason why we find babies such irresistible creatures.

  6. All Trans Retinoic Acid, Transforming Growth Factor β and Prostaglandin E2 in Mouse Plasma Synergize with Basophil-Secreted Interleukin-4 to M2 Polarize Murine Macrophages.

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    Victor W Ho

    Full Text Available In previous studies we found that macrophages (MФs from SH2-containing inositol-5'-phosphatase (SHIP deficient mice are M2 polarized while their wild type (WT counterparts are M1 polarized and that this difference in MФ phenotype can be recapitulated during in vitro derivation from bone marrow if mouse plasma (MP, but not fetal calf serum, is added to standard M-CSF-containing cultures. In the current study we investigated the mechanism by which MP skews SHIP-/- but not +/+ MФs to an M2 phenotype. Our results suggest that SHIP-/- basophils constitutively secrete higher levels of IL-4 than SHIP+/+ basophils and this higher level of IL-4 is sufficient to skew both SHIP+/+ and SHIP-/- MФs to an M2 phenotype, but only when MP is present to increase the sensitivity of the MФs to this level of IL-4. MP increases the IL-4 sensitivity of both SHIP+/+ and -/- MФs not by increasing cell surface IL-4 or CD36 receptor levels, but by triggering the activation of Erk and Akt and the production of ROS, all of which play a critical role in sensitizing MФs to IL-4-induced M2 skewing. Studies to identify the factor(s in MP responsible for promoting IL-4-induced M2 skewing suggests that all-trans retinoic acid (ATRA, TGFβ and prostaglandin E2 (PGE2 all play a role. Taken together, these results indicate that basophil-secreted IL-4 plays an essential role in M2 skewing and that ATRA, TGFβ and PGE2 within MP collaborate to dramatically promote M2 skewing by acting directly on MФs to increase their sensitivity to IL-4.

  7. Overexpression of HOXA4 and HOXA9 genes promotes self-renewal and contributes to colon cancer stem cell overpopulation.

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    Bhatlekar, Seema; Viswanathan, Vignesh; Fields, Jeremy Z; Boman, Bruce M

    2018-02-01

    Because HOX genes encode master regulatory transcription factors that regulate stem cells (SCs) during development and aberrant expression of HOX genes occurs in various cancers, our goal was to determine if dysregulation of HOX genes is involved in the SC origin of colorectal cancer (CRC). We previously reported that HOXA4 and HOXD10 are expressed in the colonic SC niche and are overexpressed in CRC. HOX gene expression was studied in SCs from human colon tissue and CRC cells (CSCs) using qPCR and immunostaining. siRNA-mediated knockdown of HOX expression was used to evaluate the role of HOX genes in modulating cancer SC (CSC) phenotype at the level of proliferation, SC marker expression, and sphere formation. All-trans-retinoic-acid (ATRA), a differentiation-inducing agent was evaluated for its effects on HOX expression and CSC growth. We found that HOXA4 and HOXA9 are up-regulated in CRC SCs. siRNA knockdown of HOXA4 and HOXA9 reduced: (i) proliferation and sphere-formation and (ii) gene expression of known SC markers (ALDH1, CD166, LGR5). These results indicate that proliferation and self-renewal ability of CRC SCs are reduced in HOXA4 and HOXA9 knockdown cells. ATRA decreased HOXA4, HOXA9, and HOXD10 expression in parallel with reduction in ALDH1 expression, self-renewal, and proliferation. Overall, our findings indicate that overexpression of HOXA4 and HOXA9 contributes to self-renewal and overpopulation of SCs in CRC. Strategies designed to modulate HOX expression may provide ways to target malignant SCs and to develop more effective therapies for CRC. © 2017 Wiley Periodicals, Inc.

  8. Exogenous Modulation of Retinoic Acid Signaling Affects Adult RGC Survival in the Frog Visual System after Optic Nerve Injury.

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    Mildred V Duprey-Díaz

    Full Text Available After lesions to the mammalian optic nerve, the great majority of retinal ganglion cells (RGCs die before their axons have even had a chance to regenerate. Frog RGCs, on the other hand, suffer only an approximately 50% cell loss, and we have previously investigated the mechanisms by which the application of growth factors can increase their survival rate. Retinoic acid (RA is a vitamin A-derived lipophilic molecule that plays major roles during development of the nervous system. The RA signaling pathway is also present in parts of the adult nervous system, and components of it are upregulated after injury in peripheral nerves but not in the CNS. Here we investigate whether RA signaling affects long-term RGC survival at 6 weeks after axotomy. Intraocular injection of all-trans retinoic acid (ATRA, the retinoic acid receptor (RAR type-α agonist AM80, the RARβ agonist CD2314, or the RARγ agonist CD1530, returned axotomized RGC numbers to almost normal levels. On the other hand, inhibition of RA synthesis with disulfiram, or of RAR receptors with the pan-RAR antagonist Ro-41-5253, or the RARβ antagonist LE135E, greatly reduced the survival of the axotomized neurons. Axotomy elicited a strong activation of the MAPK, STAT3 and AKT pathways; this activation was prevented by disulfiram or by RAR antagonists. Finally, addition of exogenous ATRA stimulated the activation of the first two of these pathways. Future experiments will investigate whether these strong survival-promoting effects of RA are mediated via the upregulation of neurotrophins.

  9. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

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    Shriram Nallamshetty

    Full Text Available The effects of retinoids, the structural derivatives of vitamin A (retinol, on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA and its precursor all trans retinaldehyde (Rald, exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1, the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT demonstrated that Aldh1a1-deficient (Aldh1a1(-/- female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/- mice. In serum assays, Aldh1a1(-/- mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/- mesenchymal stem cells (MSCs expressed significantly higher levels of bone morphogenetic protein 2 (BMP2 and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/- mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/- mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

  10. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

    Science.gov (United States)

    Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J; Plutzky, Jorge

    2013-01-01

    The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

  11. Influence of larval and pupal products on the oviposition behavior of Aedes Fluviatilis (Lutz (Diptera: Culicidae

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    Rotraut A. G. B. Consoli

    1988-06-01

    Full Text Available Several larval and pupal products of Aedes fluviatilis (Lutz were tested for their influence on the oviposition behaviour of females of the same species. Significant (alfa = 0,05 atractiveness was shown by: larval water, previously containing 5 to 15 larvae/1,5 ml; larval water, preserved up to 38 days; evaporate and reconstructed larval water extracts up to 2 years after production and water filtered through fresh or dried ground larvae. hexanic larval water extracts and water filtered through fresh or dired ground pupae did not influence oviposition.Estudou-se a influência sobre o comportamento de oviposição das fêmeas de Aedes fluviatilis (Lutz de produtos derivados das formas imaturas da mesma espécie. As fêmeas foram atraídas significativamente (x=0,05 por ocasião da ovoposição por: água destilada que contivera 5 ou 15 larvas/1,5 ml, a mesma água (5 larvas/1,5 mlapós sua preservação por 38 dias; extratos evaporados e reconstituídos de água que conteve larvas, por até dois anos a sua produção, e filtrados de macerados frescos e secos de larvas. Extratos hexânicos de água que conteve larvas e filtrados de macerados descos e secos de pupas não atraíram a ovoposição das fêmeas.

  12. Role of lichens in weathering of granodiorite in the Sila uplands (Calabria, southern Italy)

    Science.gov (United States)

    Scarciglia, Fabio; Saporito, Natalina; La Russa, Mauro F.; Le Pera, Emilia; Macchione, Maria; Puntillo, Domenico; Crisci, Gino M.; Pezzino, Antonino

    2012-12-01

    This paper explores the role of five recurrent epilithic lichen species (Aspicilia intermutans (Nyl.) Arnold, Xanthoparmelia pulla (Ach.) O. Blanco, A. Crespo, Elix, D. Hawksw. & Lumbsch, Rhizocarpon lecanorinum Anders, Tephromela atra (Huds.) Hafellner and Lecanora bolcana (Pollini) Poelt), which encrust granodiorite spheroidal boulders exposed in the Sila uplands (Calabria, southern Italy), in weathering of plutonic rocks in a typical mountainous Mediterranean environment. A detailed investigation was carried out on the lichen-rock interface of each species, by comparing them mutually and with lichen-free granodiorite samples. For this purpose, the lichen species were sampled together with the encrusted rock surface for detailed mineral-petrographic analyses performed in thin and ultra-thin sections. Optical and scanning electron microscopy of these sections and of bulk samples permitted us to highlight the peculiar modes of physical and chemical attacks of lichen thalli and hyphae on and into the substratum for each species. Crack systems often parallel to the outer rock surface appear often intruded by hyphae, which cause rupture of primary minerals, with detachment and progressive incorporation of their fragments into the thallus. In particular, the species L. bolcana and T. atra revealed an unexpected, partly endolithic behavior, presumably enhanced by the presence of rock fractures earlier generated by other physical breakage processes already affecting the spheroidal boulders in the Sila mountains. Dissolution features often affect primary minerals (even quartz), that may show very peculiar patterns which are suggestive of a biologically-induced control. Various phyllosilicate clay minerals were identified using SEM-EDS microprobe analyses and FT-IR spectroscopy, which also enabled the identification of possible amorphous silica (or quartz micrograins), rhizocarpic acid and carotenoid at the encrusted granodiorite interface. In contrast, neither oxalic

  13. Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration.

    Science.gov (United States)

    Maier, Oliver; Böhm, Julia; Dahm, Michael; Brück, Stefan; Beyer, Cordian; Johann, Sonja

    2013-06-01

    Alpha-motoneurons appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Morphological and physiological degeneration of this neuronal phenotype is typically characterized by a marked decrease of neuronal markers and by alterations of cholinergic metabolism such as reduced choline acetyltransferase (ChAT) expression. The motoneuron-like cell line NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells. In order to further establish this cell line as a valid model system to investigate cholinergic neurodegeneration, NSC-34 cells were differentiated by serum deprivation and additional treatment with all-trans retinoic acid (atRA). Cell maturation was characterized by neurite outgrowth and increased expression of neuronal and cholinergic markers, including MAP2, GAP-43 and ChAT. Subsequently, we used differentiated NSC-34 cells to study early degenerative responses following exposure to various neurotoxins (H2O2, TNF-α, and glutamate). Susceptibility to toxin-induced cell death was determined by means of morphological changes, expression of neuronal marker proteins, and the ratio of pro-(Bax) to anti-(Bcl-2) apoptotic proteins. NSC-34 cells respond to low doses of neurotoxins with increased cell death of remaining undifferentiated cells with no obvious adverse effects on differentiated cells. Thus, the different vulnerability of differentiated and undifferentiated NSC-34 cells to neurotoxins is a key characteristic of NSC-34 cells and has to be considered in neurotoxic studies. Nonetheless, application of atRA induced differentiation of NSC-34 cells and provides a suitable model to investigate molecular events linked to neurodegeneration of differentiated neurons. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes.

    Science.gov (United States)

    Moradzadeh, Maliheh; Tabarraei, Alijan; Sadeghnia, Hamid Reza; Ghorbani, Ahmad; Mohamadkhani, Ashraf; Erfanian, Saiedeh; Sahebkar, Amirhossein

    2018-02-01

    Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 μM) and all-trans retinoic acid (ATRA; 10 μM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients. © 2017 Wiley Periodicals, Inc.

  15. Highly Efficient Differentiation and Enrichment of Spinal Motor Neurons Derived from Human and Monkey Embryonic Stem Cells

    Science.gov (United States)

    Wada, Tamaki; Honda, Makoto; Minami, Itsunari; Tooi, Norie; Amagai, Yuji; Nakatsuji, Norio; Aiba, Kazuhiro

    2009-01-01

    Background There are no cures or efficacious treatments for severe motor neuron diseases. It is extremely difficult to obtain naïve spinal motor neurons (sMNs) from human tissues for research due to both technical and ethical reasons. Human embryonic stem cells (hESCs) are alternative sources. Several methods for MN differentiation have been reported. However, efficient production of naïve sMNs and culture cost were not taken into consideration in most of the methods. Methods/Principal Findings We aimed to establish protocols for efficient production and enrichment of sMNs derived from pluripotent stem cells. Nestin+ neural stem cell (NSC) clusters were induced by Noggin or a small molecule inhibitor of BMP signaling. After dissociation of NSC clusters, neurospheres were formed in a floating culture containing FGF2. The number of NSCs in neurospheres could be expanded more than 30-fold via several passages. More than 33% of HB9+ sMN progenitor cells were observed after differentiation of dissociated neurospheres by all-trans retinoic acid (ATRA) and a Shh agonist for another week on monolayer culture. HB9+ sMN progenitor cells were enriched by gradient centrifugation up to 80% purity. These HB9+ cells differentiated into electrophysiologically functional cells and formed synapses with myotubes during a few weeks after ATRA/SAG treatment. Conclusions and Significance The series of procedures we established here, namely neural induction, NSC expansion, sMN differentiation and sMN purification, can provide large quantities of naïve sMNs derived from human and monkey pluripotent stem cells. Using small molecule reagents, reduction of culture cost could be achieved. PMID:19701462

  16. DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies.

    Science.gov (United States)

    Le Pogam, Carole; Patel, Satyananda; Gorombei, Petra; Guerenne, Laura; Krief, Patricia; Omidvar, Nader; Tekin, Nilgun; Bernasconi, Elena; Sicre, Flore; Schlageter, Marie-Helene; Chopin, Martine; Noguera, Maria-Elena; West, Robert; Abu, Ansu; Mathews, Vikram; Pla, Marika; Fenaux, Pierre; Chomienne, Christine; Padua, Rose Ann

    2015-10-20

    We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNγ) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-κB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers.

  17. A study of ribonuclease activity in venom of vietnam cobra

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    Thiet Van Nguyen

    2017-09-01

    Full Text Available Abstract Background Ribonuclease (RNase is one of the few toxic proteins that are present constantly in snake venoms of all types. However, to date this RNase is still poorly studied in comparison not only with other toxic proteins of snake venom, but also with the enzymes of RNase group. The objective of this paper was to investigate some properties of RNase from venom of Vietnam cobra Naja atra. Methods Kinetic methods and gel filtration chromatography were used to investigate RNase from venom of Vietnam cobra. Results RNase from venom of Vietnam cobra Naja atra has some characteristic properties. This RNase is a thermostable enzyme and has high conformational stability. This is the only acidic enzyme of the RNase A superfamily exhibiting a high catalytic activity in the pH range of 1–4, with pHopt = 2.58 ± 0.35. Its activity is considerably reduced with increasing ionic strength of reaction mixture. Venom proteins are separated by gel filtration into four peaks with ribonucleolytic activity, which is abnormally distributed among the isoforms: only a small part of the RNase activity is present in fractions of proteins with molecular weights of 12–15 kDa and more than 30 kDa, but most of the enzyme activity is detected in fractions of polypeptides, having molecular weights of less than 9 kDa, that is unexpected. Conclusions RNase from the venom of Vietnam cobra is a unique member of RNase A superfamily according to its acidic optimum pH (pHopt = 2.58 ± 0.35 and extremely low molecular weights of its major isoforms (approximately 8.95 kDa for RNase III and 5.93 kDa for RNase IV.

  18. 15-Deoxy-Δ12,14-Prostaglandin J2 regulates leukemia inhibitory factor signaling through JAK-STAT pathway in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Rajasingh, Johnson; Bright, John J.

    2006-01-01

    Embryonic stem (ES) cells are genetically normal, pluripotent cells, capable of self-renewal and differentiation into all cell lineages. While leukemia inhibitory factor (LIF) maintains pluripotency in mouse ES cells, retinoic acid and other nuclear hormones induce neuro-glial differentiation in mouse and human ES cells in culture. Peroxisome-proliferator-activated receptors (PPARs) are ligand-dependent nuclear receptor transcription factors that regulate cell growth and differentiation in many cell types. However, the role of PPARs in the regulation of ES cell growth and differentiation is not known. In this study, we show that LIF induces proliferation and self-renewal of mouse D3-ES cells in culture. However, treatment with 15-Deoxy-Δ 12,14 -Prostaglandin J 2 (15d-PGJ2), a natural ligand for PPARγ, or all-trans retinoic acid (ATRA) results in a dose-dependent decrease in proliferation and self-renewal in D3-ES cells. Immunoprecipitation and Western blot analyses showed that LIF induces tyrosine phosphorylation of JAK1, TYK2 and STAT3 in 30 min and treatment with 15d-PGJ2 or ATRA results in a dose-dependent decrease in LIF-induced phosphorylation of JAK1 and STAT3 in D3-ES cells. However, treatment of D3-ES cells with Ciglitazone or 15d-PGJ2 for 48 h in culture resulted in a dose-dependent increase in PPARγ protein expression. These results suggest that PPARγ agonists regulate LIF signaling through JAK-STAT pathway leading to growth and self-renewal of ES cells

  19. Study of apoptotic mechanisms induced by all-trans retinoic acid and its 13-cis isomer on cellular lines of human hepato carcinoma Hep3B and HepG2

    International Nuclear Information System (INIS)

    Arce Vargas, Frederick

    2006-01-01

    Two cellular lines of liver cancer (Hep3B and HepG2) were incubated during different periods of time with some concentrations of two retinoic acid isomers (ATRA and 13-cis AR) and with 5-fu chemotherapeutic agents, cisplatin and paclitaxel. It was determined if these substances leaded cytotoxicity, apoptosis and if they modified the expression of different genes related to cellular death by apoptosis, in order to explain the hepatocellular carcinoma resistance to these drugs. HepG2 cells showed more resistance than Hep3B cells to 72 hours of treatment, as much ATRA as the 13-cis AR were toxic and produced apoptosis in two cellular lines. This type of cellular death seems to be mediated by a decrease in Bcl-xL concentration in Hep3B cells treated with both retinoids an increase in bax concentration in HepG2 cells treated with 13-cis AR. It were observed 3 and 8 proteolysis of procaspase in Hep3B cells, suggesting extrinsic via activation of the apoptosis, while cellular death in HepG2 cells seems to be independent of caspases. Cisplatin and paclitaxel leaded cytotoxicity to 48 hours of treatment, with significant differences between two cellular lines only in case of paclitaxel. Hep3B cells treated with cisplatin and HepG2 cells treated with paclytaxel suffered apoptosis. 5-FU produced toxicity only when it was used to high concentrations and the mechanism of cellular death induced by this agent seems to be primarily necrosis in Hep3B cells and apoptosis in HepG2. There was decrease in the Bcl-xL concentration in two cellular lines when it was treated with cisplatin and in HepG2 cells treated with 5-FU. Bax concentration there no was modified with no treatment. Activation of the 3 caspases seems to happen only in HepG2 cells with 5-FU and paclytaxel. These two agents, also, decreased the survivin concentration of HepG2 cells. Treatments of the three drugs produced an increase in the expression of this gen in Hep3B cells, which might explain partially the resistance

  20. Study of apoptotic mechanisms induced by all-trans retinoic acid and its 13-cis isomer on cellular lines of human hepato carcinoma Hep3B and HepG2; Estudio de los mecanismos apoptoticos inducidos por el acido retinoico todo-trans y su isomero 13-cis en las lineas celulares de hepatocarcinoma humano Hep3B y HepG2

    Energy Technology Data Exchange (ETDEWEB)

    Arce Vargas, Frederick [Costa Rica

    2006-07-01

    Two cellular lines of liver cancer (Hep3B and HepG2) were incubated during different periods of time with some concentrations of two retinoic acid isomers (ATRA and 13-cis AR) and with 5-fu chemotherapeutic agents, cisplatin and paclitaxel. It was determined if these substances leaded cytotoxicity, apoptosis and if they modified the expression of different genes related to cellular death by apoptosis, in order to explain the hepatocellular carcinoma resistance to these drugs. HepG2 cells showed more resistance than Hep3B cells to 72 hours of treatment, as much ATRA as the 13-cis AR were toxic and produced apoptosis in two cellular lines. This type of cellular death seems to be mediated by a decrease in Bcl-xL concentration in Hep3B cells treated with both retinoids an increase in bax concentration in HepG2 cells treated with 13-cis AR. It were observed 3 and 8 proteolysis of procaspase in Hep3B cells, suggesting extrinsic via activation of the apoptosis, while cellular death in HepG2 cells seems to be independent of caspases. Cisplatin and paclitaxel leaded cytotoxicity to 48 hours of treatment, with significant differences between two cellular lines only in case of paclitaxel. Hep3B cells treated with cisplatin and HepG2 cells treated with paclytaxel suffered apoptosis. 5-FU produced toxicity only when it was used to high concentrations and the mechanism of cellular death induced by this agent seems to be primarily necrosis in Hep3B cells and apoptosis in HepG2. There was decrease in the Bcl-xL concentration in two cellular lines when it was treated with cisplatin and in HepG2 cells treated with 5-FU. Bax concentration there no was modified with no treatment. Activation of the 3 caspases seems to happen only in HepG2 cells with 5-FU and paclytaxel. These two agents, also, decreased the survivin concentration of HepG2 cells. Treatments of the three drugs produced an increase in the expression of this gen in Hep3B cells, which might explain partially the resistance

  1. Música, comportamento social e relações interpessoais Music, social behavior and interpersonal relationships

    Directory of Open Access Journals (Sweden)

    Beatriz Ilari

    2006-04-01

    Full Text Available O objetivo desta investigação foi verificar o papel da música na atração interpessoal, escolha de parceiros e relacionamentos afetivos. Cinqüenta adultos não-músicos escolheram possíveis parceiros através de classificados pessoais, descreveram as características de ouvintes de 7 gêneros musicais diferentes e responderam a questões referentes ao uso da música em seus relacionamentos afetivos. Embora a música não tenha tido um efeito direto sobre a atração interpessoal e a escolha de parceiros, ela aparentou ter alguns efeitos indiretos nas relações interpessoais. Alguns estereótipos de personalidade associados aos gêneros musicais foram encontrados, sugerindo que o gosto musical pode influenciar na escolha de parceiros. Além disso, emergiram quatro categorias relacionadas ao uso da música no contexto das relações interpessoais: objetivos de excitação, fundo acústico, facilitadora de atividades que promovem a aproximação e artefato mnemônico. Os dados desta investigação reforçam a idéia de que a música exerce um papel importante nas relações interpessoais.The purpose of this study was to investigate the effects of music on interpersonal relationships by means of attraction, choice of partners, and romantic relationships. Fifty adult non-musicians chose potential partners in newspaper ads, described the characteristics of listeners of 7 different musical styles, and answered open-ended questions related to the uses of music in interpersonal relationships of a romantic nature. Although music did not seem to impact interpersonal attraction and choice of partners directly, it was found to impact social bonding in indirect ways. Personality types associated with musical styles emerged, suggesting that musical taste influences interpersonal relationships. Additionally, four categories related to the uses of music in the context of interpersonal relationships emerged including arousal goals, background, facilitator

  2. Fish community structure on coral habitats with contrasting architecture in the Tropical Eastern Pacific

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    María del Mar Palacios

    2014-02-01

    Full Text Available La arquitectura del paisaje arrecifal, definida por la morfología de los corales dominantes, puede desempeñar un papel importante en la estructura y composición de las comunidades de peces al afectar la disponibilidad de nichos y recursos y modificar las interacciones interespecíficas. Hicimos un estudio comparativo entre la comunidad de peces asociada a una comunidad de corales masivos (CCM y a una de corales ramificados (CCR en la isla Gorgona, Pacífico Oriental Tropical. En cada formación coralina, el sustrato bentónico se evaluó a través de “transectos de cadena”, mientras que la comunidad de peces se valoró con el uso censos visuales en transectos de banda. Hubo diferencias en la abundancia, diversidad (H’ y equitatividad (J’ de las dos comunidades de peces. La CCR, a pesar de estar formada por colonias morfológicamente complejas de corales pocillóporidos, presentó una arquitectura simple y relativamente plana que atrajo principalmente peces territoriales y de talla pequeña. Abundancias significativamente altas de Chromis atrilobata y Thalassoma lucasanum en la CCR, aumentaron la abundancia total de peces, pero ocasionaron una baja diversidad y equitatividad de la comunidad. Por el contrario, la CCM constituida principalmente por especies de corales masivos con diversos tamaños y formas, presentó una arquitectura compleja y de alto relieve capaz de mantener una comunidad de peces mucho más diversa y equitativa, aunque con la misma riqueza de especies de peces que la CCR. Los peces de gran talla, con comportamiento errante y hábitos carnívoros fueron atraídos a la MCC. En general, nuestro estudio evidenció que aunque las especies de coral con crecimiento masivo son importantes en la formación de una arquitectura compleja, cada una de las morfologías de coral dominante (masivo y ramificado atrae y brinda recursos a distintos grupos de peces según su tamaño y grupo trófico. La pérdida de corales masivos o un

  3. HIV/STD transmission in gold-mining areas of Bolívar State, Venezuela: interventions for diagnosis, treatment, and prevention Transmisión de VIH/ETS en zonas de explotación minera de oro en el estado de Bolívar, Venezuela: intervenciones con fines de diagnóstico, tratamiento y prevención

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    Lily Faas

    1999-01-01

    Full Text Available En este trabajo se presenta la implementación de una serie de talleres sobre la prevención de la infección por VIH y otra enfermedades de transmisión sexual (ETS para beneficio de diversas poblaciones de habitantes del territorio con minas de oro que comprende El Callao, Tumeremo, El Dorado y Las Claritas, en el estado de Bolívar, Venezuela, y también un estudio de prevalencia que se realizó en la misma población. Atraídos por las oportunidades económicas, millares de hombres jóvenes han migrado a esa zona y su presencia en ella ha atraído, al mismo tiempo, a muchas trabajadoras sexuales. La situación, sumada a otros factores sociales, económicos y culturales, facilita la propagación de la infección por VIH y de otras ETS en el territorio. Más de 2 000 personas asistieron a los talleres sobre la prevención de la infección por VIH/ETS, que también se aprovecharon para reunir información sobre las prácticas sexuales en la zona minera. El estudio reveló prácticas sexuales de alto riesgo en todos los grupos estudiados. Antes de este proyecto de investigación se disponía de información epidemiológica escasa e incompleta sobre las infeccions por VIH/ETS en esa zona. Para el presente estudio se tomaron 893 muestras de sangre de habitantes de la localidad. Las pruebas realizadas revelaron una altísima frecuencia de infección sifilítica y de infección por VIH, virus de la hepatitis B y virus humanos linfotrópicos t de tipos I y II. Los resultados de los tallers sobre prevención y del estudio epidemiológico se usarán para crear un plan bien dirigido a largo plazo para la prevención de VIH/ETS en la zona de explotación minera de oro.

