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Sample records for rapidly proliferating lymphohematopoietic

  1. Clipboard: Lymphohematopoietic licence: Sterol C-14 reductase ...

    Indian Academy of Sciences (India)

    Clipboard: Lymphohematopoietic licence: Sterol C-14 reductase activity of lamin B receptor (Lbr) is essential for neutrophil differentiation. Durgadas P Kasbekar. Volume 37 ... Keywords. Greenberg/HEM dysplasia; lymphohematopoietic progenitor cells; nuclear envelope; Pelger-Huët anomaly; promyelocyte differentiation ...

  2. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (Final Report)

    Science.gov (United States)

    EPA announced the release of the final report, Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment . This report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induc...

  3. Fatty acid metabolites in rapidly proliferating breast cancer.

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    Joseph T O'Flaherty

    Full Text Available Breast cancers that over-express a lipoxygenase or cyclooxygenase are associated with poor survival possibly because they overproduce metabolites that alter the cancer's malignant behaviors. However, these metabolites and behaviors have not been identified. We here identify which metabolites among those that stimulate breast cancer cell proliferation in vitro are associated with rapidly proliferating breast cancer.We used selective ion monitoring-mass spectrometry to quantify in the cancer and normal breast tissue of 27 patients metabolites that stimulate (15-, 12-, 5-hydroxy-, and 5-oxo-eicosatetraenoate, 13-hydroxy-octadecaenoate [HODE] or inhibit (prostaglandin [PG]E2 and D2 breast cancer cell proliferation. We then related their levels to each cancer's proliferation rate as defined by its Mib1 score.13-HODE was the only metabolite strongly, significantly, and positively associated with Mib1 scores. It was similarly associated with aggressive grade and a key component of grade, mitosis, and also trended to be associated with lymph node metastasis. PGE2 and PGD2 trended to be negatively associated with these markers. No other metabolite in cancer and no metabolite in normal tissue had this profile of associations.Our data fit a model wherein the overproduction of 13-HODE by 15-lipoxygenase-1 shortens breast cancer survival by stimulating its cells to proliferate and possibly metastasize; no other oxygenase-metabolite pathway, including cyclooxygenase-PGE2/D2 pathways, uses this specific mechanism to shorten survival.

  4. Lymphohematopoietic Cancer Mortality and Morbidity of Workers in a Refinery/Petrochemical Complex in Korea

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    Dong-Hee Koh

    2011-03-01

    Conclusion: The results showed a potential relationship between leukemia and lymphohematopoietic cancers and exposure to benzene in refinery/petrochemical complex workers. This study yielded limited results due to a short observational period; therefore, a follow-up study must be performed to elucidate the relationship between petrochemical exposure and cancer rates.

  5. Occupational Risk Factors of Lymphohematopoietic Cancer in Rayong Province, Thailand.

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    Punjindasup, Apinya; Sangrajrang, Suleeporn; Ekpanyaskul, Chatchai

    2015-11-01

    The Lymphohematopoietic Cancer (LHC) incidence rate in Thailand has been rising over the past decade with unknown etiology, including Rayong province. One hypothesis of LHC risks is exposure to occupational carcinogens. To determine the association of occupational exposure and LHC risks in Rayong province, Thailand. This matched hospital-based case-control study was conducted in a Rayong provincial hospital from September 2009 to January 2013. One LHC case was matched with four controls in gender and age, ±5 years. Demographic data, residential factors, behavioral factors, and occupational exposure-including chemical exposure-were obtained by interviews and collected by occupational health care officers. The risk factor was analyzed by conditional logistic regression and reported in odds ratio with 95% confidence interval. This study found 105 LHC cases which met the inclusion criteria and were included in the study, yielding a 66% cover rate of cases reported in the database. The histology of LHC were 51 leukemia cases (47.7%), 43 lymphoma cases (42.0%), and 11 multiple myeloma cases (10.3%). The results revealed that occupational exposure to pesticide and smoke were statistically significantly associated with LHC with adjusted ORs 2.26 (95% CI 1.30-3.91) and 1.99 (95% CI = 1.13-3.51), respectively. When stratified to histological subtype of LHC by WHO 2000, leukemia was statistically significantly associated with occupational exposure to smoke, adjusted ORs 2.43 (95% CI 1.11-5.36), with occupational pesticide exposure a significant risk of lymphoma, adjusted ORs 4.69 (95% CI 2.01-10.96). However, neither fumes, wood dust, working outdoors, cleaners, contact with animals, petroleum products and chlorine; nor occupational exposure to volatile organic compounds (VOCs) such as benzene or organic solvents, were statistically significant risk factors of LHC. In addition, there were no significant risks in the demographic data, residential factors, and behavioral

  6. Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

    DEFF Research Database (Denmark)

    Münstermann, U; Fritz, G; Seitz, G

    1990-01-01

    Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

  7. Extracellular ATP in the lymphohematopoietic system: P2Z purinoceptors and membrane permeabilization

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    Persechini P.M.

    1998-01-01

    Full Text Available The effects of extracellular nucleosides and nucleotides on many organs and systems have been recognized for almost 50 years. The effects of extracellular ATP (ATPo, UTPo, ADPo, and other agonists are mediated by P2 purinoceptors. One of the most dramatic effects of ATPo is the permeabilization of plasma membranes to low molecular mass solutes of up to 900 Da. This effect is evident in several cells of the lymphohematopoietic system and is supposed to be mediated by P2Z, an ATP4--activated purinoceptor. Here, we review some basic information concerning P2 purinoceptors and focus our attention on P2Z-associated phenomena displayed by macrophages. Using fluorescent dye uptake, measurement of free intracellular Ca2+ concentration and electrophysiological recordings, we elucidate some of the events that follow the application of ATP to the extracellular surface of macrophages. We propose a regulatory mechanism for the P2Z-associated permeabilization pore. The presence of P2 purinoceptors in cells of the lymphohematopoietic system makes them potential candidates to mediate immunoregulatory events

  8. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (External Review Draft)

    Science.gov (United States)

    This draft report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induced by chemical agents and radiation in humans, with a primary emphasis on leukemia and leukemia-inducing agents. It focuses on how mechanistic information on human l...

  9. Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

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    Katharine Askew

    2017-01-01

    Full Text Available Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis.

  10. Farm residence and lymphohematopoietic cancers in the Iowa Women's Health Study.

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    Jones, Rena R; Yu, Chu-Ling; Nuckols, John R; Cerhan, James R; Airola, Matthew; Ross, Julie A; Robien, Kim; Ward, Mary H

    2014-08-01

    Cancer incidence in male farmers has been studied extensively; however, less is known about risk among women residing on farms or in agricultural areas, who may be exposed to pesticides by their proximity to crop fields. We extended a previous follow-up of the Iowa Women's Health Study cohort to examine farm residence and the incidence of lymphohematopoietic cancers. Further, we investigated crop acreage within 750 m of residences, which has been associated with higher herbicide levels in Iowa homes. We analyzed data for a cohort of 37,099 Iowa women aged 55-69 years who reported their residence location (farm, rural (not a farm), town size based on population) at enrollment in 1986. We identified incident lymphohematopoietic cancers (1986-2009) by linkage with the Iowa Cancer Registry. Using a geographic information system, we geocoded addresses and calculated acreage of pasture and row crops within 750 m of homes using the 1992 National Land Cover Database. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariate analyses of cancer risk in relation to both residence location and crop acreage. As found in an earlier analysis of residence location, risk of acute myeloid leukemia (AML) was higher among women living on farms (HR=2.23, 95%CI: 1.25-3.99) or rural areas (but not on a farm) (HR=1.95, 95%CI: 0.89-4.29) compared with women living in towns of >10,000 population. We observed no association between farm or rural residence and non-Hodgkin lymphoma (NHL; overall or for major subtypes) or multiple myeloma. In analyses of crop acreage, we observed no association between pasture or row crop acreage within 750 m of homes and risk of leukemia overall or for the AML subtype. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) risk was nonsignificantly elevated among women with pasture acreage within 750 m of their home (HRs for increasing tertiles=1.8, 1.8 and 1.5) and with row crop acreage within 750 m

  11. Farm residence and lymphohematopoietic cancers in the Iowa Women’s Health Study

    Science.gov (United States)

    Jones, Rena R.; Yu, Chu-Ling; Nuckols, John R.; Cerhan, James R.; Airola, Matthew; Ross, Julie A.; Robien, Kim; Ward, Mary H.

    2014-01-01

    Background Cancer incidence in male farmers has been studied extensively; however, less is known about risk among women residing on farms or in agricultural areas, who may be exposed to pesticides by their proximity to crop fields. We extended a previous follow-up of the Iowa Women’s Health Study cohort to examine farm residence and the incidence of lymphohematopoietic cancers. Further, we investigated crop acreage within 750 m of residences, which has been associated with higher herbicide levels in Iowa homes. Methods We analyzed data for a cohort of 37,099 Iowa women aged 55–69 years who reported their residence location (farm, rural (not a farm), town size based on population) at enrollment in 1986. We identified incident lymphohematopoietic cancers (1986–2009) by linkage with the Iowa Cancer Registry. Using a geographic information system, we geocoded addresses and calculated acreage of pasture and row crops within 750 m of homes using the 1992 National Land Cover Database. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariate analyses of cancer risk in relation to both residence location and crop acreage. Results As found in an earlier analysis of residence location, risk of acute myeloid leukemia (AML) was higher among women living on farms (HR= 2.23, 95%CI: 1.25–3.99) or rural areas (but not on a farm) (HR= 1.95, 95%CI: 0.89–4.29) compared with women living in towns of > 10,000 population. We observed no association between farm or rural residence and non-Hodgkin lymphoma (NHL; overall or for major subtypes) or multiple myeloma. In analyses of crop acreage, we observed no association between pasture or row crop acreage within 750 m of homes and risk of leukemia overall or for the AML subtype. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) risk was nonsignificantly elevated among women with pasture acreage within 750 m of their home (HRs for increasing tertiles= 1.8, 1.8 and 1

  12. The caudal regeneration blastema is an accumulation of rapidly proliferating stem cells in the flatworm Macrostomum lignano.

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    Egger, Bernhard; Gschwentner, Robert; Hess, Michael W; Nimeth, Katharina T; Adamski, Zbigniew; Willems, Maxime; Rieger, Reinhard; Salvenmoser, Willi

    2009-07-15

    Macrostomum lignano is a small free-living flatworm capable of regenerating all body parts posterior of the pharynx and anterior to the brain. We quantified the cellular composition of the caudal-most body region, the tail plate, and investigated regeneration of the tail plate in vivo and in semithin sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts) in S-phase. The tail plate accomodates the male genital apparatus and consists of about 3,100 cells, about half of which are epidermal cells. A distinct regeneration blastema, characterized by a local accumulation of rapidly proliferating neoblasts and consisting of about 420 cells (excluding epidermal cells), was formed 24 hours after amputation. Differentiated cells in the blastema were observed two days after amputation (with about 920 blastema cells), while the male genital apparatus required four to five days for full differentiation. At all time points, mitoses were found within the blastema. At the place of organ differentiation, neoblasts did not replicate or divide. After three days, the blastema was made of about 1420 cells and gradually transformed into organ primordia, while the proliferation rate decreased. The cell number of the tail plate, including about 960 epidermal cells, was restored to 75% at this time point. Regeneration after artificial amputation of the tail plate of adult specimens of Macrostomum lignano involves wound healing and the formation of a regeneration blastema. Neoblasts undergo extensive proliferation within the blastema. Proliferation patterns of S-phase neoblasts indicate that neoblasts are either determined to follow a specific cell fate not before, but after going through S-phase, or that they can be redetermined after S-phase. In pulse-chase experiments, dispersed distribution of label suggests that S-phase labeled progenitor cells of the male genital apparatus undergo further proliferation before differentiation, in contrast to progenitor cells of

  13. The caudal regeneration blastema is an accumulation of rapidly proliferating stem cells in the flatworm Macrostomum lignano

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    Adamski Zbigniew

    2009-07-01

    Full Text Available Abstract Background Macrostomum lignano is a small free-living flatworm capable of regenerating all body parts posterior of the pharynx and anterior to the brain. We quantified the cellular composition of the caudal-most body region, the tail plate, and investigated regeneration of the tail plate in vivo and in semithin sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts in S-phase. Results The tail plate accomodates the male genital apparatus and consists of about 3,100 cells, about half of which are epidermal cells. A distinct regeneration blastema, characterized by a local accumulation of rapidly proliferating neoblasts and consisting of about 420 cells (excluding epidermal cells, was formed 24 hours after amputation. Differentiated cells in the blastema were observed two days after amputation (with about 920 blastema cells, while the male genital apparatus required four to five days for full differentiation. At all time points, mitoses were found within the blastema. At the place of organ differentiation, neoblasts did not replicate or divide. After three days, the blastema was made of about 1420 cells and gradually transformed into organ primordia, while the proliferation rate decreased. The cell number of the tail plate, including about 960 epidermal cells, was restored to 75% at this time point. Conclusion Regeneration after artificial amputation of the tail plate of adult specimens of Macrostomum lignano involves wound healing and the formation of a regeneration blastema. Neoblasts undergo extensive proliferation within the blastema. Proliferation patterns of S-phase neoblasts indicate that neoblasts are either determined to follow a specific cell fate not before, but after going through S-phase, or that they can be redetermined after S-phase. In pulse-chase experiments, dispersed distribution of label suggests that S-phase labeled progenitor cells of the male genital apparatus undergo further proliferation before

  14. Formaldehyde Exposure and Mortality Risks From Acute Myeloid Leukemia and Other Lymphohematopoietic Malignancies in the US National Cancer Institute Cohort Study of Workers in Formaldehyde Industries

    Science.gov (United States)

    Dell, Linda D.; Boffetta, Paolo; Gallagher, Alexa E.; Crawford, Lori; Lees, Peter SJ.; Mundt, Kenneth A.

    2015-01-01

    Objectives: To evaluate associations between cumulative and peak formaldehyde exposure and mortality from acute myeloid leukemia (AML) and other lymphohematopoietic malignancies. Methods: Cox proportional hazards analyses. Results: Acute myeloid leukemia was unrelated to cumulative exposure. Hodgkin lymphoma relative risk estimates in the highest exposure categories of cumulative and peak exposures were, respectively, 3.76 (Ptrend = 0.05) and 5.13 (Ptrend = 0.003). There were suggestive associations with peak exposure observed for chronic myeloid leukemia, albeit based on very small numbers. No other lymphohematopoietic malignancy was associated with either chronic or peak exposure. Conclusions: Insofar as there is no prior epidemiologic evidence supporting associations between formaldehyde and either Hodgkin leukemia or chronic myeloid leukemia, any causal interpretations of the observed risk patterns are at most tentative. Findings from this re-analysis do not support the hypothesis that formaldehyde is a cause of AML. PMID:26147546

  15. Rapid selection and proliferation of CD133+ cells from cancer cell lines: chemotherapeutic implications.

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    Sarah E Kelly

    2010-04-01

    Full Text Available Cancer stem cells (CSCs are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133+] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB (Celdyne, Houston, TX. For comparison, another bioreactor, the rotary cell culture system (RCCS manufactured by Synthecon (Houston, TX was used. Both the HFB and the RCCS bioreactors simulate aspects of hypogravity. In our study, the HFB increased CD133+ cell growth from various cell lines compared to the RCCS vessel and to normal gravity control. We observed a +15-fold proliferation of the CD133+ cellular fraction with cancer cells that were cultured for 7-days at optimized conditions. The RCCS vessel instead yielded a (-4.8-fold decrease in the CD133+cellular fraction respect to the HFB after 7-days of culture. Interestingly, we also found that the hypogravity environment of the HFB greatly sensitized the CD133+ cancer cells, which are normally resistant to chemo treatment, to become susceptible to various chemotherapeutic agents, paving the way to less toxic and more effective chemotherapeutic treatment in patients. To be able to test the efficacy of cytotoxic agents in vitro prior to their use in clinical setting on cancer cells as well as on cancer stem cells may pave the way to more effective chemotherapeutic strategies in patients. This could be an important advancement in the therapeutic options of oncologic patients, allowing for more targeted and personalized chemotherapy regimens as well as for higher response rates.

  16. Measurement of proliferation and disappearance of rapid turnover cell populations in human studies using deuterium-labeled glucose.

    Science.gov (United States)

    Macallan, Derek C; Asquith, Becca; Zhang, Yan; de Lara, Catherine; Ghattas, Hala; Defoiche, Julien; Beverley, Peter C L

    2009-01-01

    Cell proliferation may be measured in vivo by quantifying DNA synthesis with isotopically labeled deoxyribonucleotide precursors. Deuterium-labeled glucose is one such precursor which, because it achieves high levels of enrichment for a short period, is well suited to the study of rapidly dividing cells, in contrast to the longer term labeling achieved with heavy water ((2)H(2)O). As deuterium is non-radioactive and glucose can be readily administered, this approach is suitable for clinical studies. It has been widely applied to investigate human lymphocyte proliferation, but solid tissue samples may also be analyzed. Rate, duration and route (intravenous or oral) of [6,6-(2)H(2)]-glucose administration should be adapted to the target cell of interest. For lymphocytes, cell separation is best achieved by fluorescence activated cell sorting (FACS), although magnetic bead separation is an alternative. DNA is then extracted, hydrolyzed enzymatically and analyzed by gas chromatography mass spectrometry (GC/MS). Appropriate mathematical modeling is critical to interpretation. Typical time requirements are as follows: labeling, 10-24 h; sampling, approximately 3 weeks; DNA extraction/derivatization, 2-3 d; and GC/MS analysis, approximately 2 d.

  17. Rapid multiplication of Dalbergia sissoo Roxb.: a timber yielding tree legume through axillary shoot proliferation and ex vitro rooting.

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    Vibha, J B; Shekhawat, N S; Mehandru, Pooja; Dinesh, Rachana

    2014-01-01

    An efficient and improved method for in vitro propagation of mature tree of Dalbergia sissoo, an ecologically and commercially important timber yielding species, has been developed through axillary shoot proliferation. Bud breaking occurred from nodal shoot segments derived from rejuvenated shoots produced during early spring from a 20-25-year-old lopped tree, on MS medium containing 8.88 μM benzylaminopurine (BAP). Multiple shoots differentiated (20-21shoots/node) on re-culture of explants on half-strength agar gelled amended MS medium with a combination of 2.22 μM of BAP and 0.002 μM of thidiazuron (TDZ) with 1.0 mM each of Ca(NO3)2, K2SO4, KCl, and NH4(SO4)2. The maximum shoot multiplication (29-30 shoots/node) was achieved on subculturing in the above mentioned but liquid medium. Furthermore, the problem of shoot tip necrosis and defoliation observed on solid medium were overcome by the use of liquid medium. Ex vitro rooting was achieved on soilrite after basal treatment of microshoots with 984 μM of indole-3-butyric acid (IBA) for 2 min. About 90 % microshoots were rooted on soilrite within 2-3 weeks under the greenhouse conditions. From 20 nodal shoot segments, about 435 hardened plants were acclimatized and transplanted. This is the first report for rapid in vitro propagation of mature trees of D. sissoo on liquid medium followed by ex vitro rooting.

  18. Young adult chondrocytes proliferate rapidly and produce a cartilaginous tissue at the gel-media interface in agarose cultures.

    Science.gov (United States)

    Tran-Khanh, Nicolas; Chevrier, Anik; Lascau-Coman, Viorica; Hoemann, Caroline D; Buschmann, Michael D

    2010-06-01

    Primary chondrocytes cultured in agarose can escape the gel, accumulate at the interface between agarose and the culture medium, and form an outgrowing tissue. These outgrowths can appear as voluminous cartilage-like nodules that have never been previously investigated. In the present study, bovine articular chondrocytes from three age groups (fetal, young adult, aged) were seeded and cultured in agarose to test the hypothesis that hyaline-like cartilage outgrowths develop at the interface by appositional growth, in an age-dependant manner. Macroscopic appearance, cell content, cell division, cytoskeletal morphology, and extracellular matrix (ECM) composition were analyzed. Fetal chondrocytes produced a fibrous interfacial tissue while aged chondrocytes produced ECM-poor cell clusters. In contrast young adult chondrocytes produced large cartilaginous outgrowths, rich in proteoglycan and collagen II, where cells in the central region displayed a chondrocyte morphology. Cell proliferation was confined to the peripheral edge of these outgrowths, where elongated cell morphology, cell-cell contacts, and cell extensions toward the culture medium were seen. Thus these voluminous cartilaginous outgrowths formed in an appositional growth process and only for donor chondrocytes from young adult animals. This system offers an interesting ability to proliferate chondrocytes in a manner that results in a chondrocyte morphology and a cartilaginous ECM in central regions of the outgrowing tissue. It also provides an in vitro model system to study neocartilage appositional growth.

  19. Rapid proliferation of Vibrio parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae during freshwater flash floods in French Mediterranean coastal lagoons.

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    Esteves, Kevin; Hervio-Heath, Dominique; Mosser, Thomas; Rodier, Claire; Tournoud, Marie-George; Jumas-Bilak, Estelle; Colwell, Rita R; Monfort, Patrick

    2015-11-01

    Vibrio parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae of the non-O1/non-O139 serotype are present in coastal lagoons of southern France. In these Mediterranean regions, the rivers have long low-flow periods followed by short-duration or flash floods during and after heavy intense rainstorms, particularly at the end of the summer and in autumn. These floods bring large volumes of freshwater into the lagoons, reducing their salinity. Water temperatures recorded during sampling (15 to 24°C) were favorable for the presence and multiplication of vibrios. In autumn 2011, before heavy rainfalls and flash floods, salinities ranged from 31.4 to 36.1‰ and concentrations of V. parahaemolyticus, V. vulnificus, and V. cholerae varied from 0 to 1.5 × 10(3) most probable number (MPN)/liter, 0.7 to 2.1 × 10(3) MPN/liter, and 0 to 93 MPN/liter, respectively. Following heavy rainstorms that generated severe flash flooding and heavy discharge of freshwater, salinity decreased, reaching 2.2 to 16.4‰ within 15 days, depending on the site, with a concomitant increase in Vibrio concentration to ca. 10(4) MPN/liter. The highest concentrations were reached with salinities between 10 and 20‰ for V. parahaemolyticus, 10 and 15‰ for V. vulnificus, and 5 and 12‰ for V. cholerae. Thus, an abrupt decrease in salinity caused by heavy rainfall and major flooding favored growth of human-pathogenic Vibrio spp. and their proliferation in the Languedocian lagoons. Based on these results, it is recommended that temperature and salinity monitoring be done to predict the presence of these Vibrio spp. in shellfish-harvesting areas of the lagoons. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Non-cytotoxic organic-inorganic hybrid bioscaffolds: An efficient bedding for rapid growth of bone-like apatite and cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    John, Lukasz, E-mail: lukasz.john@chem.uni.wroc.pl [Faculty of Chemistry, University of Wroclaw, 14 F. Joliot-Curie, 50-383 Wroclaw (Poland); Baltrukiewicz, Marta; Sobota, Piotr [Faculty of Chemistry, University of Wroclaw, 14 F. Joliot-Curie, 50-383 Wroclaw (Poland); Brykner, Renata; Cwynar-Zajac, Lucja [Department of Histology and Embryology, Wroclaw Medical University, 6a Chalubinskiego, 50-368 Wroclaw (Poland); Dziegiel, Piotr [Department of Histology and Embryology, Wroclaw Medical University, 6a Chalubinskiego, 50-368 Wroclaw (Poland); Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecickiego, 61-781 Poznan (Poland)

    2012-10-01

    Synthesis and characterization of organic-inorganic macroporous hybrid scaffolds were investigated. The materials were prepared by combining 2-hydroxyethylmethacrylate (HEMA) and triethoxyvinylsilane (TEVS) chemically modified by Ca{sup 2+} and PO{sub 4}{sup 3-} ions via sol-gel route. In this study we have constructed a sugar-based cracks-free three-dimensional (3D) network with interconnected porous architecture within the range of 150-300 {mu}m and rough topography. The obtained results revealed that both topography and composition of prepared materials allow rapid growth of the bone-like apatite (HAp) layer on their surface after soaking in biological medium. Preliminary studies have shown that hybrids covered by HAp are non-cytotoxic and allow cell proliferation that make them a promising scaffolds in the field of bone regenerative medicine. The materials were mainly characterized by powder X-ray diffraction analysis (PXRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and transmission electron microscopy-energy-dispersive spectroscopy (TEM-EDS). Highlights: Black-Right-Pointing-Pointer Sol-gel derived biomaterials. Black-Right-Pointing-Pointer 3D organic-inorganic hybrid composites for bone tissue engineering. Black-Right-Pointing-Pointer Sugar-templated cracks-free macroporous scaffolds. Black-Right-Pointing-Pointer 2-hydroxyethylmethacrylate/triethoxyvinylsilane blend doped with calcium and phosphate ions. Black-Right-Pointing-Pointer Non-cytotoxic bedding for fibroblasts proliferation.

  1. Incidence and survival of lymphohematopoietic neoplasms according to the World Health Organization classification: a population-based study from the Victorian Cancer Registry in Australia.

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    Jayasekara, Harindra; Karahalios, Amalia; Juneja, Surender; Thursfield, Vicky; Farrugia, Helen; English, Dallas R; Giles, Graham G

    2010-03-01

    We studied the incidence and relative survival of 39 837 cases of lymphohematopoietic neoplasms (LHN) reported to the Victorian Cancer Registry during 1982-2004, classified according to the World Health Organization (WHO) classification. We modeled excess mortality using Poisson regression to estimate differences in survival by age, sex, and time period. Age-standardized incidence rates varied across subtypes of lymphoid and myeloid neoplasms. All major subtypes predominantly affected the elderly except Hodgkin lymphoma (incidence peaks at 20-24 and 75-79 years) and acute lymphoblastic leukemia (0-9 years). After an initial rise, overall lymphoid and myeloid incidence stabilized in the mid-1990s. The 5-year relative survival was 58% for lymphoid and 35% for myeloid neoplasms. Survival improved during 1990-2004 for diffuse large B-cell lymphoma, follicular lymphoma, acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndromes (p  < 0.001) and declined with advancing age for all subtypes (p <  0.001). Female sex was associated with higher survival for most myeloid subtypes. The results represent a rare epidemiological characterization of the whole range of LHN according to WHO subtypes.

  2. Rapid infection and proliferation of dactylogyrid monogeneans on gills of spotted rose snapper (Lutjanus guttatus) after transfer to a sea-cage.

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    Soler-Jiménez, Lilia C; Morales-Serna, Francisco N; Fajer-Ávila, Emma J

    2015-06-15

    Finfish mariculture is typically threatened by parasite and disease outbreaks. Therefore, it is important to identify parasite species of potential risk for this activity. Snappers are valuable food fish worldwide. In the Eastern Pacific, spotted rose snapper (Lutjanus guttatus [Steindachner, 1869]) is a firm candidate for sea-cage aquaculture. In the current study, the parasitism of caged L. guttatus by dactylogyrids was evaluated for the first time during a complete farming period. Twenty five thousand juvenile fish produced at the Research Center for Food and Development (CIAD, Mazatlan Unit) were reared in a sentinel sea-cage from February to November 2012 in Mazatlan Bay, Mexico. A fish sample (n=15) was obtained every month. Dactylogyrids from the left second gill arch were identified and quantified. A total of 18,704 dactylogyrids distributed in three species, Euryhaliotrema perezponcei García-Vargas, Fajer-Ávila and Lamothe-Argumedo, 2008, E. mehen (Soler-Jiménez, García-Gasca and Fajer-Ávila, 2012), and Haliotrematoides guttati García-Vargas, Fajer-Ávila and Lamothe-Argumedo, 2008 (Monogenea: Dactylogyridae) was found, which were able to infect caged L. guttatus since the first month of the farming period. Prevalence of these parasite species was 100% all the time, except for initial low values for E. mehen and H. guttati. The mean intensity of infection of each dactylogyrid species varied significantly between sampling months. Euryhaliotrema perezponcei was the most abundant parasite, reaching the highest mean intensity in May, June and July (154.3, 296.9 and 176.6 parasites/host, respectively). No clear seasonality of infection was observed; however, the influence of the water temperature on the observed infection levels is discussed. There was no mortality, change on behavior or pathological signs. However, given the rapid infection and proliferation of dactylogyrids, particularly E. perezponcei on L. guttaus reared in a sentinel sea

  3. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

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    Lund, Thomas; Søe, Kent; Abildgaard, Niels; Garnero, Patrick; Pedersen, Per T; Ormstrup, Tina; Delaissé, Jean-Marie; Plesner, Torben

    2010-01-01

    Objectives: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. Methods: Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions: Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. PMID:20528908

  4. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    DEFF Research Database (Denmark)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels

    2010-01-01

    OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients...... received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also...... studied in vitro. RESULTS: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro...

  5. Facile and rapid generation of large-scale microcollagen gel array for long-term single-cell 3D culture and cell proliferation heterogeneity analysis.

    Science.gov (United States)

    Guan, Zhichao; Jia, Shasha; Zhu, Zhi; Zhang, Mingxia; Yang, Chaoyong James

    2014-03-04

    Microfabricated devices are suitable for single-cell analysis due to their high throughput, compatible dimensions and controllable microenvironment. However, existing devices for single-cell culture and analysis encounter some limitations, such as nutrient depletion, random cell migration and complicated fluid shear influence. Moreover, most of the single-cell culture and analysis devices are based on 2D cell culture conditions, even though 3D cell culture methods have been demonstrated to better mimic the real cell microenvironment in vivo. To solve these problems, herein we develop a microcollagen gel array (μCGA) based approach for high-throughput long-term single-cell culture and single-cell analysis under 3D culture conditions. Type-I collagen, a well-established 3D cell culture medium, was used as the scaffold for 3D cell growth. A 2 × 2 cm PDMS chip with 10 000 μCGA units was fabricated to encapsulate thousands of single cells in less than 15 min. Single cells were able to be confined and survive in μCGA units for more than 1 month. The capability of large-scale and long-term single-cell 3D culture under open culture conditions allows us to study cellular proliferation heterogeneity and drug cytotoxicity at the single-cell level. Compared with existing devices for single-cell analysis, μCGA solves the problems of nutrient depletion and random cellular migration, avoids the influence of complicated fluid shear, and mimics the real 3D growth environment in vivo, thereby providing a feasible 3D long-term single-cell culture method for single-cell analysis and drug screening.

  6. Proliferation Security Initiative (PSI)

    National Research Council Canada - National Science Library

    Squassoni, Sharon

    2005-01-01

    President Bush announced the Proliferation Security Initiative (PSI) on May 31, 2003. Since then, 16 nations have pledged their cooperation in interdicting shipments of weapons of mass destruction-related...

  7. Cell proliferation in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M.; Ellwein, L.B. (Univ. of Nebraska Medical Center, Omaha (USA))

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  8. JPRS Report, Proliferation Issues

    Science.gov (United States)

    1992-05-27

    JPRS-TND-92-016 27 MAY 1992 JPRS Repor Proliferation Issues ÄBpxovea tcz pursue ieiaaM| Ipfe. fötmbuasa OsüoaÜBd .^L ■ — —— au »** 19980112...6 MOROCCO Berrada on Proposed Nuclear Power Plant [ MAROC SOIR 22 Apr] 6 JPRS-TND-92-016 27 May 1992 2 CENTRAL EURASIA Proposals on...three days of talks here on normalizing relations with Japan, which were largely stalemated over Tokyo’s demand for Pyongyang’s assurance that it did

  9. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  10. The ROCO Kinase QkgA Is Necessary for Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum▿

    OpenAIRE

    Jonathan E Phillips; Gomer, Richard H.

    2010-01-01

    AprA and CfaD are secreted proteins that function as autocrine signals to inhibit cell proliferation in Dictyostelium discoideum. Cells lacking AprA or CfaD proliferate rapidly, and adding AprA or CfaD to cells slows proliferation. Cells lacking the ROCO kinase QkgA proliferate rapidly, with a doubling time 83% of that of the wild type, and overexpression of a QkgA-green fluorescent protein (GFP) fusion protein slows cell proliferation. We found that qkgA− cells accumulate normal levels of ex...

  11. Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

    2016-06-10

    Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

  12. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-07-10

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  13. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-03-13

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts. news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  14. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-07-16

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  15. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-02-21

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  16. PMP27 PROMOTES PEROXISOMAL PROLIFERATION

    NARCIS (Netherlands)

    MARSHALL, PA; KRIMKEVICH, YI; LARK, RH; DYER, JM; VEENHUIS, M; GOODMAN, JM; Krimkevich, Yelena I.; Lark, Richard H.; Dyer, John M.; Goodman, Joel M.

    Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by

  17. Rapid Prototyping

    Science.gov (United States)

    1999-01-01

    Javelin, a Lone Peak Engineering Inc. Company has introduced the SteamRoller(TM) System as a commercial product. The system was designed by Javelin during a Phase II NASA funded small commercial product. The purpose of the invention was to allow automated-feed of flexible ceramic tapes to the Laminated Object Manufacturing rapid prototyping equipment. The ceramic material that Javelin was working with during the Phase II project is silicon nitride. This engineered ceramic material is of interest for space-based component.

  18. Cell Proliferation and Cytotoxicity Assays.

    Science.gov (United States)

    Adan, Aysun; Kiraz, Yağmur; Baran, Yusuf

    Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.

  19. Oropharyngeal candidiasis in children with lymphohematopoietic malignancies in Mashhad, Iran

    Directory of Open Access Journals (Sweden)

    Fariba Berenji

    2015-03-01

    Conclusion: In the present study, Candida species were the most common fungal pathogens in pediatric cancer patients; therefore, efforts should be made to prevent fungemia and fungal pneumonia. Also, non-C. albicans species must be considered as a new risk factor for pediatric cancer patients.

  20. Domestic Politics and Nuclear Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chul Min; Yim, Man Sung [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    The external security threat is known as the most important factor of nuclear weapons program, the domestic politics situation can also affect the nuclear proliferation decision of a country. For example, when a leader wants nuclear weapons as an ultimate weapon, the domestic politics situation can determine the effectiveness of the weapons program of a country. This study analyzes the current knowledge of the relationship between domestic politics and nuclear proliferation and suggests the main challenges of the quantitative models trying to calculate nuclear proliferation risk of countries. The domestic politics status is one of the most important indicators of nuclear program. However, some variables have never been used in quantitative analyses; for example, number of veto players and the public opinion on nuclear weapons; despite they are considered to be important in various qualitative studies. Future studies should focus on how should they be coded and how can they be linked with existing domestic politics variables.

  1. Calcium signaling and cell proliferation.

    Science.gov (United States)

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation

    OpenAIRE

    Vander Heiden, Matthew G.; Lunt, Sophia Yunkyungkwon

    2011-01-01

    Warburg's observation that cancer cells exhibit a high rate of glycolysis even in the presence of oxygen (aerobic glycolysis) sparked debate over the role of glycolysis in normal and cancer cells. Although it has been established that defects in mitochondrial respiration are not the cause of cancer or aerobic glycolysis, the advantages of enhanced glycolysis in cancer remain controversial. Many cells ranging from microbes to lymphocytes use aerobic glycolysis during rapid proliferation, which...

  3. Nuclear Proliferation: A Historical Overview

    Science.gov (United States)

    2008-03-01

    unsuccessful, however, and in 1981 Egypt ratified the Nuclear Non-Proliferation Treaty. In 1982 Egypt’s Hydrometallurgy Pilot Plant for reprocessing...Country Profile: Egypt,” http://www.iaea.org/DataCenter/index.html (accessed ɠ/8/2007>). 1982: Hydrometallurgy Pilot Plant for reprocessing

  4. Nuclear Proliferation Technology Trends Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

    2005-10-04

    A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

  5. anterior hyaloidal fibrovascular proliferation (ahfvp)

    African Journals Online (AJOL)

    Okonkwo

    fibrovascular proliferation in ischaemic diabetic eyes is known to occur predominantly in the region posterior to the equator, ie, the pre-equatorial fundus. There is a. 5 preponderance of posterior neovascularization occurring in proliferative diabetic retinopathy. This posterior. 7,8,9 proliferative disease in ischaemic diabetic ...

  6. Proliferation Vulnerability Red Team report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, J.P.; Barnard, R.W.; Bennett, D.E. [and others

    1996-10-01

    This report is the product of a four-month independent technical assessment of potential proliferation vulnerabilities associated with the plutonium disposition alternatives currently under review by DOE/MD. The scope of this MD-chartered/Sandia-led study was limited to technical considerations that could reduce proliferation resistance during various stages of the disposition processes below the Stored Weapon/Spent Fuel standards. Both overt and covert threats from host nation and unauthorized parties were considered. The results of this study will be integrated with complementary work by others into an overall Nonproliferation and Arms Control Assessment in support of a Secretarial Record of Decision later this year for disposition of surplus U.S. weapons plutonium.

  7. Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Alan M. [School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH (United Kingdom); Paxton, Jennifer Z.; Hung, Yi-Pei; Hadley, Martin J.; Bowen, James; Williams, Richard L. [School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT (United Kingdom); Grover, Liam M., E-mail: l.m.grover@bham.ac.uk [School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT (United Kingdom)

    2015-03-01

    Calcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40 years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macro-scale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation. - Highlights: • Crystallinity of HA at the nano-scale was dominant over macro-scale topography. • Lower crystallinity caused rapid cell attachment and proliferation rate. • Crystallinity could be easily adjusted by without compromising coating purity.

  8. Organizational Inertia and Excessive Product Proliferation

    OpenAIRE

    Sakuraki, Rie

    2015-01-01

    This study investigates the internal factors of excessive product proliferation. Since empirical literature on product over-proliferation focused on how to optimize existing product portfolio, the causes of excessive product proliferation have so far attracted little attention. This study employs a case study of Shiseido, a famous Japanese cosmetics company, with particular attention to product proliferation in the Shiseido chain store channel, because external factors are mostly absent from ...

  9. Printed Proliferation: The Implications of Additive Manufacturing and Nuclear Weapons Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lindsey, Nicholas C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-26

    The growth of additive manufacturing as a disruptive technology poses nuclear proliferation concerns worthy of serious consideration. Additive manufacturing began in the early 1980s with technological advances in polymer manipulation, computer capabilities, and computer-aided design (CAD) modeling. It was originally limited to rapid prototyping; however, it eventually developed into a complete means of production that has slowly penetrated the consumer market. Today, additive manufacturing machines can produce complex and unique items in a vast array of materials including plastics, metals, and ceramics. These capabilities have democratized the manufacturing industry, allowing almost anyone to produce items as simple as cup holders or as complex as jet fuel nozzles. Additive manufacturing, or three-dimensional (3D) printing as it is commonly called, relies on CAD files created or shared by individuals with additive manufacturing machines to produce a 3D object from a digital model. This sharing of files means that a 3D object can be scanned or rendered as a CAD model in one country, and then downloaded and printed in another country, allowing items to be shared globally without physically crossing borders. The sharing of CAD files online has been a challenging task for the export controls regime to manage over the years, and additive manufacturing could make these transfers more common. In this sense, additive manufacturing is a disruptive technology not only within the manufacturing industry but also within the nuclear nonproliferation world. This paper provides an overview of additive manufacturing concerns of proliferation.

  10. 15 CFR 12.2 - Undue proliferation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Undue proliferation. 12.2 Section 12.2 Commerce and Foreign Trade Office of the Secretary of Commerce FAIR PACKAGING AND LABELING § 12.2 Undue proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or...

  11. Microscopic dissipative structuring and proliferation at the origin of life.

    Science.gov (United States)

    Michaelian, Karo

    2017-10-01

    Some fundamental molecules of life are suggested to have been formed, proliferated, and evolved through photochemical microscopic dissipative structuring and autocatalytic proliferation under the UV-C/UV-B solar environment prevalent at Earth's surface throughout the Archean. Evidence is given in the numerous salient characteristics of these, including their strong absorption in this spectral region and their rapid non-radiative excited state decay through inherent conical intersections. The examples of the dissipative structuring and dissipative proliferation of the purines and of single strand DNA are given. UV-C and UV-B-induced stationary state isomerizations and tautomerizations are shown to be crucial to the formation of the purines from hydrogen cyanide in an aqueous environment under UV-C light, while UV-C induced phosphorylation of nucleosides and denaturing of double helix RNA and DNA are similarly important to the production and proliferation of single strand DNA. This thermodynamic dissipation perspective provides a physical-chemical foundation for understanding the origin and evolution of life.

  12. The ROCO kinase QkgA is necessary for proliferation inhibition by autocrine signals in Dictyostelium discoideum.

    Science.gov (United States)

    Phillips, Jonathan E; Gomer, Richard H

    2010-10-01

    AprA and CfaD are secreted proteins that function as autocrine signals to inhibit cell proliferation in Dictyostelium discoideum. Cells lacking AprA or CfaD proliferate rapidly, and adding AprA or CfaD to cells slows proliferation. Cells lacking the ROCO kinase QkgA proliferate rapidly, with a doubling time 83% of that of the wild type, and overexpression of a QkgA-green fluorescent protein (GFP) fusion protein slows cell proliferation. We found that qkgA(-) cells accumulate normal levels of extracellular AprA and CfaD. Exogenous AprA or CfaD does not slow the proliferation of cells lacking qkgA, and expression of QkgA-GFP in qkgA(-) cells rescues this insensitivity. Like cells lacking AprA or CfaD, cells lacking QkgA tend to be multinucleate, accumulate nuclei rapidly, and show a mass and protein accumulation per nucleus like those of the wild type, suggesting that QkgA negatively regulates proliferation but not growth. Despite their rapid proliferation, cells lacking AprA, CfaD, or QkgA expand as a colony on bacteria less rapidly than the wild type. Unlike AprA and CfaD, QkgA does not affect spore viability following multicellular development. Together, these results indicate that QkgA is necessary for proliferation inhibition by AprA and CfaD, that QkgA mediates some but not all of the effects of AprA and CfaD, and that QkgA may function downstream of these proteins in a signal transduction pathway regulating proliferation.

  13. The ROCO Kinase QkgA Is Necessary for Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum▿

    Science.gov (United States)

    Phillips, Jonathan E.; Gomer, Richard H.

    2010-01-01

    AprA and CfaD are secreted proteins that function as autocrine signals to inhibit cell proliferation in Dictyostelium discoideum. Cells lacking AprA or CfaD proliferate rapidly, and adding AprA or CfaD to cells slows proliferation. Cells lacking the ROCO kinase QkgA proliferate rapidly, with a doubling time 83% of that of the wild type, and overexpression of a QkgA-green fluorescent protein (GFP) fusion protein slows cell proliferation. We found that qkgA− cells accumulate normal levels of extracellular AprA and CfaD. Exogenous AprA or CfaD does not slow the proliferation of cells lacking qkgA, and expression of QkgA-GFP in qkgA− cells rescues this insensitivity. Like cells lacking AprA or CfaD, cells lacking QkgA tend to be multinucleate, accumulate nuclei rapidly, and show a mass and protein accumulation per nucleus like those of the wild type, suggesting that QkgA negatively regulates proliferation but not growth. Despite their rapid proliferation, cells lacking AprA, CfaD, or QkgA expand as a colony on bacteria less rapidly than the wild type. Unlike AprA and CfaD, QkgA does not affect spore viability following multicellular development. Together, these results indicate that QkgA is necessary for proliferation inhibition by AprA and CfaD, that QkgA mediates some but not all of the effects of AprA and CfaD, and that QkgA may function downstream of these proteins in a signal transduction pathway regulating proliferation. PMID:20709790

  14. An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T cell proliferation.

    Directory of Open Access Journals (Sweden)

    Yoshiko Iwai

    Full Text Available Rapid proliferation is one of the important features of memory CD8(+ T cells, ensuring rapid clearance of reinfection. Although several cytokines such as IL-15 and IL-7 regulate relatively slow homeostatic proliferation of memory T cells during the maintenance phase, it is unknown how memory T cells can proliferate more quickly than naïve T cells upon antigen stimulation. To examine antigen-specific CD8(+ T cell proliferation in recall responses in vivo, we targeted a model antigen, ovalbumin(OVA, to DEC-205(+ dendritic cells (DCs with a CD40 maturation stimulus. This led to the induction of functional memory CD8(+ T cells, which showed rapid proliferation and multiple cytokine production (IFN-gamma, IL-2, TNF-alpha during the secondary challenge to DC-targeted antigen. Upon antigen-presentation, IL-18, an IFN-gamma-inducing factor, accumulated at the DC:T cell synapse. Surprisingly, IFN-gamma receptors were required to augment IL-18 production from DCs. Mice genetically deficient for IL-18 or IFN-gamma-receptor 1 also showed delayed expansion of memory CD8(+ T cells in vivo. These results indicate that a positive regulatory loop involving IFN-gamma and IL-18 signaling contributes to the accelerated memory CD8(+ T cell proliferation during a recall response to antigen presented by DCs.

  15. Proliferation of life from Enceladus

    Science.gov (United States)

    Czechowski, L.

    2017-09-01

    Enceladus is a medium-sized icy satellite (MIS) of Saturn. MIS are built of mixtures of rocks and ices. In 2014 [4] indicates that conditions in the core of this satellite allow for the life. In fact for hundreds of Myr the conditions in the interior of Enceladus were more favourable for origin of life than on the Earth [5, 6]. Presently we continue the research on the possible mechanism of life proliferation including additionally gravity assist as mechanism for deceleration of the body.

  16. 2012: the world on the brink of a nuclear proliferation crisis; Annee 2012: le monde au bord d'une crise de proliferation nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Norlain, Bernard

    2012-02-15

    The author's determined plea that France gives up its dogmatic position on nuclear weapons and takes the lead in a nuclear disarmament movement is based on a conviction that the concept of nuclear deterrence is outdated, the fear of rapidly-growing proliferation in 2012 and the excessive cost of ownership of the French nuclear arsenal

  17. Reducing Proliferation Rick Through Multinational Fuel Cycle Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Amanda Rynes

    2010-11-01

    With the prospect of rapid expansion of the nuclear energy industry and the ongoing concern over weapons proliferation, there is a growing need for a viable alternative to traditional nation-based fuel production facilities. While some in the international community remain apprehensive, the advantages of multinational fuel cycle facilities are becoming increasingly apparent, with states on both sides of the supply chain able to garner the security and financial benefits of such facilities. Proliferation risk is minimized by eliminating the need of states to establish indigenous fuel production capabilities and the concept's structure provides an additional internationally monitored barrier against the misuse or diversion of nuclear materials. This article gives a brief description of the arguments for and against the implementation of a complete multinational fuel cycle.

  18. Proliferation resistance fuel cycle technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Ko, W. I

    1999-02-01

    The issues of dual use in nuclear technology are analysed for nuclear fuel cycle with special focus on uranium enrichment and spent fuel reprocessing which are considered as the most sensitive components in terms of vulnerability to diversion. Technical alternatives to mitigrate the vulnerability, as has been analysed in depth during the NASAP and INFCE era in the late seventies, are reviewed to characterize the DUPIC fuel cycle alternative. On the other hand, the new realities in nuclear energy including the disposition of weapon materials as a legacy of cold war are recast in an angle of nuclear proliferation resistance and safeguards with a discussion on the concept of spent fuel standard concept and its compliance with the DUPIC fuel cycle technology. (author)

  19. Proliferation resistance: issues, initiatives and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, Joseph F [Los Alamos National Laboratory

    2009-01-01

    The vision of a nuclear renaissance has highlighted the issue of proliferation resistance. The prospects for a dramatic growth in nuclear power may depend on the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen proliferation resistance. The GenIV International Forum (GIF) and others have devoted attention and resources to proliferation resistance. However, the hope of finding a way to make the peaceful uses of nuclear energy resistant to proliferation has reappeared again and again in the history of nuclear power with little practical consequence. The concept of proliferation resistance has usually focused on intrinsic (technological) as opposed to extrinsic (institutional) factors. However, if there are benefits that may yet be realized from reactors and other facilities designed to minimize proliferation risks, it is their coupling with effective safeguards and other nonproliferation measures that likely will be critical. Proliferation resistance has also traditionally been applied only to state threats. Although there are no technologies that can wholly eliminate the risk of proliferation by a determined state, technology can play a limited role in reducing state threats and perhaps in eliminating many non-state threats. These and other issues are not academic. They affect efforts to evaluate proliferation resistance, including the methodology developed by GIF's Proliferation Resistance and Physical Protection (PR&PP) Working Group as well as the proliferation resistance initiatives that are being pursued or may be developed in the future. This paper will offer a new framework for thinking about proliferation resistance issues, including the ways the output of the methodology could be developed to inform the decisions that states, the International Atomic Energy (IAEA) and others will have to make in order to fully realize the promise of a nuclear renaissance.

  20. Biofilm-associated indole acetic acid producing bacteria and their impact in the proliferation of biofilm mats in solar salterns

    Digital Repository Service at National Institute of Oceanography (India)

    Kerkar, S.; Raiker, L.; Tiwari, A.; Mayilraj, S.; Dastager, S.

    viz. Nerul and Curca to find a possible reason for the rapid proliferation of these solar biofilms. Out of the 125 bacteria isolated from these biofilms, 16 produced indole-3-acetic acid (IAA). Rapid in-situ assay with Salkowski reagent and HPLC...

  1. RhoA promotes epidermal stem cell proliferation via PKN1-cyclin D1 signaling.

    Directory of Open Access Journals (Sweden)

    Fan Wang

    Full Text Available Epidermal stem cells (ESCs play a critical role in wound healing, but the mechanism underlying ESC proliferation is not well defined. Here, we explore the effects of RhoA on ESC proliferation and the possible underlying mechanism.Human ESCs were enriched by rapid adhesion to collagen IV. RhoA(+/+(G14V, RhoA(-/-(T19N and pGFP control plasmids were transfected into human ESCs. The effect of RhoA on cell proliferation was detected by cell proliferation and DNA synthesis assays. Induction of PKN1 activity by RhoA was determined by immunoblot analysis, and the effects of PKN1 on RhoA in terms of inducing cell proliferation and cyclin D1 expression were detected using specific siRNA targeting PKN1. The effects of U-46619 (a RhoA agonist and C3 transferase (a RhoA antagonist on ESC proliferation were observed in vivo.RhoA had a positive effect on ESC proliferation, and PKN1 activity was up-regulated by the active RhoA mutant (G14V and suppressed by RhoA T19N. Moreover, the ability of RhoA to promote ESC proliferation and DNA synthesis was interrupted by PKN1 siRNA. Additionally, cyclin D1 protein and mRNA expression levels were up-regulated by RhoA G14V, and these effects were inhibited by siRNA-mediated knock-down of PKN1. RhoA also promoted ESC proliferation via PKN in vivo.This study shows that the effect of RhoA on ESC proliferation is mediated by activation of the PKN1-cyclin D1 pathway in vitro, suggesting that RhoA may serve as a new therapeutic target for wound healing.

  2. Identification of transcriptional networks involved in peroxisome proliferator chemical-induced hepatocyte proliferation

    Science.gov (United States)

    Peroxisome proliferator chemical (PPC) exposure leads to increases in rodent liver tumors through a non-genotoxic mode of action (MOA). The PPC MOA includes increased oxidative stress, hepatocyte proliferation and decreased apoptosis. We investigated the putative genetic regulato...

  3. The effect of cerium valence states at cerium oxide nanoparticle surfaces on cell proliferation

    KAUST Repository

    Naganuma, Tamaki

    2014-05-01

    Understanding and controlling cell proliferation on biomaterial surfaces is critical for scaffold/artificial-niche design in tissue engineering. The mechanism by which underlying integrin ligates with functionalized biomaterials to induce cell proliferation is still not completely understood. In this study, poly-l-lactide (PL) scaffold surfaces were functionalized using layers of cerium oxide nanoparticles (CNPs), which have recently attracted attention for use in therapeutic application due to their catalytic ability of Ce4+ and Ce3+ sites. To isolate the influence of Ce valance states of CNPs on cell proliferation, human mesenchymal stem cells (hMSCs) and osteoblast-like cells (MG63) were cultured on the PL/CNP surfaces with dominant Ce4+ and Ce3+ regions. Despite cell type (hMSCs and MG63 cells), different surface features of Ce4+ and Ce3+ regions clearly promoted and inhibited cell spreading, migration and adhesion behavior, resulting in rapid and slow cell proliferation, respectively. Cell proliferation results of various modified CNPs with different surface charge and hydrophobicity/hydrophilicity, indicate that Ce valence states closely correlated with the specific cell morphologies and cell-material interactions that trigger cell proliferation. This finding suggests that the cell-material interactions, which influence cell proliferation, may be controlled by introduction of metal elements with different valence states onto the biomaterial surface. © 2014 Elsevier Ltd.

  4. Proliferation after the Iraq war; La proliferation apres la guerre d'Irak

    Energy Technology Data Exchange (ETDEWEB)

    Daguzan, J.F

    2004-09-15

    This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

  5. Drosophila Pez acts in Hippo signaling to restrict intestinal stem cell proliferation

    DEFF Research Database (Denmark)

    Poernbacher, Ingrid; Baumgartner, Roland; Marada, Suresh K

    2012-01-01

    (EB) that differentiates into an enterocyte (EC) or an enteroendocrine (EE) cell, enable rapid tissue turnover in response to intestinal stress. The damage-related increase in ISC proliferation requires deactivation of the Hippo pathway and consequential activation of the transcriptional coactivator...

  6. Control of cell proliferation by Myc

    DEFF Research Database (Denmark)

    Bouchard, C; Staller, P; Eilers, M

    1998-01-01

    Myc proteins are key regulators of mammalian cell proliferation. They are transcription factors that activate genes as part of a heterodimeric complex with the protein Max. This review summarizes recent progress in understanding how Myc stimulates cell proliferation and how this might contribute ...

  7. Teaching Activities on Horizontal Nuclear Proliferation.

    Science.gov (United States)

    Zola, John

    1990-01-01

    Provides learning activities concerning the horizontal proliferation of nuclear weapons. Includes step-by-step directions for four activities: (1) the life cycle of nuclear weapons; (2) nuclear nonproliferation: pros and cons; (3) the nuclear power/nuclear weapons connection; and (4) managing nuclear proliferation. (NL)

  8. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1995-11-17

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author`s. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia`s Nuclear Legacy.

  9. Rebamipide delivered by brushite cement enhances osteoblast and macrophage proliferation.

    Directory of Open Access Journals (Sweden)

    Michael Pujari-Palmer

    Full Text Available Many of the bioactive agents capable of stimulating osseous regeneration, such as bone morphogenetic protein-2 (BMP-2 or prostaglandin E2 (PGE2, are limited by rapid degradation, a short bioactive half-life at the target site in vivo, or are prohibitively expensive to obtain in large quantities. Rebamipide, an amino acid modified hydroxylquinoline, can alter the expression of key mediators of bone anabolism, cyclo-oxygenase 2 (COX-2, BMP-2 and vascular endothelial growth factor (VEGF, in diverse cell types such as mucosal and endothelial cells or chondrocytes. The present study investigates whether Rebamipide enhances proliferation and differentiation of osteoblasts when delivered from brushite cement. The reactive oxygen species (ROS quenching ability of Rebampide was tested in macrophages as a measure of bioactivity following drug release incubation times, up to 14 days. Rebamipide release from brushite occurs via non-fickian diffusion, with a rapid linear release of 9.70% ± 0.37% of drug per day for the first 5 days, and an average of 0.5%-1% per day thereafter for 30 days. Rebamipide slows the initial and final cement setting time by up to 3 and 1 minute, respectively, but does not significantly reduce the mechanical strength below 4% (weight percentage. Pre-osteoblast proliferation increases by 24% upon exposure to 0.4 uM Rebamipide, and by up to 73% when Rebamipide is delivered via brushite cement. Low doses of Rebamipide do not adversely affect peak alkaline phosphatase activity in differentiating pre-osteoblasts. Rebamipide weakly stimulates proliferation in macrophages at low concentrations (118 ± 7.4% at 1 uM, and quenches ROS by 40-60%. This is the first investigation of Rebamipide in osteoblasts.

  10. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  11. Autocrine regulation of human urothelial cell proliferation and migration during regenerative responses in vitro.

    Science.gov (United States)

    Varley, Claire; Hill, Gemma; Pellegrin, Stephanie; Shaw, Nicola J; Selby, Peter J; Trejdosiewicz, Ludwik K; Southgate, Jennifer

    2005-05-15

    Regeneration of the urothelium is rapid and effective in order to maintain a barrier to urine following tissue injury. Whereas normal human urothelial (NHU) cells are mitotically quiescent and G0 arrested in situ, they rapidly enter the cell cycle upon seeding in primary culture and show reversible growth arrest at confluency. We have used this as a model to investigate the role of EGF receptor signaling in urothelial regeneration and wound-healing. Transcripts for HER-1, HER-2, and HER-3 were expressed by quiescent human urothelium in situ. Expression of HER-1 was upregulated in proliferating cultures, whereas HER-2 and HER-3 were more associated with a growth-arrested phenotype. NHU cells could be propagated in the absence of exogenous EGF, but autocrine signaling through HER-1 via the MAPK and PI3-kinase pathways was essential for proliferation and migration during urothelial wound repair. HB-EGF was expressed by urothelium in situ and HB-EGF, epiregulin, TGF-alpha, and amphiregulin were expressed by proliferating NHU cells. Urothelial wound repair in vitro was attenuated by neutralizing antibodies against HER-1 ligands, particularly amphiregulin. By contrast, the same ligands applied exogenously promoted migration, but inhibited proliferation, implying that HER-1 ligands provoke differential effects in NHU cells depending upon whether they are presented as soluble or juxtacrine ligands. We conclude that proliferation and migration during wound healing in NHU cells are mediated through an EGFR autocrine signalling loop and our results implicate amphiregulin as a key mediator.

  12. A caudal proliferating growth center contributes to both poles of the forming heart tube.

    Science.gov (United States)

    van den Berg, Gert; Abu-Issa, Radwan; de Boer, Bouke A; Hutson, Mary R; de Boer, Piet A J; Soufan, Alexandre T; Ruijter, Jan M; Kirby, Margaret L; van den Hoff, Maurice J B; Moorman, Antoon F M

    2009-01-30

    Recent studies have shown that the primary heart tube continues to grow by addition of cells from the coelomic wall. This growth occurs concomitantly with embryonic folding and formation of the coelomic cavity, making early heart formation morphologically complex. A scarcity of data on localized growth parameters further hampers the understanding of cardiac growth. Therefore, we investigated local proliferation during early heart formation. Firstly, we determined the cell cycle length of primary myocardium of the early heart tube to be 5.5 days, showing that this myocardium is nonproliferating and implying that initial heart formation occurs solely by addition of cells. In line with this, we show that the heart tube rapidly lengthens at its inflow by differentiation of recently divided precursor cells. To track the origin of these cells, we made quantitative 3D reconstructions of proliferation in the forming heart tube and the mesoderm of its flanking coelomic walls. These reconstructions show a single, albeit bilateral, center of rapid proliferation in the caudomedial pericardial back wall. This center expresses Islet1. Cell tracing showed that cells from this caudal growth center, besides feeding into the venous pole of the heart, also move cranially via the dorsal pericardial mesoderm and differentiate into myocardium at the arterial pole. Inhibition of caudal proliferation impairs the formation of both the atria and the right ventricle. These data show how a proliferating growth center in the caudal coelomic wall elongates the heart tube at both its venous and arterial pole, providing a morphological mechanism for early heart formation.

  13. Fabrication of mediator-free hybrid nano-interfaced electrochemical biosensor for monitoring cancer cell proliferation.

    Science.gov (United States)

    Madhurantakam, Sasya; Jayanth Babu, K; Balaguru Rayappan, John Bosco; Krishnan, Uma Maheswari

    2017-01-15

    Glucose, a chief energy source in cellular metabolism, has a significant role in cell proliferation. Cancer cells utilize more glucose than normal cells to meet the energy demand arising due to their uncontrolled proliferation. The present work reports the development of a nano-interfaced amperometric biosensor for rapid and accurate monitoring of glucose utilization by cancer cells. A hybrid nano-interface comprising a blend of carbon nanotubes (CNTs) and graphene (GR) was employed to enhance the surface area of the working electrode and favour direct electron transfer. Glucose oxidase (GOx) immobilized on the interface serves as the sensing element due to its high selectivity and sensitivity towards glucose. Utilization of glucose was monitored at pre-determined time intervals in MiaPaCa-2 cancer cells. The results obtained from the amperometric technique were compared with the values obtained from a commercial glucometer. Alamar blue assay was performed to check the proliferation rate of the cells. A good correlation was obtained between the proliferation rate and glucose utilization. The designed biosensor was found to be unaffected by the presence of potential interferents and hence may serve as a novel in vitro tool to rapidly quantify the proliferation rates of cancer cells in response to different treatment strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. NATO's Response to the Proliferation Challenge

    National Research Council Canada - National Science Library

    Joseph, Robert

    1996-01-01

    ... operations in an NBC environment. The success of the NATO initiative to counter the proliferation threat, however, will only be assured when allies make national and collective commitments to field the necessary military capabilities...

  15. Handbook for nuclear non-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok

    1997-05-01

    This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs.

  16. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  17. Cell proliferation alterations in Chlorella cells under stress conditions

    Energy Technology Data Exchange (ETDEWEB)

    Rioboo, Carmen [Laboratorio de Microbiologia, Facultad de Ciencias, Universidad de A Coruna, Campus da Zapateira s/n, 15008 A Coruna (Spain); O' Connor, Jose Enrique [Laboratorio de Citomica, Unidad Mixta de Investigacion CIPF-UVEG, Centro de Investigacion Principe Felipe, Avda. Autopista del Saler, 16, 46013 Valencia (Spain); Prado, Raquel; Herrero, Concepcion [Laboratorio de Microbiologia, Facultad de Ciencias, Universidad de A Coruna, Campus da Zapateira s/n, 15008 A Coruna (Spain); Cid, Angeles, E-mail: cid@udc.es [Laboratorio de Microbiologia, Facultad de Ciencias, Universidad de A Coruna, Campus da Zapateira s/n, 15008 A Coruna (Spain)

    2009-09-14

    Very little is known about growth and proliferation in relation to the cell cycle regulation of algae. The lack of knowledge is even greater when referring to the potential toxic effects of pollutants on microalgal cell division. To assess the effect of terbutryn, a triazine herbicide, on the proliferation of the freshwater microalga Chlorella vulgaris three flow cytometric approaches were used: (1) in vivo cell division using 5-,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) staining was measured, (2) the growth kinetics were determined by cytometric cell counting and (3) cell viability was evaluated with the membrane-impermeable double-stranded nucleic acid stain propidium iodide (PI). The results obtained in the growth kinetics study using CFSE to identify the microalgal cell progeny were consistent with those determined by cytometric cell counting. In all C. vulgaris cultures, each mother cell had undergone only one round of division through the 96 h of assay and the cell division occurred during the dark period. Cell division of the cultures exposed to the herbicide was asynchronous. Terbutryn altered the normal number of daughter cells (4 autospores) obtained from each mother cell. The number was only two in the cultures treated with 250 nM. The duration of the lag phase after the exposure to terbutryn could be dependent on the existence of a critical cell size to activate cytoplasmic division. Cell size, complexity and fluorescence of chlorophyll a of the microalgal cells presented a marked light/dark (day/night) cycle, except in the non-dividing 500 nM cultures, where terbutryn arrested cell division at the beginning of the cycle. Viability results showed that terbutryn has an algastatic effect in C. vulgaris cells at this concentration. The rapid and precise determination of cell proliferation by CFSE staining has allowed us to develop a model for assessing both the cell cycle of C. vulgaris and the in vivo effects of pollutants on growth and

  18. Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

    Science.gov (United States)

    Delmaghani, Sedigheh; Defourny, Jean; Aghaie, Asadollah; Beurg, Maryline; Dulon, Didier; Thelen, Nicolas; Perfettini, Isabelle; Zelles, Tibor; Aller, Mate; Meyer, Anaïs; Emptoz, Alice; Giraudet, Fabrice; Leibovici, Michel; Dartevelle, Sylvie; Soubigou, Guillaume; Thiry, Marc; Vizi, E Sylvester; Safieddine, Saaid; Hardelin, Jean-Pierre; Avan, Paul; Petit, Christine

    2015-11-05

    A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Voltage-Gated Ion Channels in Cancer Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Vidhya R.; Perez-Neut, Mathew [Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago 2160 S. 1st Ave, Maywood, IL 60153 (United States); Kaja, Simon [Department of Ophthalmology and Vision Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes St., Kansas City, MO 64108 (United States); Gentile, Saverio, E-mail: sagentile@luc.edu [Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago 2160 S. 1st Ave, Maywood, IL 60153 (United States)

    2015-05-22

    Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K{sup +}, Ca{sup ++}, Cl{sup −}, Na{sup +}. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting that VGIC play a major role in cancer cell biology, in this review we discuss the role of distinct VGIC in cancer cell proliferation and possible therapeutic potential of VIGC pharmacological manipulation.

  20. The CALM and CALM/AF10 interactor CATS is a marker for proliferation.

    Science.gov (United States)

    Archangelo, Leticia Fröhlich; Greif, Philipp A; Hölzel, Michael; Harasim, Thomas; Kremmer, Elisabeth; Przemeck, Gerhard K H; Eick, Dirk; Deshpande, Aniruddha Jayant; Buske, Christian; de Angelis, Martin Hrabé; Saad, Sara Teresinha Olalla; Bohlander, Stefan K

    2008-12-01

    The CATS protein was recently identified as a novel CALM interacting protein. CATS increases the nuclear and specifically the nucleolar localization of the leukemogenic CALM/AF10 fusion protein. We cloned and characterized the murine Cats gene. Detailed analysis of murine Cats expression during mouse embryogenesis showed an association with rapidly proliferating tissues. Interestingly, the Cats transcript is highly expressed in murine hematopoietic cells transformed by CALM/AF10. The CATS protein is highly expressed in leukemia, lymphoma and tumor cell lines but not in non-proliferating T-cells or human peripheral blood lymphocytes. CATS protein levels are cell cycle dependent and it is induced by mitogens, suggesting a role of CATS in the control of cell proliferation and possibly CALM/AF10-mediated leukemogenesis.

  1. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C. [ed.

    1993-09-07

    Two essays are included in this booklet. Their titles are ``The Dynamics of the NPT Extension Decision`` and ``North Korea`s Nuclear Gambit.`` The first paper discusses the conference to be held in 1995 to review the Nuclear Non-Proliferation Treaty (NPT) which will decide whether the treaty shall continue in force indefinitely, or shall be extended for an additional fixed period or periods. Topics relevant to this discussion are: Arms control issues, the nuclear test ban, the limited test ban treaty, the French nuclear testing moratorium, former Soviet nuclear weapons, Iraq, North Korea, nuclear-weapon-free zones, security, controls on nuclear weapon materials, peaceful uses of nuclear energy, safeguards, politics, and organizational and procedural issues. The second paper examines short, medium, and long term issues entailed in Korea`s nuclear proliferation. Topics considered include: Korean unification, North Korean politics, the nuclear issue as leverage, and the Nuclear Non- Proliferation Treaty.

  2. Leukocytic promotion of prostate cellular proliferation.

    Science.gov (United States)

    McDowell, Kristy L; Begley, Lesa A; Mor-Vaknin, Nirit; Markovitz, David M; Macoska, Jill A

    2010-03-01

    Histological evidence of pervasive inflammatory infiltrate has been noted in both benign prostatic hyperplasia/hypertrophy (BPH) and prostate cancer (PCa). Cytokines known to attract particular leukocyte subsets are secreted from prostatic stroma consequent to aging and also from malignant prostate epithelium. Therefore, we hypothesized that leukocytes associated with either acute or chronic inflammation attracted to the prostate consequent to aging or tumorigenesis may promote the abnormal cellular proliferation associated with BPH and PCa. An in vitro system designed to mimic the human prostatic microenvironment incorporating prostatic stroma (primary and immortalized prostate stromal fibroblasts), epithelium (N15C6, BPH-1, LNCaP, and PC3 cells), and inflammatory infiltrate (HL-60 cells, HH, and Molt-3 T-lymphocytes) was developed. Modified Boyden chamber assays were used to test the ability of prostate stromal and epithelial cells to attract leukocytes and to test the effect of leukocytes on prostate cellular proliferation. Antibody arrays were used to identify leukocyte-secreted cytokines mediating prostate cellular proliferation. Leukocytic cells migrated towards both prostate stromal and epithelial cells. CD4+ T-lymphocytes promoted the proliferation of both transformed and non-transformed prostate epithelial cell lines tested, whereas CD8+ T-lymphocytes as well as dHL-60M macrophagic and dHL-60N neutrophilic cells selectively promoted the proliferation of PCa cells. The results of these studies show that inflammatory cells can be attracted to the prostate tissue microenvironment and can selectively promote the proliferation of non-transformed or transformed prostate epithelial cells, and are consistent with differential role(s) for inflammatory infiltrate in the etiologies of benign and malignant proliferative disease in the prostate. Prostate 70: 377-389, 2010. (c) 2009 Wiley-Liss, Inc.

  3. Dedifferentiation and proliferation of mammalian cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Yiqiang Zhang

    2010-09-01

    Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

  4. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1994-12-27

    The Director`s Series on Proliferation is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The seven papers presented in this issue cover the following topics: Should the Treaty on the Nonproliferation of Nuclear Weapons (NPT) be amended?; NPT extension - Legal and procedural issues; An Indonesian view of NPT review conference issues; The treaty of Tlatelolco and the NPT - Tools for peace and development; Perspectives on cut-off, weapons dismantlement, and security assurances; Belarus and NPT challenges; A perspective on the chemical weapons convention - Lessons learned from the preparatory commission.

  5. Fatty acids and breast cancer cell proliferation.

    Science.gov (United States)

    Hardy, R W; Wickramasinghe, N S; Ke, S C; Wells, A

    1997-01-01

    We and others have shown that fatty acids are important regulators of breast cancer cell proliferation. In particular individual fatty acids specifically alter EGF-induced cell proliferation in very different ways. This regulation is mediated by an EGFR/G-protein signaling pathway. Understanding the molecular mechanisms of how this signaling pathway functions and how fatty acids regulate it will provide important information on the cellular and molecular basis for the association of dietary fat and cancer. Furthermore these in vitro studies may explain data previously obtained from in vivo animal studies and identify "good" as well as "bad" fatty acids with respect to the development of cancer.

  6. Proliferation risks; Proliferatierisico's

    Energy Technology Data Exchange (ETDEWEB)

    Carchon, R

    1998-09-01

    The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed.

  7. Supervised Semantic Classification for Nuclear Proliferation Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Vatsavai, Raju [ORNL; Cheriyadat, Anil M [ORNL; Gleason, Shaun Scott [ORNL

    2010-01-01

    Existing feature extraction and classification approaches are not suitable for monitoring proliferation activity using high-resolution multi-temporal remote sensing imagery. In this paper we present a supervised semantic labeling framework based on the Latent Dirichlet Allocation method. This framework is used to analyze over 120 images collected under different spatial and temporal settings over the globe representing three major semantic categories: airports, nuclear, and coal power plants. Initial experimental results show a reasonable discrimination of these three categories even though coal and nuclear images share highly common and overlapping objects. This research also identified several research challenges associated with nuclear proliferation monitoring using high resolution remote sensing images.