  4. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

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    Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: sskumar@barc.gov.in

    2015-09-15

    Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

  5. Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals.

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    Susanne Vogeler

    Full Text Available Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor's functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species. Here, we isolated three nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer modelling of the receptors based on 3D crystal structures of human proteins was used to predict each receptor's ability to bind to different ligands in silico. CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and the organotin tributyltin (TBT. Computer modelling of CgRAR revealed six residues in the ligand binding domain, which prevent the successful interaction with natural and synthetic retinoid ligands. This supports an existing theory of loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable due to high discrepancies in sequence to its human ortholog. Yet, there are suggestions of binding to TBT, but not to rosiglitazone. The effect of potential receptor ligands on early oyster development was assessed after 24h of chemical exposure. TBT oxide (0.2μg/l, all-trans retinoic acid (ATRA (0.06 mg/L and perfluorooctanoic acid (20 mg/L showed high effects on development (>74% abnormal developed D-shelled larvae, while rosiglitazone (40 mg/L showed no effect. The results are discussed in relation to a putative direct (TBT disruption effect on nuclear receptors. The inability of direct binding of ATRA to CgRAR suggests

  6. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia

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    Rafael Henriques Jácomo

    2008-02-01

    Full Text Available A leucemia promielocítica aguda (LPA é um modelo da aplicabilidade clínica dos conhecimentos moleculares fisiopatológicos. Caracteriza-se por alterações genéticas recorrentes que envolvem o gene do receptor alfa do ácido retinóico. A conseqüência é uma proteína com sensibilidade reduzida ao ligante, com bloqueio da diferenciação mielóide. Entretanto, doses suprafisiológicas do ácido all-trans-retinóico (ATRA são capazes de suplantar esta deficiência, e este é o princípio fundamental do tratamento da LPA, permitindo uma sobrevida livre de doença acima de 80% quando adequadamente tratada. Epidemiologicamente, difere dos demais subtipos de leucemia mielóide aguda por apresentar incidência predominante em adultos jovens e, aparentemente, maior incidência em países de colonização "latina". Contrastando com os excelentes resultados observados em países desenvolvidos, a mortalidade por LPA no Brasil ainda é alta, apesar da ampla disponibilidade das medicações no país.Acute promyelocytic leukemia (APL is a model of clinical applicability of the knowledge of molecular physiopathology. It is characterized by recurrent genetic involvement of the retinoic acid alpha receptor. The consequence is a protein with low sensibility to its ligand and a myeloid maturation arrest. However, higher doses of all-trans-retinoic acid (ATRA are able to supersede this deficiency and this is the mainstay of APL treatment leading to over 80% disease free survival, when adequately treated. Epidemiologically, it differs from other acute myeloid leukemia due to a higher incidence in young adults and in countries of "Latin" colonization. Differing from excellent results observed in developed countries, APL mortality in Brazil is still high, despite the wide availability of drugs.

  7. Pressure gradient of a two-region solid-liquid flow in horizontal wells; Gradiente de presion de un flujo bifasico solido-liquido de dos regiones en pozos horizontales

    Energy Technology Data Exchange (ETDEWEB)

    Salazar Mendoza, R.; Garcia Gutierrez, A. [Centro Nacional de Investigacion y Desarrollo Tecnologico (CENIDET), Cuernavaca, Morelos (Mexico); Espinosa Paredes, G. [Universidad Autonoma Metropolitana-Iztapalapa, Mexico, D.F. (Mexico)

    2005-12-01

    relacion de la altura del lecho estacionario y del diametro de la tuberia, y esta se basa en una aproximacion discreta hacia atras de diferencias finitas explicitas. El sistema fisico simulado se basa en una aproximacion discreta hacia atras de diferencias finitas explicitas. El sistema fisico simulado es una tuberia horizontal de 4.135 m de longitud y 0.0508 m de diametro. Se usa una cuadricula unidimensional de malla centrada de 10 nodos. Los resultados numericos se compararon con datos experimentales encontrandose una comparacion satisfactoria entre los perfiles medidos y los simulados.

  8. Olfactory mediated interactions between Citrus aurantium Toxoptera citricida and Lysiphlebus testaceipes Interação olfativa entre Citrus aurantium Toxoptera citricida e Lysiphlebus testaceipes

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    Reetu Bahadoorsingh

    2006-11-01

    Full Text Available The objective of this study was to establish whether there are olfactory interactions in the Lysiphlebus testaceipes Toxoptera citricida and Citrus aurantium tritrophic system. The response of male and female L. testaceipes to different odour sources of the host plant C. aurantium, the aphid host T. citricida and aphid-plant complex were investigated using a Y-tube olfactometer. Laboratory experiments were conducted by exposing individually aged male and female L. testaceipes to eight different odour treatments. Response of the parasitoids was taken after 15 min exposure to the volatiles from the different odour sources and based on their orientation to the particular chamber. Seventy percent of both male and female L. testaceipes showed high attractivity to aphid infested leaves. There was no significant difference based on age and sex of the parasitoid on their choice of odour. The organic compounds released by these combinations acted as semiochemicals in the tritrophic interactions and it is suggested that insect feeding induced attraction of the parasitoid L. testaceipes.O objetivo deste estudo foi investigar se existe interação olfativa no sistema tritrófico entre Lysiphlebus testaceipes Toxoptera citricida e Citrus aurantium. A resposta de machos e fêmeas de L. testaceipes a diferentes fontes de odor da planta hospedeira C. aurantium, o afideo parasita T. citricida e o complexo afideo-planta foram investigados com um olfatômetro do tipo tubo em Y. Os experimentos de laboratório foram conduzidos, expondo-se machos e fêmeas de L. testaceipes de diferentes idades, individualmente, a oito tratamentos com diferentes fontes de odor. A resposta do parasitóide foi tomada depois de 15 minutos de exposição aos voláteis de diferentes fontes de odor, baseando-se na orientação dos parasitóides a uma câmara particular. Setenta por cento de L. testaceipes machos e fêmeas, exibiram maior atração ao odor das folhas infestadas pelo af

  9. In vitro activities of novel 4-HPR derivatives on a panel of rhabdoid and other tumor cell lines

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    Das Bhaskar C

    2011-09-01

    Full Text Available Abstract Background Rhabdoid tumors (RTs are aggressive pediatric malignancies with poor prognosis. N-(4-hydroxy phenyl retinamide (4-HPR or fenretinide is a potential chemotherapeutic for RTs with activity correlated to its ability to down-modulate Cyclin D1. Previously, we synthesized novel halogen-substituted and peptidomimetic-derivatives of 4-HPR that retained activity in MON RT cells. Here we analyzed the effect of 4-HPR in inhibiting the growth of several RT, glioma, and breast cancer cell lines and tested their effect on cell cycle, apoptosis and Cyclin D1 expression. Methods Effect of compounds on RT cell cycle profiles, and cell death were assessed by MTS cell survival assays and FACS analysis. The effects of treatment on Cyclin D1 expression were determined by immunoblotting. The efficacy of these compounds on glioma and breast cancer cell lines was also determined using MTS assays. Results Low micromolar concentrations of 4-HPR derivatives inhibited cell survival of all RT cells tested. The 4-HPR derivatives altered RT cell cycle profiles and induced high levels of cell death that was correlated with their potency. ATRA exhibited high IC50 values in all cell lines tested and did not cause cell death. In MON RT cells, the iodo-substituted compounds were more active than 4-HPR in inducing cell cycle arrest and apoptosis. Additionally, the activity of the compounds correlated with their ability to down-modulate Cyclin D1: while active compounds reduced Cyclin D1 levels, inactive ATRA did not. In glioma and breast cancer cell lines, 4-HPR and 4-HPR derivatives showed variable efficacy. Conclusions Here we demonstrate, for the first time, that the inhibitory activities of novel halogen-substituted and peptidomimetic derivatives of 4-HPR are correlated to their ability to induce cell death and down-modulate Cyclin D1. These 4-HPR derivatives showed varied potencies in breast cancer and glioma cell lines. These data indicate that further

  10. Clinical features and treatment outcomes of pediatric acute promyelocytic leukemia in a Mexican pediatric hospital.

    Science.gov (United States)

    Dorantes-Acosta, Elisa; Medina-Sanson, Aurora; Jaimes-García, Yanet; López-Martínez, Briceida

    2013-01-01

    Acute promyelocytic leukemia (APL) is a distinct type of acute myeloid leukemia (AML) characterized by chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. APL is a relatively rare blood disease that is highly curable with current treatment strategies; however, patient outcomes are heterogeneous in countries with limited resources. Promyelocytic leukemia accounts for 20-25% of all AML cases in Latin American countries. We conducted a study from July 2007 to July 2012 and applied the IC-APL2006 protocol. This case study reports the results from eleven patients with AML M3 (five males and six females). In all cases, the diagnoses were made by aspirating bone marrow and evaluating the t(15:17) or t(11:17) transcript. In eight cases, the molecular biology-based diagnostics for the PLM-RARa transcript were positive, and they were negative in two cases. One patient was positive for the PLZF-RARa transcript. The mean WBC at the time of diagnosis was 10.1 x 10(9)/L, and the mean platelet count was 17.1 x 10(9)/L. The mean percentage of abnormal promyelocytes in the bone marrow aspirates was 68%. Of the eleven patients, four presented with disseminated intravascular coagulation. All of the patients began treatment with transretinoic acid (ATRA) (45 mg/m(2)/day), which led to 4 cases of ATRA syndrome. There were 2 relapses, and the patient died in one case. The remaining ten patients were alive after the median follow-up period of 33.6 months (range from 11 to 60 months). The authors report on a series of cases involving pediatric patients with AML M3 seen at a single institution; the patients were stratified and treated with a standard protocol to obtain satisfactory results. Although the number of patients is limited, the health outcomes are relevant. To our knowledge, this is the first series of pediatric APL patients in Mexico who were treated with the IC-APL2006 protocol.

  11. Molecular networks of human muscle adaptation to exercise and age.

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    Bethan E Phillips

    2013-03-01

    Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

  12. [Clinical analysis of real-time iris recognition guided LASIK with femtosecond laser flap creation for myopic astigmatism].

    Science.gov (United States)

    Jie, Li-ming; Wang, Qian; Zheng, Lin

    2013-08-01

    To assess the safety, efficacy, stability and changes in cylindrical degree and axis after real-time iris recognition guided LASIK with femtosecond laser flap creation for the correction of myopic astigmatism. Retrospective case series. This observational case study comprised 136 patients (249 eyes) with myopic astigmatism in a 6-month trial. Patients were divided into 3 groups according to the pre-operative cylindrical degree: Group 1, -0.75 to -1.25 D, 106 eyes;Group 2, -1.50 to -2.25 D, 89 eyes and Group 3, -2.50 to -5.00 D, 54 eyes. They were also grouped by pre-operative astigmatism axis:Group A, with the rule astigmatism (WTRA), 156 eyes; Group B, against the rule astigmatism (ATRA), 64 eyes;Group C, oblique axis astigmatism, 29 eyes. After femtosecond laser flap created, real-time iris recognized excimer ablation was performed. The naked visual acuity, the best-corrected visual acuity, the degree and axis of astigmatism were analyzed and compared at 1, 3 and 6 months postoperatively. Static iris recognition detected that eye cyclotorsional misalignment was 2.37° ± 2.16°, dynamic iris recognition detected that the intraoperative cyclotorsional misalignment range was 0-4.3°. Six months after operation, the naked visual acuity was 0.5 or better in 100% cases. No eye lost ≥ 1 line of best spectacle-corrected visual acuity (BSCVA). Six months after operation, the naked vision of 227 eyes surpassed the BSCVA, and 87 eyes gained 1 line of BSCVA. The degree of astigmatism decreased from (-1.72 ± 0.77) D (pre-operation) to (-0.29 ± 0.25) D (post-operation). Six months after operation, WTRA from 157 eyes (pre-operation) decreased to 43 eyes (post-operation), ATRA from 63 eyes (pre-operation) decreased to 28 eyes (post-operation), oblique astigmatism increased from 29 eyes to 34 eyes and 144 eyes became non-astigmatism. The real-time iris recognition guided LASIK with femtosecond laser flap creation can compensate deviation from eye cyclotorsion, decrease

  13. Top five medical innovations in China mainland since Xinhai revolution [1911]: results of AME survey-002.

    Science.gov (United States)

    Wáng, Yì-Xiáng J; Xiao, Fan

    2015-06-01

    This survey aims to scrutinize important medical innovations in Chinese mainland since Xinhai (Hsin-hai) revolution in 1911, which marked the end of Manchurian imperial rule and the beginning of China's republican era. An online cross-sectional survey was carried out during the period of Dec 29, 2014 to Feb 5, 2015, totaling 37 days. The survey was conducted on the platform provided by DXY (www.dxy.cn), which is the largest medical and paramedical related website in China. An email was sent to all DXY registered users to invite them to participate in a 5-minute survey. The participants were asked to nominate up to four important medical innovations in China mainland since Xinhai revolution. The participant could select 'zero' which means he/she felt there was no important medical innovations, or he/she did not know important medical innovations. It was noted that important medical innovations refer to (I) those with practical and almost immediate significance to improve healthcare; (II) should not only be introducing western technique to China, but those involve major improvement of existing western techniques count; (III) should not be those with important theoretical discovery but did not have almost immediate significance to improve healthcare. In total 1,513 DXY users participated in the voting. Totally 489 (32.3%), 441 (29.1%), 342 (22.6%), 150 (9.9%), 91 (6.0%) participants provided 0, 1, 2, 3, 4 nominations respectively. (I) Artemisine (Qinghaosu) for malaria treatment (Project 523 team, 1972); (II) arsenic Trioxide (As2O3) for acute promyelocytic leukemia (APL) treatment (ZHANG Ting-Dong and colleagues, 1970s); (III) limb re-plantation (CHEN Zhong-Wei and colleagues, 1963); (IV) all-trans retinoic acid (ATRA) for APL treatment (WANG Zhen-Yi and colleagues, 1988); and (V) Wu's mask for plague prevention (WU Lien-The, 1910), were voted as the top five innovations in China mainland since Xinhai revolution, with 375, 96, 91, 53, and 8 votes respectively. In

  14. Three new species of the genus Ripipteryx from Colombia (Orthoptera, Ripipterygidae

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    Nathalie Baena-Bejarano

    2015-05-01

    Full Text Available Three new species of Ripipteryx Newman (Orthoptera: Tridactyloidea: Ripipterygidae are described from Colombia; namely R. diegoi sp. n. (Forceps Group and R. guacharoensis sp. n. (Marginipennis Group from Parque Nacional Natural Cueva de los Guacharos in Huila, and R. gorgonaensis sp. n. (Crassicornis Group from Parque Nacional Natural Gorgona in Cauca. Ripipteryx diegoi sp. n. is characterized by the antennae black with white spots on flagellomeres 3–7, male subgenital plate with median ridge forming a bilobed setose process, epiproct produced laterally near its base and phallic complex with virga thickened distally and not reaching beyond the membrane. Ripipteryx guacharoensis sp. n. is characterized by the antennae thick with white spots present dorsally on flagellomeres 1–4 and 8, epiproct narrow and triangular, uncus reduced and lacking a distal hook, phallic complex with a concave ventral plate and a dorsal elevation in the middle extended to the virga, and the virga itself with two small projections basally. Ripipteryx gorgonaensis sp. n. is characterized by the epiproct with a lateral notch, antennae with a white dorsal spot on flagellomere 1 and flagellomeres 4–7 entirely white. The antennal color pattern of R. gorgonaensis sp. n. strongly resembles that of R. atra but differs from the latter in the absence of any significant morphological modification of the flagellomeres.

  15. Comportamiento del mercado turístico extranjero en el Caribe Mexicano

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    Dr. Francisco J. Güemes-Ricalde

    2009-11-01

    Full Text Available El Caribe mexicano atrae visitantes de regiones distintas en diferentes épocas del año. A los prestadores de servicios turísticos les resulta difícil conocer y separar las preferencias de actividades que realizan los visitantes de cada país. Arriban visitantes mexicanos y extranjeros, las preferencias de estos últimos en relación a la demanda de servicios son diferentes. Contrario a lo que se conocía, el estudio de mercado determinó que la demanda mexicana representa un mercado importante en marcadas épocas del año. Se calcula que cada año alrededor de dos millones de turistas nacionales arriban a la Riviera y Costa Maya en la región norte de Quintana Roo. Conocer las preferencias de consumo de los diferentes segmentos de turistas y la forma en que evalúan la posibilidad de demandar los servicios turísticos da la pauta para ofrecérselos en forma diferenciada y adecuada a cada segmento y en relación a cada una de las diversas actividades turísticas que realizan, entre ellas el ecoturismo de la cual poco se conoce en esta región del país.

  16. Los tres muros de Paimio

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    Julio Grijalba Bengoetxea

    2017-04-01

    Full Text Available La trayectoria de Alvar Aalto es ciertamente compleja y ha sido relatada por la historiografía oficial diseccionada en etapas más o menos definidas por familias unitarias de proyectos en el tiempo. Así, el sanatorio de Paimio ha pasado a la historia de la arquitectura como la consolidación del Proyecto Moderno en Finlandia, protagonizando, aparentemente, su momento de mayor ortodoxia. Aalto se sintió atraído, desde sus comienzos, por la posibilidad de generar un discurso proyectual propio. Encontró que investigar en torno a la capacidad evocadora de la conciliación de los opuestos le permitía disponer de instrumentos eficaces al servicio del proyecto. La singular presencia de elementos opuestos dialogando define la tarea rectora de una manera de hacer en arquitectura. En Paimio algunas verdades se resisten a ser ocultadas bajo la uniformidad moderna aparente, tantas veces exaltada. Todo ello se revela en innumerables episodios, pero es especialmente visible en la singular composición de los tres muros de las habitaciones. El muro moderno que resulta ingrávido desde su condición abstracta. El muro pesado, definido a través de sus cualidades materiales, vinculado a la tradición decimonónica. Y finalmente el muro inmaterial, dotado de atributos próximos a la invisibilidad, de profundas referencias orientales.

  17. Los flujos de capital y el Estado en Colombia The capital inflows and the State in Colombia

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    Kalmanovitz Salomón

    1994-12-01

    Full Text Available El artículo hace un breve análisis de los flujos de capital hacia América Latina durante el último lustro, atraídos por economías menos intervenidas por el Estado, más abiertas al comercio internacional, más estables y equilibradas en sus variables macroeconómicas fundamentales. Seguidamente se examina la economía colombiana en los aspectos de crecimiento, inflación, agregados externos, monetarios y fiscales para concluir la apreciación del peso causada por la repatriación de capitales y las expectativas sobre una nueva bonanza petrolera hacen más difícil el desarrollo de la producción de bienes transables en el país.This paper analyses briefly capital inflows in Latin America duringthe last five years which were attracted by less state intervention,more openness to international trade and more stable economies in their macro variables.Next, the paper examines the Colombian economy in themes such asgrowth, inflation, external and fiscal balances, to conclude that the appreciation of the peso, caused by the capital inflow and the expectations of a new oil boom, makes it more difficult to developthe development of tradable within the country.

  18. Identidade e Gênero: Representações Femininas nos programas televisivos Bah!

    Directory of Open Access Journals (Sweden)

    Mariana Nogueira Henriques

    2017-09-01

    Full Text Available A presente pesquisa busca analisar os modos como são produzidos os sentidos sobre a mulher gaúcha, a partir dos especiais “Bah! Um programa muito gaúcho”, “Bah! Eu Sou do Sul” e “Bah! Um fandango muito especial”, exibidos em 20 de setembro de 2013 e 2014 e 19 de setembro de 2015, respectivamente, na RBS.TV. Para isso, buscamos aporte na perspectiva teórica dos estudos culturais aliados aos estudos de gênero, considerando, ainda, o contexto cultural gaúcho em que as atrações se passam. Da pesquisa inferimos que os três principais sentidos: ocultamento, objetificação e masculinização formam uma identidade feminina estereotipada. Além disso, percebemos que os especiais atuam na intenção de perpetuar uma identidade hegemônica e masculina transmitindo uma falsa ideia de empoderamento feminino, na busca por gerar audiência e reconhecimento.

  19. Redes sociais e conflito organizacional

    Directory of Open Access Journals (Sweden)

    Jorge Ávila de Lima

    2016-06-01

    Full Text Available As organizações são redes sociais cujos membros estabelecem entre si ligações de diversos tipos, formais e informais, positivas e negativas. O conflito entre atores é um processo comum que pode ser explicado com base num conjunto diverso de fatores. Contudo, o conflito interno às organizações tem sido pouco estudado, numa perpetiva de redes sociais. Para além disto, o conflito interorganizacional, analisado ao nível dos atores individuais, tem sido ainda menos estudado. No presente artigo, procuramos abordar o modo como as redes sociais das organizações estão associadas a perceções de conflito, quer intra-organizacional, quer interorganizacional, num contexto de proximidade física entre organizações. O estudo empírico, que envolveu duas organizações que partilhavam o mesmo espaço físico, mostra que, apesar da grande proximidade espacial entre ambas, os laços de amizade tendiam a concentrar-se no interior de cada organização e as perceções de conflito eram maiores entre as organizações do que no interior das mesmas. Os resultados são discutidos à luz das teses sobre os efeitos da propinquidade física sobre a atração interpessoal entre membros de grupos distintos

  20. Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

    Directory of Open Access Journals (Sweden)

    Xiao-Na Pan

    Full Text Available Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA. Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.

  1. Eva en el Paraíso: La construcción y representación del cuerpo femenino en la playa como espacio turístico en Costa Rica

    Directory of Open Access Journals (Sweden)

    Esteban Barboza Núñez

    2016-10-01

    Full Text Available El artículo analiza la representación del cuerpo femenino como destino turístico, en la promoción de las playas en Costa Rica. Se hace un esbozo del estatus de la figura femenina en el imaginario androcéntrico occidental, desde sus raíces judeocristianas y de pensamiento clásico, hasta el advenimiento de la modernidad. Se reseñan postulados acerca del estatus del cuerpo femenino y la forma en que se construye en las representaciones gráficas; se parte de que la manera en que el cuerpo femenino es representado en la publicidad, enfocada a atraer turistas a la playa, le genera una doble otredad. La primera como mujer, cuyo físico es controlado por un imaginario androcéntrico que lo usa cual Eva-sirena, que tienta y atrae al posible visitante. La segunda como elemento que recrea una fantasía de exploración colonial de una playa prístina y “virginal”, y que la aleja de la modernidad racional cartesiana, en la cual la mente se impone a un cuerpo que debe ser controlado y domesticado por la razón.

  2. Identification and characterization of novel reptile cathelicidins from elapid snakes.

    Science.gov (United States)

    Zhao, Hui; Gan, Tong-Xiang; Liu, Xiao-Dong; Jin, Yang; Lee, Wen-Hui; Shen, Ji-Hong; Zhang, Yun

    2008-10-01

    Three cDNA sequences coding for elapid cathelicidins were cloned from constructed venom gland cDNA libraries of Naja atra, Bungarus fasciatus and Ophiophagus hannah. The open reading frames of the cloned elapid cathelicidins were all composed of 576bp and coded for 191 amino acid residue protein precursors. Each of the deduced elapid cathelicidin has a 22 amino acid residue signal peptide, a conserved cathelin domain of 135 amino acid residues and a mature antimicrobial peptide of 34 amino acid residues. Unlike the highly divergent cathelicidins in mammals, the nucleotide and deduced protein sequences of the three cloned elapid cathelicidins were remarkably conserved. All the elapid mature cathelicidins were predicted to be cleaved at Valine157 by elastase. OH-CATH, the deduced mature cathelicidin from king cobra, was chemically synthesized and it showed strong antibacterial activity against various bacteria with minimal inhibitory concentration of 1-20microg/ml in the presence of 1% NaCl. Meanwhile, the synthetic peptide showed no haemolytic activity toward human red blood cells even at a high dose of 200microg/ml. Phylogenetic analysis of cathelicidins from vertebrate suggested that elapid and viperid cathelicidins were grouped together in the tree. Snake cathelicidins were evolutionary closely related to the neutrophilic granule proteins (NGPs) from mouse, rat and rabbit. Snake cathelicidins also showed a close relationship with avian fowlicidins (1-3) and chicken myeloid antimicrobial peptide 27. Elapid cathelicidins might be used as models for the development of novel therapeutic drugs.

  3. Isolation and cloning of a metalloproteinase from king cobra snake venom.

    Science.gov (United States)

    Guo, Xiao-Xi; Zeng, Lin; Lee, Wen-Hui; Zhang, Yun; Jin, Yang

    2007-06-01

    A 50 kDa fibrinogenolytic protease, ohagin, from the venom of Ophiophagus hannah was isolated by a combination of gel filtration, ion-exchange and heparin affinity chromatography. Ohagin specifically degraded the alpha-chain of human fibrinogen and the proteolytic activity was completely abolished by EDTA, but not by PMSF, suggesting it is a metalloproteinase. It dose-dependently inhibited platelet aggregation induced by ADP, TMVA and stejnulxin. The full sequence of ohagin was deduced by cDNA cloning and confirmed by protein sequencing and peptide mass fingerprinting. The full-length cDNA sequence of ohagin encodes an open reading frame of 611 amino acids that includes signal peptide, proprotein and mature protein comprising metalloproteinase, disintegrin-like and cysteine-rich domains, suggesting it belongs to P-III class metalloproteinase. In addition, P-III class metalloproteinases from the venom glands of Naja atra, Bungarus multicinctus and Bungarus fasciatus were also cloned in this study. Sequence analysis and phylogenetic analysis indicated that metalloproteinases from elapid snake venoms form a new subgroup of P-III SVMPs.

  4. Juventudes universitarias de izquierda. De la lucha ideológica a la violencia política

    Directory of Open Access Journals (Sweden)

    Álvaro Acevedo Tarazona

    2016-01-01

    Full Text Available Tal como sucedió en otros lugares del mundo, en Colombia du - rante las décadas de los sesenta y los setenta primó un ambien - te de lucha revolucionaria. Los líderes sindicales, los antiguos militantes del partido Comunista, algunos literatos y artistas de avanzada y los jóvenes universitarios fueron atraídos, desde puntos de vista ideológico, emocional y político por las corrien - tes discursivas que abogaban por una revolución total. Este artí - culo analiza los casos de cinco jóvenes que pasaron de la lucha ideológica a empuñar las armas. Son los casos de Jaime Arenas Reyes, Víctor Medina Morón, Fabio y Manuel Vásquez Castaño y Ricardo Lara Parada, quienes conformaron el primer núcleo de lo que se conocería después como Ejército de Liberación Nacio - nal (ELN. Un análisis prosopográfico de estos cinco casos nos permitirá ver la estrecha relación entre el ambiente universitario de las décadas de los sesenta y setenta y el surgimiento de la lu - cha armada en Colombia.

  5. Nonsteroidal Anti-inflammatory Drugs (NSAIDS) Inhibit the Growth and Reproduction of Chaetomium globosum and Other Fungi Associated with Water-Damaged Buildings.

    Science.gov (United States)

    Dalmont, Kelsey; Biles, Charles L; Konsure, Heather; Dahal, Sujita; Rowsey, Tyler; Broge, Matthew; Poudyal, Shubhra; Gurung, Tara; Shrestha, Sabina; Biles, Caleb L; Cluck, Terry; Howard, Alisha

    2017-12-01

    Indoor mold due to water damage causes serious human respiratory disorders, and the remediation to homes, schools, and businesses is a major expense. Prevention of mold infestation of building materials would reduce health problems and building remediation costs. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit yeasts and a limited number of filamentous fungi. The purpose of this research was to determine the possible inhibitory activity of nonsteroidal anti-inflammatory drugs (NSAIDs) on germination, fungal growth, and reproduction of Chaetomium globosum and other important filamentous fungi that occur in water-damaged buildings. Several NSAIDs were found to inhibit C. globosum germination, growth, and reproduction. The most effective NSAIDs inhibiting C. globosum were ibuprofen, diflunisal, and diclofenac. Fusarium oxysporum, Fusarium solani, Aspergillus niger, and Stachybotrys atra were also tested on the various media with similar results obtained. However, F. oxysporum and A. niger exhibited a higher level of resistance to aspirin and NaSAL when compared to the C. globosum isolates. The inhibition exhibited by NSAIDs was variable depending on growth media and stage of fungal development. These compounds have a great potential of inhibiting fungal growth on building materials such as gypsum board. Formulations of sprays or building materials with NSAID-like chemical treatments may hold promise in reducing mold in homes and buildings.

  6. El proceso de gentrificación en Génova a partir de las trasformaciones urbanas de 1992

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    Francesco Gastaldi

    2015-12-01

    Full Text Available Este estudio sigue algunas actividades de investigación y publicaciones relativas a las políticas urbanas en la ciudad de Génova, con especial interés en los proyectos relacionados con el centro histórico de la ciudad y el frente marítimo, así como con el papel que los grandes eventos juegan en el proceso de regeneración urbana. En este marco, el tema de la gentrificación que se investiga, es la dinámica de los nuevos residentes con mayores niveles de ingreso que se ubican en el centro histórico y el consiguiente desplazamiento de los residentes anteriores, observable a partir de los años noventa. La decisión de reubicarse en edificios degradados comenzó a verse no como una opción inevitable para las poblaciones con menos recursos económicos, sino como una solución ideal para ciertas personas con una fuerte necesidad de interacción y de representación social, atraídos por el patrimonio histórico, cultural y valores del entorno urbano, por la centralidad de la zona, y por las oportunidades de inversión.

  7. La comida típica dentro de la internacionalización de la oferta gastronómica en Bogotá

    Directory of Open Access Journals (Sweden)

    Diana Marcela Valcárcel García

    2015-06-01

    Full Text Available Debido la importancia que Bogotá ha otorgado a la oferta gastronómica de Colombia durante los últimos veinte años, la ciudad se ha convertido en un espacio donde se dan cita sus habitantes y viajeros para satisfacer todos los gustos del paladar en los restaurantes que ofrecen los mejores platos de la comida internacional y, por supuesto, los que se enorgullecen de resaltar la comida típica colombiana. Gracias a la zonificación gastronómica de Bogotá, la proliferación de restaurantes se ha hecho más evidente, situación que moviliza un mayor número de personas dentro de las fronteras nacionales y que incluso atrae visitantes extranjeros con el único objetivo de conocer la oferta gastronómica que la ciudad ostenta. Los objetivos de este artículo son 1 exponer el análisis realizado sobre la permanencia en el sector gastronómico de los mejores restaurantes de comida típica colombiana en Bogotá y 2 dar a conocer las características administrativas, operativas y los factores de perdurabilidad de ellos, así como el posicionamiento que la comida típica colombiana ocupa actualmente y su protagonismo dentro del patrimonio nacional.

  8. Bioaccumulation of uranium 234U and 238U in marine birds

    International Nuclear Information System (INIS)

    Borylo, A.; Skwarzec, B.

    2010-01-01

    In the paper was presented results of our study about uranium 234 U and 238 U radioactivity in the marine birds samples, collected in the Polish area of the southern Baltic Sea. We chose 11 species of sea birds: three species permanently residing at southern Baltic, four species of wintering birds and three species of migrating birds. The obtained results indicated that uranium is very irregularly distributed in organs and tissues of marine birds. The highest uranium content is characterized in liver, rest of viscera and feathers, the smallest in skin and muscles. The uranium concentration was higher for carnivorous species (long-tailed duck (C. hyemalis), common eider (S. mollissima), lower for species eating fish (great cormorant (P. carbo), common guillemot (U. aalge), red-throated diver (G. stellata) and razorbill (A. tarda)), but the biggest amounts for herbivorous species [tufted duck (A. fuligula) and eurasian coot (F. atra)]. About 63-67% of uranium, which was located in feathers of two species of marine birds: razorbill (A. tarda) and long-tailed duck (C. hymealis), was apparently adsorbed, which suggests that uranium adsorption on the feathers may be an important transfer from air to water. (author)

  9. Atrayendo Talento: Estrategias de Movilidad de los profesionales altamente cualificados en España

    Directory of Open Access Journals (Sweden)

    Ana M. González Ramos

    2016-02-01

    Full Text Available En las últimas décadas, se ha realizado un gran esfuerzo centrado en la formación de los profesionales españoles altamente cualificados. Además, la competitividad económica y la evolución positiva de los indicadores de ciencia y la innovación tecnológica han atraído el talento extranjero. El presente artículo se centra en las estrategias protagonizadas por el personal altamente cualificado en el sistema nacional de I+D+I, así como en la adecuación de los programas de movilidad y la normativa legal aplicada a este colectivo. Aunque se ha avanzado bastante, las políticas de atracción y retención del talento nacional y extranjero son aún insuficientes pues se aplican rígidamente sobre un modelo de movilidad estereotipado, basado en los individuos y en estrategias temporales, en vez de ser flexible, basado en las personas y en estrategias de una duración variable.

  10. Resonance Raman imaging as a tool to assess the atmospheric pollution level: carotenoids in Lecanoraceae lichens as bioindicators.

    Science.gov (United States)

    Ibarrondo, I; Prieto-Taboada, N; Martínez-Arkarazo, I; Madariaga, J M

    2016-04-01

    Raman spectroscopy differentiation of carotenoids has traditionally been based on the ν 1 position (C = C stretching vibrations in the polyene chain) in the 1500-1600 cm(-1) range, using a 785 nm excitation laser. However, when the number of conjugated double bonds is similar, as in the cases of zeaxanthin and β-carotene, this distinction is still ambiguous due to the closeness of the Raman bands. This work shows the Raman results, obtained in resonance conditions using a 514 mm laser, on Lecanora campestris and Lecanora atra species, which can be used to differentiate and consequently characterize carotenoids. The presence of the carotenoid found in Lecanoraceae lichens has been demonstrated to depend on the atmospheric pollution level of the environment they inhabit. Astaxanthin, a superb antioxidant, appears as the principal xanthophyll in highly polluted sites, usually together with the UV screening pigment scytonemin; zeaxanthin is the major carotenoid in medium polluted environments, while β-carotene is the major carotenoid in cleaner environments. Based on these observations, an indirect classification of the stress suffered in a given environment can be assessed by simply analysing the carotenoid content in the Lecanoraceae lichens by using resonance Raman imaging.

  11. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Xueqing Jiang

    Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

  12. The diversity and distribution of Holothuroidea in shallow waters of Baluran National Park, Indonesia

    Directory of Open Access Journals (Sweden)

    ARIF MOHAMMAD SIDDIQ

    2016-04-01

    Full Text Available Abstract. Siddiq AM, Atmowidi T, Qayim I. 2015. The diversity and distribution of Holothuroidea in shallow waters of Baluran National Park, Indonesia. Biodiversitas 17: 55-60. A study of the diversity and distribution of sea cucumber (Holothuroidea in shallow waters at Baluran National Park, East Java, Indonesia was carried out from July until September 2015. The method used in this study was systematic transect in low tide condition. Samples were collected by hands at intertidal sites. Identification of sea cucumber species based on morphological ossicles. Twenty one species of Holothuroidea belonging two orders and four families were found in this study. The most dominant family found was Holothuriidae (16 species, followed by Stichopodidae (2 species, Synaptidae (2 species, and Chiridotidae (1 spesies. Four species (Holothuria olivacea, H. verrucosa, Labidodemas rugosum, and Chiridota smirnovi are new record for Java waters and one species (H. papillifera is a new record for Indonesian waters. Two morphospecies (H. aff. macroperona and Stichopus cf. monotuberculatus need reconfirmation to species level. The highest abundance species of Holothuroidea was found at under rock with 15 species. Whereas, the highest number of individuals was found in seagrass areas with 5457 individuals. H. atra has extensive habitat distribution, such as seagrass, macroalgae, coral reef, dead coral, sand, and under rock.

  13. MODIFICACIÓN DE OLFATÓMETROS DE CUATRO BRAZOS PARA EXPERIMENTACIÓN EN BROCA DEL CAFÉ, HYPOTHENEMUS HAMPEI FERRARI (COLEOPTERA: CURCULIONIDAE

    Directory of Open Access Journals (Sweden)

    Arturo Pacheco

    2012-01-01

    tratamiento en cada olfatómetro. En el olfatómetro de 90° los insectos se vieron claramente atraídos al brazo que contenía el atrayente, con un porcentaje del 45%, mientras que el olfatómetro de 30° tan solo alcanzó un 1,5% de atracción. Las observaciones realizadas durante estas pruebas dejaron en evidencia que las estrategias de ingreso de los insectos a los olfatómetros y el área de ambientación influyeron de manera importante en estos resultados. En una segunda etapa se evaluó el olfatómetro de 90º, al comparar los promedios de atracción de cada uno de sus 4 brazos, y se verificó que las diferencias de atracción en cada brazo no fueron significativas (p<=0,05. Se concluye que el diseño del olfatómetro de 90º es apropiado para realizar pruebas de atracción a compuestos volátiles en hembras adultas de H. hampei.

  14. Colosalidad, ópera y espíritu del lugar: una impresión antropológica de la arena de Verona

    Directory of Open Access Journals (Sweden)

    José Antonio González Alcantud

    2009-01-01

    Full Text Available Que los genii loci, o espíritus del lugar, no son sólo azarosas conjunciones de lugares arquitectónicos o paisajísticos con (figura 1, un destino prefijado nos lo puede mostrar la historia cultural de la Arena de Verona, antiguo anfiteatro romano, construido en el siglo I, cuya fábrica se conserva en extraordinarias condiciones en el día de hoy. La Rena es conocida mundialmente por ser el anfiteatro más grande después del Coliseo romano, y por su estado de conservación que ha permitido su uso continuado como albergue de espectáculos. Lo ha sido más aún desde 1913, en que se celebró una espectacular Aida con motivo del centenario del nacimiento de Verdi, manteniendo continuadamente una temporada veraniega de ópera, con un fuerte marchamo verdiano, que atrae a aficionados y turistas de toda procedencia. Esta imagen ha prosperado y ha producido la conjunción entre la colosalidad del anfiteatro y la grandiosidad de las óperas de Verdi, con el público de masas, dando lugar a un espectáculo cuanto menos singular.

  15. Presencia de una diáspora global: comerciantes armenios y comercio intercultural en Manila, c. 1660-1800

    Directory of Open Access Journals (Sweden)

    Baena Zapatero, Alberto

    2014-12-01

    Full Text Available This article analyses the presence in Manila of Armenian merchants from New Julfa, and aims to bring together Spanish primary sources and the rich historiography on the Julfan trade diaspora. Attracted by the silver arriving from Acapulco, Armenians played an important commercial role in the Philippines. We address their complicated relationship with the Spanish authorities, their participation in both inter-Asiatic and trans-Pacific exchanges, and their life experiences as told in their own words before the court of the Spanish Inquisition in Manila.Este artículo analiza la presencia de comerciantes armenios de Nueva Julfa en Manila, y tiene por objeto tender un puente entre las fuentes documentales españolas y la rica historiografía sobre la diáspora comercial julfana. Atraídos por la plata que llegaba de Acapulco, los armenios jugaron un importante papel comercial en las Filipinas. Abordamos su complicada relación con las autoridades españolas, su participación en los intercambios tanto inter-asiáticos como transpacíficos, y sus experiencias vitales relatadas por ellos mismos ante el Tribunal de la Inquisición en Manila.

  16. A Turn-on Fluorescence Sensor for Heparin Detection Based on a Release of Taiwan Cobra Cardiotoxin from a DNA Aptamer or Adenosine-Based Molecular Beacon.

    Science.gov (United States)

    Shi, Yi-Jun; Wang, Liang-Jun; Lee, Yuan-Chin; Huang, Chia-Hui; Hu, Wan-Ping; Chang, Long-Sen

    2018-02-19

    This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the fluorescent signal of the aptamer or MB 5'-end labeled with carboxyfluorescein (FAM) and 3'-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid (DABCYL) was observed upon the addition of CTX3. The presence of heparin and formation of the CTX3-heparin complex caused CTX3 detachment from the MB or aptamer, and restoration of FAM fluorescence of the 5'-FAM-and-3'-DABCYL-labeled MB and aptamer was subsequently noted. Moreover, the detection of heparin with these CTX3-aptamer and CTX3-MB sensors showed high sensitivity and selectivity toward heparin over chondroitin sulfate and hyaluronic acid regardless of the presence of plasma. The limit of detection for heparin in plasma was determined to be 16 ng/mL and 15 ng/mL, respectively, at a signal-to-noise ratio of 3. This study validates the practical utility of the CTX3-aptamer and CTX3-MB systems for determining the concentration of heparin in a biological matrix.

  17. O papel do biólogo no gerenciamento do perigo aviário em aeroportos = The role of biologist in airport bird hazard management

    Directory of Open Access Journals (Sweden)

    Bezerra, George Christian Linhares

    2011-01-01

    Full Text Available A segurança operacional da aviação demanda o gerenciamento do perigo aviário. A maior parte dos eventos de colisão entre aves e aeronaves ocorre nas proximidades dos aeroportos, o que está relacionado à menor altitude de voo e concentração de aves devido a fatores atrativos. O artigo foca o papel do profissional de ciências biológicas no processo de gerenciamento do perigo aviário em aeroportos, tendo como objetivo descrever as atividades por ele executadas. A pesquisa consistiu de revisão da literatura, identificação da regulamentação aplicável e as práticas adotadas e, através de estudo de caso realizado em aeroporto localizado na região amazônica, foi possível coletar informações de interesse para a pesquisa. Os resultados apontam que o biólogo atua especificamente na identificação do perigo, identificando focos de atração de aves, espécies presentes e hábitos de comportamento. Além disso, assessora a avaliação de risco com informações sobre a probabilidade da ocorrência de colisões e sobre a gravidade das suas consequências

  18. Immunoreactivity between venoms and commercial antiserums in four Chinese snakes and venom identification by species-specific antibody.

    Science.gov (United States)

    Gao, Jian-Fang; Wang, Jin; Qu, Yan-Fu; Ma, Xiao-Mei; Ji, Xiang

    2013-01-31

    We studied the immunoreactivity between venoms and commercial antiserums in four Chinese venomous snakes, Bungarus multicinctus, Naja atra, Deinagkistrodon acutus and Gloydius brevicaudus. Venoms from the four snakes shared common antigenic components, and most venom components expressed antigenicity in the immunological reaction between venoms and antiserums. Antiserums cross-reacted with heterologous venoms. Homologous venom and antiserum expressed the highest reaction activity in all cross-reactions. Species-specific antibodies (SSAbs) were obtained from four antiserums by immunoaffinity chromatography: the whole antiserum against each species was gradually passed through a medium system coated with heterologous venoms, and the cross-reacting components in antiserum were immunoabsorbed by the common antigens in heterologous venoms; the unbound components (i.e., SSAbs) were collected, and passed through Hitrap G protein column and concentrated. The SSAbs were found to have high specificity by western blot and enzyme-linked immunosorbent assay (ELISA). A 6-well ELISA strip coated with SSAbs was used to assign a venom sample and blood and urine samples from the envenomed rats to a given snake species. Our detections could differentiate positive and negative samples, and identify venoms of a snake species in about 35 min. The ELISA strips developed in this study are clinically useful in rapid and reliable identification of venoms from the above four snake species. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Comportamiento del consumidor de productos agroecológicos frente a la aplicación de buenas prácticas agrícolas

    Directory of Open Access Journals (Sweden)

    Jorge Merino Toro

    2016-06-01

    Full Text Available La presente investigación evalúa el comportamiento del consumidor de productos agroecológicos comercializados por productores de PACAT (Corporación de Asociaciones de Productores Agroecológicos y Comercio Asociativo de Tungurahua frente a la aplicación de Buenas Prácticas Agrícolas (BPA, tomando como punto de partida el aumento descontrolado de ferias que comercializan productos bajo la denominación de agroecológicos en la provincia de Tungurahua. La principal herramienta utilizada en esta investigación fue la encuesta, aplicada a una muestra de 217 consumidores y 33 productores agroecológicos, con el uso de esta herramienta se determinó el comportamiento del consumidor de la Plaza Pachano y además se analizó la aplicación de Buenas Prácticas Agrícolas. Se reconoce la alta calidad como la principal razón para consumir productos agroecológicos, la frescura constituye la característica física que más atrae, y el producto más comprado fueron las hortalizas. Respecto a productores se determinó que aplican correctamente BPA. Palabras clave: Economía del consumidor, mercados agrarios y marketing, análisis de la oferta y de la demanda, producción, consumo.

  20. Pedagogía de la Tierra: los sujetos del campo y la Enseñanza Superior

    Directory of Open Access Journals (Sweden)

    Fernando José Martins

    2013-07-01

    Full Text Available Resumen: En el contexto de las políticas y prácticas de la enseñanza superior, de manera general, cada vez más atraídas por la lógica de mercado, se intenta en este artículo dar visibilidad a una experiencia en este nivel de enseñanza, que pretende posicionarse en la contracorriente de aquella lógica: la Pedagogía de la Tierra. Bajo la forma de política pública afirmativa, encarada hacia los sujetos del campo, se construye en Brasil un curso especial con características singulares y propias, que ha llamado la atención de los investigadores y de la sociedad civil. Esta experiencia señala elementos significativos que sustentan la definición de políticas y prácticas de una enseñanza superior vinculada a una perspectiva emancipatoria, orientada específicamente a las clases populares. Palabras clave: movimientos sociales, participación, universidad.