  8. Rapid Airplane Parametric Input Design (RAPID)

    Science.gov (United States)

    Smith, Robert E.

    1995-01-01

    RAPID is a methodology and software system to define a class of airplane configurations and directly evaluate surface grids, volume grids, and grid sensitivity on and about the configurations. A distinguishing characteristic which separates RAPID from other airplane surface modellers is that the output grids and grid sensitivity are directly applicable in CFD analysis. A small set of design parameters and grid control parameters govern the process which is incorporated into interactive software for 'real time' visual analysis and into batch software for the application of optimization technology. The computed surface grids and volume grids are suitable for a wide range of Computational Fluid Dynamics (CFD) simulation. The general airplane configuration has wing, fuselage, horizontal tail, and vertical tail components. The double-delta wing and tail components are manifested by solving a fourth order partial differential equation (PDE) subject to Dirichlet and Neumann boundary conditions. The design parameters are incorporated into the boundary conditions and therefore govern the shapes of the surfaces. The PDE solution yields a smooth transition between boundaries. Surface grids suitable for CFD calculation are created by establishing an H-type topology about the configuration and incorporating grid spacing functions in the PDE equation for the lifting components and the fuselage definition equations. User specified grid parameters govern the location and degree of grid concentration. A two-block volume grid about a configuration is calculated using the Control Point Form (CPF) technique. The interactive software, which runs on Silicon Graphics IRIS workstations, allows design parameters to be continuously varied and the resulting surface grid to be observed in real time. The batch software computes both the surface and volume grids and also computes the sensitivity of the output grid with respect to the input design parameters by applying the precompiler tool

  9. Bubble Proliferation in Shock Wave Lithotripsy Occurs during Inertial Collapse

    Science.gov (United States)

    Pishchalnikov, Yuri A.; McAteer, James A.; Pishchalnikova, Irina V.; Williams, James C.; Bailey, Michael R.; Sapozhnikov, Oleg A.

    2008-06-01

    In shock wave lithotripsy (SWL), firing shock pulses at slow pulse repetition frequency (0.5 Hz) is more effective at breaking kidney stones than firing shock waves (SWs) at fast rate (2 Hz). Since at fast rate the number of cavitation bubbles increases, it appears that bubble proliferation reduces the efficiency of SWL. The goal of this work was to determine the basis for bubble proliferation when SWs are delivered at fast rate. Bubbles were studied using a high-speed camera (Imacon 200). Experiments were conducted in a test tank filled with nondegassed tap water at room temperature. Acoustic pulses were generated with an electromagnetic lithotripter (DoLi-50). In the focus of the lithotripter the pulses consisted of a ˜60 MPa positive-pressure spike followed by up to -8 MPa negative-pressure tail, all with a total duration of about 7 μs. Nonlinear propagation steepened the shock front of the pulses to become sufficiently thin (˜0.03 μm) to impose differential pressure across even microscopic bubbles. High-speed camera movies showed that the SWs forced preexisting microbubbles to collapse, jet, and break up into daughter bubbles, which then grew rapidly under the negative-pressure phase of the pulse, but later coalesced to re-form a single bubble. Subsequent bubble growth was followed by inertial collapse and, usually, rebound. Most, if not all, cavitation bubbles emitted micro-jets during their first inertial collapse and re-growth. After jetting, these rebounding bubbles could regain a spherical shape before undergoing a second inertial collapse. However, either upon this second inertial collapse, or sometimes upon the first inertial collapse, the rebounding bubble emerged from the collapse as a cloud of smaller bubbles rather than a single bubble. These daughter bubbles could continue to rebound and collapse for a few cycles, but did not coalesce. These observations show that the positive-pressure phase of SWs fragments preexisting bubbles but this initial

  10. [Development of MTS/pms colorimetric assay in the proliferation of leukemic cells].

    Science.gov (United States)

    Chen, Xiu-Sheng; Fang, Tie-Lan; Cai, Rui-Bo; Guo, Gui-Lan

    2002-10-01

    In order to establish a new more rapid, safe and sensitive colorimetric assay for the proliferation of leukemic cells, MTS/pms has been developed. This automated colorimetric assay is based on the characteristic of viable and metabolically active leukemic cells to cleave MTS/pms into a water-soluble product whose optical density is determined at 492 nm by an automated microtiter-plate reader photometer. The results indicated that only active leukemic cells cleaved MTS/pms into product measured, and dead cells did not reduce MTS/pms. A linear relations hip were found between the viable cell number and optical density of MTS/pms cleaved by HL-60 and K562 cell (r = 0.963). Compared with MTT and INT assays, the reduced product of MTS/pms is water-soluble. It is concluded that MTS/pms colorimetric assay is more rapid, accurate and sensitive for the bioassay of proliferation of leukemic cells.

  11. Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology.

    Directory of Open Access Journals (Sweden)

    Alexei Vazquez

    2011-04-01

    Full Text Available Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions.

  12. Lowering of tumor interstitial fluid pressure reduces tumor cell proliferation in a xenograft tumor model.

    Science.gov (United States)

    Hofmann, Matthias; Guschel, Maike; Bernd, August; Bereiter-Hahn, Jürgen; Kaufmann, Roland; Tandi, Christa; Wiig, Helge; Kippenberger, Stefan

    2006-02-01

    High tumor interstitial fluid pressure (TIFP) is a characteristic of most solid tumors. TIFP may hamper adequate uptake of macromolecular therapeutics in tumor tissue. In addition, TIFP generates mechanical forces affecting the tumor cortex, which might influence the growth parameters of tumor cells. This seems likely as, in other tissues (namely, blood vessels or the skin), mechanical stretch is known to trigger proliferation. Therefore, we hypothesize that TIFP-induced stretch modulates proliferation-associated parameters. Solid epithelial tumors (A431 and A549) were grown in Naval Medical Research Institute nude mice, generating a TIFP of about 10 mm Hg (A431) or 5 mm Hg (A549). Tumor drainage of the central cystic area led to a rapid decline of TIFP, together with visible relaxation of the tumor cortex. It was found by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis that TIFP lowering yields a decreased phosphorylation of proliferation-associated p44/42 mitogen-activated protein kinase and tumor relaxation. In confirmation, immunohistochemical staining showed a decrease of tumor-associated proliferation marker Ki-67 after TIFP lowering. These data suggest that the mechanical stretch induced by TIFP is a positive modulator of tumor proliferation.

  13. Lowering of Tumor Interstitial Fluid Pressure Reduces Tumor Cell Proliferation in a Xenograft Tumor Model

    Directory of Open Access Journals (Sweden)

    Matthias Hofmann

    2006-02-01

    Full Text Available High tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. TIFP may hamper adequate uptake of macromolecular therapeutics in tumor tissue. In addition, TIFP generates mechanical forces affecting the tumor cortex, which might influence the growth parameters of tumor cells. This seems likely as, in other tissues (namely, blood vessels or the skin, mechanical stretch is known to trigger proliferation. Therefore, we hypothesize that TIFP-induced stretch modulates proliferation-associated parameters. Solid epithelial tumors (A431 and A549 were grown in Naval Medical Research Institute nude mice, generating a TIFP of about 10 mm Hg (A431 or 5 mm Hg (A549. Tumor drainage of the central cystic area led to a rapid decline of TIFP, together with visible relaxation of the tumor cortex. It was found by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis that TIFP lowering yields a decreased phosphorylation of proliferation-associated p44/42 mitogen-activated protein kinase and tumor relaxation. In confirmation, immunohistochemical staining showed a decrease of tumor-associated proliferation marker Ki-67 after TIFP lowering. These data suggest that the mechanical stretch induced by TIFP is a positive modulator of tumor proliferation.

  14. Lowering of Tumor Interstitial Fluid Pressure Reduces Tumor Cell Proliferation in a Xenograft Tumor Model1

    Science.gov (United States)

    Hofmann, Matthias; Guschel, Maike; Bernd, August; Bereiter-Hahn, Jürgen; Kaufmann, Roland; Tandi, Christa; Wiig, Helge; Kippenberger, Stefan

    2006-01-01

    Abstract High tumor interstitial fluid pressure (TIFP) is a characteristic of most solid tumors. TIFP may hamper adequate uptake of macromolecular therapeutics in tumor tissue. In addition, TIFP generates mechanical forces affecting the tumor cortex, which might influence the growth parameters of tumor cells. This seems likely as, in other tissues (namely, blood vessels or the skin), mechanical stretch is known to trigger proliferation. Therefore, we hypothesize that TIFP-induced stretch modulates proliferation-associated parameters. Solid epithelial tumors (A431 and A549) were grown in Naval Medical Research Institute nude mice, generating a TIFP of about 10 mm Hg (A431) or 5 mm Hg (A549). Tumor drainage of the central cystic area led to a rapid decline of TIFP, together with visible relaxation of the tumor cortex. It was found by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis that TIFP lowering yields a decreased phosphorylation of proliferation-associated p44/42 mitogen-activated protein kinase and tumor relaxation. In confirmation, immunohistochemical staining showed a decrease of tumor-associated proliferation marker Ki-67 after TIFP lowering. These data suggest that the mechanical stretch induced by TIFP is a positive modulator of tumor proliferation. PMID:16611401

  15. Activation of proliferation and differentiation of dental follicle stem cells (DFSCs) by heat stress.

    Science.gov (United States)

    Rezai Rad, M; Wise, G E; Brooks, H; Flanagan, M B; Yao, S

    2013-02-01

    Adult stem cells (ASCs) remain in a slowly cycling/quiescent state under normal physiological conditions, but they can be awakened from this by certain factors, such as injury signals. Previously, our group has shown that dental follicle stem cells (DFSCs) appear to proliferate more rapidly than their non-stem cell counterparts at elevated temperatures. The study described here has aimed to (i) elucidate optimal temperature in which to culture DFSCs, (ii) determine whether elevated temperatures could enhance differentiation capability of DFSCs and (iii) characterize stem cell and osteogenic marker expression of DFSCs at elevated temperatures. DFSCs obtained from rat first molars were cultured at 37 (control), 38, 39, 40 and 41 ºC. Cell proliferation was evaluated by Alamar blue reduction assay and mean numbers of viable dissociated cells. Osteogenic differentiation was evaluated after 7 or 14 days osteogenic induction. Expression of selected marker genes was also assessed during proliferation and differentiation of the cells. Increased cell proliferation was seen at heat-stress temperatures of 38º, 39º and 40 ºC. DFSCs revealed maximal osteogenesis when cultured at 39 and 40 ºC. Moreover, some stem cell and osteogensis-associated markers had elevated expression in heat-stress conditions. Under determined heat-stress conditions, DFSCs increased their proliferation, osteogenic differentiation and expression of some marker genes. Thus, it is likely that elevated temperature could serve as a factor to activate adult stem cells. © 2013 Blackwell Publishing Ltd.

  16. Microenvironmental stiffness enhances glioma cell proliferation by stimulating epidermal growth factor receptor signaling.

    Directory of Open Access Journals (Sweden)

    Vaibhavi Umesh

    Full Text Available The aggressive and rapidly lethal brain tumor glioblastoma (GBM is associated with profound tissue stiffening and genomic lesions in key members of the epidermal growth factor receptor (EGFR pathway. Previous studies from our laboratory have shown that increasing microenvironmental stiffness in culture can strongly enhance glioma cell behaviors relevant to tumor progression, including proliferation, yet it has remained unclear whether stiffness and EGFR regulate proliferation through common or independent signaling mechanisms. Here we test the hypothesis that microenvironmental stiffness regulates cell cycle progression and proliferation in GBM tumor cells by altering EGFR-dependent signaling. We began by performing an unbiased reverse phase protein array screen, which revealed that stiffness modulates expression and phosphorylation of a broad range of signals relevant to proliferation, including members of the EGFR pathway. We subsequently found that culturing human GBM tumor cells on progressively stiffer culture substrates both dramatically increases proliferation and facilitates passage through the G1/S checkpoint of the cell cycle, consistent with an EGFR-dependent process. Western Blots showed that increasing microenvironmental stiffness enhances the expression and phosphorylation of EGFR and its downstream effector Akt. Pharmacological loss-of-function studies revealed that the stiffness-sensitivity of proliferation is strongly blunted by inhibition of EGFR, Akt, or PI3 kinase. Finally, we observed that stiffness strongly regulates EGFR clustering, with phosphorylated EGFR condensing into vinculin-positive focal adhesions on stiff substrates and dispersing as microenvironmental stiffness falls to physiological levels. Our findings collectively support a model in which tissue stiffening promotes GBM proliferation by spatially and biochemically amplifying EGFR signaling.

  17. Microenvironmental Stiffness Enhances Glioma Cell Proliferation by Stimulating Epidermal Growth Factor Receptor Signaling

    Science.gov (United States)

    Umesh, Vaibhavi; Rape, Andrew D.; Ulrich, Theresa A.; Kumar, Sanjay

    2014-01-01

    The aggressive and rapidly lethal brain tumor glioblastoma (GBM) is associated with profound tissue stiffening and genomic lesions in key members of the epidermal growth factor receptor (EGFR) pathway. Previous studies from our laboratory have shown that increasing microenvironmental stiffness in culture can strongly enhance glioma cell behaviors relevant to tumor progression, including proliferation, yet it has remained unclear whether stiffness and EGFR regulate proliferation through common or independent signaling mechanisms. Here we test the hypothesis that microenvironmental stiffness regulates cell cycle progression and proliferation in GBM tumor cells by altering EGFR-dependent signaling. We began by performing an unbiased reverse phase protein array screen, which revealed that stiffness modulates expression and phosphorylation of a broad range of signals relevant to proliferation, including members of the EGFR pathway. We subsequently found that culturing human GBM tumor cells on progressively stiffer culture substrates both dramatically increases proliferation and facilitates passage through the G1/S checkpoint of the cell cycle, consistent with an EGFR-dependent process. Western Blots showed that increasing microenvironmental stiffness enhances the expression and phosphorylation of EGFR and its downstream effector Akt. Pharmacological loss-of-function studies revealed that the stiffness-sensitivity of proliferation is strongly blunted by inhibition of EGFR, Akt, or PI3 kinase. Finally, we observed that stiffness strongly regulates EGFR clustering, with phosphorylated EGFR condensing into vinculin-positive focal adhesions on stiff substrates and dispersing as microenvironmental stiffness falls to physiological levels. Our findings collectively support a model in which tissue stiffening promotes GBM proliferation by spatially and biochemically amplifying EGFR signaling. PMID:25000176

  18. Rapid shallow breathing

    Science.gov (United States)

    ... the smallest air passages of the lungs in children ( bronchiolitis ) Pneumonia or other lung infection Transient tachypnea of the newborn Anxiety and panic Other serious lung disease Home Care Rapid, shallow breathing should not be treated at home. It is ...

  19. Rapid Strep Test

    Science.gov (United States)

    ... worse than normal. Your first thoughts turn to strep throat. A rapid strep test in your doctor’s office ... your suspicions.Viruses cause most sore throats. However, strep throat is an infection caused by the Group A ...

  20. RAPID3? Aptly named!

    Science.gov (United States)

    Berthelot, J-M

    2014-01-01

    The RAPID3 score is the sum of three 0-10 patient self-report scores: pain, functional impairment on MDHAQ, and patient global estimate. It requires 5 seconds for scoring and can be used in all rheumatologic conditions, although it has mostly been used in rheumatoid arthritis where cutoffs for low disease activity (12/30) have been set. A RAPID3 score of ≤ 3/30 with 1 or 0 swollen joints (RAPID3 ≤ 3 + ≤ SJ1) provides remission criteria comparable to Boolean, SDAI, CDAI, and DAS28 remission criteria, in far less time than a formal joint count. RAPID3 performs as well as the DAS28 in separating active drugs from placebos in clinical trials. RAPID3 also predicts subsequent structural disease progression. RAPID3 can be determined at short intervals at home, allowing the determination of the area under the curve of disease activity between two visits and flare detection. However, RAPID3 should not be seen as a substitute for DAS28 and face to face visits in routine care. Monitoring patient status with only self-report information without a rheumatologist's advice (including joints and physical examination, and consideration of imaging and laboratory tests) may indeed be as undesirable for most patients than joint examination without a patient questionnaire. Conversely, combining the RAPID3 and the DAS28 may consist in faster or more sensitive confirmation that a medication is effective. Similarly, better enquiring of most important concerns of patients (pain, functional status and overall opinion on their disorder) should reinforces patients' confidence in their rheumatologist and treatments.

  1. Nuclear Proliferation and Authority in World Politics

    Directory of Open Access Journals (Sweden)

    Brian Frederking

    2009-11-01

    Full Text Available We apply the “security-hierarchy paradox” to nuclear proliferation. Global security requires a certain amount of hierarchy. A world in which no nuclear proliferation rules exist to constrain states, for example, would not be secure. Global security requires legitimate and authoritative rules, which we define as rules that are mutually negotiated, binding to all andwhich provide a stable social order. Too much hierarchy, however, amounts to coercion andundermines global security. Rules that are not mutually negotiated, binding to all or do not provide a stable social order are not authoritative. We argue that North Korea and Iran haveattempted to build nuclear weapons because they interpret the proliferation rules to lack authority. The coercive U.S. approaches to enforcing proliferation rules – including diplomatic isolation, preemption, and regime change – have undermined the legitimacy of those rules. When the U.S. pursues less hierarchical policies, as it has recently toward North Korea, the ensuing negotiations have facilitated progress toward an agreement. When theU.S. pursues a consistently hierarchical approach, as it has toward Iran, no progress is made. Our analysis suggests that it is worth attempting a less hierarchical approach toward Iran and encourage it to accept a deal similar to the one negotiated with North Korea.

  2. Does programmed CTL proliferation optimize virus control?

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Thomsen, Allan Randrup

    2005-01-01

    CD8 T-cell or cytotoxic T-lymphocyte responses develop through an antigen-independent proliferation and differentiation program. This is in contrast to the previous thinking, which was that continuous antigenic stimulation was required. This Opinion discusses why nature has chosen the proliferati...

  3. The Global Chilling Effects of Antidumping Proliferation

    NARCIS (Netherlands)

    Vandenbussche, H.; Zanardi, M.

    2006-01-01

    Advocates of antidumping (AD) laws downplay their effects by arguing that the trade flows that are subject to AD are small and their distortions negligible.This paper is the first to counter that notion by quantifying the worldwide effect of AD laws on aggregate trade flows.The recent proliferation

  4. Luteoloside Inhibits Proliferation of Human Chronic Myeloid ...

    African Journals Online (AJOL)

    Purpose: To investigate the effects of luteoloside on the proliferation of human chronic myeloid leukemia K562 cells and whether luteoloside induces cell cycle arrest and apoptosis in K562 cells. Methods: Luteoloside's cytotoxicity was assessed using a cell counting kit. Cell cycle distribution was analysed by flow cytometry ...

  5. Nuclear war, nuclear proliferation, and their consequences

    Energy Technology Data Exchange (ETDEWEB)

    Sanruddin, A.K.

    1986-01-01

    The proceedings of a colloquium convened by the Groupe de Bellerive offers the contributions of Carl Sagan, Gabriel Garcia Marquez, Kenneth Galbraith, Pierre Trudeau, Edward Kennedy, and other eminent scientists, politicians, and strategists on the subject of the proliferation of nuclear weaponry and its potential ramifications.

  6. [Humoral regulation of stem cell proliferation].

    Science.gov (United States)

    Musashi, M; Ogawa, M

    1991-05-01

    The central feature of hematopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The recruitment of the dormant stem cells into cell cycle may be promoted by such factors as interleukin (IL)-1, IL-6, granulocyte-colony stimulating factor (G-CSF), and newly discovered IL-11. The effects of IL-1 on stem cells may be indirect. Once the stem cells leave Go and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. Though several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a stochastic process. The proliferation of early hemopoietic progenitors requires the presence of IL-3 and/or IL-4, and the intermediate process appears to be supported by granulocyte/macrophage-CSF (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin (erythropoiesis), G-CSF (neutrophil production), and IL-5 (eosinophilopoiesis). Thus, hemopoietic proliferation appears to be regulated by a cascade of factors directed at different developmental stages.

  7. Fibrosarcoma in bizarre parosteal osteochondromatous proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J.H.; Gu, M.J.; Kim, M.J.; Choi, W.H. [Dept. of Pathology, College of Medicine, Yeungnam Univ. (Korea); Shin, D.S. [Dept. of Orthopedic Surgery, College of Medicine, Yeungnam Univ. (Korea); Cho, K.H. [Dept. of Diagnostic Radiology, College of Medicine, Yeungnam Univ. (Korea)

    2001-01-01

    Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion predominantly involving the small bones of the hands and feet. Malignant transformation in BPOP has not been documented in the English literature. This report presents the coexistence of fibrosarcoma with BPOP in the right distal fibula of an 18-year-old woman. (orig.)

  8. Immunohistochemical Assessment of Proliferating Cell Nuclear ...

    African Journals Online (AJOL)

    Background: Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S‑phase of the cell cycle. ... Two sections were taken from each one for H and E. Other sections were stained according to super sensitive polymer horseradish peroxidase method for identifying PCNA expression.

  9. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increase...

  10. Transcriptional peroxisome proliferator-activated receptor γ ...

    African Journals Online (AJOL)

    user

    Peroxisome proliferator-activated receptor γ coactivator (PGC)-1ɑ, a well-known member of PGC-1 transcriptional coactivator's family, plays a key role in various metabolic pathways. Here, we investigated the role of PGC-1ɑ in the transformation of muscle fiber type in Schizothorax prenanti. The expression of PGC-1ɑ was ...

  11. Proliferation, angiogenesis and differentiation related markers in ...

    African Journals Online (AJOL)

    The upregulation of these proliferation- and angiogenesis-related factors in endothelial cells and/or fibroblasts and not in follicular cells of compact carcinoma compared to healthy glands supports the relevance of stromal cells in cancer progression. Keywords: Canine, Histology, Immunohistochemistry, Thyroid carcinoma.

  12. Nuclear non proliferation and disarmament; Non-proliferation nucleaire et desarmement

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

  13. Blue light inhibits proliferation of melanoma cells

    Science.gov (United States)

    Becker, Anja; Distler, Elisabeth; Klapczynski, Anna; Arpino, Fabiola; Kuch, Natalia; Simon-Keller, Katja; Sticht, Carsten; van Abeelen, Frank A.; Gretz, Norbert; Oversluizen, Gerrit

    2016-03-01

    Photobiomodulation with blue light is used for several treatment paradigms such as neonatal jaundice, psoriasis and back pain. However, little is known about possible side effects concerning melanoma cells in the skin. The aim of this study was to assess the safety of blue LED irradiation with respect to proliferation of melanoma cells. For that purpose we used the human malignant melanoma cell line SK-MEL28. Cell proliferation was decreased in blue light irradiated cells where the effect size depended on light irradiation dosage. Furthermore, with a repeated irradiation of the melanoma cells on two consecutive days the effect could be intensified. Fluorescence-activated cell sorting with Annexin V and Propidium iodide labeling did not show a higher number of dead cells after blue light irradiation compared to non-irradiated cells. Gene expression analysis revealed down-regulated genes in pathways connected to anti-inflammatory response, like B cell signaling and phagosome. Most prominent pathways with up-regulation of genes were cytochrome P450, steroid hormone biosynthesis. Furthermore, even though cells showed a decrease in proliferation, genes connected to the cell cycle were up-regulated after 24h. This result is concordant with XTT test 48h after irradiation, where irradiated cells showed the same proliferation as the no light negative control. In summary, proliferation of melanoma cells can be decreased using blue light irradiation. Nevertheless, the gene expression analysis has to be further evaluated and more studies, such as in-vivo experiments, are warranted to further assess the safety of blue light treatment.

  14. Proliferation of the Golgi apparatus in tobacco BY-2 cells during cell proliferation after release from the stationary phase of growth.

    Science.gov (United States)

    Abiodun, Moses; Matsuoka, Ken

    2013-08-01

    We have recently developed a new method aimed at mass photo-conversion of photo-convertible fluorescence protein (PFP) fluorescence in transformed tobacco BY-2 cells. Using this method we reported recently that the Golgi apparatus is generated by the de novo formation from ER and the division of pre-existing Golgi stacks with similar extents In this work we report that the proliferation of the Golgi apparatus in tobacco cells that enter the growing cycle from the non-dividing cycle is quite similar to that in rapidly growing cells and that de novo formation from the ER and division of pre-existing stacks seems to contribute almost equally to the proliferation.

  15. Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast

    OpenAIRE

    Guzman-Ayala, Marcela; Sachs, Michael; Koh, Fong Ming; Onodera, Courtney; Bulut-Karslioglu, Aydan; Lin, Chih-Jen; Wong, Priscilla; Nitta, Rachel; Song, Jun S.; Ramalho-Santos, Miguel

    2015-01-01

    The pluripotent mammalian epiblast undergoes unusually fast cell proliferation. This rapid growth is expected to generate a high transcriptional demand, but the underlying mechanisms remain unknown. We show here that the chromatin remodeler Chd1 is required for transcriptional output and development of the mouse epiblast. Chd1−/− embryos exhibit proliferation defects and increased apoptosis, are smaller than controls by E5.5 and fail to grow, to become patterned or to gastrulate. Removal of p...

  16. Rapid small lot manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Harrigan, R.W.

    1998-05-09

    The direct connection of information, captured in forms such as CAD databases, to the factory floor is enabling a revolution in manufacturing. Rapid response to very dynamic market conditions is becoming the norm rather than the exception. In order to provide economical rapid fabrication of small numbers of variable products, one must design with manufacturing constraints in mind. In addition, flexible manufacturing systems must be programmed automatically to reduce the time for product change over in the factory and eliminate human errors. Sensor based machine control is needed to adapt idealized, model based machine programs to uncontrolled variables such as the condition of raw materials and fabrication tolerances.

  17. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Makiko Okada

    2010-10-01

    Full Text Available Our previous study indicated that both 17β-estradiol (E2, known to be an endogenous estrogen, and bisphenol A (BPA, known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs. The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2, which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1 the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2 the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane‑associated ERs.

  18. Rapid Cycling and Its Treatment

    Science.gov (United States)

    ... Announcements Public Service Announcements Partnering with DBSA Rapid Cycling and its Treatment What is bipolar disorder? Bipolar ... to Depression and Manic Depression . What is rapid cycling? Rapid cycling is defined as four or more ...

  19. New approaches to nuclear proliferation policy.

    Science.gov (United States)

    Nye, J S

    1992-05-29

    Nuclear proliferation is not one but a complex of problems. One relates to the collapse of the Soviet Union and its effect on the spread of nuclear weapons and knowledge. Second, Iraq's violation of its Non-Proliferation Treaty obligation has exposed certain weaknesses in the traditional regime of multilateral nonproliferation institutions and treaties. Third, Pakistan's achievement of a nuclear weapons capability in the late 1980s brings the postproliferation question to the forefront in South Asia. There is no single solution to this complex set of problems, but the beginning of wisdom is to build upon the successes of the past, add new policy procedures, and, above all, increase the priority given to the issue. Otherwise, we may be faced with the ironic outcome that the widely welcomed end of the Cold War may increase the prospect of nuclear use.

  20. The putative bZIP transcription factor BzpN slows proliferation and functions in the regulation of cell density by autocrine signals in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Jonathan E Phillips

    Full Text Available The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN(- cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation.

  1. The putative bZIP transcription factor BzpN slows proliferation and functions in the regulation of cell density by autocrine signals in Dictyostelium.

    Science.gov (United States)

    Phillips, Jonathan E; Huang, Eryong; Shaulsky, Gad; Gomer, Richard H

    2011-01-01

    The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN(-) cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation.

  2. The Putative bZIP Transcripton Factor BzpN Slows Proliferation and Functions in the Regulation of Cell Density by Autocrine Signals in Dictyostelium

    Science.gov (United States)

    Phillips, Jonathan E.; Huang, Eryong; Shaulsky, Gad; Gomer, Richard H.

    2011-01-01

    The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN− cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation. PMID:21760904

  3. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1994-10-17

    This series is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. Essays contained in this document include: Key issues on NPT renewal and extension, Africa and nuclear nonproliferation, Kenya`s views on the NPT, Prospects for establishing a zone free of weapons of mass destruction in the middle east, effects of a special nuclear weapon materials cut-off convention, and The UK view of NPT renewal.

  4. Proliferation Persuasion. Coercive Bargaining with Nuclear Technology

    Energy Technology Data Exchange (ETDEWEB)

    Volpe, Tristan A. [George Washington Univ., Washington, DC (United States)

    2015-08-31

    Why do states wait for prolonged periods of time with the technical capacity to produce nuclear weapons? Only a handful of countries have ever acquired the sensitive nuclear fuel cycle technology needed to produce fissile material for nuclear weapons. Yet the enduring trend over the last five decades is for these states to delay or forgo exercising the nuclear weapons option provided by uranium enrichment or plutonium reprocessing capabilities. I show that states pause at this threshold stage because they use nuclear technology to bargain for concessions from both allies and adversaries. But when does nuclear latency offer bargaining benefits? My central argument is that challengers must surmount a dilemma to make coercive diplomacy work: the more they threaten to proliferate, the harder it becomes to reassure others that compliance will be rewarded with nuclear restraint. I identify a range of mechanisms able to solve this credibility problem, from arms control over breakout capacity to third party mediation and confidence building measures. Since each step towards the bomb raises the costs of implementing these policies, a state hits a sweet spot when it first acquires enrichment and/or reprocessing (ENR) technology. Subsequent increases in proliferation capability generate diminishing returns at the bargaining table for two reasons: the state must go to greater lengths to make a credible nonproliferation promise, and nuclear programs exhibit considerable path dependency as they mature over time. Contrary to the conventional wisdom about power in world politics, less nuclear latency thereby yields more coercive threat advantages. I marshal new primary source evidence from archives and interviews to identify episodes in the historical record when states made clear decisions to use ENR technology as a bargaining chip, and employ this theory of proliferation persuasion to explain how Japan, North Korea, and Iran succeeded and failed to barter concessions from the

  5. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available . Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  6. Rapid Prototyping in PVS

    Science.gov (United States)

    Munoz, Cesar A.; Butler, Ricky (Technical Monitor)

    2003-01-01

    PVSio is a conservative extension to the PVS prelude library that provides basic input/output capabilities to the PVS ground evaluator. It supports rapid prototyping in PVS by enhancing the specification language with built-in constructs for string manipulation, floating point arithmetic, and input/output operations.

  7. Rapid Prototyping Reconsidered

    Science.gov (United States)

    Desrosier, James

    2011-01-01

    Continuing educators need additional strategies for developing new programming that can both reduce the time to market and lower the cost of development. Rapid prototyping, a time-compression technique adapted from the high technology industry, represents one such strategy that merits renewed evaluation. Although in higher education rapid…

  8. Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.

    Science.gov (United States)

    Zhu, Jiaxue; Gu, Jianhua; Ma, Jie; Xu, Zhixing; Tao, Hairong

    2015-01-01

    Due to the high resistance to conventional therapy, there is still no convincingly effective treatment for chondrosarcoma. As a promising new treatment strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce cell arrest, apoptosis and differentiation in some kinds of malignancies, but how HDACi exert their effects on chondrosarcoma is not well understood yet. We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were investigated by assessing the chondrosarcoma growth in a mouse xenograft model. Our results showed that TSA and VPA significantly repressed the proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in mice treated with TSA and VPA. HDACIs significantly repress the proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply that HDACIs may provide a novel therapeutic target for the treatment of chondrosarcoma.

  9. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  10. Regulation of the Balance Between Proliferation and Differentiation in Germ Line Stem Cells.

    Science.gov (United States)

    Singh, Ramya; Hansen, Dave

    In many animals, reproductive fitness is dependent upon the production of large numbers of gametes over an extended period of time. This level of gamete production is possible due to the continued presence of germ line stem cells. These cells can produce two types of daughter cells, self-renewing daughter cells that will maintain the stem cell population and differentiating daughter cells that will become gametes. A balance must be maintained between the proliferating self-renewing cells and those that differentiate for long-term gamete production to be maintained. Too little proliferation can result in depletion of the stem cell population, while too little differentiation can lead to a lack of gamete formation and possible tumor formation. In this chapter, we discuss our current understanding of how the balance between proliferation and differentiation is achieved in three well-studied germ line model systems: the Drosophila female, the mouse male, and the C. elegans hermaphrodite. While these three systems have significant differences in how this balance is regulated, including differences in stem cell population size, signaling pathways utilized, and the use of symmetric and/or asymmetric cell divisions, there are also similarities found between them. These similarities include the reliance on a predominant signaling pathway to promote proliferation, negative feedback loops to rapidly shutoff proliferation-promoting cues, close association of the germ line stem cells with a somatic niche, cytoplasmic connections between cells, projections emanating from the niche cell, and multiple mechanisms to limit the spatial influence of the niche. A comparison between different systems may help to identify elements that are essential for a proper balance between proliferation and differentiation to be achieved and elements that may be achieved through various mechanisms.

  11. Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells.

    Science.gov (United States)

    Mukherjee, Abir; Ma, Yibao; Yuan, Fang; Gong, Yongling; Fang, Zhenyu; Mohamed, Esraa M; Berrios, Erika; Shao, Huanjie; Fang, Xianjun

    2015-09-01

    Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2) was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the human HK2 gene promoter identified the sterol regulatory element-binding protein as the primary mediator of LPA-induced HK2 transcription. The effects of LPA on HK2 and glycolysis rely on LPA2, an LPA receptor subtype overexpressed in ovarian cancer and many other malignancies. We further examined the general role of growth factor-induced glycolysis in cell proliferation. Like LPA, epidermal growth factor (EGF) elicited robust glycolytic and proliferative responses in ovarian cancer cells. Insulin-like growth factor 1 (IGF-1) and insulin, however, potently stimulated cell proliferation but only modestly induced glycolysis. Consistent with their differential effects on glycolysis, LPA and EGF-dependent cell proliferation was highly sensitive to glycolytic inhibition while the growth-promoting effect of IGF-1 or insulin was more resistant. These results indicate that LPA- and EGF-induced cell proliferation selectively involves up-regulation of HK2 and glycolytic metabolism. The work is the first to implicate LPA signaling in promotion of glucose metabolism in cancer cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Knock-out transmembrane prostate androgen-induced protein gene suppressed triple-negative breast cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    Bantari W.K. Wardhani

    2017-11-01

    Full Text Available Background: Triple negative breast cancer (TNBC tends to grow more rapidly and has poorer prognosis compared to others. High expression of transmembrane prostate androgen-induced protein (TMEPAI correlates with poor prognosis in TNBC patients. However, the mechanistic role of TMEPAI in tumorigenic remains unknown. This study aimed to knock-out TMEPAI in TNBC cell line to determine its function further in cells proliferation.Methods: CRISPR-Cas9 has been used previously to knock-out TMEPAI in Hs857T TNBC cell line. Hs587T TNBC parental cell line (wild-type/WT and TMEPAI knock out Hs 586T cell lines were cultured in Dulbecco’s modified eagle medium (DMEM supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin and amphotericin B. Both cell lines were seeded in 24-well plates and counted every two days, then proliferation rates were plotted. Afterwards, total RNA were isolated from the cells and Ki-67, and TGF-β mRNA expression levels as proliferation markers were determined.Results: Cell proliferation rates as displayed in growth curve plots showed that WT-TMEPAI cell line grew more rapidly than KO-TMEPAI. In accordance, mRNA expression levels of  Ki-67 and TGF-β  were significantly decreased KO-TMEPAI as compare to TMEPAI-WT.Conclusion: Knock-out of TMEPAI attenuates cell proliferation in TNBC.