  1. Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro

    Directory of Open Access Journals (Sweden)

    Kazuhisa Murai

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC frequently develops from hepatitis C virus (HCV and hepatitis B virus (HBV infection. We previously reported that peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity. Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA, and all-trans-retinoic acid (ATRA, had no effect or rather increased HBV replication. Mechanistically, although peretinoin increased the expression of HBV-related transcription factors, as observed for other retinoids, peretinoin enhanced the binding of histone deacetylase 1 (HDAC1 to cccDNA in the nucleus and negatively regulated HBV transcription. Moreover, peretinoin significantly inhibited the expression of SPHK1, a potential inhibitor of HDAC activity, and might be involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in cells cancelled the inhibition of HBV replication induced by peretinoin. This indicates that peretinoin activates HDAC1 and thereby suppresses HBV replication by inhibiting the sphingosine metabolic pathway. Therefore, peretinoin may be a novel therapeutic agent for HBV replication and chemoprevention against HCC.

  2. O problema do mal: a interpretação de São Boaventura = The problem of evil: the interpretation of Saint Bonaventure

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    Vasconcellos, Manoel

    2012-01-01

    Full Text Available Tomando, especialmente, o Breviloquium como guia, podemos entender o modo como São Boaventura analisa o problema do mal e sua relação com o pecado. O homem foi criado bom, para viver num mundo bom. Com o pecado, rompeu com o projeto divino, instaurando o mal no mundo. Deus, o princípio primeiro e perfeitíssimo, contudo, não deixa de levar à perfeição sua obra, razão pela qual vem ao encontro do homem para vencer o pecado e o mal. Numa reflexão em que Filosofia e Teologia se entrecruzam, Boaventura, ao discorrer sobre a origem, transmissão e superação do mal, deixa transparecer o papel singular e afirmativo do homem, pois, apesar do pecado, não perdeu sua atração natural às virtudes, sendo capaz de agir bem

  3. Grupo Semco y las prácticas de recursos humanos de alto compromiso, una ventaja competitiva

    Directory of Open Access Journals (Sweden)

    Juan Nicolás Montoya Monsalve

    2012-12-01

    Full Text Available El presente artículo de reflexión trata de determinar si las prácticas de recursos humanos orientadas a mejorar el compromiso de los empleados con la empresa reportan una identidad común y diferenciadora del resto de empresas, logrando de esta forma una ventaja competitiva. Además de la fundamentación teórica, para analizar el objetivo principal señalado se han utilizado elementos del método del caso, que ayudan a determinar nuevas variables de estudio y permiten comprobar si existen realidades empresariales que consigan alcanzar, a través de las prácticas de alto compromiso, un mejor desempeño y una mayor pertinencia con las organizaciones, y estudiar cómo lo han conseguido. En esta parte de análisis empírico, se analiza la organización Semco, una compañía brasileña que ha atraído el interés de los expertos por las innovadoras prácticas en la gestión del talento humano, su diseño organizativo y la generación de una identidad propia, como base de su ventaja competitiva.

  4. Qualitative and Quantitative Saponin Contents in Five Sea Cucumbers from the Indian Ocean

    Science.gov (United States)

    Van Dyck, Séverine; Gerbaux, Pascal; Flammang, Patrick

    2010-01-01

    To avoid predation, holothuroids produce feeding-deterrent molecules in their body wall and viscera, the so-called saponins. Five tropical sea cucumber species of the family Holothuriidae were investigated in order to study their saponin content in two different organs, the body wall and the Cuvierian tubules. Mass spectrometry techniques (MALDI- and ESI-MS) were used to detect and analyze saponins. The smallest number of saponins was observed in Holothuria atra, which contained a total of four congeners, followed by Holothuria leucospilota, Pearsonothuria graeffei and Actinopyga echinites with six, eight and ten congeners, respectively. Bohadschia subrubra revealed the highest saponin diversity (19 congeners). Saponin mixtures also varied between the two body compartments within a given animal. A semi-quantitative approach completed these results and showed that a high diversity of saponins is not particularly correlated to a high saponin concentration. Although the complexity of the saponin mixtures described makes the elucidation of their respective biological roles difficult, the comparisons between species and between body compartments give some clues about how these molecules may act as predator repellents. PMID:20161976

  5. PML nuclear bodies in the pathogenesis of acute promyelocytic leukemia: active players or innocent bystanders?

    Science.gov (United States)

    Brown, Nicola J M; Ramalho, Michal; Pedersen, Eva W; Moravcsik, Eva; Solomon, Ellen; Grimwade, David

    2009-01-01

    The promyelocytic leukemia gene (PML) encodes a protein which localizes to PML-nuclear bodies (NBs), sub-nuclear multi-protein structures, which have been implicated in diverse biological functions such as apoptosis, cell proliferation and senescence. However, the exact biochemical and molecular basis of PML function up until now has not been defined. Strikingly, over a decade ago, PML-NBs were found to be disrupted in acute promyelocytic leukemia (APL) in which PML is fused to the gene encoding retinoic acid receptor alpha (RARA) due to the t(15;17) chromosomal translocation, generating the PML-RARA chimeric protein. The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. This review focuses on the current theories for molecular and biochemical functions of the PML-NBs, which would imply a role in the pathogenesis of APL, whilst also discussing the intriguing possibility that their disruption may not be in itself a significant oncogenic event.

  6. Evolução do construto liderança autêntica: Uma revisão de literatura

    Directory of Open Access Journals (Sweden)

    Maria Isabel de Campos

    2018-03-01

    Full Text Available A Liderança Autêntica (LA tem atraído a atenção de profissionais da academia e da prática organizacional desde o início deste século. Este estudo teve por objetivo realizar uma revisão da literatura publicada entre 2011 e 2016, visando a avaliar o estágio de evolução do construto LA. Foram analisados 106 artigos de autoria de estudiosos de todos os continentes, sendo nove teóricos e 97 empíricos. Os resultados indicam que o construto evoluiu, em consequência, entre outros, da corroboração empírica de pressupostos teóricos e que a existência de possível redundância por parte da LA e da liderança transformacional ainda permanece em questionamento. Sugerem-se novas pesquisas no tocante à forma como os líderes autênticos desenvolvem seus liderados, em contraste com o realizado por outros estilos de liderança, e a novas formas de medida, visando a responder as indagações em aberto.

  7. Habitat characteristic of two selected locations for sea cucumber ranching purposes

    Science.gov (United States)

    Hartati, Retno; Trianto, Agus; Widianingsih

    2017-02-01

    Sea cucumbers face heavily overfished because of their high prices and very strong market demand. One effort suggested to overcome this problem is sea ranching. The objectives of present works were to determine biological, physical, and chemical characteristics of prospective location for sea ranching of sea cucumber Holothuria atra. Two location at Jepara Waters (Teluk Awur and Bandengan WateRs of Jepara Regency) were selected. The determination of chemical (salinity, temperature, dissolved oxygen of water, phosphate, nitrate, nitrite and ammonium of water and sediment, organic matters of sediment), physical (transparancy, sedimen grains size, water current direction and its velocity), biologycal characteristic (coverage of seagrass and its macroalgae associated, phytoplankton as well as chlorophyl-a and phaeopytin of water and sediment) ware determined. The result of present work showed that some characteristic were matched with requirement as sea ranching location of sea cucumber because the density of sea cucumber in the sea is a function of habitat features. For sediment feeding holothurians of the family Aspidochirotida, the biologycal characteristic act as very important considerations by providing sea cucumber food. High cholophyl-a and phaeopytin in sediment also represent a prosperous habitat for sea cucumber ranching.

  8. Distribusi Teripang (Holothuroidea Pada Perairan Pesisir Nusa Lembongan, Kecamatan Nusa Penida, Kabupaten Klungkung, Bali

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    Deptson Baringin Silaen

    2017-11-01

    Full Text Available Sea cucumbers have a high economic potential and widely used by the community as food with nutrient content and high enough protein. The occurrence of an organism, including sea cucumbers in a waters is determined by the environmental factors of the waters, one of which is habitat. This study aims to determine the distribution of sea cucumbers (Holoturoidea in the Coastal Waters of Nusa Lembongan, District Nusa Penida, Klungkung regency, Bali. This research was conducted in April-May 2017 in the Coastal Waters of Nusa Lembongan. This study looked at the distribution of sea cucumbers (Holoturoidea, substrate composition, physics-chemical parameters of waters (temperature, depth, salinity, pH, dissolved oxygen and their relation to habitat conditions spread over Nusa Lembongan Coastal Waters. Data analysis in this study include the composition of sea cucumber, density of sea cucumber, the diversity of sea cucumber, and distribution of sea cucumbers. The results of the research conducted found 4 species of sea cucumber namely the type of Holothuria atra, Bohadchia vitiensis, Holothuria fuscocinerea and Holothuria sp. Physical-chemical parameters of the waters obtained in the research results are still categorized normal for the survival of sea cucumbers. Distribution of sea cucumbers during the study obtained by the results pattern of dispersal is clumped in all station with the index distribution value from 1.72 to 6.60.

  9. Effect of Diel Activity Patterns and Harvesting Pressure on the Diversity and Biomass of Sea Cucumbers in Marovo Lagoon, Solomon Islands

    Science.gov (United States)

    Buckius, Christine; Albert, Simon; Tibbetts, Ian; Udy, James

    2010-05-01

    A marked decline in the contribution by Marovo Lagoon to the annual total bêche-de-mer production of the Solomon Islands from 58% in 1989 to 17% in 2003 prompted investigation of their current biomass and diversity. We also assessed changes to critical ecological services and the prospects for population recovery following a fisheries closure. Day time and nocturnal transects revealed a mean abundance of 32.4 (SD = 5.3) low value species per ha (e.g. Holothuria atra, H. edulis, H. coluber and Thelenota anax) and 15.2 (SD = 2.7) high value species per ha (e.g. H. fuscogilva, Actinopyga lecanora, Stichopus hermanni and Thelenota ananas). Following a 17 month closure of the fishery (2005-2007), the abundance of bêche-de-mer was reported by local fisherman to have increased; however, no scientific studies were conducted that can substantiate this community held belief. The current study aimed to document the impact of re-opening the fishery in 2007 and documented a decline in high value species of 9% over a 5 month period following the opening of the fishery, while low value species continued to increase in abundance by 11%, over the same period based on nocturnal surveys. Continued observation of the recovery, post closure, and any subsequent harvest in Marovo will be required to properly understand population dynamics and provide a sustainable harvest plan for bêche-de-mer in the future.

  10. Qualitative and Quantitative Saponin Contents in Five Sea Cucumbers from the Indian Ocean

    Directory of Open Access Journals (Sweden)

    Patrick Flammang

    2010-01-01

    Full Text Available To avoid predation, holothuroids produce feeding-deterrent molecules in their body wall and viscera, the so-called saponins. Five tropical sea cucumber species of the family Holothuriidae were investigated in order to study their saponin content in two different organs, the body wall and the Cuvierian tubules. Mass spectrometry techniques (MALDI- and ESI-MS were used to detect and analyze saponins. The smallest number of saponins was observed in Holothuria atra, which contained a total of four congeners, followed by Holothuria leucospilota, Pearsonothuria graeffei and Actinopyga echinites with six, eight and ten congeners, respectively. Bohadschia subrubra revealed the highest saponin diversity (19 congeners. Saponin mixtures also varied between the two body compartments within a given animal. A semi-quantitative approach completed these results and showed that a high diversity of saponins is not particularly correlated to a high saponin concentration. Although the complexity of the saponin mixtures described makes the elucidation of their respective biological roles difficult, the comparisons between species and between body compartments give some clues about how these molecules may act as predator repellents.

  11. Apuntes para la dinamizacion turística del municipio de águilas, a partir de la interpretación del patrimonio

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    R. Borrega

    2000-01-01

    Full Text Available Águilas, desde el punto de vista turístico, es un municipio cuyos recursos patrimoniales no están suficientemente aprovechados. Su oferta turística se ha basado siempre en productos y servicios relacionados con aspectos de sol y playa, es decir, alojamientos, restauración, comercios ... La única demanda de carácter cultural se da en el segmento de público que practica deportes náuticos y subacuáticos, y en el universitario, este último atraído por los cursos de verano que organiza la Universidad del Mar en el municipio. Todo esto da como resultado un bajo rendimiento económico y un estado de abandono de recursos patrimoniales de interés, así como de vida tradicional. En este trabajo se presentan unas posibilidades de actuación para dinamizar el sector turístico de la localidad y poner en valor su patrimonio cultural, partiendo de que cuenta con lo más importante, la afluencia de público y un amplio patrimonio que ofertar.

  12. Effects of lead exposure on oxidative stress biomarkers and plasma biochemistry in waterbirds in the field.

    Science.gov (United States)

    Martinez-Haro, Monica; Green, Andy J; Mateo, Rafael

    2011-05-01

    Medina lagoon in Andalusia has one of the highest densities of spent lead (Pb) shot in Europe. Blood samples from waterbirds were collected in 2006-2008 to measure Pb concentration (PbB), δ-aminolevulinic acid dehydratase (ALAD), oxidative stress biomarkers and plasma biochemistry. PbB above background levels (>20 μg/dl) was observed in 19% (n=59) of mallards (Anas platyrhynchos) and in all common pochards (Aythya ferina) (n=4), but common coots (Fulica atra) (n=37) and moorhens (Gallinula chloropus) (n=12) were all 6 μg/dl. In mallards, an inhibition of glutathione peroxidase (GPx) and an increased level of oxidized glutathione (oxGSH) in red blood cells (RBC) were associated with PbB levels >20 μg/dl. In coots, PbB levels were negatively related to vitamin A and carotenoid levels in plasma, and total glutathione in RBCs; and positively related with higher superoxide dismutase and GPx activities and % oxGSH in RBCs. Overall, the results indicate that previously assumed background levels of PbB for birds need to be revised. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Viejos problemas y nuevos vecinos. Consecuencias de una gran reforma urbana en el barrio del Raval, Barcelona

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    Miquel Fernández González

    2016-05-01

    Full Text Available El barrio del Raval de Barcelona, conocido anteriormente como Distrito V y asociado a la mitificada sordidez del Barrio Chino (uno de los más populares barrios rojos de Europa, se encuentra actualmente en una fase terminal de su reforma urbanística. Esta se inició en 1988 a rebufo de la elección de Barcelona como sede de los Juegos Olímpicos de 1992. Arrancando el presente siglo, se implementó la última intervención urbanística sobre el barrio, concretamente sobre la zona de estudio, la conocida como Illa Robador. La calle d'en Robador ha sido hasta época muy reciente -y probablemente aún lo siga siendo- el nuevo epicentro y quizás el último bastión del Barrio Chino. El mito y la reforma urbanística se convocan en la etnografía que aquí se presenta. Se ha querido levantar acta de los encuentros y encontronazos entre «viejos vecinos», que han sobrevivido a toda clase de mistificaciones y estigmatizaciones, y «nuevos vecinos» atraídos por la posibilidad de vivir en un lugar céntrico, en el nuevo distrito cultural de Barcelona. Se concluye interpretando estos conflictos a la luz de lo que algunos autores llaman un nuevo colonialismo urbano.

  14. Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral chemotherapy

    International Nuclear Information System (INIS)

    Kesel, Andreas J.

    2003-01-01

    The synthesis of retinoid vitamin A-vitamin B 6 conjugate analogues from a vitamin B 6 coenzyme analogue and putative HIV-1 trans-activating transcriptional regulatory protein Tat antagonist (Z)-5 ' -O-phosphono-pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)-B6PRNa8.5H 2 O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to B6PR by a modified Stork enamine acylation. It results in a product library of more than eight compounds, each with at least one intact all-trans or 13-cis vitamin A double bond system. This yellow oily concentrate mixture was subjected to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic resonance spectroscopy ( 1 H-NMR). The chemical structures of six components of the concentrate mixture could be established by combination of these analytical methods. The two main components are 65% 2 ' C,3O-(all-trans-retinylidyne)B6PT (B6RA) and 25% 2 ' C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5-(5 ' -O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid selection could be of further interest in antiviral applications, especially treating conditions caused by RNA viruses like HIV

  15. "Eu quero uma casa no campo": a busca do verde em Belo Horizonte, 1966-1976

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    Regina Horta Duarte

    Full Text Available A expansão de condomínios horizontais esteve diretamente relacionada às condições históricas que acarretaram a deterioração e o abandono do centro urbano de Belo Horizonte, entre meados das décadas de 1960 e 1970. Nesse contexto, alguns tiveram o privilégio de escolher o sonho da casa no campo, atraídos por promessas de uma vida renovada, mergulhados nos paradoxos do desenvolvimento e dos dramas sociais, políticos e ambientais em curso no Brasil durante a ditadura civil-militar. Cientistas e técnicos realizavam as primeiras avaliações dos dilemas da poluição ambiental urbana. Entretanto, temas ambientais se configuravam como assunto extemporâneo e distante da política, subestimados por setores brasileiros de direita e esquerda. A perda de qualidade de vida em Belo Horizonte recebeu soluções individuais, por vezes com aspectos comunitários. O caráter simultâneo desses processos na capital mineira esclarece casos históricos similares em outras grandes metrópoles brasileiras e latino-americanas.

  16. Protozoa in a stressed area of the Egyptian Mediterranean coast of Damietta, Egypt

    Directory of Open Access Journals (Sweden)

    Mohamed Moussa Dorgham

    2013-08-01

    Full Text Available The Damietta coast is part of the Egyptian Mediterranean coast off the Nile Delta and has recently been polluted as a result of intensive human activities.The environmental parameters and protozoan community in the area were studied biweekly from January to December 2007. The results of the environmentalparameters indicated low salinity, oxic and anoxic conditions, high nutrient levels and intensive phytoplankton growth. A total of 69 protozoan specieswere identified, belonging to Amoebozoa (8 species, Foraminifera (12 species, non-tintinnid ciliates (22 species and tintinnids (27 species. The numerical density of protozoans was high over the whole area, with annual averages between 8.2 × 103 cells m-3 and 51.4 × 103 cells m-3.Spring was the most productive season for protozoans, but several distinct peaks were observed during the year at the sampling sites. The protozoangroups showed clearly different spatial patterns in both composition and abundance: whereas amoebozoans and non-tintinnid ciliates were dominant in themore polluted areas (sites IV and V, tintinnids dominated in the less polluted areas (sites, I, II and III. Several pollution indicators wererecorded: amoebozoans - Centropyxis aculeata, Centropyxis sp., Cochliopodium sp.,Difflugia sp.; non-tintinnids - Bursaridium sp., Frontonia atra,Holophrya sp., Paramecium sp., Paramecium bursaria,Vasicola ciliata, Vorticella sp., Strombidium sp.; tintinnids- Favella ehrenbergii, Helicostomella subulata, Leprotintinnus nordgvisti,Tintinnopsis beroidea, Stenosemella ventricosa, Tintinnopsis campanula,T. cylindrica, T. lobiancoi, Eutintinnus lusus-undae.

  17. Upwelling dynamics in the Baltic Sea studied by a combined SAR/infrared satellite data and circulation model analysis

    Directory of Open Access Journals (Sweden)

    Evgenia Gurova

    2013-08-01

    Full Text Available The Damietta coast is part of the Egyptian Mediterranean coast off the Nile Delta and has recently been polluted as a result of intensive human activities.The environmental parameters and protozoan community in the area were studied biweekly from January to December 2007. The results of the environmentalparameters indicated low salinity, oxic and anoxic conditions, high nutrient levels and intensive phytoplankton growth. A total of 69 protozoan specieswere identified, belonging to Amoebozoa (8 species, Foraminifera (12 species, non-tintinnid ciliates (22 species and tintinnids (27 species. The numerical density of protozoans was high over the whole area, with annual averages between 8.2 × 103 cells m-3 and 51.4 × 103 cells m-3.Spring was the most productive season for protozoans, but several distinct peaks were observed during the year at the sampling sites. The protozoangroups showed clearly different spatial patterns in both composition and abundance: whereas amoebozoans and non-tintinnid ciliates were dominant in themore polluted areas (sites IV and V, tintinnids dominated in the less polluted areas (sites, I, II and III. Several pollution indicators wererecorded: amoebozoans - Centropyxis aculeata, Centropyxis sp., Cochliopodium sp.,Difflugia sp.; non-tintinnids - Bursaridium sp., Frontonia atra,Holophrya sp., Paramecium sp., Paramecium bursaria,Vasicola ciliata, Vorticella sp., Strombidium sp.; tintinnids- Favella ehrenbergii, Helicostomella subulata, Leprotintinnus nordgvisti,Tintinnopsis beroidea, Stenosemella ventricosa, Tintinnopsis campanula,T. cylindrica, T. lobiancoi, Eutintinnus lusus-undae.

  18. del turista politizado en Chiapas

    Directory of Open Access Journals (Sweden)

    Gabriela Coronado

    2008-01-01

    Full Text Available El artículo analiza las interrelaciones entre turismo y política considerando el impacto de la rebelión indígena zapatista en el turismo en Chiapas, México. Mediante el análisis de productos turísticos y observaciones de campo la transformación de la industria turística se explica como efecto de las presiones de un nuevo tipo de visitante, el “turista politizado’. Atraído por el movimiento indígena y su relevancia como movimiento social global su posición política e ideológica creó demandas que impactaron sobre las redes organizacionales interétnicas y el valor social de la actividad turística. Como respuesta agentes turísticos indígenas y no indígenas generaron nuevas estrategias para la recuperación de su economía, incluyendo cambios en las redes organizacionales y comercializando símbolos e ideologías como “productos” turísticos.

  19. de marca de un destino turístico

    Directory of Open Access Journals (Sweden)

    Antonio Rial Boubeta

    2008-01-01

    Full Text Available El artículo analiza las interrelaciones entre turismo y política considerando el impacto de la rebelión indígena zapatista en el turismo en Chiapas, México. Mediante el análisis de productos turísticos y observaciones de campo la transformación de la industria turística se explica como efecto de las presiones de un nuevo tipo de visitante, el “turista politizado’. Atraído por el movimiento indígena y su relevancia como movimiento social global su posición política e ideológica creó demandas que impactaron sobre las redes organizacionales interétnicas y el valor social de la actividad turística. Como respuesta agentes turísticos indígenas y no indígenas generaron nuevas estrategias para la recuperación de su economía, incluyendo cambios en las redes organizacionales y comercializando símbolos e ideologías como “productos” turísticos.

  20. Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

    Science.gov (United States)

    Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

    2017-12-01

    Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

  1. Presence of plastic particles in waterbirds faeces collected in Spanish lakes.

    Science.gov (United States)

    Gil-Delgado, J A; Guijarro, D; Gosálvez, R U; López-Iborra, G M; Ponz, A; Velasco, A

    2017-01-01

    Plastic intake by marine vertebrates has been widely reported, but information about its presence in continental waterfowl is scarce. Here we analyzed faeces of waterbirds species (European coot, Fulica atra, mallard, Anas platyrhynchos and shelduck, Tadorna tadorna) for plastic debris in five wetlands in Central Spain. We collected 89 faeces of shelduck distributed in four lakes, 43.8% of them presented plastic remnants. Sixty percent of 10 faeces of European coot and 45% of 40 faeces of mallard contained plastic debris. Plastic debris found was of two types, threads and fragments, and were identified as remnants of plastic objects used in agricultural fields surrounding the lakes. Differences in prevalence of plastic in faeces, number of plastic pieces per excrement and size of the plastic pieces were not statistically significant between waterfowl species. Thus, our results suggest that plastic may also be frequently ingested by waterfowl in continental waters, at least in our study area. Future studies should address this potential problem for waterbird conservation in other wetlands to evaluate the real impact of this pollutant on waterbirds living in inland water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Bioprospecção dos potenciais farmacológicos do monoterpeno 7-hidroxicitronelal: Ensaios in silico

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    Marcus Antônio Bezerra da Silva

    2017-03-01

    Full Text Available Os óleos essenciais de plantas, bem como os compostos derivados destes óleos como os terpenos, têm atraído cada vez mais interesse por causa das suas propriedades antioxidantes. O 7-hidroxicitronelal é um monoterpeno derivado do citronelal, apresentando fórmula molecular C10H20O2. Objetivou-se avaliar as atividades farmacológicas in silico do monoterpeno, entre elas a atividade antioxidante. Para isso, utilizou-se as técnicas in silico através do programa: PASS® online, para avaliação das propriedades farmacológicas teóricas da substância. Os resultados mostraram amplo espectro de atividades farmacológicas in silico, entre elas efeito antioxidante. Assim conclui-se que o monoterpeno é portador de atividade antioxidante teórica in silico. Contudo mais estudos in vitro e em organismos vivos devem ser realizados para corroborar essas atividades.