  13. Nuclear Energy, Nuclear Weapons Proliferation, and the Arms Race.

    Science.gov (United States)

    Hollander, Jack, Ed.

    A symposium was organized to reexamine the realities of vertical proliferation between the United States and the Soviet Union and to place into perspective the horizontal proliferation of nuclear weapons throughout the world, including the possible role of commercial nuclear power in facilitating proliferation. The four invited symposium…

  14. Oxidative stress induced pulmonary endothelial cell proliferation is ...

    African Journals Online (AJOL)

    Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

  15. Combating the Proliferation of Weapons of Mass Destruction.

    Science.gov (United States)

    Jenkins, Bonnie

    1997-01-01

    Reveals the growing threat posed to all countries by the proliferation of weapons of mass destruction. Discusses the international effort combating this proliferation including the Nuclear Non-Proliferation Treaty, Strategic Arms Reduction Treaties, Biological Weapons Convention, and Chemical Weapons Convention. Also considers regional arms…

  16. Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

    Energy Technology Data Exchange (ETDEWEB)

    Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

    1979-01-19

    This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is more acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables.

  17. Effects of hypoxia on the proliferation, mineralization and ultrastructure of human periodontal ligament fibroblasts in vitro.

    Science.gov (United States)

    Zhang, Hai-Yuan; Liu, Rui; Xing, Yong-Jun; Xu, Ping; Li, Yan; Li, Chen-Jun

    2013-12-01

    This study aimed to investigate the effects of hypoxia on the proliferation, mineralization and ultrastructure of human periodontal ligament fibroblasts (HPLFs) at various times in vitro in order to further study plateau-hypoxia-induced periodontal disease. HPLFs (fifth passage) cultured by the tissue culture method were assigned to the slight (5% O2), middle (2% O2), and severe hypoxia (1% O2) groups and the control (21% O2) group, respectively. At 12, 24, 48 and 72 h, the proliferation and alkaline phosphatase (ALP) activities were detected. The ultrastructure of the severe hypoxia group was observed. HPLFs grew more rapidly with an increase in the degree of hypoxia at 12 and 24 h, and significant levels of proliferation (Pstructures, in the severe hypoxia group at 24 h. At 48 h, the number of mitochondria and RER decreased as the mitochondria increased in size. Furthermore, mitochondrial cristae appeared to be vague, and a RER structural disorder was observed. At 72 h, the number of mitochondria and RER decreased further when the mitochondrial cristae were broken, vacuolar degeneration occurred, and the RER particles were reduced while the number of lysosomes increased. HPLF proliferation and mineralization was restrained. Additionally, HPLF structure was broken for a relatively long period of time in the middle and severe hypoxia groups. This finding demonstrated that hypoxia was capable of damaging the metabolism, reconstruction and recovery of HPLFs. The poor state of HPLFs under hypoxic conditions may therefore initiate or aggravate periodontal disease.

  18. Adult Muscle Formation Requires Drosophila Moleskin for Proliferation of Wing Disc-Associated Muscle Precursors.

    Science.gov (United States)

    Vishal, Kumar; Brooks, David S; Bawa, Simranjot; Gameros, Samantha; Stetsiv, Marta; Geisbrecht, Erika R

    2017-05-01

    Adult muscle precursor (AMP) cells located in the notum of the larval wing disc undergo rapid amplification and eventual fusion to generate the Drosophila melanogaster indirect flight muscles (IFMs). Here we find that loss of Moleskin (Msk) function in these wing disc-associated myoblasts reduces the overall AMP pool size, resulting in the absence of IFM formation. This myoblast loss is due to a decrease in the AMP proliferative capacity and is independent of cell death. In contrast, disruption of Msk during pupal myoblast proliferation does not alter the AMP number, suggesting that Msk is specifically required for larval AMP proliferation. It has been previously shown that Wingless (Wg) signaling maintains expression of the Vestigial (Vg) transcription factor in proliferating myoblasts. However, other factors that influence Wg-mediated myoblast proliferation are largely unknown. Here we examine the interactions between Msk and the Wg pathway in regulation of the AMP pool size. We find that a myoblast-specific reduction of Msk results in the absence of Vg expression and a complete loss of the Wg pathway readout β-catenin/Armadillo (Arm). Moreover, msk RNA interference knockdown abolishes expression of the Wg target Ladybird (Lbe) in leg disc myoblasts. Collectively, our results provide strong evidence that Msk acts through the Wg signaling pathway to control myoblast pool size and muscle formation by regulating Arm stability or nuclear transport. Copyright © 2017 by the Genetics Society of America.

  19. Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water.

    Science.gov (United States)

    Farthing, Don E; Buxbaum, Nataliya P; Lucas, Philip J; Maglakelidze, Natella; Oliver, Brittany; Wang, Jiun; Hu, Kevin; Castro, Ehydel; Bare, Catherine V; Gress, Ronald E

    2017-06-22

    Deuterated water (2H2O) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo research reports important stable isotopic labeling enrichment differences into the DNA nucleosides and their isotopologues (e.g. deoxyadenosine (dA) M + 1, dA M + 2, dA M + 3), as well as tumor cell proliferation effects for various forms of commercially available stable heavy water (2H2O, H218O, and 2H218O). Using an in vitro mouse thymus tumor cell line, we determined that H218O provides superior DNA labeling enrichment quantitation, as measured by GC-positive chemical ionization (PCI)-MS/MS. In addition, at higher but physiologically relevant doses, both 2H218O and 2H2O down modulated mouse thymus tumor cell proliferation, whereas H218O water had no observable effects on cell proliferation. The in vivo labeling studies, where normal mouse bone marrow cells (i.e. high turnover) were evaluated post labeling, demonstrated DNA enrichments concordant with measurements from the in vitro studies. Our research also reports a headspace-GC-NCI-MS method, which rapidly and quantitatively measures stable heavy water levels in total body water.

  20. Selective estrogen receptor down-regulator and selective estrogen receptor modulators differentially regulate lactotroph proliferation.

    Directory of Open Access Journals (Sweden)

    Sanjay Kansra

    2010-04-01

    Full Text Available We recently reported that estrogen receptor alpha (ERalpha, even in absence of estrogen (E2, plays a critical role in lactotroph homeostasis. The anti-estrogen ICI 182780 (ICI, but not tamoxifen or raloxifene, rapidly promoted the degradation of ERalpha, and inhibited cell proliferation. However, all three ER antagonists suppressed PRL release, suggesting that receptor occupation is sufficient to inhibit prl gene expression whereas receptor degradation is required to suppress lactotroph proliferation. In this study our objective was to determine whether ERalpha degradation versus occupation, differentially modulates the biological outcome of anti-estrogens.Using the rat lactotroph cell line, GH3 cells, we report that ICI induced proteosome mediated degradation of ERalpha. In contrast, an ERalpha specific antagonist, MPP, that does not promote degradation of ERalpha, did not inhibit cell proliferation. Further, ICI, but not MPP, abolished anchorage independent growth of GH3 cells. Yet, both ICI and MPP were equally effective in suppressing prl expression and release, as well as ERE-mediated transcriptional activity.Taken together, our results demonstrate that in lactotrophs, ERalpha degradation results in decreased cell proliferation, whereas ERalpha occupation by an antagonist that does not promote degradation of ERalpha is sufficient to inhibit prl expression.

  1. Activation of the proliferation and differentiation of dental follicle stem cells (DFSCs) by heat-stress

    Science.gov (United States)

    Rad, Maryam Rezai; Wise, Gary E.; Brooks, Hunter; Flanagan, Michael B.; Yao, Shaomian

    2012-01-01

    Objectives Adult stem cells (ASCs) are maintained in a slow cycling and quiescent state under normal physiological conditions. This state could be awakened by certain factors, such as injury signals. Previously, we have shown that dental follicle stem cells (DFSCs) appear to grow more rapidly than their non-stem cell counterparts at elevated temperatures. This study aimed to (a) elucidate the optimal temperature to grow DFSCs, (b) determine if the elevated temperatures could enhance the differentiation capability of DFSCs, and (c) characterize the stem cell and osteogenic markers expression in DFSCs under elevated temperatures. Materials and methods DFSCs obtained from rat first molar were cultured at 37 (control), 38, 39, 40, and 41°C. Cell proliferation was evaluated by Alamar blue reduction assay and mean number of viable dissociated cells. Osteogenic differentiation was evaluated after 7 or 14 days of osteogenic induction. Expression of selected marker genes was also assessed during proliferation and differentiation of the DFSCs. Results Increased cell proliferation was seen at heat-stress temperatures of 38, 39 and 40 °C, DFSCs showed maximal osteogenesis when cultured at 39 and 40°C. Moreover, some stem cell and osteogenic associated markers increased their expression under heat-stress conditions. Conclusions Under proper heat-stress conditions, DFSCs increased proliferation, osteogenic differentiation, and expression of some marker genes. Thus, it is likely that elevated temperature could serve as a factor to activate ASCs. PMID:23278983

  2. Rapid manufacturing facilitated customisation

    OpenAIRE

    Tuck, Christopher John; Hague, Richard; Ruffo, Massimiliano; Ransley, Michelle; Adams, Paul Russell

    2008-01-01

    Abstract This paper describes the production of body-fitting customised seat profiles utilising the following digital methods: three dimensional laser scanning, reverse engineering and Rapid Manufacturing (RM). The seat profiles have been manufactured in order to influence the comfort characteristics of an existing ejector seat manufactured by Martin Baker Aircraft Ltd. The seat, known as Navy Aircrew Common Ejection Seat (NACES), was originally designed with a generic profile. ...

  3. Rapid Detection of Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Perlin

    2005-08-14

    Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleic acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development

  4. Tiber Personal Rapid Transit

    Directory of Open Access Journals (Sweden)

    Diego Carlo D'agostino

    2011-02-01

    Full Text Available The project “Tiber Personal Rapid Transit” have been presented by the author at the Rome City Vision Competition1 2010, an ideas competition, which challenges architects, engineers, designers, students and creatives individuals to develop visionary urban proposals with the intention of stimulating and supporting the contemporary city, in this case Rome. The Tiber PRT proposal tries to answer the competition questions with the definition of a provocative idea: a Personal Rapid transit System on the Tiber river banks. The project is located in the central section of the Tiber river and aims at the renewal of the river banks with the insertion of a Personal Rapid Transit infrastructure. The project area include the riverbank of Tiber from Rome Transtevere RFI station to Piazza del Popolo, an area where main touristic and leisure attractions are located. The intervention area is actually no used by the city users and residents and constitute itself a strong barrier in the heart of the historic city.

  5. Bizarre parosteal osteochondromatous proliferation of bone

    Energy Technology Data Exchange (ETDEWEB)

    Bandiera, S. [Orthopedic Clinic, Rizzoli Orthopedic Institute, Bologna (Italy); Bacchini, P.; Bertoni, F. [Department of Anatomy and Pathologic Histology, Rizzoli Orthopedic Institute, Bologna (Italy)

    1998-03-01

    A 47-year-old man presented with a painless mass of 7 months` duration, on the plantar aspect of the great toe of the right foot. Radiographs and CT images initially suggested an osteochondroma arising from the proximal phalanx of the great toe but there was no continuity between the medullary canal of the phalanx and the lesion. The mass was excised and a histological diagnosis of bizarre parosteal osteochondromatous proliferation of bone (Nora`s disease) was made. The aggressive growth of this lesion may clinically suggest a neoplasm. Histological features, however, are those of a reactive lesion. (orig.) With 4 figs., 10 refs.

  6. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1994-08-12

    This fifth edition contains some of the papers that were presented in July 1994 at the Lawrence Livermore National conference entitled ``NPT: Review and Extension.`` Topics covered include: strategic warning and new nuclear states, the future for nuclear weapons, possibly stopping North Korean nukes without a war, Article VI of the nuclear non-proliferation treaty from the Chinese perspective, Article VI issues, Article VI and other NPT issues form the perspective of Russia, NPT review and extension, and finally problems facing total nuclear disarmament.

  7. Vitrification preserves proliferation capacity in human spermatogonia.

    Science.gov (United States)

    Poels, Jonathan; Van Langendonckt, Anne; Many, Marie-Christine; Wese, François-Xavier; Wyns, Christine

    2013-03-01

    Does vitrification of human immature testicular tissue (ITT) have potential benefits for future fertility preservation? Does vitrification of human ITT have potential benefits in an in vivo murine xenotransplantation model? Vitrification is able to maintain proliferation capacity in spermatogonial cells after 6 months of xenografting. Controlled slow-freezing is the procedure currently applied for ITT cryobanking in clinical practice. Vitrification has been proposed as a promising technique for long-term storage of ITT, with a view to preserving spermatogonial stem cells (SSCs) for future fertility restoration in young boys suffering from cancer. After vitrification of ITT, in vitro survival of SSCs was demonstrated, but their functionality was not evaluated. Ten ITT pieces issuing from 10 patients aged 2-12 years were used. Fragments of fresh tissue (serving as controls) and fresh, frozen-thawed and vitrified-warmed testicular pieces xenografted to the scrotum of nude mice for 6 months were compared. Upon graft removal, histological and immunohistochemical analyses were performed to evaluate spermatogonia (SG) (MAGE-A4), intratubular proliferation (Ki67), proliferating SG and Leydig cells (3β-HSD). The entire piece of grafted tissue was assessed in each case. Seminiferous tubules showed good integrity after cryopreservation and xenografting for 6 months in all three groups. Survival of SG and their ability to proliferate was observed by immunohistochemistry in all grafted groups. SG were able to initiate spermatogenesis, but blockage at the pachytene stage was observed. The recovery rate of SG was 3.4 ± 3.8, 4.1 ± 7.3 and 7.3 ± 6.3%, respectively, for fresh, slow-frozen and vitrified-warmed tissue after 6 months of xenografting. The study is limited by the low availability of ITT samples of human origin. The mouse xenotransplantation model needs to be refined to study human spermatogenesis. The findings of the present study have potential implications for

  8. Sensor Fusion for Nuclear Proliferation Activity Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Adel Ghanem, Ph D

    2007-03-30

    The objective of Phase 1 of this STTR project is to demonstrate a Proof-of-Concept (PoC) of the Geo-Rad system that integrates a location-aware SmartTag (made by ZonTrak) and a radiation detector (developed by LLNL). It also includes the ability to transmit the collected radiation data and location information to the ZonTrak server (ZonService). The collected data is further transmitted to a central server at LLNL (the Fusion Server) to be processed in conjunction with overhead imagery to generate location estimates of nuclear proliferation and radiation sources.

  9. Proliferation risks from nuclear power infrastructure

    Science.gov (United States)

    Squassoni, Sharon

    2017-11-01

    Certain elements of nuclear energy infrastructure are inherently dual-use, which makes the promotion of nuclear energy fraught with uncertainty. Are current restraints on the materials, equipment, and technology that can be used either to produce fuel for nuclear electricity generation or material for nuclear explosive devices adequate? Technology controls, supply side restrictions, and fuel market assurances have been used to dissuade countries from developing sensitive technologies but the lack of legal restrictions is a continued barrier to permanent reduction of nuclear proliferation risks.

  10. Urothelial proliferation and regeneration after spinal cord injury.

    Science.gov (United States)

    Kullmann, F Aura; Clayton, Dennis R; Ruiz, Wily G; Wolf-Johnston, Amanda; Gauthier, Christian; Kanai, Anthony; Birder, Lori A; Apodaca, Gerard

    2017-07-01

    The basal, intermediate, and superficial cell layers of the urothelium undergo rapid and complete recovery following acute injury; however, the effects of chronic injury on urothelial regeneration have not been well defined. To address this discrepancy, we employed a mouse model to explore urothelial changes in response to spinal cord injury (SCI), a condition characterized by life-long bladder dysfunction. One day post SCI there was a focal loss of umbrella cells, which are large cells that populate the superficial cell layer and normally express uroplakins (UPKs) and KRT20, but not KRT5, KRT14, or TP63. In response to SCI, regions of urothelium devoid of umbrella cells were replaced with small superficial cells that lacked KRT20 expression and appeared to be derived in part from the underlying intermediate cell layer, including cells positive for KRT5 and TP63. We also observed KRT14-positive basal cells that extended thin cytoplasmic extensions, which terminated in the bladder lumen. Both KRT14-positive and KRT14-negative urothelial cells proliferated 1 day post SCI, and by 7 days, cells in the underlying lamina propria, detrusor, and adventitia were also dividing. At 28 days post SCI, the urothelium appeared morphologically patent, and the number of proliferative cells decreased to baseline levels; however, patches of small superficial cells were detected that coexpressed UPKs, KRT5, KRT14, and TP63, but failed to express KRT20. Thus, unlike the rapid and complete restoration of the urothelium that occurs in response to acute injuries, regions of incompletely differentiated urothelium were observed even 28 days post SCI. Copyright © 2017 the American Physiological Society.

  11. Ustilago maydis reprograms cell proliferation in maize anthers.

    Science.gov (United States)

    Gao, Li; Kelliher, Timothy; Nguyen, Linda; Walbot, Virginia

    2013-09-01

    The basidiomycete Ustilago maydis is a ubiquitous pathogen of maize (Zea mays), one of the world's most important cereal crops. Infection by this smut fungus triggers tumor formation in aerial plant parts within which the fungus sporulates. Using confocal microscopy to track U. maydis infection on corn anthers for 7 days post-injection, we found that U. maydis is located on the epidermis during the first 2 days, and has reached all anther lobe cell types by 3 days post-injection. Fungal infection alters cell-fate specification events, cell division patterns, host cell expansion and host cell senescence, depending on the developmental stage and cell type. Fungal effects on tassel and plant growth were also quantified. Transcriptome profiling using a dual organism microarray identified thousands of anther genes affected by fungal infection at 3 days post-injection during the cell-fate specification and rapid cell proliferation phases of anther development. In total, 4147 (17%) of anther-expressed genes were altered by infection, 2018 fungal genes were expressed in anthers, and 206 fungal secretome genes may be anther-specific. The results confirm that U. maydis deploys distinct genes to cause disease in specific maize organs, and suggest mechanisms by which the host plant is manipulated to generate a tumor. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  12. Advances in the treatment of retinal angiomatous proliferation

    Directory of Open Access Journals (Sweden)

    Wang-Yi Fang

    2017-12-01

    Full Text Available Retinal angiomatous proliferation(RAP, also known as “type 3 neovascularization”, is a well-recognized variation of neovascular age-related macular degeneration(nARMD. Neovascularization is the basic pathological characteristic. Current view on the origin of the neovascularization is the deep retinal capillaries. The main clinical features include retinal pigment epithelium detachment(PEDand reticular pseudodrusen. These two features have close relation to the retinal pigment epithelium(RPEtear and geographic atrophy(GA, respectively, which may ultimately result in severe irreversible visual impairment. The disease has a rapid natural course and the majority of patients in early stage can develop into vision loss within 6mo. However, classical therapeutic managements, such as laser therapy, have limited efficacy and poor prognosis. Recently, RAP has been further understood with the application of OCT angiography and other new technologies in diagnosing, staging and monitoring RAP. Varieties of research on intravitreal injection of anti-vascular endothelial growth factor(VEGFtreatment to RAP have also revealed its promising results and proved its safety as well as effectiveness. All these have provided new knowledge on choosing the optimal treatment regimen in clinical.

  13. The nucleolus: a paradigm for cell proliferation and aging

    Directory of Open Access Journals (Sweden)

    Comai L.

    1999-01-01

    Full Text Available The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA genes are rapidly transcribed by RNA polymerase I (pol I molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  14. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  15. Rapid prototype and test

    Energy Technology Data Exchange (ETDEWEB)

    Gregory, D.L.; Hansche, B.D.

    1996-06-01

    In order to support advanced manufacturing, Sandia has acquired the capability to produce plastic prototypes using stereolithography. Currently, these prototypes are used mainly to verify part geometry and ``fit and form`` checks. This project investigates methods for rapidly testing these plastic prototypes, and inferring from prototype test data actual metal part performance and behavior. Performances examined include static load/stress response, and structural dynamic (modal) and vibration behavior. The integration of advanced non-contacting measurement techniques including scanning laser velocimetry, laser holography, and thermoelasticity into testing of these prototypes is described. Photoelastic properties of the epoxy prototypes to reveal full field stress/strain fields are also explored.

  16. Right-Rapid-Rough

    Science.gov (United States)

    Lawrence, Craig

    2003-01-01

    IDEO (pronounced 'eye-dee-oh') is an international design, engineering, and innovation firm that has developed thousands of products and services for clients across a wide range of industries. Its process and culture attracted the attention of academics, businesses, and journalists around the world, and are the subject of a bestselling book, The Art of Innovation by Tom Kelley. One of the keys to IDEO's success is its use of prototyping as a tool for rapid innovation. This story covers some of IDEO's projects, and gives reasons for why they were successful.

  17. Proliferation and fission of peroxisomes - An update.

    Science.gov (United States)

    Schrader, Michael; Costello, Joseph L; Godinho, Luis F; Azadi, Afsoon S; Islinger, Markus

    2016-05-01

    In mammals, peroxisomes perform crucial functions in cellular metabolism, signalling and viral defense which are essential to the health and viability of the organism. In order to achieve this functional versatility peroxisomes dynamically respond to molecular cues triggered by changes in the cellular environment. Such changes elicit a corresponding response in peroxisomes, which manifests itself as a change in peroxisome number, altered enzyme levels and adaptations to the peroxisomal structure. In mammals the generation of new peroxisomes is a complex process which has clear analogies to mitochondria, with both sharing the same division machinery and undergoing a similar division process. How the regulation of this division process is integrated into the cell's response to different stimuli, the signalling pathways and factors involved, remains somewhat unclear. Here, we discuss the mechanism of peroxisomal fission, the contributions of the various division factors and examine the potential impact of post-translational modifications, such as phosphorylation, on the proliferation process. We also summarize the signalling process and highlight the most recent data linking signalling pathways with peroxisome proliferation.

  18. Measuring cross-country proliferation: Towards a new non-proliferation treaty?

    NARCIS (Netherlands)

    Schulpen, L.W.M.; Habraken, R.

    2016-01-01

    Emphasising 'in-country' harmonisation in discussions about the division of labour obscures our understanding of the importance of 'cross-country' harmonisation. This article proceeds from the idea that it is more important to fight proliferation than to fight fragmentation. However, there is no

  19. Rapid mineralocorticoid receptor trafficking.

    Science.gov (United States)

    Gekle, M; Bretschneider, M; Meinel, S; Ruhs, S; Grossmann, C

    2014-03-01

    The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor that physiologically regulates water-electrolyte homeostasis and controls blood pressure. The MR can also elicit inflammatory and remodeling processes in the cardiovascular system and the kidneys, which require the presence of additional pathological factors like for example nitrosative stress. However, the underlying molecular mechanism(s) for pathophysiological MR effects remain(s) elusive. The inactive MR is located in the cytosol associated with chaperone molecules including HSP90. After ligand binding, the MR monomer rapidly translocates into the nucleus while still being associated to HSP90 and after dissociation from HSP90 binds to hormone-response-elements called glucocorticoid response elements (GREs) as a dimer. There are indications that rapid MR trafficking is modulated in the presence of high salt, oxidative or nitrosative stress, hypothetically by induction or posttranslational modifications. Additionally, glucocorticoids and the enzyme 11beta hydroxysteroid dehydrogenase may also influence MR activation. Because MR trafficking and its modulation by micro-milieu factors influence MR cellular localization, it is not only relevant for genomic but also for nongenomic MR effects. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Rapid response manufacturing (RRM)

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-02-18

    US industry is fighting to maintain its competitive edge in the global market place. Today markets fluctuate rapidly. Companies, to survive, have to be able to respond with quick-to-market, improved, high quality, cost efficient products. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies. The RRM project was established to leverage the expertise and resources of US private industries and federal agencies to develop, integrate, and deploy new technologies that meet critical needs for effective product realization. The RRM program addressed a needed change in the US Manufacturing infrastructure that will ensure US competitiveness in world market typified by mass customization. This project provided the effort needed to define, develop and establish a customizable infrastructure for rapid response product development design and manufacturing. A major project achievement was the development of a broad-based framework for automating and integrating the product and process design and manufacturing activities involved with machined parts. This was accomplished by coordinating and extending the application of feature-based product modeling, knowledge-based systems, integrated data management, and direct manufacturing technologies in a cooperative integrated computing environment. Key technological advancements include a product model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering environment, knowledge-based software aids for design and process planning, and new production technologies to make products directly from design application software.

  1. Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available Great controversy exists regarding the biologic responses of osteoblasts to X-ray irradiation, and the mechanisms are poorly understood. In this study, the biological effects of low-dose radiation on stimulating osteoblast proliferation, differentiation and fracture healing were identified using in vitro cell culture and in vivo animal studies. First, low-dose (0.5 Gy X-ray irradiation induced the cell viability and proliferation of MC3T3-E1 cells. However, high-dose (5 Gy X-ray irradiation inhibited the viability and proliferation of osteoblasts. In addition, dynamic variations in osteoblast differentiation markers, including type I collagen, alkaline phosphatase, Runx2, Osterix and osteocalcin, were observed after both low-dose and high-dose irradiation by Western blot analysis. Second, fracture healing was evaluated via histology and gene expression after single-dose X-ray irradiation, and low-dose X-ray irradiation accelerates fracture healing of closed femoral fractures in rats. In low-dose X-ray irradiated fractures, an increase in proliferating cell nuclear antigen (PCNA-positive cells, cartilage formation and fracture calluses was observed. In addition, we observed more rapid completion of endochondral and intramembranous ossification, which was accompanied by altered expression of genes involved in bone remodeling and fracture callus mineralization. Although the expression level of several osteoblast differentiation genes was increased in the fracture calluses of high-dose irradiated rats, the callus formation and fracture union were delayed compared with the control and low-dose irradiated fractures. These results reveal beneficial effects of low-dose irradiation, including the stimulation of osteoblast proliferation, differentiation and fracture healing, and highlight its potential translational application in novel therapies against bone-related diseases.

  2. Filamin B regulates chondrocyte proliferation and differentiation through Cdk1 signaling.

    Directory of Open Access Journals (Sweden)

    Jianjun Hu

    Full Text Available Humans who harbor loss of function mutations in the actin-associated filamin B (FLNB gene develop spondylocarpotarsal syndrome (SCT, a disorder characterized by dwarfism (delayed bone formation and premature fusion of the vertebral, carpal and tarsal bones (premature differentiation. To better understand the cellular and molecular mechanisms governing these seemingly divergent processes, we generated and characterized FlnB knockdown ATDC5 cell lines. We found that FlnB knockdown led to reduced proliferation and enhanced differentiation in chondrocytes. Within the shortened growth plate of postnatal FlnB(-/- mice long bone, we observed a similarly progressive decline in the number of rapidly proliferating chondrocytes and premature differentiation characterized by an enlarged prehypertrophic zone, a widened Col2a1(+/Col10a1(+ overlapping region, but relatively reduced hypertrophic zone length. The reduced chondrocyte proliferation and premature differentiation were, in part, attributable to enhanced G2/M phase progression, where fewer FlnB deficient ATDC5 chondrocytes resided in the G2/M phase of the cell cycle. FlnB loss reduced Cdk1 phosphorylation (an inhibitor of G2/M phase progression and Cdk1 inhibition in chondrocytes mimicked the null FlnB, premature differentiation phenotype, through a β1-integrin receptor- Pi3k/Akt (a key regulator of chondrocyte differentiation mediated pathway. In this context, the early prehypertrophic differentiation provides an explanation for the premature differentiation seen in this disorder, whereas the progressive decline in proliferating chondrocytes would ultimately lead to reduced chondrocyte production and shortened bone length. These findings begin to define a role for filamin proteins in directing both cell proliferation and differentiation through indirect regulation of cell cycle associated proteins.

  3. Interleukin-21 induces proliferation and modulates receptor expression and effector function in canine natural killer cells.

    Science.gov (United States)

    Shin, Dong-Jun; Lee, Soo-Hyeon; Park, Ji-Yun; Kim, Ju-Sun; Lee, Je-Jung; Suh, Guk-Hyun; Lee, Youn-Kyung; Cho, Duck; Kim, Sang-Ki

    2015-05-15

    Interleukin (IL)-21 is an important modulator of natural killer (NK) cell function. However, little is known about IL-21 function in canine NK cells because the phenotype of these cells remains undefined. In this study, we selectively expanded non-B and non-T large granular NK lymphocytes (CD3(-)CD21(-)CD5(-)CD4(-)TCRαβ(-)TCRγδ(-)) ex vivo from the peripheral blood mononuclear cells (PBMCs) of healthy dogs using a combination of IL-2, IL-15, and IL-21 in the presence of 100 Gy-irradiated K562 cells. We investigated the effects of varying the duration and timing of IL-21 treatment on stimulation of proliferation, expression of NK-related receptors, anti-tumor activity and production of interferon (IFN)-γ. The expanded NK cells in each treatment group became enlarged and highly granular after 21 days in culture. NK cells proliferated rapidly in response to activation by IL-21 for 3 weeks, and IL-21 was able to induce changes in the mRNA expression of NK cell-related receptors and enhance the effector function of NK cells in perforin- and granzyme-B-dependent manners. The duration, frequency and timing of IL-21 stimulation during culture affected the rate of proliferation, patterns of receptor expression, cytokine production, and anti-tumor activity. The optimal conditions for maximizing the IL-21-induced proliferation and effector function of NK cells in the presence of IL-2 and IL-15 were seen in cells treated with IL-21 for the first 7 days of culture but without any further IL-21 stimulation other than an additional 2-day treatment prior to harvesting on day 21. The results of this study suggest that synergistic interactions of IL-21 with IL-2 and IL-15 play an important role in the proliferation, receptor expression, and effector function of canine NK cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Proliferation and the Civilian Nuclear Fuel Cycle. Towards a Simplified Recipe to Measure Proliferation Risk

    Energy Technology Data Exchange (ETDEWEB)

    Brogli, R.; Krakowski, R.A

    2001-08-01

    The primary goal of this study is to frame the problem of nuclear proliferation in the context of protection and risks associated with nuclear materials flowing in the civilian nuclear fuel cycle. The perspective adopted for this study is that of a nuclear utility and the flow of fresh and spent nuclear fuel with which that utility must deal in the course of providing economic, safe, and ecologically acceptable electrical power to the public. Within this framework quantitative approaches to a material-dependent, simplified proliferation-risk metric are identified and explored. The driving force behind this search for such a proliferation metric derives from the need to quantify the proliferation risk in the context of evaluating various commercial nuclear fuel cycle options (e.g., plutonium recycle versus once-through). While the formulation of the algebra needed to describe the desired, simplified metric(s) should be straight forward once a modus operandi is defined, considerable interaction with the user of any final product that results is essential. Additionally, a broad contextual review of the proliferation problem and past efforts in the quantification of associated risks was developed as part of this study. This extensive review was essential to setting perspectives and establishing (feasibility) limits to the search for a proliferation metric(s) that meets the goals of this study. Past analyses of proliferation risks associated with the commercial nuclear fuel cycle have generally been based on a range of decision-analysis, operations-research tools. Within the time and budget constraints, as well as the self-enforced (utility) customer focus, the more subjective and data-intensive decision-analysis methodologies where not pursued. Three simplified, less-subjective approaches were investigated instead: a) a simplified 'four-factor' formula expressing as a normalized product political, material-quantity, material-quality, and material

  5. Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruoxing [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States); Guo, Yan-Lin, E-mail: yanlin.guo@usm.edu [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States)

    2012-10-01

    Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black

  6. Rapid Refresh (RAP) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  7. Rapid Refresh (RAP) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  8. Rapidly progressive periodontitis. A distinct clinical condition.

    Science.gov (United States)

    Page, R C; Altman, L C; Ebersole, J L; Vandesteen, G E; Dahlberg, W H; Williams, B L; Osterberg, S K

    1983-04-01

    We report radiographic, clinical, historical, and laboratory observations on seven patients selected to illustrate the features and characteristics of rapidly progressive periodontitis, with the aim of establishing this disease as a distinct clinical entity. This form of periodontitis is seen most commonly in young adults in their twenties, but it can occur in postpubertal individuals up to approximately 35 years of age. During the active phase, the gingival tissues are extremely inflamed and there is hemorrhage, proliferation of the marginal gingiva, and exudation. Destruction is very rapid, with loss of much of the alveolar bone occurring within a few weeks or months. This phase may be accompanied by general malaise, weight loss, and depression, although these symptoms are not seen in all patients. The disease may progress, without remission, to tooth loss, or alternatively, it may subside and become quiescent with or without therapy. The quiescent phase is characterized by the presence of clinically normal gingiva that may be tightly adapted to the roots of teeth with very advanced bone loss and deep periodontal pockets. The quiescent phase may be permanent, it may persist for an indefinite period, or the disease activity may return. Most patients with rapidly progressive periodontitis have serum antibodies specific for various species of Bacteroides, Actinobacillus, or both, and manifest defects in either neutrophil or monocyte chemotaxis. Affected patients generally respond favorably to treatment by scaling and open or closed curettage, especially when accompanied by standard doses of antibiotics for conventional time periods. A small minority of patients do not respond to any treatment, including antibiotics, and the disease progresses inexorably to tooth loss even in the presence of aggressive periodontal therapy and maintenance. At the present time it is not possible to distinguish prior to treatment which individuals will respond to therapy and which will

  9. Rapid chemical separations

    CERN Document Server

    Trautmann, N

    1976-01-01

    A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

  10. Hydrothermal vents in Lake Tanganyika harbor spore-forming thermophiles with extremely rapid growth

    DEFF Research Database (Denmark)

    Elsgaard, Lars; Prieur, Daniel

    2010-01-01

    and peptone. The optimum temperature for growth was 60 °C, while minimum and maximum temperatures were 40 and 75 °C. The pH response was alkalitolerant with optimum pH at 7.4 and 8.5 depending on the growth medium. The distinct feature of rapid proliferation and endospore formation may allow the novel...

  11. Laser isotope separation and proliferation risks

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, Werner

    2015-02-15

    There is an ongoing discussion on the proliferation danger of laser enrichment of uranium by the Silex process. Here this risk is compared to that of other processes, in particular centrifuges. The two methods need a similar size of the plant for a comparable production rate (in separative work units per year) and the time and costs for their construction do not differ much. This conclusion from published material does not depend on technical details of Silex. But enough details are known to allow for additional conclusions: Whereas the selectivity (enrichment factor) in the Silex process seems higher, the energy consumption is probably larger. Due to the laser's repetition rate being insufficient for the molecular beam, the method has probably a low depletion factor; this is a serious disadvantage for cascading for high enrichment such as for bomb uranium, although it may be acceptable for low enrichment without cascading for reactor purposes.

  12. Profitable solutions to climate, oil, and proliferation.

    Science.gov (United States)

    Lovins, Amory B

    2010-05-01

    Protecting the climate is not costly but profitable (even if avoided climate change is worth zero), mainly because saving fuel costs less than buying fuel. The two biggest opportunities, both sufficiently fast, are oil and electricity. The US, for example, can eliminate its oil use by the 2040s at an average cost of $15 per barrel ($2000), half by redoubled efficiency and half by alternative supplies, and can save three-fourths of its electricity more cheaply than operating a thermal power station. Integrative design permits this by making big energy savings cheaper than small ones, turning traditionally assumed diminishing returns into empirically observed expanding returns. Such efficiency choices accelerate climate-safe, inexhaustible, and resilient energy supply-notably the "micropower" now delivering about a sixth of the world's electricity and 90% of its new electricity. These cheap, fast, market-financeable, globally applicable options offer the most effective, yet most underestimated and overlooked, solutions for climate, proliferation, and poverty.