  3. El café Internet: un espacio real para la virtualidad. Jóvenes y ciberespacio en el noroeste de México

    Directory of Open Access Journals (Sweden)

    Ana Lucía Castro Luque

    2004-01-01

    Full Text Available De las nu evas tecnologías de la información, Internet se erige como la más influyente, pues en un lapso mu y corto ha logrado trastocar nuestra vida. La polémica generada por la red de redes, también conocida como el sexto continente, apenas comenzó y aún es temprano para tener respuestas a las preguntas que plantea. A partir de esta confluencia de ideas, se propone contri buir al análisis que sobre Internet y su efectos se ha iniciado en el noroeste del país. El acercamiento al análisis de las nu evas relaciones humanas establecidas en el espacio virtual se realiza en estos nu evos recintos: el café Internet espacio real donde la navegación se democratiza haciéndose posible para quienes tener una computadora resulta difícil y colgarla a la red aún más. Los jóvenes, como el grupo más asiduo al café Internet —y quizá el más atraído por esta tecnología—, son el objeto de análisis a través del cual se exploran las nuevas formas de comunicación y entretenimiento alrededor de la red.

  4. Uso do feromônio sexual sintético para captura de machos da traça-das-crucíferas

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    MICHEREFF MIRIAN FERNANDES FURTADO

    2000-01-01

    Full Text Available Este trabalho teve como objetivo estudar a atração dos machos da traça-das-crucíferas (Plutella xylostella L., Lepidoptera: Yponomeutidae por diferentes formulações do feromônio sexual sintético. Os tratamentos consistiram em: 1 formulação comercial; 2 Z11,16:Ald; 3 Z11,16:Ac; 4 mistura 7:3 de 2+3; 5 mistura 5:5 de 2+3; 6 septos de borracha com hexano (testemunha; e 7 cinco fêmeas virgens. A formulação comercial do feromônio sexual sintético propiciou maior captura de machos, não diferindo significativamente de fêmeas virgens e da mistura 5:5 utilizadas como isca. Os componentes isoladamente foram pouco atrativos aos machos. Foram testados cinco modelos de armadilhas. A armadilha Pherocon 1 CP (33,2 machos/armadilha/noite foi a mais eficiente na captura de machos, seguida pelas armadilhas Cilíndrica Aberta, Cilíndrica Fechada, Delta e Redonda Aberta. Três alturas de instalação da armadilha foram avaliadas. Ocorreu significativamente maior captura de machos na altura do ápice das plantas (30 cm do solo. As alturas de 5 e 60 cm não diferiram entre si.

  5. Freqüência horária e sazonalidade de Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae na Ilha de São Luís, Maranhão, Brasil

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    Rebêlo José Manuel Macário

    2001-01-01

    Full Text Available A distribuição sazonal e horária de Lutzomyia longipalpis foi estudada nos ambientes peri e intradomiciliar de duas localidades da Ilha de São Luís, estado do Maranhão. Os 11.200 exemplares capturados foram atraídos por quatro armadilhas CDC nos anos de 1996 e 1997, mensalmente, das 18h às 6h. L. longipalpis comportou-se como uma espécie anual, tendo sido encontrada em alta freqüência em todos os meses do ano, tendendo a ser mais abundante no período chuvoso (57,2% do que no seco (42,8%. As maiores freqüências foram observadas nos meses de janeiro e abril, no período chuvoso, e em julho e novembro, no período seco. Foi encontrada a noite inteira, porém foi mais freqüente entre 18h e 22h no peridomicílio, e entre 20h e 2h no intradomicílio.

  6. ZBTB16-RARα variant of acute promyelocytic leukemia with tuberculosis: a case report and review of literature.

    Science.gov (United States)

    Palta, Anshu; Dhiman, Pratibha; Cruz, Sanjay D

    2012-09-01

    A 23-year-old male presented with pulmonary tuberculosis and swelling of both lower limbs. He was put on antitubercular treatment. Hemogram showed mild anemia and Pseudo Pelger-huet cells. The bone marrow (BM) examination showed 52% promyelocytes with regular round to oval nuclei, few granules and were positive for CD13 and CD33, and negative for HLA-DR. Cytogenetic analysis of the BM aspirate revealed an apparently balanced t(11;17)(q23;q21). Final diagnosis rendered was acute promyelocytic leukemia (APL) with t(11;17)(q23;q21); ZBTB16/RARA. APL is a distinct subtype of acute myeloid leukemia. The variant APL with t(11;17)(q23;q21) cases that are associated with the ZBTB16/RARA fusion gene have been reported as being resistant to all-trans-retinoic acid (ATRA). Therefore, differential diagnosis of variant APL with t(11;17)(q23;q12) from classical APL with t(15;17)(q22;q12); PML-RARA is very important. Here we have discussed the importance of distinct morphology of variant APL and also significance of rare presentation with tuberculosis.

  7. EUCARISTIA: VOLTEMOS À SACROSSANCTUM CONCILIUM

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    . Editorial

    2000-01-01

    Full Text Available Aos domingos, em dezenas de estúdios de televisão pelo Brasil a fora, realiza-se uma missa para ser transmitida ao vivo para os lares da região ou do país. Enquanto neste canto do estúdio se celebra o mistério da fé, ali no outro funcionários já preparam as câmaras para o seguinte item da programação. Logo ao lado do cenário da missa estão os de outras “atrações” do mesmo canal que talvez não só não tenham a ver com o mistério que ora se celebra, como até mesmo o contradigam. O que agora é altar, daqui a pouco servirá para algum empregado afobado descansar suas ferramentas, ou quem sabe para se deitar, tirando um descanso à espera de seu momento de agir. Tem sentido celebrar aí a eucaristia? E que assembléia é essa, artificialmente reunida para responder às orações e aos diálogos litúrgicos, ou para, com seu canto, dar “brilho” à celebração?

  8. Espaço Público e Shopping Center na Cidade Contemporânea: Novos Significados do North Shopping em Fortaleza - CE

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    Tiago Estevam Gonçalves

    2012-03-01

    Full Text Available Iniciar uma reflexão acerca da cidade atual nos remete à necessidade de construirmos uma análise sobre os shopping centers como espaços que tem atraído um fluxo considerável da população, ocasionando mudanças na relação dos citadinos com os espaços públicos. Nesta perspectiva, temos como objetivo analisar o North Shopping, localizado na cidade de Fortaleza, como um espaço de uso popular onde as camadas de menor poder aquisitivo podem adentrar e usufruir de seus atributos. Imbuídos de tal finalidade nosso aporte teórico fundamentou-se em Pintaudi (1992, Dantas (1995, Silva (1996 Lefebvre (1999, Carlos (2001, Gomes (2002 e Serpa (2007. Conclui-se que na cidade de Fortaleza, o North Shopping é um verdadeiro simulacro da realidade, substituindo as experiências cotidianas dos espaços públicos, configurando-se, assim, a supervalorização do espaço privado que se traveste de público tendo repercussões na nova urbanidade fortalezense.

  9. High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA

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    Benjamin Powers

    2015-01-01

    Full Text Available Acute promyelocytic leukemia (APL is classically characterized by chromosomal translocation (15;17, resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17 which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.

  10. Characteristics features and factors influencing early death in Acute promyelocytic leukemia; Experience from United Arab Emirates (UAE).

    Science.gov (United States)

    Hassan, Inaam Bashir; Zaabi, Mariam R Al; Alam, Arif; Hashim, Mohammed Jawad; Tallman, Martin S; Kristensen, Jorgen

    2017-07-01

    Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0.030), WBC count >20 × 10 9 /L (P = 0.010), the breakpoints other than bcr1 (P = 0.043) and fibrinogen level 10 × 10 9 /L and expression of HLA-DR (P = 0.018) or CD2 (P = 0.017) were significant predictors for differentiation syndrome (DS) which was found to be a predictor of ED (P = 0.002). Reducing the APL related ED rate in centers with limited resources is feasible provided early initiation of ATRA administration and early correction of coagulopathy in high-risk patients in addition to prompt treatment of DS. To our knowledge this is the first report from the Arabian Gulf describing ED in APL.

  11. Tomé, futuro turístico y renacer industrial

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    Carol Andaluz Sandoval

    2003-01-01

    Full Text Available La ciudad de Tomé, ubicada en la ribera N.E. de la bahía de Talcahuano, distante a sólo 32 kilómetros al norte del Gran Concepción, se ha desarrollado económica y territorialmente por los diferentes aconteceres que le ha correspondido presenciar durante la historia. Es así como encontramos vestigios de la grandeza de su apogeo pesquero, portuario, molinero, vitivinícola y textil, tanto en el ordenamiento de su trama urbana como en obras arquitectónicas que muestran un claro reflejo de las inmigraciones extranjeras que se vieron atraídas por esta próspera ciudad, que nació como caleta de pescadores y se transformó en un centro industrial de gran importancia nacional. Tal fue su significancia dentro de las zonas costeras del país que en el año 1858, el Congreso Nacional declaró a Tomé Puerto Mayor, lo que se tradujo en un aumento importante de la población, la industria y las actividades que esto conllevaba.

  12. Bibliotecas públicas e ciberviolência em tempos de uma sociedade em rede: Novos papéis diante de um novo fenômeno

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    Rubens da Silva Ferreira

    2012-10-01

    Full Text Available Reflete sobre o papel das bibliotecas públicas na educação de usuários para o conhecimento da ciberviolência. Tal fenômeno é expresso através das Tecnologias de Informação e Comunicação (TIC, as quais são utilizadas para causar danos às vítimas. O trabalho fundamenta-se em três casos de ciberviolência: um de homicídio; um de estelionato e um de pedofilia. Os casos dão sustentação à reflexão sobre a necessidade de intervenção das bibliotecas públicas. O quadro teórico que serve a análise constitui-se das contribuições teóricas da Ciência da Informação, da Sociologia e da Antropologia. Os resultados apontam para o envolvimento das bibliotecas públicas no enfrentamento da ciberviolência, uma vez que atuam como centros de atração de usuários distintos para o acesso à informação na Internet

  13. Industria y territorio rural: la constitución de un corredor agropecuario e industrial en el estado de Querétaro

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    Alfonso Serna Jiménez

    2010-01-01

    Full Text Available Los municipios de Ezequiel Montes y Cadereyta se han vuelto un punto de referencia en el análisis de los procesos territoriales de Querétaro, pues han constituido un lugar de actividad primaria vigorosa. Capitales agroalimentarios los han reconocido como un ámbito favorable para la producción avícola, y han invertido en granjas muy tecnificadas en sus territorios rurales, así como en sus vecinos Colón y Tequisquiapan. Estos cuatro municipios han configurado un corredor agroindustrial que ha atraído a maquiladoras y procesadoras de alimentos, entre otras, y es parte de la organización actual del estado, sobre todo ante la desconcentración industrial de la ciudad capital. El objetivo del artículo es destacar la configuración paulatina de un corredor económico distinto a los constituidos por parques industriales y localizado fuera de los corredores nacionales.

  14. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    International Nuclear Information System (INIS)

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-01-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFβ1-mediated lytic phase. EBV lytic reactivation by TGFβ1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM 1 81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  15. Análise da estrutura populacional de Trachemys scripta elegans (Chelonia no Parque Ecológico Olhos D’água – Brasília - DF - doi: 10.5102/ucs.v4i1.18

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    Camilla Silva Vieira

    2008-04-01

    Full Text Available A tartaruga Trachemys scripta elegans nativa da América do Norte, é encontrada na Lagoa do Sapo, no Parque Ecológico Olhos d’Água, Asa Norte, em Brasília. Este trabalho tem por objetivo analisar a estrutura da população desta subespécie. As tartarugas foram coletadas em pontos definidos na lagoa, por meio da atração, para análise morfométrica, sexagem, pesagem e marcação. O estudo foi desenvolvido entre dezembro de 2005 e julho de 2006, sendo marcados 77 indivíduos. Na lagoa, predominam fêmeas adultas, com razão sexual de 5:1, e a freqüência de jovens é baixa. As fêmeas são maiores e mais pesadas que os machos. A análise da estrutura etária revela a ausência de filhotes e a predominância de adultos. Apesar de observados rituais de corte, não foram encontrados ninhos nem outros sinais de reprodução, indicando que, embora possua condições reprodutivas, esta população encontra-se estagnada, e seu crescimento dá-se pela soltura de indivíduos, feita pelos visitantes do Parque.

  16. Iglesia de San Francisco, en Hüttwilen, Suiza

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    Dahinden, J.

    1969-07-01

    Full Text Available This church is beautifully integrated in the landscape, including the villalle which has retained its old time style. The building has room for 200 worshippers on the higher level, and below there are facilities for meetings, classrooms, a sacristy, coatroom, services, etc. The spectator is attracted by the shape of the tower and the roof. Fibrocement has been used as roofing material, and also as surfacing for some of the outer walls. Untreated concrete, timber and subtle illumination have contributed to create a suitable atmosphere for meditation inside the church.Plenamente integrada en el paisaje que ofrecen las casas de un pueblo que ha sabido conservar su auténtico carácter, esta iglesia, con capacidad para 200 fieles en su nivel superior, alberga en su planta baja: una sala de reuniones, un aula, la sacristía, guardarropas, servicios, etc. El espectador se siente atraído por la forma de su torre y la de toda la cubierta; han sido empleados como elementos de cobertura, y también para revestimiento de algunos de sus paramentos exteriores, placas de amianto-cemento. El empleo del hormigón visto, de la madera, y el logro de una iluminación discreta han contribuido a crear en el interior un ambiente propicio a la meditación.

  17. O fundamento estrutural do pensamento de Umberto Eco

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    Winfried Nöth

    2016-08-01

    Full Text Available Uma análise detalhada apresenta o método argumentativo a contrario, característico do artigo "Existe a contracultura?", de Umberto Eco, como paradigmático do princípio estruturalista da constituição do sentido por meio de oposições semânticas. O artigo argumenta que muitos dos escritos de Eco podem ser lidos como aplicações do princípio estruturalista de que apenas diferenças ou oposições carregam significação. A evidência do modo como o pensamento de Eco está sob o encanto do princípio das oposições e da dialética da presença e da ausência é apresentada através do levantamento dos escritos gerais de Eco e também da inspeção das obras A estrutura ausente e Semiótica e filosofia da linguagem. Além disso, o artigo revela que o pensamento de Eco é igualmente atraído tanto por processos nos quais oposições anulam ou dissolvem a si próprias quanto pela crítica pós-estruturalista do pensamento estruturalista.

  18. Resposta de Euphalerus clitoriae (Hemiptera: Psyllidae a armadilhas adesivas de diferentes cores Response of Euphalerus clitoriae (Hem: Psyllidae to adhesive traps of different colors

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    Mariângela Guajará

    2004-02-01

    Full Text Available Retângulos de alumínio, medindo 10 x 24,5 cm, pintados de branco, vermelho, azul e amarelo, foram revestidos com cola incolor e inodora e dispostos no campo, entre árvores de Clitoria fairchildiana, para verificação da responsividade dos adultos de E. clitoriae às diferentes cores. Retângulos transparentes, de iguais dimensões, foram utilizados como controle. O número significativamente superior de adultos atraídos e capturados pelas armadilhas amarelas, em comparação com as demais, indica uma resposta orientada, sendo elas, portanto, recomendadas para o monitoramento de adultos de E. clitoriae.Aluminum rectangles measuring 10 x 24.5 cm and painted white, red, blue and yellow were covered with colorless and scentless glue and disposed in the field among trees of Clitoria fairchildiana, for verification of response of E. clitoriae adults to the different colors. Transparent rectangles of the same dimensions were also used as controls. The number of adults attracted and captured by the yellow traps was significantly greater than that attracted by the other colors, suggesting a color-oriented response. Thus, the yellow adhesive traps are recommended for monitoring of E. clitoriae adults.

  19. Acute myeloid leukemia in children: Current status and future directions.

    Science.gov (United States)

    Taga, Takashi; Tomizawa, Daisuke; Takahashi, Hiroyuki; Adachi, Souichi

    2016-02-01

    Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML-DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all-trans retinoic acid (ATRA)-combined regimen with an 80-90% OS. Children with ML-DS are treated with a less intensive regimen compared with non-DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high-risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials. © 2015 Japan Pediatric Society.

  20. Universidad de Essex, en Wivenhoe, Inglaterra

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    Co-Partnership, Arquitectos

    1969-10-01

    Full Text Available The new Essex University, for an estimated 6 000 students, has two types of buildings: those devoted to various academic purposes, and those attending to such functions as restaurants, students' tall building residence, social and recreational facilities, and clubs. The whole project has been located along a central road. The main buildings are sited close to this main artery, although there are a number of independent buildings, such as the residential blocks, placed elsewhere. The whole project is attractive because of its tasteful simplicity.La nueva Universidad de Essex, prevista para una población estudiantil de 6.000 alumnos, consta de edificios de dos clases: los destinados a distintos fines académicos; y los dedicados a otros objetivos, tales como restaurante; edificios-torres residenciales para estudiantes; instalaciones sociales y recreativas; tiendas; clubs; etc. El conjunto ha sido desarrollado a lo largo de una arteria central de circulación, con las principales unidades constructivas organizadas a ambos lados de esa espina central, si bien hay diferentes cuerpos de edificación independientes que constituyen los edificios especiales y las torres residenciales. El complejo atrae por su distinguida sencillez.

  1. Diccionarios bio-bibliográficos: de la antigüedad al mundo cristiano y al islámico

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    Ramírez del Río, José

    2016-06-01

    Full Text Available The bio-bibliographic dictionaries have received a great deal of attention in the field of Classical, Mediaeval and Arabic Studies, even if independently from one another. In this paper we attempt to show some continuity lines shared by all of them since Calimacus’ catalogue work in the Library of Alexandria to the works of Saint Jerome and Saint Isidore until the later Bizantine world of 6th to 8th centuries AD, both in Greek and in Syriac literary output. From there it crept into the Islamic world.Los diccionarios bio-bibliográficos han atraído un gran interés tanto en el campo de los Estudios Clásicos como en los Medievales y en los Estudios Árabes, aunque de forma aislada unos de otros. En este artículo intentaremos mostrar las líneas de continuidad que se producen desde los trabajos de catalogación de Calímaco, en la Biblioteca de Alejandría, hasta las obras de San Jerónimo y San Isidoro y, posteriormente, hasta el mundo bizantino en los siglos VI-VIII A.D., tanto en las letras griegas como en las siríacas, desde donde pasó al Islam.

  2. Nanosecond pulsed electric field suppresses development of eyes and germ cells through blocking synthesis of retinoic acid in Medaka (Oryzias latipes.

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    Eri Shiraishi

    Full Text Available Application of nanosecond pulsed electric fields (nsPEFs has attracted rising attention in various scientific fields including medical, pharmacological, and biological sciences, although its effects and molecular mechanisms leading to the effects remain poorly understood. Here, we show that a single, high-intensity (10-30 kV/cm, 60-ns PEF exposure affects gene expression and impairs development of eyes and germ cells in medaka (Oryzias latipes. Exposure of early blastula stage embryos to nsPEF down-regulated the expression of several transcription factors which are essential for eye development, causing abnormal eye formation. Moreover, the majority of the exposed genetic female embryos showed a fewer number of germ cells similar to that of the control (unexposed genetic male at 9 days post-fertilization (dpf. However, all-trans retinoic acid (atRA treatment following the exposure rescued proliferation of germ cells and resumption of normal eye development, suggesting that the phenotypes induced by nsPEF are caused by a decrease of retinoic acid levels. These results confirm that nsPEFs induce novel effects during embryogenesis in medaka.

  3. La literatura sobre gobierno abierto en español. Análisis sobre las dinámicas de producción y citación

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    Diego Barria Traverso

    2019-01-01

    Full Text Available Gobierno abierto es uno de los conceptos que más ha atraído a profesionales y académicos dedicados a la administración pública. Es posible advertir la aparición de un volumen creciente de trabajos académicos dedicados a analizar el concepto y experiencias de gobierno abierto en la región. Este artículo analiza la producción académica en español sobre gobierno abierto. Se identifican textos publicados en revistas especializadas entre 2009 y 2015, y se caracterizan los principales canales de publicación, los niveles de indización de las revistas que publican artículos del tema y las referencias bibliográficas. Esto se complementa con un análisis de redes de citación y un modelo estadístico que evalúa determinantes de centralidad en la red. Entre los hallazgos destaca que los documentos no académicos tienen mayores probabilidades de ser centrales en la red de citación.

  4. Divergências convergentes: a nova cultura radiofônica

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    Lilian Zaremba

    2001-02-01

    Full Text Available Há mais ou menos vinte anos o rádio começou a se transformar na digitalização e sob o impacto da chamada convergência dos massmedia, o computador e a telecomunicação, oferecendo terreno para o aparecimento de formas híbridas: as concepções tradicionais enfrentam o embate no mutante espaço cibernético. Mutatis Mutandis, mudar o que precisa ser mudado, o rádio se desloca no dial encruzilhada das opções. O médium das gigantescas organizações internacionais, o rádio público, comunitário ou pirata, atraídos por este ímã até então estranho da nova media eletrônica, temem ser dissolvidos por ela. A resistência dos padrões sucumbe na pressão comercial tornando urgente a preservação de algum espaço para reflexão. Este trabalho pretendeu operar nesta urgência contribuindo para o debate, vasculhando nas origens deste médium de comunicação a compreensão mesma do que seja e possa talvez continuar a ser, Rádio.

  5. Ataque de las polillas Scrobipalpopsis solanivora y phthorimaea operculella (Lepidoptera, Gelechiidae y su relación con la fenología de la papa en Cartago, Costa Rica.

    Directory of Open Access Journals (Sweden)

    Luko Hilje

    2016-03-01

    Full Text Available Se estudió el crecimiento de las estructuras vegetativas (parte aérea, tubérculos y raíces y la presencia de las estructuras reproductivas, en las variedades de papa Atzimba y “Segura”. Conforme avanzó la temporada del cultivo, el número de hojas aumentó casi linealmente y la altura en forma sigmoidea; el peso fresco y la biomasa de las estructuras vegetativas se incrementó en forma curvilínea. La máxima producción de biomasa aérea se registró entre las semanas 5a y 7a y la de los tubérculos entre la 13a y la 15a. A partir de la 6a semana se iniciaron la floración y la tuberización. La presencia de polillas en los campos coincidió con la floración, por lo que propone la hipótesis de que ellas son atraídas por la presencia de flores. Se plantea un modelo fenológico para el cultivo, con base en el cual se discuten varias posibilidades para reducir el impacto económico de las polillas.

  6. Taxonomic notes on the afrotropical genera Hapalogenius Hagedorn, Hylesinopsis Eggers, and Rhopalopselion Hagedorn (Coleoptera, Curculionidae, Scolytinae

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    Roger Beaver

    2010-09-01

    Full Text Available Taxonomic confusion among the afrotropical scolytine genera Hapalogenius Hagedorn, Hylesinopsis Eggers and Rhopalopselion Hagedorn, and their synonyms is discussed with especial reference to the catalogues of Wood and Bright (1992, and Alonso-Zarazaga and Lyal (2009. A key is given to separate the three genera recognised, and the species considered to be included in each genus are listed. Hylesinopsis is resurrected from synonymy with Hapalogenius, and shown not to be closely related to it. Chilodendron Schedl is considered to be a synonym of Hylesinopsis and not of Xylechinus Chapuis. The following new synonymy is proposed at specific level: Hapalogenius africanus (Eggers (= Hapalogenius lesnei Eggers, = Metahylesinus brincki Schedl; Hapalogenius fuscipennis (Chapuis (= Hapalogenius bimaculatus Eggers; Hapalogenius oblongus (Eggers (= Metahylesinus striatus Schedl; Hylesinopsis fasciata (Hagedorn (= Kissophagus punctatus Eggers; Phrixosoma niger Eggers (= Hapalogenius niger Schedl. The following species are returned to Hylesinopsis from Hapalogenius to which they were transferred by Alonso-Zarazaga and Lyal (2009: Hylesinopsis alluaudi (Lepesme, H. angolensis (Schedl, H. arabiae (Schedl, H. atra (Nunberg, H. confusa (Eggers, H. decellei (Nunberg, H. dubia Eggers, H. emarginata (Nunberg, H. fasciata (Hagedorn, H. ficus (Schedl, H. granulata (Lepesme, H. hirsuta (Schedl, H. joveri (Schedl, H. pauliani (Lepesme, H. punctata (Eggers, H. saudiarabiae (Schedl. The following new combination is given: Hylesinopsis leprosula (Browne from Cryphalus Erichson. New distributional records are given for some species.

  7. La reconversión industrial de la siderúrgica integrada en Colombia

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    Patricia Carolina Barreto Bernal

    2014-01-01

    Full Text Available La reconversión industrial en Colombia tiene su origen como iniciativa política, buscando modernizar y preparar su aparato productivo, ante la entrada de competidores atraídos por el cambio de modelo económico. Los autores pretenden explicar los principales cambios y transformaciones surgidas en el proceso de reconversión industrial del país, particularmente el caso de Acerías Paz del Río, mediante la implementación de un método hermenéutico y la técnica de análisis documental. Como resultado de la revisión se puede establecer que los procesos de reconversión están relacionados con las formas de gestión organizacional y la disposición de la estructura de capital de la empresa. Para la empresa Acerías el proceso de reconversión resultaría importante para apalancar su perdurabilidad, no obstante las dificultades a las cuales tuvo que hacer frente la gestión de la compañía.

  8. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

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    Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  9. Os novos territórios da produção e do trabalho: a indústria de calçados no Ceará

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    Jacob Carlos Lima

    Full Text Available Este artigo objetiva analisar a relocalização industrial do setor calçadista para o Nordeste a partir da década de 1990, bem como o perfil dos "novos" contingentes de trabalhadores decorrentes desse processo. A quase inexistência de um mercado de trabalho formal anterior torna o emprego fabril nesses novos territórios atrativo para trabalhadores mais escolarizados. Para as empresas, a atração encontra-se nos incentivos fiscais, no baixo custo da força de trabalho e na baixa mobilização desses contingentes de trabalhadores. O recorte empírico é o Ceará, que se tornou, com a política de interiorização industrial, o terceiro produtor de calçados no País, com unidades fabris distribuídas de forma desconcentrada pelo estado. A pesquisa constou de: dados secundários obtidos em associações e sindicatos patronais nacionais e em órgãos empresariais e governamentais; entrevistas com dirigentes sindicais de quatro cidades; e aplicação de questionário a 197 trabalhadores de seis fábricas - oriundas do Sul e Sudeste - localizadas em diferentes regiões do estado.

  10. Las abejas (Hymenoptera: Apoidea del Parque Nacional Natural Gorgona, Pacífico colombiano

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    Marcela González-Córdoba

    2014-02-01

    Full Text Available En este estudio se presenta la diversidad y abundancia de las abejas del PNN Gorgona. En tres visitas en intervalos de tres meses, se muestrearon seis zonas de la isla con cubierta vegetal variable. Los muestreos fueron indirectos usando (i trampas McPhail (cebadas con cineol, silicato de metilo y extracto clavos; (ii trampas Van Someren Rydon (con cebo de pescado o pollo o fruta podridos, (iii trampas Malaise y (iv trampas de luz y directos a lo largo de transectos de longitud indefinida, por períodos de una hora en cada área y se repitieron cuatro veces. Un total de 585 especímenes fueron capturados, de ellos, 443 pertenecen a Apidae (14 géneros, 141 a Halictidae (seis géneros y uno a Megachilidae. Con este informe, el inventario local de Abejas se eleva a 43 especies y 28 géneros. Trigona fulviventris guianae Cockerell, 1910 fue la especie más abundante, Euglossa ignita Smith, 1874 la más atraída por los cebos aromáticos y Megalopta genalis Smith, 1853 dominó durante la noche. Apis mellifera Linnaeus, 1758 no se encontró en los muestreos. La importancia de la Isla Gorgona, como sitio de la diversidad para las especies de abejas es discutida.

  11. Identifying the Relevant Factors in Newspaper Advertising Effectiveness

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    Cristóbal Benavides

    2014-01-01

    Full Text Available Este estudio explora varios factores con el fin de establecer cuáles son losmás importantes en motivar a los lectores de periódicos locales a comprar,visitar tiendas y buscar información adicional acerca de los productos oservicios promovidos en los anuncios. El comportamiento durante el pro-ceso de compra es consecuencia de una compleja interacción de dimen-siones culturales, sociales, personales y psicológicas. Este proceso –el cualse produce antes de la acción– tiene implicaciones relevantes y los depar-tamentos de mercadeo deben prestar atención a ello. Una serie de hipóte-sis basadas en la forma como la publicidad atrae a los consumidores y encómo afecta la toma de decisiones al momento de la compra fueron puestasa prueba usando una encuesta que fue administrada a una muestra de 1.333personas encuestadas en Chile. También se realizó un análisis discriminan-te para averiguar por qué algunos lectores de periódicos se ven motivadosa comprar bienes o servicios, visitar una tienda o buscar más información.Los resultados muestran que el atractivo de la oferta anunciada es el factormás importante para explicar el comportamiento posterior del consumidor.

  12. Diet of the White-Tailed Eagle During the Breeding Season in the Polesski State Radiation-Ecological Reserve, Belarus

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    Valeri V. Yurko

    2016-04-01

    Full Text Available This article presents data on the diet of the White-Tailed Eagle (Haliaeetus albicilla collected during breeding seasons of 2006–2015 in the Polesski State Radiation-Ecological Reserve. The data included 127 records of prey remains belonging to 27 species of vertebrates collected in and under the nests. We discovered that the diet of the White-Tailed Eagle mainly consists of vertebrates of three classes: fishes (Pisces 48.1 %, birds (Aves 41.7 % and mammals (Mammalia 10.2 %. At the present, the main prey species in the diet of the White-Tailed Eagle in the breeding season are: Bream (Abramis brama – 22.0 %, Black Stork (Ciconia nigra – 12.6 %, Northern Pike (Esox lucius – 10.2 %, Wild Boar (Sus scrofa – 7.1 %, White Stork (Ciconia ciconia – 6.3 %, Mallard (Anas platyrhynchos – 5.5 % and Eurasian Coot (Fulica atra – 5.5 %. Together these species makes up 69.2 % or 2/3 of the diet of this raptor. We also established that cannibalism is a character feature of the local population of White-Tailed Eagle, and its proportion is 2.4 %.

  13. DEVOTEES, WANNABES Y PRETENDERS: PARAFILIAS VINCULADAS A LA DISCAPACIDAD

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    Carolina Mora

    2016-01-01

    Full Text Available Con el desarrollo de internet se ha ido haciendo evidente la vinculación entre discapacidad y sexualidad, en la que las designaciones “devotees”, “pretedenders” y “wannabes” (DPW juegan un rol central. Los devotees son individuos sanos que se sienten atraídos sexualmente hacia personas con discapacidad, generalmente con problemas de movilidad. Los pretenders son personas que actúan como si tuvieran una discapacidad imitando sus movimientos, usando muletas, sillas de ruedas, escayolas, etc. Por último, los wannabes desean ser discapacitados, algunos de ellos han llegado al extremo de hacerse amputaciones caseras cuando la medicina tradicional se ha negado a dar respuesta a su necesidad. La presente investigación documental indaga sobre cada uno de los miembros de la taxonomía DPW, presentando: a las hipótesis existentes con relación a su etiología; b su vinculación con otras entidades diagnósticas presentes en el DSM V; c se describen algunos de los tratamientos que se han empleado en su abordaje terapéutico, y d se mencionan las interrelaciones entre estas 3 categorías, dado que los limites entre ellas son muy flexibles.

  14. Política habitacional e locação social em Curitiba

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    Tomás Antonio Moreira

    Full Text Available A partir de dados censitários, o artigo analisa a política habitacional de interesse social na Região Metropolitana de Curitiba, entre 2000 e 1010. Os dados sobre os fluxos migratórios revelam que, embora essa região atraia maior número de migrantes no estado, já não é para a capital que se dirige a maioria. As cidades de São José dos Pinhais e Colombo, dotadas de menor infraestrutura, constituem o maior polo de atração. Com foco em habitação para famílias de baixa renda, o aluguel social em especial, são apresentadas as condições das unidades habitacionais, a infraestrutura disponível e os aspectos demográficos e socioeconômicos dos chefes de família. A leitura dos dados é contextualizada por uma recuperação histórica das políticas habitacionais promovidas pelo Estado desde a década de 1970.

  15. ESTRATÉGIAS DE INTERNACIONALIZAÇÃO: ESTUDO DE CASO DO SETOR CALÇADISTA

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    EVELINE CARVALHO

    2006-01-01

    Full Text Available O presente estudo mostra os impactos da globalização e sua interferência nasestratégias de internacionalização e competitividade do setor calçadista. Apresenta comoestudo de caso empresas calçadistas situadas no estado do Ceará, o processo deinternacionalização e as estratégias utilizadas para promovê-lo. O estudo se baseia empesquisa bibliográfica bem como dados estatísticos. Analisa a globalização e as dificuldadesde gestão com que as empresas se deparam diante desse cenário, a importância da cooperaçãoentre empresas, os incentivos fiscais e financeiros concedidos pelo governo e apresenta amudança estrutural que o setor vem causando na balança comercial do estado tradicionalmenteagrícola. Conclui que a utilização de incentivos fiscais para a atração de empresas de calçadosdo sul e sudente do país tem sido muito produtiva para o estado principalmente por ter dado aosetor uma projeção internacional.

  16. Remesas como fuente de desarrollo: Un estudio bibliométrico

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    Isabel Sainz Fernández

    2016-01-01

    Full Text Available La importancia que las remesas han adquirido en la economía de los países receptores, sobre todo en los países en desarrollo, ha atraído la atención de los investigadores. El objetivo a desarrollar a través del presente artículo consiste en analizar la producción científica centrada en el estudio de las remesas como fuente de desarrollo, mediante un estudio bibliométrico, técnica que permite realizar un análisis cuantitativo de las publicaciones científicas, para el periodo 1900-2011, plasmando los resultados mediante el uso de redes sociales. Los hallazgos encontrados muestran cuatro líneas de investigación claramente definidas, como son los efectos de las remesas sobre la pobreza, la desigualdad y el desarrollo; los determinantes de las remesas; los efectos sobre la balanza de pagos y los efectos sobre la inversión en microempresas. El análisis realizado permite obtener conclusiones desde una doble perspectiva: la clasificación de las principales líneas de investigación y la identificación de futuras líneas que pueden servir de guía para los investigadores.

  17. La guerra de Granada en las probanzas de hidalguía: los Amador de Lezcano, hidalgos de Cazorla y Quesada

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    García Guzmán, María del Mar

    2002-06-01

    Full Text Available Throughout the late Middle Ages the dominion of Cazorla and the village of Quesada were fortified towns in the frontier with the nazari kingdom of Granada, a fact that favoured the establishment of knights coming from other areas of Peninsula. They came attracted by the benefits of the war against the Islam which allowed them to consolidate their social and economic positions in the archbishops of Toledo's domain.

    A lo largo de la Baja Edad Media, el Adelantamiento de Cazorla y la villa de Quesada fueron plazas avanzadas en la frontera con el reino nazarí de Granada, lo que favoreció el asentamiento de hidalgos, procedentes de otras zonas de la geografía peninsular, atraídos por los beneficios de la guerra contra el Islam, lo que les permitió consolidar su posición social y económica en el señorío de los arzobispos de Toledo.

  18. Caracterización de las antocianinas de la flor de ceibo como sensibilizadores naturales para su uso en celdas fotovoltaicas

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    María Paula Enciso

    2014-12-01

    Full Text Available La energía solar es la fuente de energía más promisoria del futuro, ya que la conversión directa de luz solar en energía eléctrica mediante el uso de celdas solares posee muchas ventajas sobre los métodos usados en la actualidad, debido a que no genera desechos o contaminantes.En particular, las celdas solares sensibilizadas con pigmentos (DSSC o celdas de Graetzel representan una alternativa a las convencionales celdas solares de silicio. En las últimas tres décadas han atraído considerable atención como una forma de producir celdas fotovoltaicas de bajo costo debido a la posibilidad de alcanzar una alta eficiencia de conversión (de aprox. 12% y su alto rendimiento durante períodos de luz prolongados e incluso en condiciones de stress térmico.En este trabajo se evalúan pigmentos de origen natural, la mezcla de antocianinas provenientes de la flor del ceibo, como sensibilizadores de estas celdas. Se utilizan medidas de absorbancia UV-visible, voltamperometría cíclica y espectroscopía de impedancia electroquímica como forma de caracterización.

  19. Literatura e História: crime e pena capital no século 19

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    Junia Barreto

    2010-12-01

    Full Text Available O romance Le Dernier jour d’un condamné, de 1829, do escritor francês Victor Hugo, coloca em cena um crime qualquer de um criminoso sem nome, cuja punição é a pena capital, através da prática da guilhotina. O texto traduz os reflexos da Revolução Francesa e do período do Terror no cotidiano e nos hábitos de uma sociedade aficionada pelo crime, dividida entre medo e atração, e de uma literatura seduzida pela estética do horror e da violência enquanto possibilidades de expressão do belo, transpondo e enaltecendo, na ficção, todo tipo de crime e criminosos, cuja figura do herói criminoso se define entre realidade e ficção. Interessa-nos mostrar a imbricação da História e da Literatura presentes no texto, no qual o crime e sua punição funcionam como instrumento principal do discurso filosófico e político de Hugo contra a pena de morte. O autor termina por inscrever-se documentalmente na história da luta pela abolição da pena de morte, enquanto método praticado de punição ao crime.

  20. Consumo adolescente de series de televisión. El caso de “La que se avecina”

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    Ana Isabel Abad

    2016-11-01

    Full Text Available Las series televisivas ejercen una influencia significativa en las creencias y opiniones de los adolescentes, especialmente en lo que atañe a estereotipos sexuales, raciales y sociales. En este contexto, este trabajo pretende conocer la implicación de los jóvenes con la ficción seriada averiguando qué tipo de series consumen y cuáles son sus motivaciones, así como los vínculos que establecen con los personajes. Para ello, a partir de una metodología mixta, se han realizado encuestas y dinámicas de grupo con 236 adolescentes procedentes de cuatro centros educativos de Zaragoza. Los resultados exponen que estos jóvenes consumen comedias de situación españolas, como La que se avecina, atraídos por el humor absurdo, y establecen vínculos con personajes de edad adulta caracterizados por su comicidad.

  1. ANÁLISE DO PROCESSO DE USO E OCUPAÇÃO DA ORLA DA PRAIA DO AREIÃO (ILHA DE MOSQUEIRO-PA, TENDO EM VISTA O CUPRIMENTO DAS DIRETRIZES DO PLANO NACIONAL DE GERENCIAMENTO COSTEIRO (LEI 7.661/88./ Analysis of using and occupation process of Areião Beach Edge

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    Ivan Gomes Viana

    2017-12-01

    Full Text Available Ao longo do processo de integração da ilha de Mosqueiro à região metropolitana de Belém, grande parte da população concentrou-se na zona costeira. Essa atração populacional se deu, sobretudo, devido às potencialidades turísticas da ilha. Segundo o Plano Nacional de Gerenciamento Costeiro, por estar localizada em um estuário, a orla de Mosqueiro está dentro da área de abrangência da zona costeira brasileira, bem como, é amparada por uma legislação específica para estes espaços. Na extensão da praia do Areião são identificadas distintas formas de uso e ocupação que interagem com a dinâmica natural da praia, podendo ser caracterizados 4 setores na praia. Estes setores apresentam particularidades com relação ao cumprimento de algumas diretrizes estabelecidas pela legislação que ordena o uso e a ocupação da zona costeira.

  2. GEOGRAFIA DA DENGUE: UMA ANÁLISE DAS POLÍTICAS DE CONTROLE E MONITORAMENTO DO AEDES AEGYPTI EM MANAUS/ Geography of Dengue: an analysis of the control and monitoring policies of Aedes aegypti in Manaus

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    Renato Ferreira de Souza

    2018-04-01

    Full Text Available Manaus apresentou uma expansão urbana impulsionada pelo advento da Zona Franca, resultando numa insuficiente infraestrutura urbana para atender o aumento populacional, atraído pelo crescimento industrial e comercial da capital amazonense, a partir da década de 1970. Dessa forma, ampliaram-se os problemas de saneamento básico, comprometendo a qualidade de vida de sua população. O controle do dengue torna-se um grande desafio, não só para os geógrafos, mas também para as políticas de controle de endemias. As zonas norte e leste de Manaus caracterizam-se por bairros mais pobres, onde degradação ambiental e desigualdades sociais ameaçam o acesso a um ambiente saudável. Infelizmente muitas pessoas não têm o cuidado de manter o ambiente limpo e livre de proliferação de mosquitos, principalmente o do vetor da dengue. Nesse sentido, é importante desenvolver um trabalho de sensibilização junto às escolas, pois as crianças e adolescentes são base para serem multiplicadores de divulgação dos cuidados necessários contra a dengue.

  3. Notas rocambolescas: histórias de escusos heróis

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    Marlyse Meyer

    1991-12-01

    Full Text Available O artigo parte da aproximação, aparentemente insólita, de dois textos: 1 Proezas de Rocambole (1857-1870, folhetim de Ponson du Terrail, cujo núcleo inicial trata de uma sociedade secreta, o Clube dos Valetes de Copas, chefiada pelo "vil" conde Andrea, e depois por seu sobrinho, Rocambole; 2 O 18º Brumário de Luís Bonaparte (1852, de Karl Marx, que narra, como um romance policial, a ascensão do sobrinho de Napoleão a partir da sociedade secreta 10 de Dezembro, e as aventuras reais e farsescas de um "canalha medíocre". Faz-se notar que a própria imprensa francesa da época assimilou a figura de Rocambole com a do Imperador. Comenta-se a atualidade de Rocambole e tenta-se uma definição do rocambolesco, nesta época de corrupção e violência. Ressalta-se a ambígua atração que aventuras de escusos heróis, tratadas com delírio imaginativo e ritmo desenfreado, exercem sobre os leitores, tomando como exemplos Machado de Assis e Graciliano Ramos.

  4. A resposta de Rhodnius prolixus a estímulos térmicos

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    Terezinha Fujita

    1976-06-01

    Full Text Available Uma série de experiências com formas adultas de Rhodnius prolixus, realizadas tanto no laboratório como em recinto de dimensões mais amplas, demonstrou uma acentuada atração para fontes de calor, com um máximo de atividades em torno dos 37 graus Centígrados. Nossos estudos revelaram que o inseto percebe estímulos térmicos a uma certa distância da fonte. Embora o reconhecimento de radiações infra-vermelhas possa servir para uma orientação do triatomíneo em direção ao animal de sangue quente, não acreditamos que seja o único fator envolvido. Com a continuação de pesquisas deste gênero visa-se o aperfeiçoamento de uma técnica que se preste para o combate ao vetor.

  5. Rotatividade migratória: um novo olhar para as migrações internas no Brasil

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    Rosana Baeninger

    Full Text Available O artigo analisa os movimentos migratórios no Brasil, acompanhando as transformações em sua dinâmica nas últimas décadas. Os movimentos migratórios internos no Brasil, dos últimos 60 anos, estão fortemente relacionados aos processos de urbanização e de redistribuição espacial da população, marcados pela intensa mobilidade populacional. Nesse contexto, os clássicos fatores de atração e expulsão se esgotam para as explicações do fenômeno migratório. As evidências empíricas dos censos demográficos e das PNADs permitem conhecer as alterações nas tendências migratórias nacionais, revelando novas condições migratórias para diferentes estados: áreas de retenção migratória, áreas de perdas migratórias e áreas de rotatividade migratória. O século 21 anuncia a expansão dos espaços da migração no Brasil, marcados pelo crescimento de áreas de rotatividade migratória.

  6. APROXIMACIONES COMPUTACIONALES PARA LA IDENTIFICACIÓN DE PROMOTORES EUCARIOTAS TIPO II

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    M. Mejía-Guerra

    2006-06-01

    Full Text Available La identificación de segmentos funcionales dentro del DNA es uno de los campos más estudiados en la actualidad, debido a la generación de grandes volúmenes de información a partir de los proyectosgenómicos, las predicciones computacionales han atraído la atención de la comunidad científica en general.En este marco la identificación de secuencias reguladoras se erige como un importante campo del análisis de genomas; sin embargo, dada la enorme complejidad del proceso de regulación de la transcripciónaunque promisorios el problema de la predicción de las zonas reguladoras no se ha solucionado en su totalidad.Este artículo presenta una descripción de algunas aproximaciones desarrolladas para la identificación de promotores y sus elementos cis-reguladores, también se describen las estructuras de señales funcionales y estructurales que son diana de reconocimiento de algunos de estos programas de predicción aplicados al gen que codifica para la subunidad NR1 del receptor de glutamato sensible a N-metil-D-aspartato (iGluR-NMDA el cual ha sido objeto de estudio desde la década de los noventa.

  7. Ducks change wintering patterns due to changing climate in the important wintering waters of the Odra River Estuary

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    Dominik Marchowski

    2017-07-01

    Full Text Available Some species of birds react to climate change by reducing the distance they travel during migration. The Odra River Estuary in the Baltic Sea is important for wintering waterfowl and is where we investigated how waterbirds respond to freezing surface waters. The most abundant birds here comprise two ecological groups: bottom-feeders and piscivores. Numbers of all bottom-feeders, but not piscivores, were negatively correlated with the presence of ice. With ongoing global warming, this area is increasing in importance for bottom-feeders and decreasing for piscivores. The maximum range of ice cover in the Baltic Sea has a weak and negative effect on both groups of birds. Five of the seven target species are bottom-feeders (Greater Scaup Aythya marila, Tufted Duck A. fuligula, Common Pochard A. ferina, Common Goldeneye Bucephala clangula and Eurasian Coot Fulica atra, and two are piscivores (Smew Mergellus albellus and Goosander Mergus merganser. Local changes at the level of particular species vary for different reasons. A local decline of the Common Pochard may simply be a consequence of its global decline. Climate change is responsible for some of the local changes in the study area, disproportionately favoring some duck species while being detrimental to others.