  13. Beyond cell proliferation in avian facial morphogenesis.

    Science.gov (United States)

    Linde-Medina, Marta; Hallgrímsson, Benedikt; Marcucio, Ralph

    2016-03-01

    The upper jaw in vertebrates forms from several prominences that arise around the stomodeum or primitive mouth. These prominences undergo coordinated growth and morphogenesis to fuse and form the face. Undirected, regionalized cell proliferation is thought to be the driving force behind the morphogenesis of the facial prominences. However, recent findings suggest that directed cell behaviors in the mesenchyme (e.g., directed cell division, directed cell movement, convergent extension) might be required for successful face formation. Here we discuss the evidence for this view and how directed behaviors may interact with the basement membrane to regulate morphogenesis of the facial region. We believe that future research in these largely unexplored areas could significantly impact our understanding of facial morphogenesis. © 2016 Wiley Periodicals, Inc.

  14. Retinal angiomatous proliferation occurring after radiotherapy.

    Science.gov (United States)

    De Salvo, G; Hannan, S R; James, N; Lotery, A J

    2013-03-01

    To describe two cases of retinal angiomatous proliferation (RAP)-like lesion following radiation therapy for primary tumor. Retrospective evaluation of two patients with previous irradiation treatment for a pleomorphic adenoma of the lacrimal gland and a vocal cord carcinoma, respectively. Visual acuity (VA), fluorescein angiography and optical coherence tomography were performed and demonstrated a RAP-like lesion in both cases. Treatment with intravitreal injections of Ranibizumab was performed with a follow-up of 19 and 10 months, respectively. Both the patients had a positive response to the treatment with improvement in VA and reduction of intraretinal fluid. RAP-like lesions can develop following radiation treatment for a primary tumor. In patients presenting with idiopathic RAP, a history of prior radiotherapy should be considered.

  15. Autism overflows: increasing prevalence and proliferating theories.

    Science.gov (United States)

    Waterhouse, Lynn

    2008-12-01

    This selective review examines the lack of an explanation for the sharply increasing prevalence of autism, and the lack of any synthesis of the proliferating theories of autism. The most controversial and most widely disseminated notion for increasing prevalence is the measles-mumps-rubella/thimerosal vaccine theory. Less controversial causes that have been proposed include changes in autism diagnostic criteria, increasing services for autism, and growing awareness of the disorder. Regardless of its causes, the increasing prevalence of autism has put pressure on the field of autism research to generate productive and predictive theories of autism. However, the heterogeneity of brain deficits, impaired behaviors, and genetic variants in autism have challenged researchers and theorists, and despite 45 years of research, no standard causal synthesis has emerged. Research going forward should assume that autism is an aggregation of myriad independent disorders of impaired sociality, social cognition, communication, and motor and cognitive skills.

  16. Proliferation conditions for human satellite cells

    DEFF Research Database (Denmark)

    Gaster, M; Beck-Nielsen, H; Schrøder, H D

    2001-01-01

    Primary satellite cell cultures have become an important tool as a model system for skeletal muscles. A common problem in human satellite cell culturing is fibroblast overgrowth. We combined N-CAM (Leu19) immunocytochemical staining of satellite cells (Sc) with stereological methods to estimate...... the fraction of Sc in culture. Evaluation of different culture conditions allowed us to find proliferation conditions preferentially for Sc: a) Sc should be cultured on surfaces coated with ECM-gel. b) Primary cell culture should be inoculated in DMEM supplemented with 10% fetal calf serum to increase cell...... adherence. c) Change of media to DMEM supplemented with 2% Ultroser-G and 2% FCS after 24 h.d) Before subcultivation, cells should be preplated for 30 min. The fractional content of Sc in passage four when applying this method of cultivation was 0.82 +/- 0.07 (mean +/- SE, N = 10). Our method enabled us...

  17. Skin Cell Proliferation Stimulated by Microneedles

    Science.gov (United States)

    Liebl, Horst; Kloth, Luther C.

    2012-01-01

    A classical wound may be defined as a disruption of tissue integrity. Wounds, caused by trauma from accidents or surgery, that close via secondary intention rely on the biological phases of healing, i.e., hemostasis, inflammation, proliferation, and remodeling (HIPR). Depending on the wound type and severity, the inflammation phase begins immediately after injury and may last for an average of 7–14 days. Concurrent with the inflammation phase or slightly delayed, cell proliferation is stimulated followed by the activation of the remodeling (maturation) phase. The latter phase can last as long as 1 year or more, and the final healed state is represented by a scar tissue, a cross-linked collagen formation that usually aligns collagen fibers in a single direction. One may assume that skin microneedling that involves the use of dozens or as many as 200 needles that limit penetration to 1.5 mm over 1 cm2 of skin would cause trauma and bleeding followed by the classical HIPR. However, this is not the case or at least the HIPR phases are significantly curtailed and healing never ends in a scar formation. Conversely dermabrasion used in aesthetic medicine for improving skin quality is based on “ablation” (destruction or wounding of superficial skin layers), which requires several weeks for healing that involves formation of new skin layers. Such procedures provoke an acute inflammatory response. We believe that a less intense inflammatory response occurs following microneedle perforation of the skin. However, the mechanism of action of microneedling appears to be different. Here we review the potential mechanisms by which microneedling of the skin facilitates skin repair without scarring after the treatment of superficial burns, acne, hyperpigmentation, and the non-advancing periwound skin surrounding the chronic ulcerations of the integument. PMID:24527373

  18. Equine Hoof Canker: Cell Proliferation and Morphology.

    Science.gov (United States)

    Apprich, V; Licka, T; Zipfl, N; Tichy, A; Gabriel, C

    2017-07-01

    Hoof canker is described as progressive pododermatitis of the equine hoof with absent epidermal cornification and extensive proliferation of the dermal papillary body; however, in-depth research on the type of proliferative activity has not yet been reported. The aim of the present study was to determine cell-specific proliferation patterns together with morphological analysis of hoof canker tissue. Tissues removed during surgery from 19 horses presented for treatment of canker were compared with similar postmortem tissues of healthy hooves of 10 horses. Morphological alterations visible in light microscopy were assessed semiquantitatively and graded for severity. Proliferative activity was evaluated by means of anti-PCNA (proliferative cell nuclear antigen) and anti-Ki67 immunohistochemistry. Histologically, canker tissue showed 5 major morphological alterations-the presence of lacunae, vacuoles, giant cells, hemorrhage, and inflammation-not seen in control tissue. Also, there was a notable koilocytotic appearance of keratinocytes in canker tissue. Immunohistochemistry revealed increased levels of PCNA protein expression in keratinocytes and fibroblasts of canker tissue compared with control tissue. In control tissue, keratinocytes showed higher levels of Ki67 compared with canker tissue, while the dermal fibroblasts of both groups showed similar levels of Ki67, indicating similar proliferative activity of less than 3% of total dermal fibroblasts. These results demonstrate that, in contrast to previous reports, there is no evidence for increased proliferative activity of the dermal papillary body associated with hoof canker. Increased levels of PCNA protein expression and morphological alterations indicate that dysregulation of keratinocyte differentiation constitutes a key event in equine hoof canker development.

  19. Modeling hormonal control of cambium proliferation.

    Science.gov (United States)

    Oles, Vladyslav; Panchenko, Alexander; Smertenko, Andrei

    2017-01-01

    Rise of atmospheric CO2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO2. Trees are known to sequester CO2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork) for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1) auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III; (2) auxin and cytokinin pathways negatively regulate each other; (3) hormonal pathways act redundantly in sustaining cambium activity; (4) individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

  20. Modeling hormonal control of cambium proliferation.

    Directory of Open Access Journals (Sweden)

    Vladyslav Oles

    Full Text Available Rise of atmospheric CO2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO2. Trees are known to sequester CO2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1 auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III; (2 auxin and cytokinin pathways negatively regulate each other; (3 hormonal pathways act redundantly in sustaining cambium activity; (4 individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

  1. The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation

    OpenAIRE

    Rajanahalli, Pavan; Stucke, Christopher J.; Hong, Yiling

    2015-01-01

    Silver nanoparticles (AgNPs) are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs) as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objec...

  2. Cell proliferation and apoptosis in gastric cancer and intestinal metaplasia

    OpenAIRE

    Nora Manoukian Forones; Ana Paula Souza Carvalho; Oswaldo Giannotti-Filho; Laércio Gomes Lourenço; Celina Tizuko Fujiyama Oshima

    2005-01-01

    BACKGROUND: Higher proliferation is commonly observed in cancer cells. Apoptosis can be a useful measure of a tumor cell kinetic. Alteration of the balance between proliferation and apoptosis is associated with cancer. AIM: To study proliferation and apoptosis on gastric cancer and in intestinal metaplasia. METHODOLOGY: Twenty-two samples from gastric adenocarcinomas and 22 biopsies from intestinal metaplasia were studied. The apoptotic bodies in hematoxylin-eosin slides and the expression of...

  3. A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation.

    Science.gov (United States)

    Chan, Leo L; Gosangari, Saujanya L; Watkin, Kenneth L; Cunningham, Brian T

    2007-06-01

    A label-free method for detecting the attachment of human cancer cells to a biosensor surface for rapid screening for biological activity is described, in which attachment of a cell results in highly localized increase of the resonant reflected wavelength of a photonic crystal narrowband reflectance filter incorporated into a standard 96-well microplate. An imaging detection instrument is used to determine the spatial distribution of attached cells by mapping the shift in reflected resonant wavelength as a function of position. The method enables monitoring of cancer cell attachment, cell proliferation, and cell detachment that is induced by exposure of the cells to drug compounds. We demonstrate the efficacy of this method as an early screening technique for the rapid quantification of the rate of cancer cell proliferation on the sensor surface, and subsequently as a means for quantifying cell detachment resulting from apoptosis that is induced by exposure of the cells to cytotoxic chemicals.

  4. A secreted factor represses cell proliferation in Dictyostelium

    OpenAIRE

    Brock, Debra A.; Gomer, Richard H.

    2005-01-01

    Many cells appear to secrete factors called chalones that limit their proliferation, but in most cases the factors have not been identified. We found that growing Dictyostelium cells secrete a 60 kDa protein called AprA for autocrine proliferation repressor. AprA has similarity to putative bacterial proteins of unknown function. Compared with wild-type cells, aprA-null cells proliferate faster, while AprA overexpressing cells proliferate slower. Growing wild-type cells secrete a factor that i...

  5. Immunomodulatory effects of turmeric: Proliferation of spleen cells in mice.

    Science.gov (United States)

    Mustafa, Rafid; Blumenthal, Elliott

    2017-01-01

    Experiments were conducted to examine the effects of turmeric on spleen cell proliferation. Cell suspensions of spleen cells from young and aged mice were treated with or without conconavalin A (Con-A) as a proliferation stimulant, and with and without turmeric (20 mg/mL) in different concentrations. Spleen cells from young mice that received turmeric showed significant increase in spleen cell proliferation (P turmeric showed no significant increase in T lymphocytes. The data indicates that turmeric increases the ability of spleen cells in young mice to proliferate, in vitro.

  6. A miR-590/Acvr2a/Rad51b Axis Regulates DNA Damage Repair during mESC Proliferation

    Directory of Open Access Journals (Sweden)

    Qidong Liu

    2014-12-01

    Full Text Available Embryonic stem cells (ESCs enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF, which maintains the self-renewal capability of mouse ESCs (mESCs, significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB and double-strand break (DSB damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (Acvr2a to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR gene, Rad51b, as a downstream molecule of the miR-590/Acvr2a pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/Acvr2a/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.

  7. Dynamics of Legionella spp. and bacterial populations during the proliferation of L. pneumophila in a cooling tower facility.

    Science.gov (United States)

    Wéry, Nathalie; Bru-Adan, Valérie; Minervini, Céline; Delgénes, Jean-Philippe; Garrelly, Laurent; Godon, Jean-Jacques

    2008-05-01

    The dynamics of Legionella spp. and of dominant bacteria were investigated in water from a cooling tower plant over a 9-month period which included several weeks when Legionella pneumophila proliferated. The structural diversity of both the bacteria and the Legionella spp. was monitored by a fingerprint technique, single-strand conformation polymorphism, and Legionella spp. and L. pneumophila were quantified by real-time quantitative PCR. The structure of the bacterial community did not change over time, but it was perturbed periodically by chemical treatment or biofilm detachment. In contrast, the structure of the Legionella sp. population changed in different periods, its dynamics at times showing stability but also a rapid major shift during the proliferation of L. pneumophila in July. The dynamics of the Legionella spp. and of dominant bacteria were not correlated. In particular, no change in the bacterial community structure was observed during the proliferation of L. pneumophila. Legionella spp. present in the cooling tower system were identified by cloning and sequencing of 16S rRNA genes. A high diversity of Legionella spp. was observed before proliferation, including L. lytica, L. fallonii, and other Legionella-like amoebal pathogen types, along with as-yet-undescribed species. During the proliferation of L. pneumophila, Legionella sp. diversity decreased significantly, L. fallonii and L. pneumophila being the main species recovered.

  8. Building a rapid response team.

    Science.gov (United States)

    Halvorsen, Lisa; Garolis, Salomeja; Wallace-Scroggs, Allyson; Stenstrom, Judy; Maunder, Richard

    2007-01-01

    The use of rapid response teams is a relatively new approach for decreasing or eliminating codes in acute care hospitals. Based on the principles of a code team for cardiac and/or respiratory arrest in non-critical care units, the rapid response teams have specially trained nursing, respiratory, and medical personnel to respond to calls from general care units to assess and manage decompensating or rapidly changing patients before their conditions escalate to a full code situation. This article describes the processes used to develop a rapid response team, clinical indicators for triggering a rapid response team call, topics addressed in an educational program for the rapid response team members, and methods for evaluating effectiveness of the rapid response team.

  9. Problems of rapid growth.

    Science.gov (United States)

    Kim, T D

    1980-01-01

    South Korea's export-oriented development strategy has achieved a remarkable growth record, but it has also brought 2 different problems: 1) since the country's exports accounted for about 1% of total world export volume, the 1st world has become fearful about Korea's aggressive export drive; and 2) the fact that exports account for over 30% of its total gross national product (GNP) exposes the vulnerability of South Korea's economy itself. South Korea continues to be a poor nation, although it is rated as 1 of the most rapidly growing middle income economies. A World Bank 1978 report shows Korea to be 28th of 58 middle income countries in terms of per capita GNP in 1976. Of 11 newly industrializing countries (NIC), 5 in the European continent are more advanced than the others. A recent emphasis on the basic human needs approach has tended to downgrade the concept of GNP. Korea has only an abundant labor force and is without any natural resources. Consequently, Korea utilized an export-oriented development strategy. Oil requirements are met with imports, and almost all raw materials to be processed into exportable products must be imported. To pay import bills Korea must export and earn foreign exchange. It must be emphasized that foreign trade must always be 2-way traffic. In order to export more to middle income countries like Korea, the countries of the 1st world need to ease their protectionist measures against imports from developing countries.

  10. Rapid Polymer Sequencer

    Science.gov (United States)

    Stolc, Viktor (Inventor); Brock, Matthew W (Inventor)

    2013-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal direction, or in a transverse direction, in the tip region, a polymer sequence is passed through the tip region, and a change in an electrical current signal is measured as each polymer component passes through the tip region. Each of the measured changes in electrical current signals is compared with a database of reference electrical change signals, with each reference signal corresponding to an identified polymer component, to identify the unknown polymer component with a reference polymer component. The nanopore preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  11. Rapidly rotating red giants

    Science.gov (United States)

    Gehan, Charlotte; Mosser, Benoît; Michel, Eric

    2017-10-01

    Stellar oscillations give seismic information on the internal properties of stars. Red giants are targets of interest since they present mixed modes, wich behave as pressure modes in the convective envelope and as gravity modes in the radiative core. Mixed modes thus directly probe red giant cores, and allow in particular the study of their mean core rotation. The high-quality data obtained by CoRoT and Kepler satellites represent an unprecedented perspective to obtain thousands of measurements of red giant core rotation, in order to improve our understanding of stellar physics in deep stellar interiors. We developed an automated method to obtain such core rotation measurements and validated it for stars on the red giant branch. In this work, we particularly focus on the specific application of this method to red giants having a rapid core rotation. They show complex spectra where it is tricky to disentangle rotational splittings from mixed-mode period spacings. We demonstrate that the method based on the identification of mode crossings is precise and efficient. The determination of the mean core rotation directly derives from the precise measurement of the asymptotic period spacing ΔΠ1 and of the frequency at which the crossing of the rotational components is observed.

  12. Peroxisome proliferator-activated receptor gamma inhibits liver cancer proliferation and metastasis in vitro

    Directory of Open Access Journals (Sweden)

    SHEN Bo

    2013-09-01

    Full Text Available ObjectiveTo investigate the inhibitory effect of peroxisome proliferator-activated receptor gamma (PPARγ on the development, progression, invasion, and metastasis of liver cancer cells. MethodsHepatocellular carcinoma (HCC MHCC97L cells were randomly assigned to be transfected with Ad-PPARγ or Ad-LacZ (control. The cells were also exposed to PPARγ agonist rosiglitazone. Cell proliferation, apoptosis, migration, and invasive ability were evaluated using MTS assay, flow cytometry, wound healing test, and transwell invasion assay. Multiple comparisons of means between groups were conducted using one-way analysis of variance with Bonferroni correction; the means of two groups were compared using the t test. ResultsAd-PPARγ transfection resulted in higher expression of PPARγ protein in HCC cells compared with control cells, which suppressed cell proliferation (P<0.01, induced cell apoptosis (P<0.01, and suppressed cell migration and invasion. Moreover, the invasiveness of HCC cells transfected with Ad-PPARγ was reduced by 20%~60%. Rosiglitazone enhanced the inhibitory effect of Ad-PPARγ on the growth and migration of HCC cells. ConclusionPPARγ exerts an inhibitory effect on the proliferative, invasive, and metastatic potential of HCC cells in vitro. This study sheds new light on the search for potential markers and gene therapies for liver cancer.

  13. Effect of lactoferrin on rat osteoblast proliferation

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2016-10-01

    Full Text Available Objective: To investigate the effect of lactoferrin on osteoblastic proliferation of rats and to explore the possible mechanisms. Methods: Isolation and purification of rat osteoblasts were performed, the second generation of osteoblasts in the logarithmic growth phase were tested. Osteoblast cells were seeded into the porous plate, adding lactoferrin solution to the final concentration 0.1 μg/mL, 1 μg/mL, 10 μg/mL and 100 μg/mL, respectively, set up the control group (lactoferrin concentration was 0 μg/mL, rat osteoblast cells proliferation was detected by MTT method, insulin-like growth factor-1 (IGF-1 mRNA expression was detected by fluorescence quantitative PCR (real-time PCR. Results: MTT results showed that compared with the 0 μg/mL group, the number of rat osteoblast cells in the other concentration groups increased significantly (P<0.05 except in the 0.1 μg/mL group; The number of 3 d and 5 d rat osteoblasts in 1 μg/mL group was significantly higher than that in 0 μg/mL group, the number of 1 d, 3 d, 5 d and 7 d rat osteoblasts in 10 μg/mL and 100 μg/mL group was significantly higher than that in 0 μg/mL group (P<0.05; With the extension of time, the number of rat osteoblasts in each concentration group was significantly increased with the increase of the concentration, the number of 7 d rat osteoblasts in the 100 μg/mL group was the highest. Real-time PCR results showed that different concentrations of lactoferrin could promote rat osteoblast cells IGF-1 mRNA expression and was dose dependent. The 7 d IGF-1 mRNA expression in 0.1 μg/mL group was significantly higher than that in 0 μg/mL group, the 3 d, 5 d and 7 d IGF-1 mRNA expression in 1 μg/mL and 10 μg/mL were significantly higher than that in 0 μg/mL group, the 1 d, 3 d, 5 d and 7 d IGF-1 mRNA expression in 100 μg/mL were significantly higher than that in 0 μg/mL group (P<0.05; With the extension of time, the expression of rat osteoblasts IGF-1 mRNA in each

  14. Extended Deterrence, Nuclear Proliferation, and START III

    Energy Technology Data Exchange (ETDEWEB)

    Speed, R.D.

    2000-06-20

    Early in the Cold War, the United States adopted a policy of ''extended nuclear deterrence'' to protect its allies by threatening a nuclear strike against any state that attacks these allies. This threat can (in principle) be used to try to deter an enemy attack using conventional weapons or one using nuclear, chemical, or biological weapons. The credibility of a nuclear threat has long been subject to debate and is dependent on many complex geopolitical factors, not the least of which is the military capabilities of the opposing sides. The ending of the Cold War has led to a significant decrease in the number of strategic nuclear weapons deployed by the United States and Russia. START II, which was recently ratified by the Russian Duma, will (if implemented) reduce the number deployed strategic nuclear weapons on each side to 3500, compared to a level of over 11,000 at the end of the Cold War in 1991. The tentative limit established by Presidents Clinton and Yeltsin for START III would reduce the strategic force level to 2000-2500. However, the Russians (along with a number of arms control advocates) now argue that the level should be reduced even further--to 1500 warheads or less. The conventional view is that ''deep cuts'' in nuclear weapons are necessary to discourage nuclear proliferation. Thus, as part of the bargain to get the non-nuclear states to agree to the renewal of the Nuclear Non-Proliferation Treaty, the United States pledged to work towards greater reductions in strategic forces. Without movement in the direction of deep cuts, it is thought by many analysts that some countries may decide to build their own nuclear weapons. Indeed, this was part of the rationale India used to justify its own nuclear weapons program. However, there is also some concern that deep cuts (to 1500 or lower) in the U.S. strategic nuclear arsenal could have the opposite effect. The fear is that such cuts might undermine extended

  15. Type I Interferons Control Proliferation and Function of the Intestinal Epithelium

    Science.gov (United States)

    Katlinskaya, Yuliya V.; Katlinski, Kanstantsin V.; Lasri, Audrey; Li, Ning; Beiting, Daniel P.; Durham, Amy C.; Yang, Ting; Pikarsky, Eli; Lengner, Christopher J.; Johnson, F. Brad; Ben-Neriah, Yinon

    2016-01-01

    Wnt pathway-driven proliferation and renewal of the intestinal epithelium must be tightly controlled to prevent development of cancer and barrier dysfunction. Although type I interferons (IFN) produced in the gut under the influence of microbiota are known for their antiproliferative effects, the role of these cytokines in regulating intestinal epithelial cell renewal is largely unknown. Here we report a novel role for IFN in the context of intestinal knockout of casein kinase 1α (CK1α), which controls the ubiquitination and degradation of both β-catenin and the IFNAR1 chain of the IFN receptor. Ablation of CK1α leads to the activation of both β-catenin and IFN pathways and prevents the unlimited proliferation of intestinal epithelial cells despite constitutive β-catenin activity. IFN signaling contributes to the activation of the p53 pathway and the appearance of apoptotic and senescence markers in the CK1α-deficient gut. Concurrent genetic ablation of CK1α and IFNAR1 leads to intestinal hyperplasia, robust attenuation of apoptosis, and rapid and lethal loss of barrier function. These data indicate that IFN play an important role in controlling the proliferation and function of the intestinal epithelium in the context of β-catenin activation. PMID:26811327

  16. Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells.

    Science.gov (United States)

    Vogetseder, Alexander; Picard, Nicolas; Gaspert, Ariana; Walch, Michael; Kaissling, Brigitte; Le Hir, Michel

    2008-01-01

    We investigated the proliferative capacity of renal proximal tubular cells in healthy rats. Previously, we observed that tubular cells originate from differentiated cells. We now found 1) by application of bromo-deoxyuridine (BrdU) for 14 days and costaining for BrdU, and the G(1)-phase marker cyclin D1 that the bulk of cells in the S3 segment of juvenile rats were involved in proliferation; 2) that although the proliferation rate was about 10-fold higher in juvenile rats compared with adult rats, roughly 40% of S3 cells were in G(1) in both groups; 3) that after a strong mitotic stimulus (lead acetate), proliferation was similar in juveniles and adults; 4) that there was a high incidence of cyclin D1-positive cells also in the healthy human kidney; and 5) by labeling dividing cells with BrdU for 2 days before the application of lead acetate and subsequent costaining for BrdU and cell cycle markers, that, although a strong mitotic stimulus does not abolish the period of quiescence following division, it shortens it markedly. Thus the capacity of the proximal tubule to rapidly recruit cells into division relies on a large reserve pool of cells in G(1) and on the shortening of the obligatory period of quiescence that follows division.

  17. Type I Interferons Control Proliferation and Function of the Intestinal Epithelium.

    Science.gov (United States)

    Katlinskaya, Yuliya V; Katlinski, Kanstantsin V; Lasri, Audrey; Li, Ning; Beiting, Daniel P; Durham, Amy C; Yang, Ting; Pikarsky, Eli; Lengner, Christopher J; Johnson, F Brad; Ben-Neriah, Yinon; Fuchs, Serge Y

    2016-01-25

    Wnt pathway-driven proliferation and renewal of the intestinal epithelium must be tightly controlled to prevent development of cancer and barrier dysfunction. Although type I interferons (IFN) produced in the gut under the influence of microbiota are known for their antiproliferative effects, the role of these cytokines in regulating intestinal epithelial cell renewal is largely unknown. Here we report a novel role for IFN in the context of intestinal knockout of casein kinase 1α (CK1α), which controls the ubiquitination and degradation of both β-catenin and the IFNAR1 chain of the IFN receptor. Ablation of CK1α leads to the activation of both β-catenin and IFN pathways and prevents the unlimited proliferation of intestinal epithelial cells despite constitutive β-catenin activity. IFN signaling contributes to the activation of the p53 pathway and the appearance of apoptotic and senescence markers in the CK1α-deficient gut. Concurrent genetic ablation of CK1α and IFNAR1 leads to intestinal hyperplasia, robust attenuation of apoptosis, and rapid and lethal loss of barrier function. These data indicate that IFN play an important role in controlling the proliferation and function of the intestinal epithelium in the context of β-catenin activation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Impaired TGF-beta induced growth inhibition contributes to the increased proliferation rate of neural stem cells harboring mutant p53

    DEFF Research Database (Denmark)

    Kumar, Praveen; Naumann, Ulrike; Aigner, Ludwig

    2015-01-01

    -beta by loss of function experiments using NPCs derived from p53 mutant mice, as well as pharmacological inhibition of TGF-beta signaling using TGF-beta receptor inhibitors. NPC derived from p53 mutant mice showed increased clonogenicity and more rapid proliferation than their wildtype counterparts. Further...

  19. Rapid mixing kinetic techniques.

    Science.gov (United States)

    Martin, Stephen R; Schilstra, Maria J

    2013-01-01

    Almost all of the elementary steps in a biochemical reaction scheme are either unimolecular or bimolecular processes that frequently occur on sub-second, often sub-millisecond, time scales. The traditional approach in kinetic studies is to mix two or more reagents and monitor the changes in concentrations with time. Conventional spectrophotometers cannot generally be used to study reactions that are complete within less than about 20 s, as it takes that amount of time to manually mix the reagents and activate the instrument. Rapid mixing techniques, which generally achieve mixing in less than 2 ms, overcome this limitation. This chapter is concerned with the use of these techniques in the study of reactions which reach equilibrium; the application of these methods to the study of enzyme kinetics is described in several excellent texts (Cornish-Bowden, Fundamentals of enzyme kinetics. Portland Press, 1995; Gutfreund, Kinetics for the life sciences. Receptors, transmitters and catalysis. Cambridge University Press, 1995).There are various ways to monitor changes in concentration of reactants, intermediates and products after mixing, but the most common way is to use changes in optical signals (absorbance or fluorescence) which often accompany reactions. Although absorbance can sometimes be used, fluorescence is often preferred because of its greater sensitivity, particularly in monitoring conformational changes. Such methods are continuous with good time resolution but they seldom permit the direct determination of the concentrations of individual species. Alternatively, samples may be taken from the reaction volume, mixed with a chemical quenching agent to stop the reaction, and their contents assessed by techniques such as HPLC. These methods can directly determine the concentrations of different species, but are discontinuous and have a limited time resolution.

  20. Intelligent hand-portable proliferation sensing system

    Energy Technology Data Exchange (ETDEWEB)

    Dieckman, S.L.; Bostrom, G.A.; Waterfield, L.G.; Jendrzejczyk, J.A.; Ahuja, S.; Raptis, A.C.

    1997-08-01

    Argonne National Laboratory, with support from DOE`s Office of Nonproliferation and National Security, is currently developing an intelligent hand-portable sensor system. This system is designed specifically to support the intelligence community with the task of in-field sensing of nuclear proliferation and related activities. Based upon pulsed laser photo-ionization time-of-flight mass spectrometry technology, this novel sensing system is capable of quickly providing a molecular or atomic analysis of specimens. The system is capable of analyzing virtually any gas phase molecule, or molecule that can be induced into the gas phase by (for example) sample heating. This system has the unique advantages of providing unprecedented portability, excellent sensitivity, tremendous fieldability, and a high performance/cost ratio. The system will be capable of operating in a highly automated manner for on-site inspections, and easily modified for other applications such as perimeter monitoring aboard a plane or drone. The paper describes the sensing system.

  1. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Sander Kersten

    2008-01-01

    Full Text Available Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs. Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels.

  2. Nuclear SMAD2 Restrains Proliferation of Glioblastoma

    Directory of Open Access Journals (Sweden)

    Yunhu Yu

    2015-03-01

    Full Text Available Aims: Although TGFβ receptor signaling has been shown to play a role in regulation of the growth and metastasis of glioblastoma multiforme (GBM, the downstream pathway through either SMAD2 or SMAD3 has not been elucidated. In this study, we investigate whether nuclear SMAD2 can restrain the proliferation of glioblastoma. Methods: A total of 23 resected specimens from GBM patients were collected for SMAD2 detection. Human GBM cell line A172, U87mg, D341m and Hs683 were maintained in Dulbecco's modified Eagle's medium and transfected with SMAD2 and SMAD3 shRNA plasmids. Gene expression was detected by RT-qPCR and Western and cell growth were detected by MTT assay. Results: Our results showed that the phosphorylated SMAD2 (pSMAD2, the nuclear and functional form of SMAD2 levels in GBM were significantly lower than the paired normal brain tissue in patients. Depletion of SMAD2, but not SMAD3, significantly abolished the inhibitory effects of TGFβ1 on the growth of GBM cells, possibly through pSMAD2-mediated increases in cell-cycle inhibitor, p27. Conclusion: Our data suggest that TGFβ/SMAD2 signaling cascades restrains growth of GBM.

  3. Satellite cell proliferation in adult skeletal muscle

    Science.gov (United States)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  4. Atypical proliferating mucinous tumors of gigantic dimensions

    Directory of Open Access Journals (Sweden)

    Likić-Lađević Ivana

    2008-01-01

    Full Text Available Background. Ovarian tumors of low malignant potential (LMP are also known as atypically proliferating tumors. Ovarian tumors of LPM account for approximately 15% of all epithelial ovarian cancers. Mean age of occurrence is 40 years and they are 15-20 cm in diameter. Case report. A 32-year-old female patient was hospitalized as an urgent case with a large tumor mass that filled the entire abdomen. Cyst was 100 × 70 cm dimensions belonging to the right ovary and filled with 18 liters of content. Right adnexectomy, resection of the second ovary, as well as biopsy of the omentum were performed. Lymphadenectomy of the right iliac and obturator area was also performed. After receiving definitive histopathological results it was decided to perform a radical reoperation. On the 10th postoperative day relaparotomy, total hysterectomy and left adnexectomy were performed. The patient was released on the 6th postoperative day. She used to come to regular examinations up to date. Conclusion. This case is a proof that LMP tumors have low malignant potential, they grow slowly and can reach great proportions.

  5. Phytoplasma associated with shoot proliferation in begonia

    Directory of Open Access Journals (Sweden)

    Ribeiro Luiz Fernando Caldeira

    2006-01-01

    Full Text Available Begonia is a very appreciated genus of ornamental plants, of economic relevancy, having species of flowers and foliage. In commercial croppings, plants exhibiting characteristic symptoms of phytoplasma infection have been observed, such as shoot proliferation, reduced plant, size small leaves and flowers, and phyllody. Leaves were sampled and total DNA was extracted to be used in nested Polymerase Chain Reaction (PCR, in order to detect and identify an expected phytoplasma. The results confirmed consistently the presence of a phytoplasma associated with symptomatic plants through the amplification of a typical genomic fragment of 1.2 kb by using the universal primers R16mF2/mR1 and R16F2n/R2. The use of specific primers R16(IIIF2/R1 allowed to identify the phytoplasma detected as a representative of the group 16SrIII. This information is very expressive, because different diseases caused by fungus, bacteria, virus and nematodes have been reported for begonia, however, reports have not been found for begonia diseases associated with phytoplasmas.

  6. Withaferin A promotes proliferation and migration of brain ...

    African Journals Online (AJOL)

    Methods: BALB-5023 mouse microvascular cells were treated with a range of withaferin A (WFA) concentrations from 10 to 100 ng/mL. Dojindo's CCK-8 cell proliferation kit was used for the analysis of cell proliferation. Transwell cell culture inserts were used to determine the migration potential of WFAtreated endothelial ...

  7. A Neural Network Based Workstation for Automated Cell Proliferation Analysis

    Science.gov (United States)

    2001-10-25

    proliferation analysis, of cytological microscope images. The software of the system assists the expert biotechnologist during cell proliferation and...work was supported by the Programa de Apoyo a Proyectos de Desarrollo e Investigacíon en Informática REDII 2000. We thank Blanca Itzel Taboada for

  8. Quantification of microglial proliferation and apoptosis by flow cytometry

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Wirenfeldt, Martin; Finsen, Bente

    2013-01-01

    of proliferation and apoptosis maintain a low rate of microglial turnover. Here, we describe quantitative analysis of proliferation and apoptosis of microglial cells isolated from individual adult mice by flow cytometry, which allows distinction from perivascular or infiltrating macrophages, based on differential...

  9. (HIF-1α) on proliferation and apoptosis of adrenocorticotropic hormone

    African Journals Online (AJOL)

    Jane

    2011-07-25

    Jul 25, 2011 ... hypoxia induced apoptosis, we investigated the effects of HIF-1α on proliferation and apoptosis of adrenocorticotropic hormone ... The effect of CoCl2 on the proliferation of AtT-20 cells was in a concentration and time dependent manner. When the ..... arrest by functionally counter-acting. Myc. Embo.

  10. Emodin inhibits proliferation and invasion, and induces apoptosis in ...

    African Journals Online (AJOL)

    Emodin inhibits proliferation and invasion, and induces apoptosis in human esophageal cancer cell line ECA109. ... Tropical Journal of Pharmaceutical Research ... Conclusion: These results suggest that emodin inhibits cell proliferation and cell invasion, but induces cell apoptosis in human esophageal cancer cell line ...

  11. Pulsed short-wave diathermy effects on human fibroblast proliferation.

    Science.gov (United States)

    Hill, Jonathan; Lewis, Martyn; Mills, Pauline; Kielty, Cay

    2002-06-01

    To investigate the influence of pulsed short-wave diathermy (PSWD) on fibroblast and chondrocyte cell proliferation rates and to establish the influences of different dosages applied. Four single-blind trials. Laboratory, in vitro study. Human adult dermal fibroblast and chondrocyte cells were plated at known concentrations and incubated for 5 days. Exposure to PSWD, twice daily, on days 2, 3, and 4. After crystal violet staining (day 5), optical density (cell number) was determined spectrophotometrically. PSWD, given at mean power of 48W for 10 minutes, increased fibroblast proliferation compared with control groups (P<.001). There was a relationship between cell proliferation and the amount of energy given (P<0.001). The optimal mean power for proliferation was estimated to be 13.8W. While keeping mean power constant at 6W, altering pulse duration and pulse repetition rate dosage parameters did not have a significant effect on proliferation (P=.519). Chondrocyte proliferation also increased with PSWD exposure of 6W at 10 minutes duration (P=.015). In addition, treatment time was significantly associated with chondrocyte proliferation (P<.001). PSWD is associated with increased rates of fibroblast and chondrocyte proliferation in vitro, which is dose dependent. These results contribute to an understanding of the physiologic mechanisms underlying the therapeutic effects of PSWD. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  12. Costs and benefits of proliferation of Christian denominations in ...

    African Journals Online (AJOL)

    ... of his or her ministry. However, this study has established other factors rather than divine call for Church proliferation. The study has also tried to explore Church proliferation in Nigeria pointing out its costs and benefits and solutions were suggested on how to curtail the trend in order for it not to blow out of proportion.

  13. SIRT1 inhibits the mouse intestinal motility and epithelial proliferation

    Science.gov (United States)

    SIRT1 inhibits the mouse intestinal motility and epithelial proliferation. Sirtuin 1 (SIRT1), a NAD+-dependent histone deacetylase, is involved in a wide array of cellular processes, including glucose homeostasis, energy metabolism, proliferation and apoptosis, and immune response. However, it is un...

  14. Apigenin inhibits proliferation and migratory properties of Barrett's ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of apigenin on Barrett's esophagus–associated esophageal adenocarcinoma (BEAC) cells OE33, and also to ascertain the mechanism by which it inhibits cellular proliferation and motility. Methods: Proliferation index of OE33 in the absence and presence of apigenin was determined by.

  15. Expanding the Proliferation Security Initiative: A Legal and Policy Analysis

    Science.gov (United States)

    2010-02-01

    13 Sharp, Walter G. “Proliferation Security Initiative: The Legacy of Operacion Socotora.” 16 Transnational Law and...Gregory S. Jones. U.S. Combat Commands’ Participation in the Proliferation Security Initiative: A Training Manual . Washington, DC: RAND National Defense

  16. 19 Costs and Benefits of Proliferation of Christian Denominations in ...

    African Journals Online (AJOL)

    Tracie1

    Abstract. The unbridled proliferation of Churches in Nigeria has steered up concerns among adherents of religious faiths, onlookers and academics alike. Nigerian society today is undergoing significant constant proliferation of Churches which has brought not only changing values, but also source of solutions to people's ...

  17. Effect of triptolide on proliferation and apoptosis of angiotensin II ...

    African Journals Online (AJOL)

    Background: The effect of triptolide (TPL) on cardiac fibroblasts (CFbs) and cardiac fibrosis remain unknown till now. This study was conducted to explore the effects of TPL on proliferation and apoptosis of angiotensin II (Ang II)-induced CFbs. Materials and Methods: Ang II was used to promote proliferation of CFbs.

  18. Proliferation of nuclear weapons: opportunities for control and abolition.

    Science.gov (United States)

    Sidel, Victor W; Levy, Barry S

    2007-09-01

    Nuclear weapons pose a particularly destructive threat. Prevention of the proliferation and use of nuclear weapons is urgently important to public health. "Horizontal" proliferation refers to nation-states or nonstate entities that do not have, but are acquiring, nuclear weapons or developing the capability and materials for producing them. "Vertical" proliferation refers to nation-states that do possess nuclear weapons and are increasing their stockpiles of these weapons, improving the technical sophistication or reliability of their weapons, or developing new weapons. Because nation-states or other entities that wish to use or threaten to use nuclear weapons need methods for delivering those weapons, proliferation of delivery mechanisms must also be prevented. Controlling proliferation--and ultimately abolishing nuclear weapons--involves national governments, intergovernmental organizations, nongovernmental and professional organizations, and society at large.

  19. Rapid Active Sampling Package

    Science.gov (United States)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  20. Rapid Robot Design Validation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robotic designs. The software will support push-button validation...

  1. Rapid Robot Design Validation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robot designs. The software will support push-button validation...

  2. Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells.

    Science.gov (United States)

    Spies, Cornelia M; Gaber, Timo; Hahne, Martin; Naumann, Lydia; Tripmacher, Robert; Schellmann, Saskia; Stahn, Cindy; Burmester, Gerd-Rüdiger; Radbruch, Andreas; Buttgereit, Frank

    2010-06-15

    Rimexolone is a lipophilic glucocorticoid drug used for local application. Only few data are available describing its effects on immune cell functions. In this study we investigated the effects of rimexolone on the proliferation of human CD4+ T-cells using dexamethasone as standard reference. Isolated CD4+ T-cells were pre-incubated with rimexolone or dexamethasone at different concentrations for 10 min (10(-11)/10(-8)/10(-5)M) and stimulated with anti-CD3/anti-CD28 for 96 h. Proliferation was determined by flow cytometry. The percentage of dividing cells was significantly reduced by 10(-5)M rimexolone and dexamethasone; however, the average number of cell divisions was unchanged. In addition, production of IL-2 and other cytokines was reduced by both glucocorticoids at 10(-5)M. Interestingly, we observed a rimexolone-induced down-regulation of CD4 expression in unstimulated and non-dividing cells. The inhibitory effects on proliferation and CD4 expression could be blocked by the glucocorticoid-antagonist RU486 and were not due to glucocorticoid-induced apoptosis. Rimexolone and dexamethasone showed a similar potential to induce IkappaBalpha gene expression. We demonstrate rimexolone and dexamethasone to impair T-cell signalling pathways by rapid non-genomic suppression of the phosphorylation of Akt, p38 and ERK. We conclude that rimexolone and dexamethasone inhibit T-cell proliferation as well as cytokine production of activated CD4+ T-cells in a similar manner. As these inhibitory effects predominantly occur at high concentrations, a relatively high occupation-rate of cytosolic glucocorticoid receptors is needed, but receptor-mediated non-genomic effects may also be involved. It is implied that these effects contribute to the well-known beneficial anti-inflammatory and immunomodulatory effects of glucocorticoid therapy. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  3. STAT6 regulates natural helper cell proliferation during lung inflammation initiated by Alternaria

    Science.gov (United States)

    Khorram, Naseem; Chang, Jinny E.; Kim, Hee-Kyoo; Rosenthal, Peter; Croft, Michael; Broide, David H.

    2012-01-01

    Asthma exacerbations can be caused by a number of factors, including the fungal allergen Alternaria, which is specifically associated with severe and near-fatal attacks. The mechanisms that trigger lung responses are unclear and might vary between allergens. A comparison between Alternaria, Aspergillus, Candida, and house dust mite, all allergens in humans, showed that only Alternaria promoted immediate innate airway eosinophilia within 12 h of inhalation in nonsensitized mice. Alternaria, but not the other allergens, induced a rapid increase in airway levels of IL-33, accompanied by IL-33 receptor (IL-33R)-positive natural helper cell (NHC) production of IL-5 and IL-13. NHCs in the lung and bone marrow constitutively expressed transcription factors [GATA-3 and E26 transformation-specific sequence-1 (ETS-1)] that could allow for rapid induction of T helper type 2 (Th2) cytokines. Lung NHC numbers and proliferation (%Ki-67), but not IL-5 or GATA-3 expression, were significantly reduced in STAT6-deficient mice 3 days after one challenge with Alternaria. Alternaria induced NHC expression of the EGF receptor ligand amphiregulin (partially dependent on STAT6), as well as EGF receptor signaling in the airway epithelium. Finally, human peripheral blood NHCs (CRTH2+CD127+ lineage-negative lymphocytes) from allergic individuals highly expressed GATA-3 and ETS-1, similar to lung NHCs in mice. In summary, Alternaria-induced lung NHC proliferation and expression of amphiregulin are regulated by STAT6. In addition, NHCs in mouse and humans are primed to express Th2 cytokines through constitutive expression of GATA-3 and ETS-1. Thus several transcription factor pathways (STAT6, GATA-3, and ETS-1) may contribute to NHC proliferation and Th2-type responses in Alternaria-induced asthma. PMID:22865552

  4. Usefulness of PKH fluorescent labelling to study leukemic cell proliferation with various cytostatic drugs or acetyl tetrapeptide – AcSDKP

    Directory of Open Access Journals (Sweden)

    Thierry Josiane

    2005-09-01

    Full Text Available Abstract Background PKH67 labelling was compared for classical proliferation assessment (using S phase evaluation to analyse the cell proliferation of 29 AML patients treated or not with various drugs. Among these drugs, the effect of tetrapeptide AcSDKP or AcSDKP-NH2 on AML cells, stimulated or not by cytokines, was also evaluated in order to determine (i if AcSDKP was able to inhibit blast cell proliferation as it inhibits haematopoietic progenitors (ii if AcSDKP-NH2 was more stable than AcSDKP with FBS. Methods For PKH labeling, cells were suspended in Diluent C, and rapidly admixed with PKH67 solution at 20 μM PKH67. Staining was stopped by addition of FBS. Results A good correlation between PKH67 labelling and bromodeoxyuridine incorporation was obtained first with 6/9 patients for control cells, then for 11/17 AML patients treated with classical antileukemic drugs (among whom 4 were also treated with AcSDKP. The effect of AcSDKP was also studied on 7 patients. The discrepancy between both methods was essentially due to an accumulation of cells into different cycle phases measured by BrdUrd incorporation secondary to drug action and PKH67 labelling which measured the dynamic proliferation. This last method allows identifying resistant cells which still proliferate. AcSDKP or AcSDKP-NH2 induced a decrease of leukemic cell proliferation in 5/7 patients when cytokines were added (in order to stimulate proliferation one day after tetrapeptide AcSDKP or AcSDKP-NH2. No effect on proliferation was noted when cytokines were added to AcSDKP-NH2. Conclusion PKH67 labelling method is a powerful tool for cell proliferation assessment in patients with AML, even in cells treated by various drugs.

  5. Rapid prototyping in medical sciences

    Directory of Open Access Journals (Sweden)

    Ákos Márk Horváth

    2015-09-01

    Full Text Available Even if it sound a bit incredible rapid prototyping (RPT as production method has been used for decades in other professions. Nevertheless medical science just started discover the possibilities of this technology and use the offered benefits of 3D printing. In this paper authors have investigated the pharmaceutical usage of rapid prototyping.

  6. Hypoxia promotes adipose-derived stem cell proliferation via VEGF

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-01-01

    Full Text Available Adipose-derived stem cells (ADSCs are a promising mesenchymal stem cell source with therapeutic applications. Recent studies have shown that ADSCs could be expanded in vitro without phenotype changes. This study aimed to evaluate the effect of hypoxia on ADSC proliferation in vitro and to determine the role of vascular endothelial growth factor (VEGF in ADSC proliferation. ADSCs were selectively cultured from the stromal vascular fraction obtained from adipose tissue in DMEM/F12 medium supplemented with 10% fetal bovine serum and 1% antibiotic-antimycotic. ADSCs were cultured under two conditions: hypoxia (5% O2 and normal oxygen (21% O2. The effects of the oxygen concentration on cell proliferation were examined by cell cycle and doubling time. The expression of VEGF was evaluated by the ELISA assay. The role of VEGF in ADSC proliferation was studied by neutralizing VEGF with anti-VEGF monoclonal antibodies. We found that the ADSC proliferation rate was significantly higher under hypoxia compared with normoxia. In hypoxia, ADSCs also triggered VEGF expression. However, neutralizing VEGF with anti-VEGF monoclonal antibodies significantly reduced the proliferation rate. These results suggest that hypoxia stimulated ADSC proliferation in association with VEGF production. [Biomed Res Ther 2016; 3(1.000: 476-482

  7. Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J.; Thompson, Sandra E.

    2009-06-01

    This Preliminary Assessment draft report will present the results of a literature search and preliminary assessment of the body of research, analysis methods, models and data deemed to be relevant to the Utility of Social Modeling for Proliferation Assessment research. This report will provide: 1) a description of the problem space and the kinds of information pertinent to the problem space, 2) a discussion of key relevant or representative literature, 3) a discussion of models and modeling approaches judged to be potentially useful to the research, and 4) the next steps of this research that will be pursued based on this preliminary assessment. This draft report represents a technical deliverable for the NA-22 Simulations, Algorithms, and Modeling (SAM) program. Specifically this draft report is the Task 1 deliverable for project PL09-UtilSocial-PD06, Utility of Social Modeling for Proliferation Assessment. This project investigates non-traditional use of social and cultural information to improve nuclear proliferation assessment, including nonproliferation assessment, proliferation resistance assessments, safeguards assessments and other related studies. These assessments often use and create technical information about the State’s posture towards proliferation, the vulnerability of a nuclear energy system to an undesired event, and the effectiveness of safeguards. This project will find and fuse social and technical information by explicitly considering the role of cultural, social and behavioral factors relevant to proliferation. The aim of this research is to describe and demonstrate if and how social science modeling has utility in proliferation assessment.

  8. Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells1

    Science.gov (United States)

    Mukherjee, Abir; Ma, Yibao; Yuan, Fang; Gong, Yongling; Fang, Zhenyu; Mohamed, Esraa M.; Berrios, Erika; Shao, Huanjie; Fang, Xianjun

    2015-01-01

    Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2) was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the human HK2 gene promoter identified the sterol regulatory element-binding protein as the primary mediator of LPA-induced HK2 transcription. The effects of LPA on HK2 and glycolysis rely on LPA2, an LPA receptor subtype overexpressed in ovarian cancer and many other malignancies. We further examined the general role of growth factor-induced glycolysis in cell proliferation. Like LPA, epidermal growth factor (EGF) elicited robust glycolytic and proliferative responses in ovarian cancer cells. Insulin-like growth factor 1 (IGF-1) and insulin, however, potently stimulated cell proliferation but only modestly induced glycolysis. Consistent with their differential effects on glycolysis, LPA and EGF-dependent cell proliferation was highly sensitive to glycolytic inhibition while the growth-promoting effect of IGF-1 or insulin was more resistant. These results indicate that LPA- and EGF-induced cell proliferation selectively involves up-regulation of HK2 and glycolytic metabolism. The work is the first to implicate LPA signaling in promotion of glucose metabolism in cancer cells. PMID:26476080

  9. Therapeutic touch stimulates the proliferation of human cells in culture.

    Science.gov (United States)

    Gronowicz, Gloria A; Jhaveri, Ankur; Clarke, Libbe W; Aronow, Michael S; Smith, Theresa H

    2008-04-01

    Our objective was to assess the effect of Therapeutic Touch (TT) on the proliferation of normal human cells in culture compared to sham and no treatment. Several proliferation techniques were used to confirm the results, and the effect of multiple 10-minute TT treatments was studied. Fibroblasts, tendon cells (tenocytes), and bone cells (osteoblasts) were treated with TT, sham, or untreated for 2 weeks, and then assessed for [(3)H]-thymidine incorporation into the DNA, and immunocytochemical staining for proliferating cell nuclear antigen (PCNA). The number of PCNA-stained cells was also quantified. For 1 and 2 weeks, varying numbers of 10-minute TT treatments were administered to each cell type to determine whether there was a dose-dependent effect. TT administered twice a week for 2 weeks significantly stimulated proliferation of fibroblasts, tenocytes, and osteoblasts in culture (p = 0.04, 0.01, and 0.01, respectively) compared to untreated control. These data were confirmed by PCNA immunocytochemistry. In the same experiments, sham healer treatment was not significantly different from the untreated cultures in any group, and was significantly less than TT treatment in fibroblast and tenocyte cultures. In 1-week studies involving the administration of multiple 10-minute TT treatments, four and five applications significantly increased [(3)H]-thymidine incorporation in fibroblasts and tenocytes, respectively, but not in osteoblasts. With different doses of TT for 2 weeks, two 10-minute TT treatments per week significantly stimulated proliferation in all cell types. Osteoblasts also responded to four treatments per week with a significant increase in proliferation. Additional TT treatments (five per week for 2 weeks) were not effective in eliciting increased proliferation compared to control in any cell type. A specific pattern of TT treatment produced a significant increase in proliferation of fibro-blasts, osteoblasts, and tenocytes in culture. Therefore, TT may

  10. The possibility of life proliferation from Enceladus

    Science.gov (United States)

    Czechowski, Leszek

    2016-04-01

    Introduction: Enceladus is a medium-sized icy satellite (MIS) of Saturn. MIS are built of mixtures of rocks and ices. Enceladus with its radius of 250 km is one of the smallest of MIS, however, it is geologically active. According to [1]: "For life to have emerged […] on the early Earth, a sustained source of chemically transducible energy was essential. The serpentinization process is emerging as an increasingly likely source of that energy. Serpentinization of ultramafic crust would have continuously supplied hydrogen, methane, […] to off-ridge alkaline hydrothermal springs that interfaced with the metal-rich carbonic Hadean Ocean" (see also [2]). We consider here conditions for origin of life in early Enceladus and possible proliferation of the life from this satellite to the rest of Solar System. Mass of serpentinite: The serpentinization on the Earth is found in neovolcanic zones along mid-oceanic spreading centers. However, only in small part of them the hydrothermal activity really occurs. After [3] we consider the following reaction: Mg2SiO4 + MgSiO3 + 2H2O -> Mg3Si2O5(OH)4 . This reaction releases 241 000 J per kg of serpentine produced. Simple calculations (e.g. [4]) indicate that mass fraction of silicatesfmas in Enceladus is ˜0.646, hence the total mass of its silicate is ˜6.97 1019 kg. [4] found that the early core in Enceladus was a relatively cold structure built from loosely packed grains with water between them. At that time, there was not mechanism of removing the water. Since rocks are permeable up to the pressure of ˜300 MPa then the entire core of Enceladus was probably permeable for liquids. This could lead to formation of extensive hydrothermal convective systems. T-p conditions in Enceladus: The pressure in the center of Enceladus is ˜2.3 107 Pa that corresponds to pressure on the depth 2300 m in a terrestrial ocean. The evolution of temperature in the Enceladus interior for the first a few hundreds Myr is considered by [4]. If

  11. TAp73 promotes anti-senescence-anabolism not proliferation.

    Science.gov (United States)

    Agostini, Massimiliano; Niklison-Chirou, Maria Victoria; Catani, Maria Valeria; Knight, Richard A; Melino, Gerry; Rufini, Alessandro

    2014-11-01

    TAp73, a member of the p53 family, has been traditionally considered a tumor suppressor gene, but a recent report has claimed that it can promote cellular proliferation. This assumption is based on biochemical evidence of activation of anabolic metabolism, with enhanced pentose phosphate shunt (PPP) and nucleotide biosynthesis. Here, while we confirm that TAp73 expression enhances anabolism, we also substantiate its role in inhibiting proliferation and promoting cell death. Hence, we would like to propose an alternative interpretation of the accumulating data linking p73 to cellular metabolism: we suggest that TAp73 promotes anabolism to counteract cellular senescence rather than to support proliferation.

  12. How Rapid is Rapid Prototyping? Analysis of ESPADON Programme Results

    Directory of Open Access Journals (Sweden)

    Ian D. Alston

    2003-05-01

    Full Text Available New methodologies, engineering processes, and support environments are beginning to emerge for embedded signal processing systems. The main objectives are to enable defence industry to field state-of-the-art products in less time and with lower costs, including retrofits and upgrades, based predominately on commercial off the shelf (COTS components and the model-year concept. One of the cornerstones of the new methodologies is the concept of rapid prototyping. This is the ability to rapidly and seamlessly move from functional design to the architectural design to the implementation, through automatic code generation tools, onto real-time COTS test beds. In this paper, we try to quantify the term “rapid” and provide results, the metrics, from two independent benchmarks, a radar and sonar beamforming application subset. The metrics show that the rapid prototyping process may be sixteen times faster than a conventional process.

  13. Analysis of Mammalian Cell Proliferation and Macromolecule Synthesis Using Deuterated Water and Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Victoria C. Foletta

    2016-10-01

    Full Text Available Deuterated water (2H2O, a stable isotopic tracer, provides a convenient and reliable way to label multiple cellular biomass components (macromolecules, thus permitting the calculation of their synthesis rates. Here, we have combined 2H2O labelling, GC-MS analysis and a novel cell fractionation method to extract multiple biomass components (DNA, protein and lipids from the one biological sample, thus permitting the simultaneous measurement of DNA (cell proliferation, protein and lipid synthesis rates. We have used this approach to characterize the turnover rates and metabolism of a panel of mammalian cells in vitro (muscle C2C12 and colon cancer cell lines. Our data show that in actively-proliferating cells, biomass synthesis rates are strongly linked to the rate of cell division. Furthermore, in both proliferating and non-proliferating cells, it is the lipid pool that undergoes the most rapid turnover when compared to DNA and protein. Finally, our data in human colon cancer cell lines reveal a marked heterogeneity in the reliance on the de novo lipogenic pathway, with the cells being dependent on both ‘self-made’ and exogenously-derived fatty acid.

  14. Cellular Retinoic Acid-Binding Protein 1 Modulates Stem Cell Proliferation to Affect Learning and Memory in Male Mice.

    Science.gov (United States)

    Lin, Yu-Lung; Persaud, Shawna D; Nhieu, Jennifer; Wei, Li-Na

    2017-09-01

    Retinoic acid (RA) is the active ingredient of vitamin A. It exerts its canonical activity by binding to nuclear RA receptors (RARs) to regulate gene expression. Increasingly, RA is also known to elicit nongenomic RAR-independent activities, most widely detected in activating extracellular regulated kinase (ERK)1/2. This study validated the functional role of cellular retinoic acid-binding protein 1 (Crabp1) in mediating nongenomic activity in RA, specifically activating ERK1/2 to rapidly augment the cell cycle by expanding the growth 1 phase and slowing down embryonic stem cell and neural stem cell (NSC) proliferation. The study further uncovered the physiological activity of Crabp1 in modulating NSC proliferation and animal behavior. In the Crabp1 knockout mouse hippocampus, where Crabp1 is otherwise detected in the subgranular zone, neurogenesis and NSC proliferation increased and hippocampus-dependent brain functions such as learning and memory correspondingly improved. This study established the physiological role of Crabp1 in modulating stem cell proliferation and hippocampus-dependent brain activities such as learning and memory. Copyright © 2017 Endocrine Society.

  15. 3'UTR Shortening Potentiates MicroRNA-Based Repression of Pro-differentiation Genes in Proliferating Human Cells.

    Directory of Open Access Journals (Sweden)

    Yonit Hoffman

    2016-02-01

    Full Text Available Most mammalian genes often feature alternative polyadenylation (APA sites and hence diverse 3'UTR lengths. Proliferating cells were reported to favor APA sites that result in shorter 3'UTRs. One consequence of such shortening is escape of mRNAs from targeting by microRNAs (miRNAs whose binding sites are eliminated. Such a mechanism might provide proliferation-related genes with an expression gain during normal or cancerous proliferation. Notably, miRNA sites tend to be more active when located near both ends of the 3'UTR compared to those located more centrally. Accordingly, miRNA sites located near the center of the full 3'UTR might become more active upon 3'UTR shortening. To address this conjecture we performed 3' sequencing to determine the 3' ends of all human UTRs in several cell lines. Remarkably, we found that conserved miRNA binding sites are preferentially enriched immediately upstream to APA sites, and this enrichment is more prominent in pro-differentiation/anti-proliferative genes. Binding sites of the miR17-92 cluster, upregulated in rapidly proliferating cells, are particularly enriched just upstream to APA sites, presumably conferring stronger inhibitory activity upon shortening. Thus 3'UTR shortening appears not only to enable escape from inhibition of growth promoting genes but also to potentiate repression of anti-proliferative genes.

  16. Effects of BAP and TIBA on Shoot Proliferation of Rosa hybrida L. cv. Full House in in vitro Culture

    Directory of Open Access Journals (Sweden)

    S. Hajian

    2016-02-01

    Full Text Available Micropropagation is a proper approach to rapid and large-scale propagation of rootstocks and rose cultivars for huge demand of flower market. Proliferation rate of shoot is decreased drastically following several subcultures. Growth regulators have remarkable effects on the key phase of proliferation in micropropagation of this popular crop. In this research the effects of BAP and antiauxin of TIBA on quality and quantity of developed shoots in Rosa hybrida cv. Full House were studied. BAP and TIBA were applied at three concentrations of 0, 2.2 and 8.8 µmol in proliferation phase of micropropagation. The experiment was conducted based on factorial and completely randomized design with four replications. After two months, the percentage of proliferated explants, survived main and lateral shoot number, length of the main and lateral shoots, number of green leaves on the shoots, the average number of shoots with chlorotic and necrotic leaves, the average axillary shoot base diameter, fresh weight of shoots and number of shoots with necrotic tip were recorded. Analysis of variance indicated that BAP was ineffective on the number of the main shoot green leaves and decreasing number of shoots with necrotic tip, but enhanced other traits. The concentration of 8.8 µmol of BAP had greater effect than 2.2 µmol of this growth regulator on mentioned traits. The higher concentration of TIBA resulted to more shoot with necrotic tip. This antiauxin had anegative impact on shoot fresh weight, but the other parameters were not significantly affected.

  17. E-cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor-κB in AGS cells.

    Science.gov (United States)

    Park, Song Yi; Shin, Jee-Hye; Kee, Sun-Ho

    2017-09-01

    β-Catenin is a central player in Wnt signaling, and activation of Wnt signaling is associated with cancer development. E-cadherin in complex with β-catenin mediates cell-cell adhesion, which suppresses β-catenin-dependent Wnt signaling. Recently, a tumor-suppressive role for E-cadherin has been reconsidered, as re-expression of E-cadherin was reported to enhance the metastatic potential of malignant tumors. To explore the role of E-cadherin, we established an E-cadherin-expressing cell line, EC96, from AGS cells that featured undetectable E-cadherin expression and a high level of Wnt signaling. In EC96 cells, E-cadherin re-expression enhanced cell proliferation, although Wnt signaling activity was reduced. Subsequent analysis revealed that nuclear factor-κB (NF-κB) activation and consequent c-myc expression might be involved in E-cadherin expression-mediated cell proliferation. To facilitate rapid proliferation, EC96 cells enhance glucose uptake and produce ATP using both mitochondria oxidative phosphorylation and glycolysis, whereas AGS cells use these mechanisms less efficiently. These events appeared to be mediated by NF-κB activation. Therefore, E-cadherin re-expression and subsequent induction of NF-κB signaling likely enhance energy production and cell proliferation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Myopericytoma proliferating in an unusual anastomosing multinodular fashion.

    Science.gov (United States)

    Inoue, Takuya; Misago, Noriyuki; Asami, Akihiko; Tokunaga, Osamu; Narisawa, Yutaka

    2016-05-01

    We herein describe a case of myopericytoma that proliferated in an unusual fashion. Myopericytoma is described as a group of rare, benign, dermal or subcutaneous tumors that are characterized histologically by a striking, concentric, perivascular proliferation of spindle cells and showing apparent differentiation towards perivascular myoid cells. Myopericytoma forms a morphological continuum with myofibroma/myofibromatosis, glomus tumor and angioleiomyoma. The patient was a 64-year-old woman who demonstrated a recurrent ulcer on an atrophic plaque on her left shin. A histopathological examination of the plaque demonstrated that tumor cells proliferated in an anastomosing multinodular fashion along the vessels in the dermis and subcutaneous tissue. In those nodules, there were numerous, small, concentric proliferations of myoid-appearing spindle cells around small vascular lumina. The present case is an unusual example of myopericytoma, manifesting in a characteristic anastomosing, multinodular, infiltrating fashion. © 2015 Japanese Dermatological Association.

  19. Arrest of cytoplasmic streaming induces algal proliferation in green paramecia.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Takahashi

    Full Text Available A green ciliate Paramecium bursaria, bearing several hundreds of endosymbiotic algae, demonstrates rotational microtubule-based cytoplasmic streaming, in which cytoplasmic granules and endosymbiotic algae flow in a constant direction. However, its physiological significance is still unknown. We investigated physiological roles of cytoplasmic streaming in P. bursaria through host cell cycle using video-microscopy. Here, we found that cytoplasmic streaming was arrested in dividing green paramecia and the endosymbiotic algae proliferated only during the arrest of cytoplasmic streaming. Interestingly, arrest of cytoplasmic streaming with pressure or a microtubule drug also induced proliferation of endosymbiotic algae independently of host cell cycle. Thus, cytoplasmic streaming may control the algal proliferation in P. bursaria. Furthermore, confocal microscopic observation revealed that a division septum was formed in the constricted area of a dividing paramecium, producing arrest of cytoplasmic streaming. This is a first report to suggest that cytoplasmic streaming controls proliferation of eukaryotic cells.

  20. Catecholamines Inhibit Gastric Epithelial [RGM-1] Cell Proliferation ...

    African Journals Online (AJOL)

    adrenergic blocker) significantly (but not totally) reversed the inhibitory action of ADR on cell proliferation. Furthermore, procaterol (selective beta-2 agonist) but not dobutamine (selective beta-1 agonist) had effects similar to those produced by ...

  1. The research progress of MSCs proliferation and differentiation in ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-02-18

    MSCs) proliferation and differentiation in vitro and vivo. This review will introduce some newest articles mainly in China focusing on the growth and differentiation of MSCs, which were treated with a single herb or formulas.

  2. (BIO) promotes the proliferation of mouse male germline s

    African Journals Online (AJOL)

    AJB2

    2012-01-18

    Jan 18, 2012 ... 1College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, ..... with quality control of these undefined components. ..... antibodies against Ki-67 protein and proliferating cell nuclear antigen.

  3. Effects of TGFβ1, PDGF-BB, and bFGF, on human corneal fibroblasts proliferation and differentiation during stromal repair.

    Science.gov (United States)

    Gallego-Muñoz, Patricia; Ibares-Frías, Lucía; Valsero-Blanco, María Cruz; Cantalapiedra-Rodriguez, Roberto; Merayo-Lloves, Jesús; Martínez-García, M Carmen

    2017-08-01

    In an effort to improve the regenerative nature of corneal repair, this study reports the use of an in vitro human corneal fibroblasts (HCFs) wound model after treatment with three of the main growth factors (GFs) involved in corneal healing: transforming growth factor beta 1 (TGFβ1), platelet-derived growth factor BB-isoform (PDGF-BB), and basic fibroblast growth factor (bFGF) in order to delve in cell proliferation and differentiation processes. HCFs were mechanically wounded. The individual effect of TGFβ1, PDGF-BB, and bFGF on cell proliferation and differentiation during the repair process was studied at different time points until wound closure. Wound dimensions and morphological changes were evaluated by microscopy. Cell proliferation and myofibroblast differentiation were analyzed by immunofluorescence cytochemistry. Changes in cell morphology were apparent at Day 4. PDGF-BB- and bFGF-treated cells had fibroblast-like morphology. TGFβ1 stimulated proliferation in the wound edge and surrounding area, induced myofibroblast differentiation and inhibited cellular migration. PDGF-BB induced rapid wound closure due to proliferation, high motility, and late myofibroblast differentiation. The time course of closure induced by bFGF was similar to that for PDGF-BB, but was mostly due to proliferation in the wound area, and inhibited myofibroblast differentiation. Each of the GFs induced increases in responses promoting stromal repair differently. This study provides insight regarding how to optimize the outcome of stromal repair following corneal injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Reciprocal control of cell proliferation and migration

    Directory of Open Access Journals (Sweden)

    De Donatis Alina

    2010-09-01

    Full Text Available Abstract In adult tissue the quiescent state of a single cell is maintained by the steady state conditions of its own microenvironment for what concern both cell-cell as well as cell-ECM interaction and soluble factors concentration. Physiological or pathological conditions can alter this quiescent state through an imbalance of both soluble and insoluble factors that can trigger a cellular phenotypic response. The kind of cellular response depends by many factors but one of the most important is the concentration of soluble cytokines sensed by the target cell. In addition, due to the intrinsic plasticity of many cellular types, every single cell is able, in response to the same stimulus, to rapidly switch phenotype supporting minimal changes of microenviromental cytokines concentration. Wound healing is a typical condition in which epithelial, endothelial as well as mesenchymal cells are firstly subjected to activation of their motility in order to repopulate the damaged region and then they show a strong proliferative response in order to successfully complete the wound repair process. This schema constitute the leitmotif of many other physiological or pathological conditions such as development vasculogenesis/angiogenesis as well as cancer outgrowth and metastasis. Our review focuses on the molecular mechanisms that control the starting and, eventually, the switching of cellular phenotypic outcome in response to changes in the symmetry of the extracellular environment.

  5. TAp73 promotes anti-senescence-anabolism not proliferation

    OpenAIRE

    Agostini, Massimiliano; Niklison-Chirou, Maria Victoria; Catani, Maria Valeria; Knight, Richard A.; Melino, Gerry; Rufini, Alessandro

    2014-01-01

    TAp73, a member of the p53 family, has been traditionally considered a tumor suppressor gene, but a recent report has claimed that it can promote cellular proliferation. This assumption is based on biochemical evidence of activation of anabolic metabolism, with enhanced pentose phosphate shunt (PPP) and nucleotide biosynthesis. Here, while we confirm that TAp73 expression enhances anabolism, we also substantiate its role in inhibiting proliferation and promoting cell death. Hence, we would li...

  6. A Rapid Coliform Detector Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid genetic detector for spaceflight water systems to enable real-time detection of E-coli with minimal...

  7. Rapid Multiplex Microbial Detector Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid nucleic acid-based detector for spaceflight water systems to enable simultaneous quantification of multiple...

  8. Urbanisation of Suweimeh area, Jordan, versus sinkholes and landslides proliferation

    Science.gov (United States)

    Closson, Damien; Abou Karaki, Najib

    2013-04-01

    The Dead Sea is a terminal lake whose level lowers each year of about one meter per year since more than one decade. This is caused mainly by the diversion of surface waters from its watershed. Currently, 1/10 of the Jordan River still reaches the salt lake. The rapid lowering of the lake level does not allow all the surrounding groundwater tables to adjust their level to that of the Dead Sea. This imbalance causes an always faster migration of a part of the groundwater causing underground erosion leading to the formation of sinkholes along the coast, especially where discontinuities, such as faults, are present. The first collapses occurred in the years 1980-90. From the 2000s, in Jordan, they have proliferated to the point of causing serious damages to the facilities of the Arab Potash Company, the agricultural area of Ghor Al Haditha, and more recently the touristic region of Suweimeh. Aware of the problem and the need for gradual rising of the lake level, the Jordanian authorities attended from 2009 to 2011 to the feasibility study of the Red Sea - Dead Sea conduit. Currently, on the one hand, the growing environmental imbalance, and, on the other hand, the desires to develop economic activities along the coast, imply that more goods will be exposed to damages. For example, the area of Wadi Mujib Bridge was rebuilt completely in the late 2000s. It is the same for the 12 km of the dam 18 of an evaporation pond Arab Potash Company. The Numeira Salt Factory was completely destroyed in Ghor Al Haditha and was relocated to Safi. In August 2012, during touristic period, a landslide destroyed half of the Holiday Inn front beach, Suweimeh area ... End of December 2012, a team lead by Prof. Najib Abou Karaki warned the Arab Potash Company of the presence of a circular depression 250 m in diameter within the evaporation pond SP-0A. Although the dike of this saltpan is closely monitored, the exact location and shape of this large sinkhole were not known to the security

  9. Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

    Directory of Open Access Journals (Sweden)

    Yumiko Mitome-Mishima

    Full Text Available After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.