  8. Biologia floral de Hedychium coronarium Koen. (Zingiberaceae.

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    Joédia Argollo de Souza

    2007-06-01

    Full Text Available No presente trabalho foi estudada a biologia floral de Hedychium coronarium Koen., que ocorre em localidades de brejos e na beira de estradas, na cidade de Teresópolis (RJ, no período compreendido entre novembro de 2003 a julho de 2004. A floração segue o padrão anual assincrônico em nível populacional e ocorre nos meses de janeiro a abril, sendo a frutificação de março a maio. As flores são brancas, zigomorfas, hermafroditas nectaríferas, têm antese noturna e emitem um forte odor perceptível à longa distância. Os estaminódios constituem a “unidade de atração” para os visitantes florais. O androceu é composto de um único estame fértil e os grãos de pólen têm “pollenkitt”. O estigma é verde, úmido, côncavo e com pêlos uniformes ao seu redor. A espécie é auto-incompatível, com índices baixos de formação de frutos sob condições naturais. As flores de H. coronarium são importantes fontes de recursos para a fauna da região, oferecendo néctar e pólen como recompensa.

  9. Estudo do crescimento de nanofitas de céria dopada com gadolínio por sistema de aquecimento por micro-ondas

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    R. F. Gonçalves

    2013-09-01

    Full Text Available O óxido de cério (céria tem atraído atenção devido às suas importantes aplicações, como em células a combustível de óxido sólido, catalisadores de gases de exaustão de automóveis, catalisadores para a obtenção de hidrogênio, bloqueadores de raios ultravioleta, biomateriais, entre outros. Controlar os métodos de síntese da céria é de grande importância para explicar ou prever essas propriedades. Desta forma, o objetivo deste trabalho foi estudar o crescimento de nanofitas de óxido de cério em um sistema hidrotérmico assistido por micro-ondas, no qual 8 min foram obtidas nanofitas com comprimentos próximos a 330 nm, em 130 ºC e pressão de 3 atm. Os resultados colaboram para pesquisas em reformadores para obtenção de etanol e/ou anodos de células combustíveis de óxido sólido.

  10. Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells.

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    Jeffrey W Streb

    2011-04-01

    Full Text Available Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β in cultured smooth muscle cells (SMC as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall.

  11. Viagens e sexo on-line: a internet na geografia do turismo sexual

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    Piscitelli Adriana

    2005-01-01

    Full Text Available Considerando a relevância da Internet na constituição do mercado transnacional do sexo, neste texto analiso as imagens de mulheres da América do Sul que, difundidas no ciberespaço, se integram na alteração dos circuitos mundiais de turismo sexual. Argumento que embora haja uma íntima relação entre turismo sexual e desigualdade, a pobreza, nem sequer quando é extrema, garante o "sucesso" de um novo centro de turismo sexual. No marco de certas condições econômicas, aspectos culturais que se expressam na imbricação entre traços étnico/regionais e estilos de sexualidade operam à maneira de atração para o surgimento de novos alvos. Apresento, primeiro, as especificidades do espaço virtual analisado e uma caracterização de seus usuários. Descrevo, depois, as interações propiciadas pelo site e os códigos nele vigentes e, levando em conta as conceitualizações associadas a diferentes regiões, analiso as características das fronteiras etno-sexuais traçadas. Finalmente retomo meu argumento inicial, refletindo sobre como os processos de racialização que operam nesse espaço virtual participam nos deslocamentos na geografia mundial do turismo sexual.

  12. Cardiotoxin III Inhibits Proliferation and Migration of Oral Cancer Cells through MAPK and MMP Signaling

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    Ching-Yu Yen

    2013-01-01

    Full Text Available Cardiotoxin III (CTXIII, isolated from the snake venom of Formosan cobra Naja naja atra, has previously been found to induce apoptosis in many types of cancer. Early metastasis is typical for the progression of oral cancer. To modulate the cell migration behavior of oral cancer is one of the oral cancer therapies. In this study, the possible modulating effect of CTXIII on oral cancer migration is addressed. In the example of oral squamous carcinoma Ca9-22 cells, the cell viability was decreased by CTXIII treatment in a dose-responsive manner. In wound-healing assay, the cell migration of Ca9-22 cells was attenuated by CTXIII in a dose- and time-responsive manner. After CTXIII treatment, the MMP-2 and MMP-9 protein expressions were downregulated, and the phosphorylation of JNK and p38-MAPK was increased independent of ERK phosphorylation. In conclusion, CTXIII has antiproliferative and -migrating effects on oral cancer cells involving the p38-MAPK and MMP-2/-9 pathways.

  13. Evaluación para la permanencia: una visión desde la experiencia docente

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    Celia Gabriela Villalpando Sifuentes

    2017-04-01

    Full Text Available La evaluación para la permanencia es un ejercicio obligatorio para docentes en servicio que actualmente atrae la atención de los actores educativos. Por ser un proceso de naturaleza subjetiva y de significación para los involucrados requiere ser abordado en una investigación de corte cualitativo, a fin de conocer las implicaciones de poner en marcha la reforma educativa a través de dicho proceso valorativo en un escenario como el actual. Ante esto, resultó imperante revisar el contenido del Diario Oficial de la Federación, por ser uno de los documentos que da vida jurídica a la evaluación mencionada. Adicionalmente se analizaron referentes teóricos de especialistas sobre evaluación, así como algunos autores, para brindar sustento a la estrategia metodológica. La investigación se posicionó en el paradigma interpretativo, específicamente mediante el estudio de caso de docentes estudiantes de una institución de posgrado en Ciudad Juárez, quienes han sido sometidos al proceso valorativo tendiente a definir su permanencia en el servicio de educación básica. Dentro de los hallazgos se rescata la incertidumbre experimentada y vivenciada por dichos docentes con respecto a sus condiciones laborales.

  14. New and already known acanthocephalans from amphibians and reptiles in Vietnam, with keys to species of Pseudoacanthocephalus Petrochenko, 1956 (Echinorhynchidae) and Sphaerechinorhynchus Johnston and Deland, 1929 (Plagiorhynchidae).

    Science.gov (United States)

    Amin, Omar M; Ha, Ngyuen Van; Heckmann, Richard A

    2008-02-01

    Adults of 2 new species in 2 orders of acanthocephalans obtained from the intestines of terrestrial amphibians and reptiles collected between 1998 and 2004 in Vietnam are described here. Pseudoacanthocephalus nguyenthileae n. sp. (Palaeacnthocephala: Echinorhynchidae) was collected from 5 species of terrestrial amphibians: (1) the common Sunda toad Bufo melanostictus Schneider (Bufonidae); (2) Paa verucospinosa (Bourret); (3) Gunther's Amoy frog Rana guentheri Boulenger; (4) Taipei frog R. taipehensis Denburgh (Ranidae), and (5) the Burmese whipping frog Polypedates mutus (Smith) (Racophoridae); as well as from the Chinese cobra Naja atra Cantor (Reptilia: Elapidae) and house gecko Hemidactylus frenatus Dumeril and Bibron (Reptilia: Gekkonidae). Sphaerechinorhynchus maximesospinus n. sp. (Plagiorhynchidae: Sphaerechinorhynchinae) was isolated from a king cobra Ophiophagus hannah (cantor) (Reptilia: Elapidae). Cystacanths of Porrorchis houdemeri (Joyeux and Baer, 1935) Schmidt and Kuntz, 1967 (Plagiorhynchidae: Porrorchinae) obtained from the mesenteries of banded krait Bungarus fasciatus (Schneider) (Reptilia: Elapidae), a paratenic host, are reported for the first time. Keys to the species of Pseudoacanthocephalus and Sphaerechinorhynchus are included. Characteristic features distinguishing the new species from related taxa include: P. nguyenthileae has 15-19 (usually 16-18) proboscis hook rows, each with 5-6 hooks that progressively increase in length and size posteriorly. The largest, intermediate, and smallest proboscis hooks of S. maximesospinus are the middle, anterior, and posterior hooks, respectively; the proboscis and neck are enclosed in a membrane. Morphometric characteristics of P. nguyenthileae show host-related variability.

  15. Diet of the west coast rock lobster Jasus Lalandii : Influence of ...

    African Journals Online (AJOL)

    The diet of small lobsters (<75mm CL) consisted of a wide range of species, which included, in order of importance, coralline algae, barnacles Notomegabalanus algicola, sponges and ribbed mussels Aulacomya ater. However, prey items rich in inorganic material were not dominant in their diet, as had been predicted.

  16. Preference of Quinoa Moth: Eurysacca Melanocampta Meyrick (Lepidoptera: Gelechiidae for Two Varieties of Quinoa (Chenopodium quinoa Willd. in Olfactometry Assays Preferencia de la Polilla de la Quinua: Eurysacca melanocampta Meyrick (Lepidoptera: Gelechiidae por dos Variedades de Quinua (Chenopodium quinoa Willd. en Ensayos de Olfatometría

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    Juan  F Costa

    2009-03-01

    de olor de las plantas de quinua en pruebas de elección cuando el control fue agua destilada (P < 0,01. Las hembras fueron más atraídas hacia la var. Blanca de Junín que hacia la var. Amarilla de Marangani (P < 0,05. Los machos fueron más atraídos por el olor de hembras que por los compuestos volátiles de las plantas (ambas variedades o por el olor derivado de hembras más plantas. El nivel de atracción de los machos hacia las hembras fue negativamente afectado por la presencia de las plantas de quinua.

  17. Health and self-care among garbage collectors: work experiences in a recyclable garbage cooperative Salud y autocuidado entre minadores de basura: vivencias en el trabajo en una cooperativa de basura reciclable Saúde e autocuidado entre catadores de lixo: vivências no trabalho em uma cooperativa de lixo reciclável

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    Clarice Maria Dall'Agnol

    2007-10-01

    Full Text Available Study performed with garbage pickers who organized a cooperative to sort recyclable garbage in Porto Alegre, Brazil, in a shed loaned by the city administration. This activity, which has attracted an increasing number of people excluded from the formal job market, presents peculiar health risks and patterns of disease. The study aimed to learn about the participants' concepts and self-care actions, proposing discussions and jointly reflection on their problems. It focuses on the working environment and on attitudes towards health risks. Through the focal group technique with ten female subjects, the expression of capacity of situational analysis of those involved was privileged, giving rise to three main themes. Each theme discussed was followed by the construction of a plan of action in order to meet compatibly the more pressing needs according to the operational feasibility of the solutions proposed.Estudio realizado con minadores de basura que organizaron una cooperativa de separación de basura reciclable en un galpón de la municipalidad de Porto Alegre, RS. Esta actividad, que ha atraído un número creciente de excluidos del mercado formal de trabajo, presenta riesgos a la salud y estándares peculiares de enfermedad. La finalidad fue conocer las concepciones y acciones de autocuidado de las participantes, todas mujeres, proponiendo discusiones y reflexiones conjuntas sobre la problemática vivida por ellas. El foco miró el ambiente de trabajo y las actitudes relacionados a los riesgos a la salud. La técnica de grupos focales con diez sujetos permitió privilegiar la expresión de su capacidad de análisis situacional, originando tres ejes temáticos. A cada tema discutido se siguió la construcción de un plan de acción de manera a compatibilizar la atención a las necesidades más demandadas con la viabilidad operacional de los encaminamientos propuestos.Estudo realizado com catadores de lixo que organizaram uma cooperativa de

  18. Sterol regulatory element-binding proteins are regulators of the sodium/iodide symporter in mammary epithelial cells.

    Science.gov (United States)

    Wen, G; Pachner, L I; Gessner, D K; Eder, K; Ringseis, R

    2016-11-01

    The sodium/iodide symporter (NIS), which is essential for iodide concentration in the thyroid, is reported to be transcriptionally regulated by sterol regulatory element-binding proteins (SREBP) in rat FRTL-5 thyrocytes. The SREBP are strongly activated after parturition and throughout lactation in the mammary gland of cattle and are important for mammary epithelial cell synthesis of milk lipids. In this study, we tested the hypothesis that the NIS gene is regulated also by SREBP in mammary epithelial cells, in which NIS is functionally expressed during lactation. Regulation of NIS expression and iodide uptake was investigated by means of inhibition, silencing, and overexpression of SREBP and by reporter gene and DNA-binding assays. As a mammary epithelial cell model, the human MCF-7 cell line, a breast adenocarcinoma cell line, which shows inducible expression of NIS by all-trans retinoic acid (ATRA), and unlike bovine mammary epithelial cells, is widely used to investigate the regulation of mammary gland NIS and NIS-specific iodide uptake, was used. Inhibition of SREBP maturation by treatment with 25-hydroxycholesterol (5 µM) for 48h reduced ATRA (1 µM)-induced mRNA concentration of NIS and iodide uptake in MCF-7 cells by approximately 20%. Knockdown of SREBP-1c and SREBP-2 by RNA interference decreased the mRNA and protein concentration of NIS by 30 to 50% 48h after initiating knockdown, whereas overexpression of nuclear SREBP (nSREBP)-1c and nSREBP-2 increased the expression of NIS in MCF-7 cells by 45 to 60%, respectively, 48h after initiating overexpression. Reporter gene experiments with varying length of NIS promoter reporter constructs revealed that the NIS 5'-flanking region is activated by nSREBP-1c and nSREBP-2 approximately 1.5- and 4.5-fold, respectively, and activation involves a SREBP-binding motif (SRE) at -38 relative to the transcription start site of the NIS gene. Gel shift assays using oligonucleotides spanning either the wild-type or the

  19. Efeito da aplicação de extratos aquosos em couve na alimentação de largatas de Ascia monuste orseis Effect of aqueous vegetal extratcts application on larva feeding behavior of Ascia monuste orseis at kale

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    Cesar Augusto Manfré Medeiros

    2005-01-01

    Full Text Available Os efeitos de extratos aquosos de amêndoas de Azadirachta indica e frutos de Sapindus saponaria, aplicados em discos de folhas de couve (Brassica oleracea var. acephala nas concentrações de 0,0117% e 1,0342% (p/v, respectivamente, foram estudados sobre a alimentação das lagartas de Ascia monuste orseis. Avaliou-se a atratividade e o consumo de área foliar de lagartas de primeiro e terceiro ínstar durante 24 horas, em condições de laboratório (T = 25 ± 2ºC, UR = 60 ± 10% e fotofase = 12 horas. Nos testes com e sem chance de escolha, para lagartas de primeiro ínstar e teste sem chance de escolha para lagartas de terceiro ínstar, não houve diferença quanto à atratividade das lagartas. No teste com chance de escolha para lagartas de terceiro ínstar, houve menor atratividade das lagartas pelos discos de folhas tratadas com S. saponaria, diferindo da testemunha. No decorrer de 24 horas de avaliações, pode-se observar 58,3% de lagartas atraídas na testemunha, não diferindo de A. indica e diferindo de S. saponaria, com 39,3% e 2,4% das lagartas atraídas, respectivamente. Quanto ao consumo de área foliar, o extrato de S. saponaria diminuiu o consumo de lagartas, em todos os testes realizados. Quando não tinham opção de escolha para se alimentar de folhas sem os extratos, as lagartas consumiram as folhas tratadas nas concentrações testadas, porém em menor quantidade. Os extratos testados neste experimento demonstram ter efeitos sobre a alimentação das lagartas de A. monuste orseis, possivelmente com propriedades deterrentes e/ou supressoras de alimentação.The effects of aqueous extracts of Azadirachta indica almonds and of Sapindus saponaria fruits, applied on disks of kale leaves (Brassica oleracea var. acephala at concentrations of 0.0117% and 1.0342% (w/v, respectively, were studied on larval feeding behavior of Ascia monuste orseis. Data on leaves attractiveness and consumption at first and third larval instar were

  20. 19-nor vitamin-D analogs: a new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines.

    Science.gov (United States)

    Asou, H; Koike, M; Elstner, E; Cambell, M; Le, J; Uskokovic, M R; Kamada, N; Koeffler, H P

    1998-10-01

    We have studied the in vitro biological activities and mechanisms of action of 1,25-dihydroxyvitamin D3 (1,25D3) and nine potent 1,25D3 analogs on proliferation and differentiation of myeloid leukemia cell lines (HL-60, retinoic acid-resistant HL-60 [RA-res HL-60], NB4 and Kasumi-1). The common novel structural motiff for almost all the analogs included removal of C-19 (19-nor); each also had unsaturation of the side chain. All the compounds were potent; for example, the concentration of analogs producing a 50% clonal inhibition (ED50) ranged between 1 x 10(-9) to 4 x 10(-11) mol/L when using the HL-60 cell line. The most active compound [1, 25(OH)2-16,23E-diene-26-trifluoro-19-nor-cholecalciferol (Ro 25-9716)] had an ED50 of 4 x 10(-11) mol/L; in contrast, the 1,25D3 produced an ED50 of 10(-9) mol/L with the HL-60 target cells. Ro 25-9716 (10(-9) mol/L, 3 days) was a strong inducer of myeloid differentiation because it caused 92% of the HL-60 cells to express CD11b and 75% of these cells to reduce nitroblue tetrazolium (NBT). This compound (10(-8) mol/L, 4 days) also caused HL-60 cells to arrest in the G1 phase of the cell cycle (88% cells in G1 v 48% of the untreated control cells). The p27(kip-1), a cyclin-dependent kinase inhibitor which is important in blocking the cell cycle, was induced more quickly and potently by Ro 25-9716 (10(-7) mol/L, 0 to 5 days) than by 1,25D3, suggesting a possible mechanism by which these analogs inhibit proliferation of leukemic growth. The NB4 promyelocytic leukemia cells cultured with the Ro 25-9716 were also inhibited in their clonal proliferation (ED50, 5 x 10(-11) mol/L) and their expression of CD11b was enhanced (80% positive [10(-9) mol/L, 4 days] v 27% untreated NB4 cells). Moreover, the combination of Ro 25-9716 (10(-9) mol/L) and all-trans retinoic acid (ATRA, 10(-7) mol/L) induced 92% of the NB4 cells to reduce NBT, whereas only 26% of the cells became NBT positive after a similar exposure to the combination of 1,25D3

  1. Gestão de matriculas como estratégia competitiva em universidades comunitárias privadas Enrollment management as competitive strategy in private community universities

    Directory of Open Access Journals (Sweden)

    Victor Meyer Jr.

    2010-10-01

    Full Text Available Este trabalho tem o objetivo de analisar as práticas de gestão da Pontifícia Universidade Católica do Paraná - PUCPR, quanto à atração e retenção de alunos. O bem sucedido modelo de gestão de matrículas, implantado pela DePaul University, foi utilizado como referência no estudo. O contexto altamente competitivo vivenciado por ambas universidades, torna a atração e a retenção de alunos um desafio a ser vencido com estratégias apropriadas. O trabalho caracteriza -se como um estudo comparativo de natureza exploratória e descritiva. A análise focalizou o planejamento estratégico, o marketing educacional e a gestão de matrícula - os três principais elementos do modelo adotado pela DePaul University e os resultados indicam que a gestão de matrículas, na Pontifícia Universidade Católica do Paraná, é praticada d e forma incipiente, mesclando atividades profissionais e amadoras. Na prática a adoção de um sistema integrado de matrículas irá proporcionar base para melhores decisões quanto ao mercado, em especial quanto à concorrência, demanda e perfil do aluno desejado, além de estratégicas mais adequadas para a retenção de alunos. As conclusões ressaltam que a gestão de matrículas requer uma gestão profissional integrada se constituindo em estratégia relevante para a sobrevivência institucional.The purpose of this study is to analyze managerial practices of the Pontifical Catholic University of Paraná—PUCPR (Curitiba, Brazil—to attract and retain students. The highly-successful model of enrollment management implemented by DePaul University (Chicago, USA serves as reference and benchmark for comparison purposes. The highly -competitive environment experienced by both institutions provides the setting for the challenge to attract and retain students through effective managerial strategies. The study is comparative and descriptive in nature. The analysis focuses on strategic planning, educational

  2. Identificação de Unidades de Paisagem e sua Implicação para o Ecoturismo no Parque Nacional da Serra dos Órgãos, Rio De Janeiro.

    Directory of Open Access Journals (Sweden)

    Sandro Nunes de Oliveira

    2007-11-01

    Full Text Available A análise da heterogeneidade da paisagem é fundamental para o planejamento do ecoturismo porque estima uma relação ótima entre a conservação e as alternativas turísticas. A metodologia de paisagem possibilita descrever não só a beleza cênica, porém também o grau de estabilidade do sistema ecológico. A pesquisa da paisagem para o ecoturismo integra os diferentes componentes naturais (relevo, condições climáticas, solo, cobertura da vegetação, etc. e avalia suas inter-relações com as características do destino turístico. A geomorfologia é sempre considerada um dos fatores mais importantes que controla a heterogeneidade espacial em áreas com alta variação topográfica. Nesse caso, os parâmetros do relevo indicam a distribuição da temperatura e da umidade, exposição à direção de vento, vegetação, habitat entre outros. A área de estudo é o Parque Nacional da Serra dos Órgãos, um dos mais visitados no Brasil, com um vasto número de opções para visitantes de ecoturismo, tais como diversidade ecológica, significado histórico e oportunidades de recreação. O presente artigo objetiva definir unidades de paisagens do  parque nacional da Serra dos Órgãos a partir de sensoriamento remoto e atributos de terreno. Além disso, o artigo analisa a distribuição das atrações turísticas em relação às unidades de paisagem. Assim o procedimento de análise considera os tipos de paisagem, estruturas espaciais e limitações. A metodologia pode ser dividida nos seguintes passos: (a processamento digital das imagens de atributos de terreno a partir do modelo digital de terreno, (b interpretação de imagens de sensoriamento remoto, e (c delimitação e análise das atrações de ecoturismo. A integração dos dados possibilitou identificar unidades em dois diferentes níveis hierárquicos de escala. Na escala de geossistema, sete classes foram identificadas apresentando diferentes dinâmicas e vulnerabilidades

  3. Comparação dos padrões de atratividade de Hermetia illucens (Diptera, Stratiomyidae associada a carcaças de Rattus norvergicus enterradas e tratadas com hormônios esteróides Comparison of attraction patterns of Hermetia illucens (Diptera, Stratiomyidae associated to buried Rattus norvergicus carcasses with steroid hormones treatment

    Directory of Open Access Journals (Sweden)

    Ana C. Ferrari

    2009-12-01

    Full Text Available Hermetia illucens (L. (Diptera, Stratiomyidae é uma espécie abundante em todo o continente americano. No entanto, ainda há poucos estudos no Brasil abordando aspectos em relação a sua biologia e ecologia, em particular associados a estudos forenses. Neste trabalho, nós observamos os efeitos de hormônios esteróides na decomposição corporal de Rattus norvergicus, variedade Wistar enterrados na atração de H. illucens. Além da presença de diversas espécies de larvas e adultos de insetos freqüentemente encontrados em carcaças nessas condições, observou-se uma grande quantidade de imaturos de H. illucens. Essa espécie representou aproximadamente 22% de todos os espécimes coletados, tendo aparecido somente nos animais que receberam tratamento com esteróides sexuais dos tipos testosterona, progesterona e estradiol. Dentre esses, a maior abundância foi verificada nos que haviam recebido testosterona (68%. A presença de imaturos de H. illucens, apenas nos animais que receberam o tratamento com esteróides, em experimentos realizados em dois anos consecutivos revela uma possível atração/seleção dessa espécie por corpos com quantidades aumentadas de hormônios sexuais. Esse comportamento pode ser particularmente útil para a entomologia forense no que diz respeito à estimativa do intervalo pós-morte (IPM, particularmente quando tem como base informações sobre o ciclo de vida e ecologia de insetos necrófagos.Hermetia illucens (L. (Diptera, Stratiomyidae is an abundant species in the entire American continent. Nevertheless, there are few studies in Brazil dealing with aspects of its biology and ecology, particularly associated with forensic studies. In this study we intended to observe the effects of steroids hormones in the corporal decomposition of buried Rattus norvergicus from the Wistar variety in the attraction of H. illucens. Besides the presence of several insect species commonly found in carcasses, a great amount of

  4. Potencializando o Papel dos Morcegos Frugívoros na Recuperação de Áreas Degradadas Improving the Role of Frugivorous Bats in Forest Restoration

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    Sandra Bos Mikich

    2011-03-01

    Full Text Available

    Os morcegos frugívoros estão entre os principais dispersores de sementes, portanto, técnicas que potencializem esse papel ecológico podem ter grande aplicação na recuperação de ambientes florestais. Nesse sentido, testes com óleos essenciais isolados de frutos quiropterocóricos maduros mostraram que eles podem atrair morcegos frugívoros no interior de remanescentes florestais e em áreas abertas. Além disso, os resultados revelaram que os indivíduos atraídos já haviam se alimentado, visto que a maioria de suas amostras fecais continham sementes. Sendo assim, o uso de óleos essenciais de frutos consumidos por morcegos frugívoros potencialmente incrementa a chuva de sementes em locais específicos, como por exemplo ao longo de rios onde seja necessário recuperar florestas ciliares ou em uma área de propriedade rural onde seja necessário implantar ou recuperar uma Reserva Legal. Em função da ampla aplicação da técnica, novos estudos estão sendo conduzidos nosentido de mensurar a chuva de sementes e a regeneração da vegetação provocadas pelo seu uso, bem como para identificar os compostos responsáveis pela atração e sintetizá-los.  
    Fruit-eating bats are amongst the main seed dispersers, so that any technique that improves this ecological role may have large application in forest restoration projects. Following this idea, we conducted tests with essential oils isolated from mature chiropterochoric fruits that revealed that these oils are able to attract frugivorous bats both inside forest remnants and in open areas (as abandoned agricultural or pasture fields. Additionaly, our results showed that the feces of most bats attracted by the oils contained seeds, indicating that they were already fed. So, the use of essencial oils of fruits consumed by bats in specific sites, as along a river whose riparian forest was destroyed or in a property that no longer has forest reserve

  5. Catálogo taxonómico-geográfico de los coleópteros de la familia Meloidae de México

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    García-París, M.