  10. Actual proliferating index in oral squamous cell carcinoma and leukoplakia.

    Science.gov (United States)

    Chandak, Abhay R; Gadbail, Amol Ramchandra; Chaudhary, Minal S; Chandak, Shweta A; Wadhwani, Ritesh

    2011-08-01

      To examine the possible association between epithelial proliferation and disease progression in the oral mucosa using the actual proliferation index.   The actual proliferation index was measured by the Ki-67 labeling index and argyrophilic nucleolar organizer region count per nucleus. Immunohistochemistry was carried out for Ki-67 by using the molecular immunology borstel-1 clone in 20 leukoplakias, 20 oral squamous cell carcinomas, and 10 normal oral mucosae.   The argyrophilic nucleolar organizer region count per nucleus, Ki-67 labeling index, and actual proliferation index were significantly higher in oral squamous cell carcinoma, followed by leukoplakia and normal oral mucosa. Leukoplakia with dysplasia showed a significantly higher Ki-67 labeling index and actual proliferation index, compared to leukoplakia without dysphasia. There was a significant correlation of Bryne's histological malignancy grading with the argyrophilic nucleolar organizer region count and the Ki-67 labeling index. There was a significant positive correlation between the argyrophilic nucleolar organizer region count and the Ki-67 labeling index among all groups.   Leukoplakia or suspected epithelial dysplasia should be stained for argyrophilic nucleolar organizer regions and Ki-67. The actual proliferation index is not only useful as a prognostic factor, but could also be a promising treatment determining modality for patients with premalignant and malignant lesions. © 2011 Blackwell Publishing Asia Pty Ltd.

  11. EDA-Containing Fibronectin Increases Proliferation of Embryonic Stem Cells

    Science.gov (United States)

    Losino, Noelia; Waisman, Ariel; Solari, Claudia; Luzzani, Carlos; Espinosa, Darío Fernández; Sassone, Alina; Muro, Andrés F.; Miriuka, Santiago; Sevlever, Gustavo; Barañao, Lino; Guberman, Alejandra

    2013-01-01

    Embryonic stem cells (ESC) need a set of specific factors to be propagated. They can also grow in conditioned medium (CM) derived from a bovine granulosa cell line BGC (BGC-CM), a medium that not only preserves their main features but also increases ESC´s proliferation rate. The mitogenic properties of this medium were previously reported, ascribing this effect to an alternative spliced generated fibronectin isoform that contains the extra domain A (FN EDA+). Here, we investigated if the FN EDA+ isoform increased proliferation of mouse and human ES cells. We analyzed cell proliferation using conditioned media produced by different mouse embryonic fibroblast (MEF) lines genetically engineered to express FN constitutively including or excluding the EDA domain (FN EDA-), and in media supplemented with recombinant peptides containing or not the EDA. We found that the presence of EDA in the medium increased mouse and human ESC’s proliferation rate. Here we showed for the first time that this FN isoform enhances ESC’s proliferation. These findings suggest a possible conserved behavior for regulation of ES cells proliferation by this FN isoform and could contribute to improve their culturing conditions both for research and cell therapy. PMID:24244705

  12. The kinetics of cellular proliferation in regenerating liver.

    Science.gov (United States)

    Fabrikant, J I

    1968-03-01

    The study concerns the kinetics of cellular proliferation in the different cell populations of the normal and regenerating rat liver. A detailed analysis is presented, which includes techniques of in vivo labeling of DNA with tritiated thymidine and high-resolution radioautography, of the temporal and spatial patterns of DNA synthesis and cell division in the parenchymal cells, littoral cells, bile duct epithelium, and other cellular components in the liver during the first 64 hr of regeneration after partial hepatectomy. The analysis of cell population kinetics indicates that (a) the rate of entry of parenchymal cells into synthesis, after an initial burst of proliferative activity, was an orderly progression at 3-4%/hr; (b) most cells divided once and a few twice, a large proportion of the cell deficit being replaced by 72 hr after the onset of proliferation; (c) T(s) was approximately 8.0 hr; T(gg2+m/2), 3.0 hr; and M, approximately 1.0 hr. Littoral cell proliferation began about 24 hr after the onset of parenchymal cell proliferation; the rate of entry of littoral cells into synthesis was greater than 4%/hr. Interlobular bile duct cell proliferation lagged well behind the parenchymal and littoral cell populations both in time and extent of proliferation.

  13. Proliferation of differentiated glial cells in the brain stem

    Directory of Open Access Journals (Sweden)

    Barradas P.C.

    1998-01-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  14. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  15. The fight against the weapons of mass destruction proliferation; La lutte contre la proliferation des armes de destruction massive

    Energy Technology Data Exchange (ETDEWEB)

    Boutherin, G. [Centre d' Etudes et de Recherches Internationales et Communautaires (CERIC), 13 - Aix-en-Provence (France)

    2007-07-01

    The author provides a stimulating analysis of the increasing risk of nuclear weapons proliferation, a major concern of the international community. This analysis is applied on juridical, strategical and political examinations. (A.L.B.)

  16. Selenium-binding protein 1 may decrease gastric cellular proliferation and migration

    National Research Council Canada - National Science Library

    ZHANG, CHENJING; XU, WEN; PAN, WENSHENG; WANG, NANA; LI, GUOGANG; FAN, XIAOYUAN; XU, XIANG; SHEN, SHENGRONG; DAS, UNDURTI N

    2013-01-01

    .... Using cell proliferation assays, immunochemical staining and immunoblotting and flow cytometry methods and in a xenograft model, we evaluated the role of SBP1 in proliferation, migration, senescence...

  17. A Dictyostelium chalone uses G proteins to regulate proliferation.

    Science.gov (United States)

    Bakthavatsalam, Deenadayalan; Choe, Jonathan M; Hanson, Nana E; Gomer, Richard H

    2009-07-27

    Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA). Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus), whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

  18. A Dictyostelium chalone uses G proteins to regulate proliferation

    Directory of Open Access Journals (Sweden)

    Hanson Nana E

    2009-07-01

    Full Text Available Abstract Background Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. Results We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA. Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus, whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. Conclusion This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

  19. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  20. Evaluation of the Cell Proliferation Process of Ovarian Follicles in Hypothyroid Rats by Proliferation Cell Nuclear Antigen Immunohistochemical Technique

    Directory of Open Access Journals (Sweden)

    M. Moghaddam Dorafshani

    2012-10-01

    Full Text Available Introduction & Objective: The normal females reproductive function , needs hypothalamus-hypophysis-ovarian extensive hormonal messages. Primary hypothyroidism is characterized by reduced production and secretion of thyroid hormones. During follicular growth PCNA (Proliferating Cell Nuclear Antigen and cycklin D complex play an important role in regulating cell proliferation .This study aimed to determine the cell proliferation index and how this process changes induced by thyroid hormone decreased in rat ovarian follicles.Materials & Methods: In this experimental study, 20 Wistar female rats were divided into experimental and control groups. Experimental group was chemically thyroidectomized by administering propylthiouracil (PTU (500 mg per liter of drinking water. The control group received normal drinking water. After three weeks rats were killed and their ovaries dissected and fixed for the histological preparation. Cell proliferation was determined by PCNA and stereological methods were used for counting cells.Results: Cell proliferation index showed a significant decrease in the frequency of follicular growth from prenatal to graafian follicles in hypothyroidism groups(P0.05 . PCNA expression determined that Primary follicle growth begins earlier. Positive PCNA cells were not observed in primordial follicles of the groups.Conclusion: According to the results of our study, this hypothesis is raised that granulosa cells in growing follicles may be increased by follicle adjacent cells in ovarian stroma . Hormonal changes following the reduction of thyroid hormones may greatly affect the cell proliferation index and lead to faster follicle degeneration.(Sci J Hamadan Univ Med Sci 2012; 19 (3:5-15

  1. Glycolysis and the pentose phosphate pathway are differentially associated with the dichotomous regulation of glioblastoma cell migration versus proliferation.

    Science.gov (United States)

    Kathagen-Buhmann, Annegret; Schulte, Alexander; Weller, Jonathan; Holz, Mareike; Herold-Mende, Christel; Glass, Rainer; Lamszus, Katrin

    2016-09-01

    The dichotomy between glioblastoma cell migration and proliferation is regulated by various parameters including oxygen tension. In glioblastoma stem-like cells, hypoxia induces downregulation of pentose phosphate pathway (PPP) enzymes and a flux shift towards glycolysis. We investigated whether the 2 parallel glucose metabolic pathways are intrinsically linked with cell function and whether these pathways are mechanistically involved in regulating functional programs. Enzyme expression, migration, and proliferation under hypoxia were studied in multiple cell types. Rapidly and slowly dividing or migrating glioblastoma cells were separated, and enzyme profiles were compared. Glucose-6-phosphate dehydrogenase (G6PD) and Aldolase C (ALDOC), the most strongly inversely regulated PPP and glycolysis enzymes, were knocked down by short hairpin RNA. Hypoxia caused downregulation of PPP enzymes and upregulation of glycolysis enzymes in a broad spectrum of cancer and nonneoplastic cells and consistently stimulated migration while reducing proliferation. PPP enzyme expression was increased in rapidly dividing glioblastoma cells, whereas glycolysis enzymes were decreased. Conversely, glycolysis enzymes were elevated in migrating cells, whereas PPP enzymes were diminished. Knockdown of G6PD reduced glioblastoma cell proliferation, whereas ALDOC knockdown decreased migration. Enzyme inhibitors had similar effects. G6PD knockdown in a highly proliferative but noninvasive glioblastoma cell line resulted in prolonged survival of mice with intracerebral xenografts, whereas ALDOC knockdown shortened survival. In a highly invasive glioblastoma xenograft model, tumor burden was unchanged by either knockdown. Cell function and metabolic state are coupled independently of hypoxia, and glucose metabolic pathways are causatively involved in regulating "go or grow" cellular programs. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro

  2. Ketamine suppresses the proliferation of rat C6 glioma cells.

    Science.gov (United States)

    Niwa, Hidetomo; Furukawa, Ken-Ichi; Seya, Kazuhiko; Hirota, Kazuyoshi

    2017-10-01

    The present study investigated the effects of N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine, on the growth of gliomas. To analyze the effects of ketamine treatment, rat C6 glioma cells arising from astrocytes, and RNB cells representing non-malignant astrocytes, were examined. In ketamine-treated C6 cells, the gene expression changes associated with cell proliferation following ketamine treatment were evaluated using a cDNA microarray. A cell proliferation assay was performed to analyze the dose-dependent proliferation of C6 glioma and RNB cells following culture (72 h) with ketamine treatment (0-100 µM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed following cell incubation with/without ketamine, to confirm if the ketamine-induced cell death of C6 glioma and RNB cells were due to apoptosis. In addition, cell proliferation and TUNEL assays were performed following cell incubations with a selective NMDAR antagonist, D-2-amino-5-phosphonovaleric acid (D-AP5). Analysis of the cDNA microarray indicated that the growth of C6 glioma cells were suppressed by the effects of ketamine. Furthermore, results of the proliferation assay confirmed that ketamine treatment inhibited C6 cell proliferation, most notably at a dose of 30 µM (n=7, 66.4%; Pcells, with a significant effect on the rate of death observed at all tested concentrations (3, 10, 30 and 100 µM). Results of the aforementioned proliferation and TUNEL assay experiments were reproduced when ketamine was replaced with a selective NMDAR antagonist, D-AP5. However, the NMDARantagonist-induced effects were not observed in RNB cell cultures. Although it would be premature to apply the results from the present study to human cases, these results indicated that ketamine is an anesthetic candidate providing potential benefit for glioma resection.

  3. Matrix stiffness regulates endothelial cell proliferation through septin 9.

    Directory of Open Access Journals (Sweden)

    Yi-Ting Yeh

    Full Text Available Endothelial proliferation, which is an important process in vascular homeostasis, can be regulated by the extracellular microenvironment. In this study we demonstrated that proliferation of endothelial cells (ECs was enhanced on hydrogels with high stiffness (HSG, 21.5 kPa in comparison to those with low stiffness (LSG, 1.72 kPa. ECs on HSG showed markedly prominent stress fibers and a higher RhoA activity than ECs on LSG. Blockade of RhoA attenuated stress fiber formation and proliferation of ECs on HSG, but had little effect on ECs on LSG; enhancement of RhoA had opposite effects. The phosphorylations of Src and Vav2, which are positive RhoA upstream effectors, were higher in ECs on HSG. The inhibition of Src/Vav2 attenuated the HSG-mediated RhoA activation and EC proliferation but exhibited nominal effects on ECs on LSG. Septin 9 (SEPT9, the negative upstream effector for RhoA, was significantly higher in ECs on LSG. The inhibition of SEPT9 increased RhoA activation, Src/Vav2 phosphorylations, and EC proliferation on LSG, but showed minor effects on ECs on HSG. We further demonstrated that the inactivation of integrin α(vβ(3 caused an increase of SEPT9 expression in ECs on HSG to attenuate Src/Vav2 phosphorylations and inhibit RhoA-dependent EC proliferation. These results demonstrate that the SEPT9/Src/Vav2/RhoA pathway constitutes an important molecular mechanism for the mechanical regulation of EC proliferation.

  4. Analysis of nuclear proliferation resistance reprocessing and recycling technologies

    Energy Technology Data Exchange (ETDEWEB)

    Patricia Paviet-Hartmann; Gary Cerefice; Marcela Stacey; Steven Bakhtiar

    2011-05-01

    The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate – and should not be equated -with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. . Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R&D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

  5. Dietary bovine lactoferrin increases intestinal cell proliferation in neonatal piglets.

    Science.gov (United States)

    Reznikov, Elizabeth A; Comstock, Sarah S; Yi, Cuiyi; Contractor, Nikhat; Donovan, Sharon M

    2014-09-01

    Lactoferrin is a bioactive milk protein that stimulates cell proliferation in vitro; however, limited in vivo evidence exists to allow lactoferrin to be incorporated into infant formula. Herein, the effect of dietary bovine lactoferrin (bLF) on neonatal intestinal growth and maturation was investigated guided by the hypothesis that bLF would increase cellular proliferation leading to functional differences in neonatal piglets. Colostrum-deprived piglets were fed formula containing 0.4 [control (Ctrl)], 1.0 (LF1), or 3.6 (LF3) g bLF/L for the first 7 or 14 d of life. To provide passive immunity, sow serum was provided orally during the first 36 h of life. Intestinal cell proliferation, histomorphology, mucosal DNA concentration, enzyme activity, gene expression, and fecal bLF content were measured. Intestinal enzyme activity, DNA concentration, and villus length were unaffected by bLF. However, crypt proliferation was 60% greater in LF1- and LF3-fed piglets than in Ctrl piglets, and crypt depth and area were 20% greater in LF3-fed piglets than in Ctrl piglets. Crypt cells from LF3-fed piglets had 3-fold higher β-catenin mRNA expression than did crypt cells from Ctrl piglets. Last, feces of piglets fed bLF contained intact bLF, suggesting that some bLF was resistant to digestion and could potentially affect intestinal proliferation through direct interaction with intestinal epithelial cells. This study is the first to our knowledge to show that dietary bLF stimulates crypt cell proliferation in vivo. The increased β-catenin expression indicates that Wnt signaling may in part mediate the stimulatory effect of bLF on intestinal cell proliferation. © 2014 American Society for Nutrition.

  6. Phospholipase Cβ1 regulates proliferation of neuronal cells.

    Science.gov (United States)

    Garwain, Osama; Valla, Kaitlyn; Scarlata, Suzanne

    2018-01-12

    Cells have developed lineage-specific mechanisms to control proliferation and drive morphologic changes upon differentiation. A hallmark of differentiation is the assembly of signaling molecules that transduce extracellular signals, such as the production of the G protein-regulated enzyme phospholipase Cβ (PLCβ), which generates calcium signals from sensory stimuli. We found that in most cancerous cell lines there is positive correlation between PLCβ1 levels and cell proliferation. In cells of neuronal lineage, however, reducing PLCβ1 levels increases the rate of proliferation. Using a combination of biochemical and biophysical methods, we find that, in the G1 phase, a cytosolic population of PLCβ1 associates with cyclin-dependent kinase 16 (CDK16), a neuron-specific enzyme that is activated by cyclin Y to inactivate the antioncogenic protein p27Kip1. Binding of PLCβ1 directly inhibits CDK16 activity and in turn reduces the ability of cells to enter the S phase. Activation of Gαq by carbachol causes movement of PLCβ from the cytosol to the plasma membrane, reducing its association with CDK16. Similarly, the overexpression of activated Gαq moves PLCβ1 to the membrane, reverses G1 arrest, and promotes proliferation, thereby connecting external stimuli with cell proliferation. Our results present a model in which the transient high expression of PLCβ1 that occurs at the onset of differentiation arrests cells in the G1 phase through its association with CDK16 and allows CDK16 to transition to its postmitotic function of neurite outgrowth and trafficking of synaptic vesicles. The novel role of PLCβ1 in neuronal cell proliferation offers a unique interaction that can be manipulated to guide cells into a neuronal phenotype or to develop therapies for neuroblastomas.-Garwain, O., Valla, K., Scarlata, S. Phospholipase Cβ1 regulates proliferation of neuronal cells.

  7. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  8. Osteoblast-like cell attachment and proliferation on turned, blasted, and anodized titanium surfaces.

    Science.gov (United States)

    Pae, Ahran; Kim, Si-Seok; Kim, Hyeong-Seob; Woo, Yi-Hyung

    2011-01-01

    The purpose of this study was to investigate the cellular activities of MG63 osteoblast-like cells on modified titanium surfaces. MG63 osteoblast-like cells were cultured on titanium disks (n = 20 in each group) with turned, resorbable blast media (RBM)-treated, or anodized surfaces. The surfaces of commercially available implants of Osstem (Osstem Implant) were reproduced for the titanium disks. The morphology of cells cultured on these disks was examined using scanning electron microscopy. X-ray photoelectron spectroscopy (XPS) was employed for the analysis of surface chemistry. Specimens were also evaluated with an initial cell adhesion assay to compare initial adhesion, with a methyl tetrazol sulfate (MTS) assay to compare the proliferation ability, and with an alkaline phosphatase (ALP) assay to compare the differentiation ability. Statistical significance of the differences was determined using the Kruskal-Wallis test for the cell adhesion assay and analysis of variance for the MTS and ALP assays. Attached cells with more defined lamellopodia and flattened morphology were observed on the anodized and RBM surfaces than on the turned surfaces. The titanium surfaces were all oxidized as titanium oxide and polluted by carbon determinants, as determined by XPS. Anodized titanium surfaces exhibited calcium and phosphorus peaks. Initial cell attachment activity, cell proliferation activity, and ALP activity were higher on the anodized surfaces than on the other surfaces. Cell differentiation on the anodized surfaces at culture day 10 was significantly higher (P < .05) than on the other surfaces. Surface treatment by anodization may improve initial attachment of cells, proliferation ability, and differentiation activity, which play important roles in providing better osseointegration of implants. More rapid and stronger osseointegration of implants may make it possible to offer the best anchorage and shorten the healing time required prior to functional loading.

  9. Proliferation and differentiation potential of mouse adult hepatic progenitor cells cultured in vitro.

    Science.gov (United States)

    Song, Lujun; Wang, Hongshan; Gao, Xiaodong; Shen, Kuntang; Niu, Weixin; Qin, Xinyu

    2010-02-01

    This study aimed to isolate the stem cells or progenitors, if exist, from normal adult mouse liver and investigate their potential of proliferation and differentiation. Hepatocytes were isolated by modified two-step liver perfusion method and centrifugation, and then cultured in modified serumcontaining DMEM for observation more than 60 days. Immunofluorescence technique was applied to check the hepatocytes and to examine the formation of colonies with albumin, alpha-fetoprotein (AFP) and cytokeratin 19 (CK19). Results showed that some hepatocytes that were strongly positive for hepatocyte specific markers albumin on Day 1 in culture, could be activated at Days 2-3, followed by rapid proliferation and formation of colonies. The colonies could expand continually for more than 60 days. On Day 5, all the cells in the colony expressed hepatic stem cell (HSC) markers AFP. With the time of culture, some cells in colonies lost ability to divide at Days 13-15, and differentiated into cells which had a large cytoplasm and some two nuclei, similar to the appearance of mature hepatocytes morphologically. These differentiated cells demonstrated strong expression of albumin. Around Day 30, some big cells appeared in colonies and expressed bile duct cell marker CK19. Therefore, this subpopulation of mouse hepatocytes could acquire some characteristics of immature hepatocytes and showed the profile of hepatic progenitor cells with a high proliferating ability and bi-potential of differentiation. They were isolated from normal adult mouse, hence, named adult hepatic progenitor cells (AHPCs). Mouse AHPCs may be used as an HSC model for hepatocytes transplantation and hepatopathy study.

  10. Convergent ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs) signalling mediate catecholoestradiol-induced proliferation of ovine uterine artery endothelial cells.

    Science.gov (United States)

    Landeros, Rosalina Villalon; Jobe, Sheikh O; Aranda-Pino, Gabrielle; Lopez, Gladys E; Zheng, Jing; Magness, Ronald R

    2017-07-15

    The catechol metabolites of 17β-oestradiol (E2 β), 2-hydroxyoestradiol (2-OHE2 ) and 4-hydroxyoestradiol (4-OHE2 ), stimulate proliferation of pregnancy-derived ovine uterine artery endothelial cells (P-UAECs) through β-adrenoceptors (β-ARs) and independently of the classic oestrogen receptors (ERs). Herein we show that activation of ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs) is necessary for 2-OHE2 - and 4-OHE2 -induced P-UAEC proliferation, as well as proliferation induced by the parent hormone E2 β and other β-AR signalling hormones (i.e. catecholamines). Conversely, although 2-OHE2 and 4-OHE2 rapidly activate phosphatidylinositol 3-kinase (PI3K), its activation is not involved in catecholoestradiol-induced P-UAEC proliferation. We also show for the first time the signalling mechanisms involved in catecholoestradiol-induced P-UAEC proliferation; which converge at the level of MAPKs with the signalling mechanisms mediating E2 β- and catecholamine-induced proliferation. The present study advances our understanding of the complex signalling mechanisms involved in regulating uterine endothelial cell proliferation during pregnancy. Previously we demonstrated that the biologically active metabolites of 17β-oestradiol, 2-hydroxyoestradiol (2-OHE2 ) and 4-hydroxyoestradiol (4-OHE2 ), stimulate pregnancy-specific proliferation of uterine artery endothelial cells derived from pregnant (P-UAECs), but not non-pregnant ewes. However, unlike 17β-oestradiol, which induces proliferation via oestrogen receptor-β (ER-β), the catecholoestradiols mediate P-UAEC proliferation via β-adrenoceptors (β-AR) and independently of classic oestrogen receptors. Herein, we aim to further elucidate the signalling mechanisms involved in proliferation induced by catecholoestradiols in P-UAECs. P-UAECs were treated with 2-OHE2 and 4-OHE2 for 0, 0.25, 0.5, 1, 2, 4, 12 and 24 h, to analyse activation of mitogen activated protein kinases (MAPKs) and

  11. Rapid Countermeasure Discovery against Francisella tularensis Based on a Metabolic Network Reconstruction

    Science.gov (United States)

    2013-05-21

    a given drug target. First, the selection of a subset of genes deemed to be essential for bacterial survival overlooks non-essential genes that may... Salmonella typhimurium during host-pathogen interaction. BMC Syst Biol 3: 38. 19. Shen Y, Liu J, Estiu G, Isin B, Ahn YY, et al. (2010) Blueprint for...and Medicine 48: 330–333. 69. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival : application to proliferation and

  12. Case report of rapidly progressive proliferative verrucous leukoplakia and a proposal for aetiology in mainland China

    Directory of Open Access Journals (Sweden)

    Zeng Xin

    2011-02-01

    Full Text Available Abstract Proliferative verrucous leukoplakia (PVL is a rare oral leukoplakia and has four features such as chronic proliferation, multiple occurrences, refractoriness to treatment and high rate of malignant transformation. As mentioned above, most PVL cases processed to malignancy over many years, sometimes 20 years. However, this report described a case of rapid progress, which had malignant transformation in a short period. Additionally, the aetiology of PVL was discussed and immunity was proposed as the possible cause.

  13. Rapid proliferation of an endemic galaxiid following eradication of an alien piscivore (Perca fluviatilis) from a reservoir.

    Science.gov (United States)

    Beatty, S J; Morgan, D L

    2017-03-01

    Following the complete eradication of the alien piscivorous perch Perca fluviatilis from a potable reservoir, the abundance of the endemic western minnow Galaxias occidentalis, which was previously undetectable prior to the initial eradication event, increased dramatically. The study reveals the potential of reservoirs to act as ecological refuges and has implications for understanding the relative effects of alien fishes v. habitat alteration on native freshwater fishes. © 2016 The Fisheries Society of the British Isles.

  14. Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life1

    OpenAIRE

    Smith, Norah L.; Wissink, Erin; Wang, Jocelyn; Pinello, Jennifer F.; Davenport, Miles P.; Grimson, Andrew; Rudd, Brian D.

    2014-01-01

    Neonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. Here we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. While adult CD8+ T cells differentiated into a heter...

  15. Effects of auxins on the production of steroidal alkaloids in rapidly proliferating tissue and cell cultures of Solanum lyratum.

    Science.gov (United States)

    Kuo, Chung-Io; Chao, Chi-Hsein; Lu, Mei-Kuang

    2012-01-01

    Solanum lyratum, a rare species, is used to treat cancer, tumours and warts. Plant cell and tissue culture of S. lyratum, producing steroidal alkaloids, could be useful supplements to natural sources. To study the production of solanine, solanidine and solasodine by adding auxin-type phytohormones including indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D) to cell and callus cultures of S. lyratum. Methanolic extracts were made from callus and cell cultures of S. lyratumand and analysed using RP C₁₈ HPLC with UV detection. 2,4-D-induced calli from roots led to a significant enhancement in solanine production with a value of 4.13 mg/g dry weight (DW). The maximal solanidine and solasodine levels of 6.26 and 7.69 mg/g DW were respectively obtained with IBA- and IAA-treated S. lyratum cells at concentrations of 1 and 5 mg/L. Auxins were found to be useful phytohormones for the production of steroidal alkaloids. The callus and cell culture system developed is simple and can hence be a method of production of steroidal alkaloids in S. lyratum and other Solanaceae species. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Formation of telomeric repeat-containing RNA (TERRA) foci in highly proliferating mouse cerebellar neuronal progenitors and medulloblastoma.

    Science.gov (United States)

    Deng, Zhong; Wang, Zhuo; Xiang, Chaomei; Molczan, Aliah; Baubet, Valérie; Conejo-Garcia, Jose; Xu, Xiaowei; Lieberman, Paul M; Dahmane, Nadia

    2012-09-15

    Telomeres play crucial roles in the maintenance of genome integrity and control of cellular senescence. Most eukaryotic telomeres can be transcribed to generate a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous nuclear RNA and can be developmentally regulated. However, the precise function and regulation of TERRA in normal and cancer cell development remains poorly understood. Here, we show that TERRA accumulates in highly proliferating normal and cancer cells, and forms large nuclear foci, which are distinct from previously characterized markers of DNA damage or replication stress. Using a mouse model for medulloblastoma driven by chronic Sonic hedgehog (SHH) signaling, TERRA RNA was detected in tumor, but not adjacent normal cells using both RNA fluorescence in situ hybridization (FISH) and northern blotting. RNA FISH revealed the formation of TERRA foci (TERFs) in the nuclear regions of rapidly proliferating tumor cells. In the normal developing cerebellum, TERRA aggregates could also be detected in highly proliferating zones of progenitor neurons. SHH could enhance TERRA expression in purified granule progenitor cells in vitro, suggesting that proliferation signals contribute to TERRA expression in responsive tissue. TERRA foci did not colocalize with γH2AX foci, promyelocytic leukemia (PML) or Cajal bodies in mouse tumor tissue. We also provide evidence that TERRA is elevated in a variety of human cancers. These findings suggest that elevated TERRA levels reflect a novel early form of telomere regulation during replication stress and cancer cell evolution, and the TERRA RNA aggregates may form a novel nuclear body in highly proliferating mammalian cells.

  17. Viability and proliferation of endothelial cells upon exposure to GaN nanoparticles

    Directory of Open Access Journals (Sweden)

    Tudor Braniste

    2016-09-01

    Full Text Available Nanotechnology is a rapidly growing and promising field of interest in medicine; however, nanoparticle–cell interactions are not yet fully understood. The goal of this work was to examine the interaction between endothelial cells and gallium nitride (GaN semiconductor nanoparticles. Cellular viability, adhesion, proliferation, and uptake of nanoparticles by endothelial cells were investigated. The effect of free GaN nanoparticles versus the effect of growing endothelial cells on GaN functionalized surfaces was examined. To functionalize surfaces with GaN, GaN nanoparticles were synthesized on a sacrificial layer of zinc oxide (ZnO nanoparticles using hydride vapor phase epitaxy. The uptake of GaN nanoparticles by porcine endothelial cells was strongly dependent upon whether they were fixed to the substrate surface or free floating in the medium. The endothelial cells grown on surfaces functionalized with GaN nanoparticles demonstrated excellent adhesion and proliferation, suggesting good biocompatibility of the nanostructured GaN.

  18. Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Handgretinger Rupert

    2010-01-01

    Full Text Available Abstract Background Human multipotent mesenchymal stromal cells (MSC can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. Results After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Conclusion Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

  19. Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation.

    Science.gov (United States)

    Jackson, Laura E; Kulkarni, Sucheta; Wang, Huabo; Lu, Jie; Dolezal, James M; Bharathi, Sivakama S; Ranganathan, Sarangarajan; Patel, Mulchand S; Deshpande, Rahul; Alencastro, Frances; Wendell, Stacy G; Goetzman, Eric S; Duncan, Andrew W; Prochownik, Edward V

    2017-11-01

    Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC "knockout" (KO) animals, the long-term regenerative potential of hepatocytes was unimpaired, and growth of aggressive experimental hepatoblastomas was only modestly slowed in the face of 80%-90% reductions in AcCoA and significant alterations in the levels of key tricarboxylic acid (TCA) cycle intermediates and amino acids. Overall, oxphos activity in KO livers and hepatoblastoma was comparable with that of control counterparts, with evidence that metabolic substrate abnormalities were compensated for by increased mitochondrial mass. These findings demonstrate that the biochemical link between glycolysis and the TCA cycle can be completely severed without affecting normal or neoplastic proliferation, even under the most demanding circumstances. Cancer Res; 77(21); 5795-807. ©2017 AACR. ©2017 American Association for Cancer Research.

  20. Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration

    Directory of Open Access Journals (Sweden)

    Shuo Luan

    2015-01-01

    Full Text Available Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls. The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF and nucleus pulposus (NP. Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use.

  1. Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration.

    Directory of Open Access Journals (Sweden)

    Chuanyong Pan

    Full Text Available Liver regeneration (LR after partial hepatectomy (PH involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells.

  2. Glycogen serves as an energy source that maintains astrocyte cell proliferation in the neonatal telencephalon.

    Science.gov (United States)

    Gotoh, Hitoshi; Nomura, Tadashi; Ono, Katsuhiko

    2017-06-01

    Large amounts of energy are required when cells undergo cell proliferation and differentiation for mammalian neuronal development. Early neonatal mice face transient starvation and use stored energy for survival or to support development. Glycogen is a branched polysaccharide that is formed by glucose, and serves as an astrocytic energy store for rapid energy requirements. Although it is present in radial glial cells and astrocytes, the role of glycogen during development remains unclear. In the present study, we demonstrated that glycogen accumulated in glutamate aspartate transporter (GLAST)+ astrocytes in the subventricular zone and rostral migratory stream. Glycogen levels markedly decreased after birth due to the increase of glycogen phosphorylase, an essential enzyme for glycogen metabolism. In primary cultures and in vivo, the inhibition of glycogen phosphorylase decreased the proliferation of astrocytic cells. The number of cells in the G1 phase increased in combination with the up-regulation of cyclin-dependent kinase inhibitors or down-regulation of the phosphorylation of retinoblastoma protein (pRB), a determinant for cell cycle progression. These results suggest that glycogen accumulates in astrocytes located in specific areas during the prenatal stage and is used as an energy source to maintain normal development in the early postnatal stage.

  3. Investigation of In Vitro Bone Cell Adhesion and Proliferation on Ti Using Direct Current Stimulation.

    Science.gov (United States)

    Bodhak, Subhadip; Bose, Susmita; Kinsel, William C; Bandyopadhyay, Amit

    2012-12-01

    Our objective was to establish an in vitro cell culture protocol to improve bone cell attachment and proliferation on Ti substrate using direct current stimulation. For this purpose, a custom made electrical stimulator was developed and a varying range of direct currents, from 5 to 25 µA, were used to study the current stimulation effect on bone cells cultured on conducting Ti samples in vitro. Cell-materials interaction was studied for a maximum of 5 days by culturing with human fetal osteoblast cells (hFOB). The direct current was applied in every 8 h time interval and the duration of electrical stimulation was kept constant at 15 min for all cases. In vitro results showed that direct current stimulation significantly favored bone cell attachment and proliferation in comparison to nonstimulated Ti surface. Immunochemistry and confocal microscopy results confirmed that the cell adhesion was most pronounced on 25 µA direct current stimulated Ti surfaces as hFOB cells expressed higher vinculin protein with increasing amount of direct current. Furthermore, MTT assay results established that cells grew 30% higher in number under 25 µA electrical stimulation as compared to nonstimulated Ti surface after 5 days of culture period. In this work we have successfully established a simple and cost effective in vitro protocol offering easy and rapid analysis of bone cell-materials interaction which can be used in promotion of bone cell attachment and growth on Ti substrate using direct current electrical stimulation in an in vitro model.

  4. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Qian-Kun Yang

    2013-01-01

    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  5. Lipotoxicity in the Pancreatic Beta Cell: Not Just Survival and Function, but Proliferation as Well?

    Science.gov (United States)

    Sharma, Rohit B.; Alonso, Laura C.

    2014-01-01

    Free fatty acids (FFAs) exert both positive and negative effects on beta cell survival and insulin secretory function, depending on concentration, duration, and glucose abundance. Lipid signals are mediated not only through metabolic pathways, but also through cell surface and nuclear receptors. Toxicity is modulated by positive signals arising from circulating factors such as hormones, growth factors and incretins, as well as negative signals such as inflammatory mediators and cytokines. Intracellular mechanisms of lipotoxicity include metabolic interference and cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and possibly autophagy. New findings strengthen an old hypothesis that lipids may also impair compensatory beta cell proliferation. Clinical observations continue to support a role for lipid biology in the risk and progression of both type 1 (T1D) and type 2 diabetes (T2D). This review summarizes recent work in this important, rapidly evolving field. PMID:24740729

  6. Metformin inhibits the proliferation of benign prostatic epithelial cells.

    Directory of Open Access Journals (Sweden)

    Zongwei Wang

    Full Text Available Benign prostatic hyperplasia (BPH is the most common proliferative abnormality of the prostate affecting elderly men throughout the world. Epidemiologic studies have shown that diabetes significantly increases the risk of developing BPH, although whether anti-diabetic medications preventing the development of BPH remains to be defined. We have previously found that stromally expressed insulin-like growth factor 1 (IGF-1 promotes benign prostatic epithelial cell proliferation through paracrine mechanisms. Here, we seek to understand if metformin, a first line medication for the treatment of type 2 diabetes, inhibits the proliferation of benign prostatic epithelial cells through reducing the expression of IGF-1 receptor (IGF-1R and regulating cell cycle.BPE cell lines BPH-1 and P69, murine fibroblasts3T3 and primary human prostatic fibroblasts were cultured and tested in this study. Cell proliferation and the cell cycle were analyzed by MTS assay and flow cytometry, respectively. The expression of IGF-1R was determined by western-blot and immunocytochemistry. The level of IGF-1 secretion in culture medium was measured by ELISA.Metformin (0.5-10mM, 6-48h significantly inhibited the proliferation of BPH-1 and P69 cells in a dose-dependent and time-dependent manner. Treatment with metformin for 24 hours lowered the G2/M cell population by 43.24% in P69 cells and 24.22% in BPH-1 cells. On the other hand, IGF-1 (100ng/mL, 24h stimulated the cell proliferation (increased by 28.81% in P69 cells and 20.95% in BPH-1 cells and significantly enhanced the expression of IGF-1R in benign prostatic epithelial cells. Metformin (5mM abrogated the proliferation of benign prostatic epithelial cells induced by IGF-1. In 3T3 cells, the secretion of IGF-1 was significantly inhibited by metformin from 574.31pg/ml to 197.61pg/ml. The conditioned media of 3T3 cells and human prostatic fibroblasts promoted the proliferation of epithelial cells and the expression of IGF-1R

  7. Cells proliferating in vitro to local brain injury are primarily of hematic origin and differ from those associated with anterograde degeneration.