    2007-12-01

    Full Text Available A comprehensive taxonomic catalogue of the Mexican representatives of the family Meloidae is presented. The catalogue includes a revised synonymical list including type localities and published geographical records for all known species. The Mexican Fauna of Meloidae currently includes 255 extant species, plus one only known from the fossil record, arranged in 21 genera within the subfamilies Meloinae, Nemognathinae and Tetraonycinae. The last comprehensive catalogue published (Blackwelder, 1945 recorded the presence of 160 species of Meloidae in México, almost 100 species less than the current known number. However the current number of species seems to be far below the actual number, since many species widely distributed along the northern border, within the United States, are likely to be found also in Mexico. Regarding taxonomic and nomenclatural changes, in this catalogue we propose the use of the names Epicauta dugesi Werner, 1957 and Tegrodera erosa extincta Beauregard, 1890; we propose three new synonymies for Nemognatha chrysomeloides (Linnaeus, 1763 (N. atra Beauregard, 1890; N. pallidicollis Beauregard, 1890 and N. violacea Beauregard, 1890 and one for E. dugesi (Epicauta tamara Adams & Selander, 1979; we designate lectotype for Lytta koltzei var. minor Haag-Rutenberg, 1880 with the goal of resolving the taxonomic problem generated by the previous invalid designation of lectotype for L. k. var. cyanescens; and finally we consider Cissites maculata (Swederus, 1787 and Tetraonyx (Tetraonyx bimaculatus (Klug, 1825 as species to be possibly excluded from the Mexican checklist.

    Se presenta un catálogo taxonómico de los representantes mexicanos de la familia Meloidae que incluye un listado revisado de sinonimias, localidades típicas y registros geográficos publicados de cada una de las especies. La fauna mexicana incluye en la actualidad 255

  6. Spatial Distribution and Coexisting Patterns of Adults and Nymphs of Tibraca limbativentris (Hemiptera: Pentatomidae) in Paddy Rice Fields.

    Science.gov (United States)

    Alves, Tavvs M; Maia, Aline H N; Barrigossi, José A F

    2016-12-01

    adultos e ninfas de T. limbativentris e determinar a coexistência espacial entre os estágios de desenvolvimento. As densidades de adultos e ninfas foram estimadas em quinze campos de arroz irrigado. A amostragem foi realizada em grades regulares com pontos de amostragem separados por ∼50 m. Moran's I e semivariogramas foram usados para determinar os padrões de distribuição espacial. A coexistência espacial foi explorada pela análise de processos pontuais. Foi observado que adultos e ninfas tiveram padrões contrastantes de distribuição espacial dentro do mesmo campo; no entanto, a frequência de agregação não foi diferente entre esses estágios de desenvolvimento. Adultos e ninfas estavam agregados em sete campos e distribuídos aleatoriamente nos outros oito campos. Não foi observada a distribuição uniforme de adultos ou ninfas. O alcance médio dos semivariogramas foi de ∼40 m para os adultos e ∼55 m para as ninfas. Ninfas e adultos coexistiram espacialmente em 67% dos campos. Os padrões de coexistência foram classificados usando um dos seguintes processos: independente do estágio de desenvolvimento, atração bilateral, atração unilateral, inibição bilateral, ou inibição unilateral. Nosso estudo poderá contribuir para o desenvolvimento de planos de amostragem para tomada de decisão e implementação de táticas para o manejo de sítios específicos. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Do coastal fronts influence bioerosion patterns along Patagonia? Late Quaternary ichnological tools from Golfo San Jorge

    Science.gov (United States)

    Richiano, Sebastián; Aguirre, Marina; Castellanos, Ignacio; Davies, Karen; Farinati, Ester

    2017-12-01

    , Iramena, Pinaceocladichnus, at Bustamante) differs across time. These variations, particularly the highest abundance in the Late Pleistocene (mainly Last Interglacial) of traces made by bryozoans- associated at present with modern enhanced productivity levels and coastal fronts in the Argentine continental shelf- point to higher productivity and more intensified northern Patagonia Front, as a result of a different palaeocirculation pattern, reinforcing previous independent sources of evidence based on molluscan palaeobiogeographical analyses. Supplementary Appendix 2 List of ichnotaxa recorded in gastropod and bivalve taxa as observed in shells from the Quaternary deposits sampled, authors and corresponding ethological classification. Abbreviations are those used along the text. Full references in Richiano et al. (2012, 2015). Supplementary Appendix 3 General biogenic composition of the beach ridge systems (Marine Terraces) at Camarones and Bustamante coastal areas and along the adjacent modern littoral. List of molluscan species and other invertebrates recovered from the deposits sampled. Modified from Aguirre et al. (2005, 2006). See also Table 1 of this paper, Aguirre et al. (2008, 2011a), Richiano et al. (2012, 2015). Supplementary Appendix 4 Independent palaeobiogeographical evidence for lower SST during the Late Pleistocene against higher during the Mid-Holocene. Geographical patterns of relationships between areas through time. PCO (Principal Coordinate analyses), CA (Cluster Analysis) and PAE (Parsimony Analysis of Endemicity) (modified from Aguirre et al., 2011a, 2013). (A1): PCO (top) and (A2): CA (middle) for Late Pleistocene, Holocene and modern molluscs. (A3): PAE showing patterns between localities for the Pleistocene (only time interval with records of Tegula atra) compared to the present. __: Areas of endemism. Note the isolation of SAO (SMCF) relative to the remaining Patagonian localities at present and during the mid-Holocene vs. its linkage to the

  8. Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.

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    Hiromichi Matsushita

    Full Text Available Recent advances in cancer biology have revealed that many malignancies possess a hierarchal system, and leukemic stem cells (LSC or leukemia-initiating cells (LIC appear to be obligatory for disease progression. Acute promyelocytic leukemia (APL, a subtype of acute myeloid leukemia characterized by the formation of a PML-RARα fusion protein, leads to the accumulation of abnormal promyelocytes. In order to understand the precise mechanisms involved in human APL leukemogenesis, we established a humanized in vivo APL model involving retroviral transduction of PML-RARA into CD34(+ hematopoietic cells from human cord blood and transplantation of these cells into immunodeficient mice. The leukemia well recapitulated human APL, consisting of leukemic cells with abundant azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and CD117, but not HLA-DR and CD34, were clustered in the same category as human APL samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As seen in human APL, the induced APL cells showed a low transplantation efficiency in the secondary recipients, which was also exhibited in the transplantations that were carried out using the sorted CD34- fraction. In order to analyze the mechanisms underlying APL initiation and development, fractionated human cord blood was transduced with PML-RARA. Common myeloid progenitors (CMP from CD34(+/CD38(+ cells developed APL. These findings demonstrate that CMP are a target fraction for PML-RARA in APL, whereas the resultant CD34(- APL cells may share the ability to maintain the tumor.

  9. Effects of sandfish (Holothuria scabra) removal on shallow-water sediments in Fiji.

    Science.gov (United States)

    Lee, Steven; Ford, Amanda K; Mangubhai, Sangeeta; Wild, Christian; Ferse, Sebastian C A

    2018-01-01

    Sea cucumbers play an important role in the recycling and remineralization of organic matter (OM) in reef sands through feeding, excretion, and bioturbation processes. Growing demand from Asian markets has driven the overexploitation of these animals globally. The implications of sea cucumber fisheries for shallow coastal ecosystems and their management remain poorly understood. To address this knowledge gap, the current study manipulated densities of Holothuria scabra within enclosures on a reef flat in Fiji, between August 2015 and February 2016, to study the effects of sea cucumber removal on sedimentary function as a biocatalytic filter system. Three treatments were investigated: (i) high density (350 g m -2 wet weight; ca . 15 individuals); (ii) natural density (60 g m -2 ; ca . 3 individuals); and (iii) exclusion (0 g m -2 ). Quantity of sediment reworked through ingestion by H. scabra , grain size distribution, O 2 penetration depth, and sedimentary oxygen consumption (SOC) were quantified within each treatment. Findings revealed that the natural population of H. scabra at the study site can rework ca . 10,590 kg dry sediment 1,000 m -2 year -1 ; more than twice the turnover rate recorded for H. atra and Stichopus chloronotus . There was a shift towards finer fraction grains in the high treatment. In the exclusion treatment, the O 2 penetration depth decreased by 63% following a 6 °C increase in water temperature over the course of two months, while in the high treatment no such change was observed. SOC rates increased ca . two-fold in the exclusion treatment within the first month, and were consistently higher than in the high treatment. These results suggest that the removal of sea cucumbers can reduce the capacity of sediments to buffer OM pulses, impeding the function and productivity of shallow coastal ecosystems.

  10. Effects of sandfish (Holothuria scabra removal on shallow-water sediments in Fiji

    Directory of Open Access Journals (Sweden)

    Steven Lee

    2018-05-01

    Full Text Available Sea cucumbers play an important role in the recycling and remineralization of organic matter (OM in reef sands through feeding, excretion, and bioturbation processes. Growing demand from Asian markets has driven the overexploitation of these animals globally. The implications of sea cucumber fisheries for shallow coastal ecosystems and their management remain poorly understood. To address this knowledge gap, the current study manipulated densities of Holothuria scabra within enclosures on a reef flat in Fiji, between August 2015 and February 2016, to study the effects of sea cucumber removal on sedimentary function as a biocatalytic filter system. Three treatments were investigated: (i high density (350 g m−2 wet weight; ca. 15 individuals; (ii natural density (60 g m−2; ca. 3 individuals; and (iii exclusion (0 g m−2. Quantity of sediment reworked through ingestion by H. scabra, grain size distribution, O2 penetration depth, and sedimentary oxygen consumption (SOC were quantified within each treatment. Findings revealed that the natural population of H. scabra at the study site can rework ca. 10,590 kg dry sediment 1,000 m−2 year−1; more than twice the turnover rate recorded for H. atra and Stichopus chloronotus. There was a shift towards finer fraction grains in the high treatment. In the exclusion treatment, the O2 penetration depth decreased by 63% following a 6 °C increase in water temperature over the course of two months, while in the high treatment no such change was observed. SOC rates increased ca. two-fold in the exclusion treatment within the first month, and were consistently higher than in the high treatment. These results suggest that the removal of sea cucumbers can reduce the capacity of sediments to buffer OM pulses, impeding the function and productivity of shallow coastal ecosystems.

  11. Carnival in the Old World and the New

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    Burke, Peter

    1996-06-01

    Full Text Available There are three distinct, traditional views of Carnival. The author, following Caro Baroja, argues that all three are equally valid. «The festival —he writes— was Protean, appealing to different people for different reasons». Besides, it has changed through time and space. When transferred to the New World by Mediterranean immigrants, it was transformed as the result of transculturation; for instance, by incorporating African components that were absent in the Old World. Nonetheless, the development of the festival in the Americas over the past two centuries has followed the same stages of the European Carnival between the l6th and the 19th centuries.La bibliografía sobre el carnaval permite distinguir tres interpretaciones diferentes de esta fiesta, ya expuestas en el siglo XVI. El autor, sin embargo, siguiendo a Caro Baroja, se niega a tener que elegir a cualquiera de ellas como la más adecuada. «El festival —escribe— era proteico; atraía a diferentes personas por razones diferentes». Además, ha cambiado en el tiempo y en el espacio. Cuando fue llevado a América por inmigrantes mediterráneos, se transformó como resultado de la transculturación; incorporando, por ejemplo, componentes africanos que no tenía el carnaval europeo. No obstante, su desarrollo en América en los dos últimos siglos ha repetido el que tuvo en Europa entre los siglos XVI y XIX.

  12. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

    2014-11-28

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

  13. Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches.

    Science.gov (United States)

    Liu, Chien-Chun; You, Chen-Hsien; Wang, Po-Jung; Yu, Jau-Song; Huang, Guo-Jen; Liu, Chien-Hsin; Hsieh, Wen-Chin; Lin, Chih-Chuan

    2017-12-01

    In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom-freeze-dried neurotoxic antivenom (FNAV)-against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two 'true' cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites.

  14. Identidad en la gastronomía de la frontera México-Belice ¿Producto turístico?

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    Francisco J. Güemes Ricalde

    2012-01-01

    Full Text Available La identidad gastronómica, desde la perspectiva del turismo cultural, se considera como un atractivo más para el mercado: platillos regionales son, en ocasiones, el motivo principal de la visita de los turistas. Por esta razón, en este artículo se analiza si existe una identidad gastronómica en la frontera sur de México con el país vecino, Belice, región con raíces culturales principalmente anglo-africanas, mexicanas y caribeñas. Fundamentalmente, se busca determinar si la gastronomía representa una oportunidad para consolidar un producto en el mercado turístico propio de la región. Mediante entrevistas personales y la técnica de muestreo se hace el análisis de la oferta actual y las preferencias de los visitantes atraídos a la zona por la promoción de un turismo cultural y de naturaleza, en combinación con la existencia de los casinos y el comercio en zona libre. Los resultados revelan que si bien hay una gran demanda gastronómica por parte del turismo nacional, éstos no perciben la presencia de una identidad gastronómica propia, desarrollada con características de producto turístico. El reciente y constante cambio de los asentamientos humanos en la zona, tradicionalmente aislada en la selva y caracterizada por constantes luchas entre castas, es una de las causas de esta falta de identidad.

  15. Inhibition of type I NKT cells by retinoids or following sulfatide-mediated activation of type II NKT cells attenuates alcoholic liver disease

    Science.gov (United States)

    Maricic, Igor; Sheng, Huiming; Marrero, Idania; Seki, Ehikiro; Kisseleva, Tatiana; Chaturvedi, Som; Molle, Natasha; Mathews, K. Stephanie; Gao, Bin; Kumar, Vipin

    2015-01-01

    Innate immune mechanisms leading to liver injury following chronic alcohol ingestion are poorly understood. Natural killer T (NKT) cells, enriched in the liver and comprised of at least two distinct subsets, type I and type II, recognize different lipid antigens presented by CD1d molecules. We have investigated whether differential activation of NKT cell subsets orchestrates inflammatory events leading to alcoholic liver disease (ALD). We found that following chronic plus binge feeding of Lieber-DeCarli liquid diet in male C57BL/6 mice, type I but not type II NKT cells are activated leading to recruitment of inflammatory Gr-1highCD11b+ cells into liver. A central finding is that liver injury following alcohol feeding is dependent upon type I NKT cells. Thus liver injury is significantly inhibited in Jα18−/− mice deficient in type I NKT cells as well as following their inactivation by sulfatide-mediated activation of type II NKT cells. Furthermore we have identified a novel pathway involving all-trans retinoic acid (ATRA) and its receptor RARγ signaling that inhibits type I NKT cells and consequently ALD. A semi-quantitative PCR analysis of hepatic gene expression of some of the key proinflammatory molecules shared in human disease indicated that their upregulation in ALD is dependent upon type I NKT cells. Conclusion Type I but not type II NKT cells become activated following alcohol feeding. Type I NKT cells-induced inflammation and neutrophil recruitment results in liver tissue damage while type II NKT cells protect from injury in ALD. Inhibition of type I NKT cells by retinoids or by sulfatide prevents ALD. Since the CD1d pathway is highly conserved between mice and humans, NKT cell subsets might be targeted for potential therapeutic intervention in ALD. PMID:25477000

  16. Células tronco mesenquimales: definiciones, cultivo y aplicaciones potenciales

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    Willy Ceron

    Full Text Available En los últimos años, las células troncales mesenquimales (Mesenchymal Stem Cells, MSC han adquirido mucha importancia debido a su gran plasticidad y su capacidad de liberar factores paracrinos con capacidad de interactuar con diversos tipos celulares, tejidos y órganos. El uso de MSC en medicina regenerativa es importante debido a que, al no expresar las moléculas del complejo mayor de histocompatibilidad (MHC clase II ni moléculas co-estimuladoras y tener baja expresión del MHC clase I, haría que no sean rechazadas por individuos de la misma especie, es posible utilizarlas no sólo de manera autóloga, sino también, eventualmente, alogénica. Sin embargo, es importante demostrar científicamente muchas de sus propiedades, entre ellas las inmunomoduladoras. Al tener varias fuentes de obtención, se debe estandarizar la que sea la mejor para garantizar la pureza y calidad de las MSC. Finalmente, es importante que cuando se trabaje con estas células se demuestre completamente las características del cultivo celular, la inmunotipificación y su capacidad de diferenciación. Se están ensayando muchas aplicaciones clínicas de las MSC. Dentro de ellas, su capacidad para mejorar la recuperación y potencial curación de úlceras crónicas como las diabéticas, ha atraído la atención por su potencial impacto terapéutico.

  17. Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its central analgesic effects under red light

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    Yang Q

    2017-05-01

    Full Text Available Qian Yang, Chuang Zhao, Jun Zhao, Yong Ye Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: Cobra neurotoxin (CNT, a peptide isolated from snake venom of Naja naja atra, shows central analgesic effects in our previous research. In order to help CNT pass through blood–brain barrier (BBB and improve its central analgesic effects, a new kind of CNT nanocapsules were prepared by double emulsification with soybean lecithin and cholesterol as the shell, and pheophorbide as the photosensitizer added to make it photoresponsive. The analgesic effects were evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT nanocapsules had an average particle size of 229.55 nm, zeta potential of -53.00 mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly distributed in outer layer of the CNT nanocapsules and increased the release of the CNT nanocapsules after 650 nm illumination. The central analgesic effects were improved after intraperitoneal injection of CNT at 25 and 50 µg·kg-1 under 650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by red light generated reactive oxygen species which opened the nanocapsules and BBB and helped the CNT enter the brain. This research provides a new drug delivery for treatment of central pain. Keywords: cobra neurotoxin, nanocapsules, photoresponsive, central analgesic effects, red light, drug delivery, photosensitizer

  18. Rapid characterization of the biomechanical properties of drug-treated cells in a microfluidic device

    International Nuclear Information System (INIS)

    Zhang, Xiaofei; Zhang, Yang; Bai, Guohua; Tan, Qiulin; Sun, Dong; Chu, Henry K; Wang, Kaiqun

    2015-01-01

    Cell mechanics is closely related to many cell functions. Recent studies have suggested that the deformability of cells can be an effective biomarker to indicate the onset and progression of diseases. In this paper, a microfluidic chip is designed for rapid characterization of the mechanics of drug-treated cells through stretching with dielectrophoresis (DEP) force. This chip was fabricated using PDMS and micro-electrodes were integrated and patterned on the ITO layer of the chip. Leukemia NB4 cells were considered and the effect of all-trans retinoic acid (ATRA) drug on NB4 cells were examined via the microfluidic chip. To induce a DEP force onto the cell, a relatively weak ac voltage was utilized to immobilize a cell at one side of the electrodes. The applied voltage was then increased to 3.5 V pp and the cell started to be stretched along the applied electric field lines. The elongation of the cell was observed using an optical microscope and the results showed that both types of cells were deformed by the induced DEP force. The strain of the NB4 cell without the drug treatment was recorded to be about 0.08 (time t = 180 s) and the drug-treated NB4 cell was about 0.21 (time t = 180 s), indicating a decrease in the stiffness after drug treatment. The elastic modulus of the cell was also evaluated and the modulus changed from 140 Pa to 41 Pa after drug treatment. This microfluidic chip can provide a simple and rapid platform for measuring the change in the biomechanical properties of cells and can potentially be used as the tool to determine the biomechanical effects of different drug treatments for drug discovery and development applications. (paper)

  19. La configuración del mercado de trabajo minero en el noroeste de México (1880-1910

    Directory of Open Access Journals (Sweden)

    Juan Manuel Romero Gil

    2001-01-01

    Full Text Available En los últimos años del siglo X I X y primera década del XX, el noroeste de México, a partir de la explotación de sus minas, experimentó un intenso desarrollo económico. Gracias a este auge minero, surgieron nuevos centros de población a consecuencia de una corriente de migración atraída por la oferta de empleo y mejor vida. Sin duda que la presencia del ferrocarril facilitó la movilización de estos contingentes que se movían del centro al norte del país. Estos movimientos de población no se explican sin considerar la demanda de manos que generó la presencia de grandes empresas mineras, casi todas extranjeras, en los estados de Baja California, Sinaloa y Sonora. En este trabajo mostramos que la minería propició en la región noroeste un dinámico mercado de trabajo en el periodo comprendido entre 1890 y 1910. Tal proceso fue producto de una política empresarial de contratación de mano de obra. En esta tarea se invirtieron importantes recursos de capital y se crearon mecanismos de enganche de trabajadores en los estados del centro y sur del país; incluso, cuando el recurso mano de obra nacional escaseó, acudieron al mercado internacional. En síntesis, el trabajo se ocupa de explicar las estrategias y mecanismos que aplicaron las empresas de la región para construir un régimen laboral capitalista en el ámbito de la actividad minera .

  20. The bird species of Kumasir lake (Kahramanmaras-Turkey) and a view of environmental ethics on sustainable wetland management.

    Science.gov (United States)

    Inac, S; Gorucu, O; Pinar, A H

    2008-05-01

    Kumasir lake is located next to towns of Donuklu and Fatih, nine km west of Kahramanmaras city center the region of east Mediterranean, Turkey This lake is of crucial importance from the point of native and immigrant birds. We located 17 birdspecies in this area during our observations carried out in the spring and autumn of 2005-2006. These were Ciconia ciconia L., Anas platyrhynchos L., Accipiter nisus L., Accipiter brevipes L., Fulica atra L., Columba palumbus L., Merops apiaster L., Upupa epops L., Alauda arvensis L., Motacilla flava L., Turdus merula L., Acrocephalus scirpaceus L., Regulus regulus L., Garrulus glandarius L., Corvus corax L., Fringilla coelebs L., Hirundo rustica L.. Among observed 17 species; 6 of them were immigrant and remaining 11 of them were native birds. Kumasir lake is surrounded by wetland of Amik and Gavur lake. Since it was greatly dried, it was transformed to farmland. Consequently the birds lost most of theirnests and settlements. However not taken in the care of environmental ethic values, the wastewaters of the villages drain to lake reservoir; herbicides and insecticides used for agriculture are polluting the water reeds have been burned, the lake's reeds are getting dry by the irrigation for the farmland. So, the wetland ecosystem is being affected negatively by these factors. On the other hand, the birds are exposed to illegal and unlawful hunting. For this reasons, this lake must be taken into a management regime of sustainable wetland (protection profiting balance) and used techniques of participation planning via the process of sustainable natural resources and planning.