    Science.gov (United States)

    Katz, I R; Iacovitti, L; Reis, D J

    1988-01-01

    (a) The PR elicited by excitotoxic destruction of intrinsic neurons in the CN has a rapid onset, peaks within 2 weeks, and persists indefinitely; (b) the majority of the proliferating cells are not intrinsic to the CNS but are of hematic origin; (c) a small mirror-image response is seen in the contralateral CN; (d) the proliferating response in anterogradely degenerating terminals in SN differs in time course, magnitude, and phenotypically from that initiated by direct neuronal loss. We conclude that the majority of proliferating cells at the site of selective neuronal injury in brain are of hematic origin in contrast to that initiated during anterograde degeneration, which consists primarily of intrinsic cells of brain (glia).

  8. Cell proliferation in cubozoan jellyfish Tripedalia cystophora and Alatina moseri.

    Directory of Open Access Journals (Sweden)

    Daniela Gurska

    Full Text Available Cubozoans (box jellyfish undergo remarkable body reorganization throughout their life cycle when, first, they metamorphose from swimming larvae to sessile polyps, and second, through the metamorphosis from sessile polyps to free swimming medusae. In the latter they develop complex structures like the central nervous system (CNS and visual organs. In the present study several aspects of cell proliferation at different stages of the life cycle of the box jellyfish Tripedalia cystophora and Alatina moseri have been examined through in vivo labeling of cells in the synthetic phase (S phase of the cell cycle. Proliferation zones were found in metamorphosing polyps, as well as in juvenile medusae, where both the rhopalia and pedalia have enhanced rates of proliferation. The results also indicate a rather fast cell turnover in the rhopalia including the rhopalial nervous system (RNS. Moreover, T. cystophora showed diurnal pattern of cell proliferation in certain body parts of the medusa, with higher proliferation rates at nighttime. This is true for two areas in close connection with the CNS: the stalk base and the rhopalia.

  9. Cell proliferation in cubozoan jellyfish Tripedalia cystophora and Alatina moseri.

    Science.gov (United States)

    Gurska, Daniela; Garm, Anders

    2014-01-01

    Cubozoans (box jellyfish) undergo remarkable body reorganization throughout their life cycle when, first, they metamorphose from swimming larvae to sessile polyps, and second, through the metamorphosis from sessile polyps to free swimming medusae. In the latter they develop complex structures like the central nervous system (CNS) and visual organs. In the present study several aspects of cell proliferation at different stages of the life cycle of the box jellyfish Tripedalia cystophora and Alatina moseri have been examined through in vivo labeling of cells in the synthetic phase (S phase) of the cell cycle. Proliferation zones were found in metamorphosing polyps, as well as in juvenile medusae, where both the rhopalia and pedalia have enhanced rates of proliferation. The results also indicate a rather fast cell turnover in the rhopalia including the rhopalial nervous system (RNS). Moreover, T. cystophora showed diurnal pattern of cell proliferation in certain body parts of the medusa, with higher proliferation rates at nighttime. This is true for two areas in close connection with the CNS: the stalk base and the rhopalia.

  10. Endogenous Proliferation after Spinal Cord Injury in Animal Models

    Science.gov (United States)

    McDonough, Ashley; Martínez-Cerdeño, Verónica

    2012-01-01

    Spinal cord injury (SCI) results in motor and sensory deficits, the severity of which depends on the level and extent of the injury. Animal models for SCI research include transection, contusion, and compression mouse models. In this paper we will discuss the endogenous stem cell response to SCI in animal models. All SCI animal models experience a similar peak of cell proliferation three days after injury; however, each specific type of injury promotes a specific and distinct stem cell response. For example, the transection model results in a strong and localized initial increase of proliferation, while in contusion and compression models, the initial level of proliferation is lower but encompasses the entire rostrocaudal extent of the spinal cord. All injury types result in an increased ependymal proliferation, but only in contusion and compression models is there a significant level of proliferation in the lateral regions of the spinal cord. Finally, the fate of newly generated cells varies from a mainly oligodendrocyte fate in contusion and compression to a mostly astrocyte fate in the transection model. Here we will discuss the potential of endogenous stem/progenitor cell manipulation as a therapeutic tool to treat SCI. PMID:23316243

  11. Endogenous Proliferation after Spinal Cord Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Ashley McDonough

    2012-01-01

    Full Text Available Spinal cord injury (SCI results in motor and sensory deficits, the severity of which depends on the level and extent of the injury. Animal models for SCI research include transection, contusion, and compression mouse models. In this paper we will discuss the endogenous stem cell response to SCI in animal models. All SCI animal models experience a similar peak of cell proliferation three days after injury; however, each specific type of injury promotes a specific and distinct stem cell response. For example, the transection model results in a strong and localized initial increase of proliferation, while in contusion and compression models, the initial level of proliferation is lower but encompasses the entire rostrocaudal extent of the spinal cord. All injury types result in an increased ependymal proliferation, but only in contusion and compression models is there a significant level of proliferation in the lateral regions of the spinal cord. Finally, the fate of newly generated cells varies from a mainly oligodendrocyte fate in contusion and compression to a mostly astrocyte fate in the transection model. Here we will discuss the potential of endogenous stem/progenitor cell manipulation as a therapeutic tool to treat SCI.

  12. Ethylene Inhibits Cell Proliferation of the Arabidopsis Root Meristem.

    Science.gov (United States)

    Street, Ian H; Aman, Sitwat; Zubo, Yan; Ramzan, Aleena; Wang, Xiaomin; Shakeel, Samina N; Kieber, Joseph J; Schaller, G Eric

    2015-09-01

    The root system of plants plays a critical role in plant growth and survival, with root growth being dependent on both cell proliferation and cell elongation. Multiple phytohormones interact to control root growth, including ethylene, which is primarily known for its role in controlling root cell elongation. We find that ethylene also negatively regulates cell proliferation at the root meristem of Arabidopsis (Arabidopsis thaliana). Genetic analysis indicates that the inhibition of cell proliferation involves two pathways operating downstream of the ethylene receptors. The major pathway is the canonical ethylene signal transduction pathway that incorporates CONSTITUTIVE TRIPLE RESPONSE1, ETHYLENE INSENSITIVE2, and the ETHYLENE INSENSITIVE3 family of transcription factors. The secondary pathway is a phosphorelay based on genetic analysis of receptor histidine kinase activity and mutants involving the type B response regulators. Analysis of ethylene-dependent gene expression and genetic analysis supports SHORT HYPOCOTYL2, a repressor of auxin signaling, as one mediator of the ethylene response and furthermore, indicates that SHORT HYPOCOTYL2 is a point of convergence for both ethylene and cytokinin in negatively regulating cell proliferation. Additional analysis indicates that ethylene signaling contributes but is not required for cytokinin to inhibit activity of the root meristem. These results identify key elements, along with points of cross talk with cytokinin and auxin, by which ethylene negatively regulates cell proliferation at the root apical meristem. © 2015 American Society of Plant Biologists. All Rights Reserved.

  13. Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells.

    Science.gov (United States)

    Meng, Meng; Chen, Shuyang; Lao, Taotao; Liang, Dongming; Sang, Nianli

    2010-10-01

    Glutaminolysis and Warburg effect are the two most noticeable metabolic features of tumor cells whereas their biological significance in cell proliferation remains elusive. A widely accepted current hypothesis is that tumor cells use glutamine as a preferred carbon source for energy and reducing power, which has been used to explain both glutaminolysis and the Warburg effect. Here we provide evidence to show that supplying nitrogen, not the carbon skeleton, underlies the major biological importance of glutaminolysis for proliferating cells. We show alternative nitrogen supplying mechanisms rescue cell proliferation in glutamine-free media. Particularly, we show that ammonia is sufficient to maintain a long-term survival and proliferation of Hep3B in glutamine-free media. We also observed that nitrogen source restriction repressed carbon metabolic pathways including glucose utilization. Based on these new observations and metabolic pathways well established in published literature, we propose an alternative model that cellular demand for glutamate as a key molecule in nitrogen anabolism is the driving force of glutaminolysis in proliferating cells. Our model suggests that the Warburg effect may be a metabolic consequence secondary to the nitrogen anabolism.

  14. Composites by rapid prototyping technology

    CSIR Research Space (South Africa)

    Kumar, S

    2010-02-01

    Full Text Available powder is a fiber, problems of manufacturing occur. The method has also been used to make Metal Matrix Composite (MMC), e.g Fe and graphite [17], WC-Co [18,19], WC-Co and Cu [20,21], Fe, Ni and TiC [22] etc and Ceramic Matrix Composite (CMC) e.g. Si... of various materials used. Key words: : Rapid Prototyping (RP), Laser, Composites 1 Introduction Rapid Prototyping (RP) initially focussed on polymers. These were later re- placed/supplemented by ceramics, metals and composites. Composites are used in RP...

  15. Polo-Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early Lineage Specification Downstream of Yes-Associated Protein 1 in Cardiac Progenitor Cells.

    Science.gov (United States)

    Mochizuki, Michika; Lorenz, Vera; Ivanek, Robert; Della Verde, Giacomo; Gaudiello, Emanuele; Marsano, Anna; Pfister, Otmar; Kuster, Gabriela M

    2017-10-24

    Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (Yes-associated protein (YAP) conserved signature and TEA domain family member 1 (TEAD1)-related genes. This early gene regulation was preceded by the rapid cytosolic sequestration and degradation of YAP on laminin. Among the most strongly regulated genes was polo-like kinase 2 (Plk2). Plk2 expression depended on YAP stability and was enhanced in CPCs transfected with a nuclear-targeted mutant YAP. Phenotypically, the early downregulation of Plk2 on laminin was succeeded by lower cell proliferation, enhanced lineage gene expression (24 hours), and facilitated differentiation (3 weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC proliferation and knockdown of Plk2 induced the expression of lineage genes. Plk2 acts as coordinator of cell proliferation and early lineage commitment in CPCs. The rapid downregulation of Plk2 on YAP inactivation marks a switch towards enhanced commitment and facilitated differentiation. These findings link early gene regulation to cell fate and provide novel insights into how CPC proliferation and differentiation are orchestrated. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Cell proliferation regulated by CO/sub 2/

    Energy Technology Data Exchange (ETDEWEB)

    Laszlo, E.; Novak, B.

    1986-01-01

    Microbial and mammalian cells don't proliferate when the CO/sub 2/ is removed from culture liquid. This means that CO/sub 2/ fixation is required for cell proliferation. CO/sub 2/ fixation is needed for the tricarboxylic acid cycle (TCAC), for purine and pyrimidine synthesis, and for lipid synthesis. Adding the purine and pyrimidine precursors and fatty acids into cell cultures, they examined the role of CO/sub 2/ in TCAC. When the CO/sub 2/ concentration increased inside the cell, increases were observed . By oversaturation of the respiration chain the alternative oxydases produce hydroxyl radicals, which cause DNA damage. The role of CO/sub 2/ in normal and abnormal cell proliferation is discussed.

  17. Regulation of germline stem cell proliferation downstream of nutrient sensing

    Directory of Open Access Journals (Sweden)

    Roy Richard

    2006-12-01

    Full Text Available Abstract Stem cells have recently attracted significant attention largely due to their potential therapeutic properties, but also because of their role in tumorigenesis and their resemblance, in many aspects, to cancerous cells. Understanding how stem cells are regulated, namely with respect to the control of their proliferation and differentiation within a functional organism, is thus primordial to safely profit from their therapeutic benefits. Here, we review recent advances in the understanding of germline stem cell proliferation control by factors that respond to the nutritional status and/or insulin signaling, through studies performed in C. elegans and Drosophila. Together, these data uncover some shared fundamental features that underlie the central control of cellular proliferation within a target stem cell population in an organism. These features may indeed be conserved in higher organisms and may apply to various other stem cell populations.

  18. Chemical Methods to Induce Beta-Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Amedeo Vetere

    2012-01-01

    Full Text Available Pancreatic beta-cell regeneration, for example, by inducing proliferation, remains an important goal in developing effective treatments for diabetes. However, beta cells have mainly been considered quiescent. This “static” view has recently been challenged by observations of relevant physiological conditions in which metabolic stress is compensated by an increase in beta-cell mass. Understanding the molecular mechanisms underlining these process could open the possibility of developing novel small molecules to increase beta-cell mass. Several cellular cell-cycle and signaling proteins provide attractive targets for high throughput screening, and recent advances in cell culture have enabled phenotypic screening for small molecule-induced beta-cell proliferation. We present here an overview of the current trends involving small-molecule approaches to induce beta-cell regeneration by proliferation.

  19. Lymphocyte mitogen-induced proliferation in patients with allergic rhinitis

    Energy Technology Data Exchange (ETDEWEB)

    Chorostowska-Wynimko, J.; Kleniewska, D.; Sokolnicka, I.; Rogala, E.; Skopinska-Rozewska, E. [Dept. of Immunology. Institute of Tuberculosis and Lung Diseases, Warsaw (Poland)

    1995-12-31

    Lymphocytes play a central regulatory role in mechanisms contributing to impaired function of immune system in atopy. The aim of our study was evaluate the mitogen-induced proliferation of lymphocytes in a group of asymptomatic, seasonal allergic rhinitis patients. A highly significant lower mitogen-induced proliferation and, in contrast to other studies, significantly lower background proliferative activity of lymphocytes were found in the atopic persons, comparing to the controls. We concluded that the decreased mitogen-induced proliferation of lymphocytes observed in allergic patients reflects abnormal T cell function, which is due to the atopic status, and not only as it was believed to the antigen-induced lymphocyte activation. (author). 26 refs, 1 tab.

  20. A new parameter of growth inhibition for cell proliferation assays.

    Science.gov (United States)

    Fiorentino, Francesco P; Bagella, Luigi; Marchesi, Irene

    2017-10-12

    Cell proliferation assays are performed by four decades to test the anti-proliferative activity of natural products and synthetic compounds in cell cultures. In cancer research, they are widely employed to evaluate drug efficacy in in vitro tumor models, such as established cell lines, primary cultures, and recently developed three-dimensional tumor organoids. In this manuscript, we demonstrated that current employed parameters used by researchers to quantify in vitro growth inhibition, IC50 and GI50 , lead to a misinterpretation of results based on the exponential, and not linear, proliferation of the cells in culture. Therefore, we introduce a new parameter for the analysis of growth inhibition in cell proliferation assays, termed relative population doubling capacity, that can be employed to properly quantify the anti-proliferative activity of tested compounds and to compare drug efficacy between distinct cell models. © 2017 Wiley Periodicals, Inc.

  1. Zag expression during aging suppresses proliferation after kidney injury.

    Science.gov (United States)

    Schmitt, Roland; Marlier, Arnaud; Cantley, Lloyd G

    2008-12-01

    Recovery after acute kidney injury is impaired in the elderly, but mechanistic information regarding why this occurs is limited. In this study, aged mouse kidneys displayed a reduced epithelial proliferative reserve in vivo and in vitro. Microarray analysis identified increased expression of zinc-alpha (2)-glycoprotein (Zag) in aged proximal tubular cells. The addition of recombinant Zag to primary renal epithelial cell cultures decreased proliferation, whereas knockdown of Zag increased proliferation. In vivo, systemic small interference RNA suppressed expression of Zag in the mouse proximal tubule; this increased the rate of epithelial cell proliferation after renal ischemia/reperfusion in aged mice but also increased parenchymal fibrosis. These results demonstrate that increased Zag expression in the aged kidney acts to suppress the proliferative response to injury and introduce Zag as a modifier of the aging phenotype.

  2. Identification of Predictive Gene Markers for Multipotent Stromal Cell Proliferation.

    Science.gov (United States)

    Bellayr, Ian H; Marklein, Ross A; Lo Surdo, Jessica L; Bauer, Steven R; Puri, Raj K

    2016-06-01

    Multipotent stromal cells (MSCs) are known for their distinctive ability to differentiate into different cell lineages, such as adipocytes, chondrocytes, and osteocytes. They can be isolated from numerous tissue sources, including bone marrow, adipose tissue, skeletal muscle, and others. Because of their differentiation potential and secretion of growth factors, MSCs are believed to have an inherent quality of regeneration and immune suppression. Cellular expansion is necessary to obtain sufficient numbers for use; however, MSCs exhibit a reduced capacity for proliferation and differentiation after several rounds of passaging. In this study, gene markers of MSC proliferation were identified and evaluated for their ability to predict proliferative quality. Microarray data of human bone marrow-derived MSCs were correlated with two proliferation assays. A collection of 24 genes were observed to significantly correlate with both proliferation assays (|r| >0.70) for eight MSC lines at multiple passages. These 24 identified genes were then confirmed using an additional set of MSCs from eight new donors using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The proliferative potential of the second set of MSCs was measured for each donor/passage for confluency fraction, fraction of EdU+ cells, and population doubling time. The second set of MSCs exhibited a greater proliferative potential at passage 4 in comparison to passage 8, which was distinguishable by 15 genes; however, only seven of the genes (BIRC5, CCNA2, CDC20, CDK1, PBK, PLK1, and SPC25) demonstrated significant correlation with MSC proliferation regardless of passage. Our analyses revealed that correlation between gene expression and proliferation was consistently reduced with the inclusion of non-MSC cell lines; therefore, this set of seven genes may be more strongly associated with MSC proliferative quality. Our results pave the way to determine the quality of an MSC population for a

  3. Developmental evolution facilitates rapid adaptation.

    Science.gov (United States)

    Lin, Hui; Kazlauskas, Romas J; Travisano, Michael

    2017-11-21

    Developmental evolution has frequently been identified as a mode for rapid adaptation, but direct observations of the selective benefits and associated mechanisms of developmental evolution are necessarily challenging to obtain. Here we show rapid evolution of greatly increased rates of dispersal by developmental changes when populations experience stringent selection. Replicate populations of the filamentous fungus Trichoderma citrinoviride underwent 85 serial transfers, under conditions initially favoring growth but not dispersal. T. citrinoviride populations shifted away from multicellular growth toward increased dispersal by producing one thousand times more single-celled asexual conidial spores, three times sooner than the ancestral genotype. Conidia of selected lines also germinated fifty percent faster. Gene expression changed substantially between the ancestral and selected fungi, especially for spore production and growth, demonstrating rapid evolution of tight regulatory control for down-regulation of growth and up-regulation of conidia production between 18 and 24 hours of growth. These changes involved both developmentally fixed and plastic changes in gene expression, showing that complex developmental changes can serve as a mechanism for rapid adaptation.

  4. Multigrade Teaching Rapid Appraisal Procedure.

    Science.gov (United States)

    Nielsen, Dean

    Multigrade classes have been recognized as part of elementary education for many years, but their special needs have been largely ignored. This manual focuses on the survey research that should predate the design of instructional management strategies in multigrade classrooms. It describes rapid and reliable ways to collect information about the…

  5. Rapid thermal processing of semiconductors

    CERN Document Server

    Borisenko, Victor E

    1997-01-01

    Rapid thermal processing has contributed to the development of single wafer cluster processing tools and other innovations in integrated circuit manufacturing environments Borisenko and Hesketh review theoretical and experimental progress in the field, discussing a wide range of materials, processes, and conditions They thoroughly cover the work of international investigators in the field

  6. Furnace for rapid thermal processing

    NARCIS (Netherlands)

    Roozeboom, F.; Duine, P.A.; Sluis, P. van der

    2001-01-01

    A Method (1) for Rapid Thermal Processing of a wafer (7), wherein the wafer (7) is heated by lamps (9), and the heat radiation is reflected by an optical switching device (15,17) which is in the reflecting state during the heating stage. During the cooling stage of the wafer (7), the heat is

  7. Rapid Energy Modeling Workflow Demonstration

    Science.gov (United States)

    2013-10-31

    BIM Building Information Modeling BPA Building Performance Analysis BTU British Thermal Unit CBECS Commercial Building ...geometry, orientation, weather, and materials, generates 3D Building Information Models ( BIM ) guided by satellite views of building footprints and...Rapid Energy Modeling (REM) workflows that employed building information modeling ( BIM ) approaches and conceptual energy analysis.

  8. Portable Diagnostics and Rapid Germination

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Zachary Spencer [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-12-01

    In the Bioenergy and Defense Department of Sandia National Laboratories, characterization of the BaDx (Bacillus anthracis diagnostic cartridge) was performed and rapid germination chemistry was investigated. BaDx was tested with complex sample matrixes inoculated with Bacillus anthracis, and the trials proved that BaDx will detect Bacillus anthracis in a variety of the medium, such as dirt, serum, blood, milk, and horse fluids. The dimensions of the device were altered to accommodate an E. coli or Listeria lateral flow immunoassay, and using a laser printer, BaDx devices were manufactured to identify E. coli and Listeria. Initial testing with E. coli versions of BaDx indicate that the device will be viable as a portable diagnostic cartridge. The device would be more effective with faster bacteria germination; hence studies were performed the use of rapid germination chemistry. Trials with calcium dipicolinic acid displayed increased cell germination, as shown by control studies using a microplate reader. Upon lyophilization the rapid germination chemistry failed to change growth patterns, indicating that the calcium dipicolinic acid was not solubilized under the conditions tested. Although incompatible with the portable diagnostic device, the experiments proved that the rapid germination chemistry was effective in increasing cell germination.

  9. Monovalent ions control proliferation of Ehrlich Lettre ascites cells

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Preisler, Sarah; Pedersen, Stine Helene Falsig

    2010-01-01

    of Ehrlich Lettre ascites (ELA) cells. We measured the intracellular concentration of each ion in G(0), G(1), and S phases of the cell cycle following synchronization by serum starvation and release. We show that intracellular concentrations and content of Na+ and Cl(-) were reduced in the G(0)-G(1) phase...... effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G(1). Our results suggest that Na+ regulates ELA cell proliferation by regulating intracellular pH while Cl(-) may regulate proliferation by fine...

  10. Gastrin-induced proliferation involves MEK partner 1 (MP1)

    OpenAIRE

    Steigedal, Tonje S; Prestvik, Wenche S.; Selvik, Linn-Karina M.; Christina S Fjeldbo; Bruland, Torunn; L?greid, Astrid; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is an important factor for the maintenance and homeostasis of the gastric mucosa. We show that gastrin stimulates proliferation in a dose-dependent manner in the human gastric adenocarcinoma cell line AGS-GR. Furthermore, we demonstrate that the MAPK scaffold protein MEK partner 1 (MP1) is important for gastrin-induced phosphorylation of ERK1 and ERK2 and that MP1 promotes gastrin-induced proliferation of AGS-GR cells. Our results suggest a role of MP1 in gastrin-i...

  11. The Effect of Cultivated Wild Ginseng Extract on Preadipocyte Proliferation

    Directory of Open Access Journals (Sweden)

    Byoung-Woo Kim

    2007-12-01

    Full Text Available Objectives : The purpose of this study is to investigate the effects of cultivated wild ginseng extract on primary cultured preadipocyte and adipocytes. Methods : Diminish preadipocyte proliferation does primary role to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures with using Sprague-Dawley rats and treated with 0.01-1mg/㎖ cultivated wild ginseng extract. Result : At all concentrations, cultivated wild ginseng extract wasn't show the suppress proliferation of preadipocytes significantly and failed to show effects on decomposition of adipocytes except high dosage. Conclusion : Based on these findings, cultivated wild ginseng is not a suitable choice for the treatment of localized obesity.

  12. Inhibition of brain tumor cell proliferation by alternating electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hyesun; Oh, Seung-ick; Hong, Sunghoi, E-mail: shong21@korea.ac.kr, E-mail: radioyoon@korea.ac.kr [School of Biosystem and Biomedical Science, Korea University, Seoul 136-703 (Korea, Republic of); Sung, Jiwon; Jeong, Seonghoon; Yoon, Myonggeun, E-mail: shong21@korea.ac.kr, E-mail: radioyoon@korea.ac.kr [Department of Bio-convergence Engineering, Korea University, Seoul 136-703 (Korea, Republic of); Koh, Eui Kwan [Seoul Center, Korea Basic Science Institute, Seoul 136-713 (Korea, Republic of)

    2014-11-17

    This study was designed to investigate the mechanism by which electric fields affect cell function, and to determine the optimal conditions for electric field inhibition of cancer cell proliferation. Low-intensity (<2 V/cm) and intermediate-frequency (100–300 kHz) alternating electric fields were applied to glioblastoma cell lines. These electric fields inhibited cell proliferation by inducing cell cycle arrest and abnormal mitosis due to the malformation of microtubules. These effects were significantly dependent on the intensity and frequency of applied electric fields.

  13. Nuclear disarmament and non-proliferation : towards a nuclear-weapon-free world?

    OpenAIRE

    Lodgaard, Sverre

    2011-01-01

    This book examines the current debate on nuclear non-proliferation and disarmament, notably the international non-proliferation regime and how to implement its disarmament provisions. Discussing the requirements of a new international consensus on nuclear disarmament and non-proliferation, this book builds on the three pillars of the nuclear non-proliferation treaty (NPT): non-proliferation, disarmament and peaceful uses of nuclear energy. It reviews the impact of Cold War and post-Cold War p...

  14. Balancing proliferation with Igκ recombination during B lymphopoiesis

    Directory of Open Access Journals (Sweden)

    Keith Michael Hamel

    2014-04-01

    Full Text Available The essential events of B-cell development are the stochastic and sequential rearrangement of immunoglobulin heavy (Igμ and then light chain (Igκ followed by Igλ loci. The counterpoint to recombination is proliferation, which both maintains populations of pro-B cells undergoing Igμ recombination and expands the pool of pre-B cells expressing the Igμ protein available for subsequent Igκ recombination. Proliferation and recombination must be segregated into distinct and mutually exclusive developmental stages. Failure to do so risks aberrant gene translocation and leukemic transformation. Recent studies have demonstrated that proliferation and recombination are each affected by different and antagonistic receptors. The IL-7 receptor drives proliferation while the pre-B cell antigen receptor, which contains Igμ and surrogate light chain, enhances Igκ accessibility and recombination. Remarkably, the principal downstream proliferative effectors of the IL-7R, STAT5 and cyclin D3, directly repress Igκ accessibility through very divergent yet complementary mechanisms. Conversely, the pre-BCR represses cyclin D3 leading to cell cycle exit and enhanced Igκ accessibility. These studies reveal how cell fate decisions can be directed and reinforced at each developmental transition by single receptors. Furthermore, they identify novel mechanisms of Igκ repression that have implications for gene regulation in general.

  15. Suppression of vascular smooth muscle cells' proliferation and ...

    African Journals Online (AJOL)

    This study aimed to determine the effects of valsartan on the proliferation and migration of isolated rat vascular smooth muscle cells (VSMCs) and the expression of phospho-p42/44 mitogen-activated protein kinase (MAPK) promoted by angiotensin II (Ang II). VSMCs from the rat thoracic aorta were cultured by ...

  16. on the proliferation, differentiation and tube formation of endothelial ...

    African Journals Online (AJOL)

    Yomi

    2011-12-21

    Dec 21, 2011 ... The proliferation, apoptosis, cell cycle, migration and tube formation of EPCs were detected after the cells expose to shear stress ... stem cells that can transfer between stem cell and endothelial cells, with the ..... hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood, 90: p ...

  17. 19 Costs and Benefits of Proliferation of Christian Denominations in ...

    African Journals Online (AJOL)

    Tracie1

    proliferation, investigate the remote and immediate causes of the phenomenon with the aim to highlighting its ..... Unemployment and youths restiveness often lead to the formation and establishment of Churches .... The explosion of global Pentecostalism in Nigeria has made many overzealous pastors to open Churches in ...

  18. Electrospun fiber membranes enable proliferation of genetically modified cells.

    Science.gov (United States)

    Borjigin, Mandula; Eskridge, Chris; Niamat, Rohina; Strouse, Bryan; Bialk, Pawel; Kmiec, Eric B

    2013-01-01

    Polycaprolactone (PCL) and its blended composites (chitosan, gelatin, and lecithin) are well-established biomaterials that can enrich cell growth and enable tissue engineering. However, their application in the recovery and proliferation of genetically modified cells has not been studied. In the study reported here, we fabricated PCL-biomaterial blended fiber membranes, characterized them using physicochemical techniques, and used them as templates for the growth of genetically modified HCT116-19 colon cancer cells. Our data show that the blended polymers are highly miscible and form homogenous electrospun fiber membranes of uniform texture. The aligned PCL nanofibers support robust cell growth, yielding a 2.5-fold higher proliferation rate than cells plated on standard plastic plate surfaces. PCL-lecithin fiber membranes yielded a 2.7-fold higher rate of proliferation, while PCL-chitosan supported a more modest growth rate (1.5-fold higher). Surprisingly, PCL-gelatin did not enhance cell proliferation when compared to the rate of cell growth on plastic surfaces.

  19. Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ...

    African Journals Online (AJOL)

    Original Research Article. Chloroquinone Inhibits Cell Proliferation and Induces. Apoptosis in Nasopharyngeal Carcinoma Cell Lines. Xin-Qing Yang, Hao Zheng, Qing Ye, Rui-Yu Li* and Yong Chen. Department of Otolaryngology Head and Neck Surgery, Fujian Provincial Clinical College, Fujian Medical University, China.

  20. Knockdown of Cripto-1 inhibits the proliferation, migration, invasion ...

    Indian Academy of Sciences (India)

    Ding Wu

    2017-07-04

    Jul 4, 2017 ... markedly inhibited cell proliferation and induced cycle arrest in G1 phase, as p21 and p27 were up-regulated, whereas cyclin D1 and ... in PCa cells. These results suggested CR-1 might be served as an effective therapeutic target in PCa. ...... role of the embryonic gene Cripto-1 in cancer, stem cells and.

  1. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Goldston

    2010-03-03

    Integrated energy, environment and economics modeling suggests electrical energy use will increase from 2.4 TWe today to 12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources. Thus nuclear power may be needed to provide ~30% by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century proliferation risks are much greater, and more resistant to mitigation. The risks of nuclear power should be compared with the risks of the estimated 0.64oC long-term global surface-average temperature rise predicted if nuclear power were replaced with coal-fired power plants without carbon sequestration. Fusion energy, if developed, would provide a source of nuclear power with much lower proliferation risks than fission.

  2. Sijunzi decoction demolition parties inhibit proliferation and induce ...

    African Journals Online (AJOL)

    In order to investigate the anticancer mechanism of SD in gastric cancer, we observed the effects of SD parties (Ginseng, Atractylodes, Poria, Licorice) on proliferation and apoptosis of SP of human gastric cancer BGC-823. Materials and Methods: 1. BGC-823 side population cells were sorted through flow cytometry. 2.

  3. Effect of Eucommia ulmoides extract on osteoblast proliferation ...

    African Journals Online (AJOL)

    Thereafter, mRNA and protein expression of ALP, collagen I, osteocalcin, transforming growth factor-β1 (TGF-β1) were measured using real-time quantitative PCR (qPCR) and western blot, respectively. Results: EUE significantly (p < 0.01) promoted osteoblast proliferation at three treatment doses (180, 360, and 540 μg/mL) ...

  4. Crude extract of Nigella sativa inhibits proliferation and induces ...

    African Journals Online (AJOL)

    admin

    2012-08-09

    Aug 9, 2012 ... including p53 and p21. These findings demonstrate that EENS inhibits proliferation and induces apoptosis in HeLa cells and suggest this extract may be a promising agent for the prevention/treatment of human cervical cancer. Key words: Nigella sativa, cervical cancers, apoptosis, caspases, cell cycle.

  5. Boko Haram group in Nigeria: religious intolerance and proliferation ...

    African Journals Online (AJOL)

    In problematising the motivations behind Boko Haram's activities against the state, academic debates have remained divided. On the one hand are scholars who attribute the violence of Boko Haram as a fallout of religious intolerance, while on the other hand, others consider the proliferation – or the widespread availability ...

  6. Effect of excess dietary copper on proliferation and differentiation of ...

    African Journals Online (AJOL)

    It was found that the application of copper sulphate doses modulates the proliferation and differentiation of stem cell progenitors and erythrocytes. Several alterations were observed and these were time- and dosedependent. Of these alterations, the predominant existence of giant pro-erythroblasts and promyeloblasts ...

  7. Baicalein and U0126 suppress bladder cancer proliferation via ...

    African Journals Online (AJOL)

    TUNEL and Annexin V/PI detection showed both baicalein and U0126 induced T24 cell apoptosis. Baicalein and U0126 significantly down-regulated MAPK signaling pathway related molecule activity in both mRNA and protein levels (p < 0.05). Conclusion: Baicalein and U0126 restrain bladder cancer cell proliferation and ...

  8. Paris polyphylla extract inhibits proliferation and promotes apoptosis ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Paris polyphylla extract (PPE) on proliferation and apoptosis in. A549 human lung cancer cells. Methods: Morphological changes were examined by microscopy in A549 cells after exposure to PPE. Trypan blue staining of living cells was used to aid the construction of the cell growth ...

  9. Paris polyphylla extract inhibits proliferation and promotes apoptosis ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Paris polyphylla extract (PPE) on proliferation and apoptosis in A549 human lung cancer cells. Methods: Morphological changes were examined by microscopy in A549 cells after exposure to PPE. Trypan blue staining of living cells was used to aid the construction of the cell growth curve ...

  10. Estimation of cell proliferation dynamics using CFSE data.

    Science.gov (United States)

    Banks, H T; Sutton, Karyn L; Thompson, W Clayton; Bocharov, Gennady; Roose, Dirk; Schenkel, Tim; Meyerhans, Andreas

    2011-01-01

    Advances in fluorescent labeling of cells as measured by flow cytometry have allowed for quantitative studies of proliferating populations of cells. The investigations (Luzyanina et al. in J. Math. Biol. 54:57-89, 2007; J. Math. Biol., 2009; Theor. Biol. Med. Model. 4:1-26, 2007) contain a mathematical model with fluorescence intensity as a structure variable to describe the evolution in time of proliferating cells labeled by carboxyfluorescein succinimidyl ester (CFSE). Here, this model and several extensions/modifications are discussed. Suggestions for improvements are presented and analyzed with respect to statistical significance for better agreement between model solutions and experimental data. These investigations suggest that the new decay/label loss and time dependent effective proliferation and death rates do indeed provide improved fits of the model to data. Statistical models for the observed variability/noise in the data are discussed with implications for uncertainty quantification. The resulting new cell dynamics model should prove useful in proliferation assay tracking and modeling, with numerous applications in the biomedical sciences.

  11. Epac inhibits migration and proliferation of human prostate carcinoma cells

    NARCIS (Netherlands)

    Grandoch, M.; Rose, A.; ter Braak, M.; Jendrossek, V.; Ruebben, H.; Fischer, J. W.; Schmidt, M.; Weber, A. A.

    2009-01-01

    BACKGROUND: It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells. METHODS: The effect of Epac activation was determined by [(3)H

  12. proliferation and shoot recovery among the east african highland ...

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    Uptake and metabolism of 6- benzyladenine in shoot proliferation of Musa and Rhododendron. Plant Cell, Tissue and. Organ Culture 25:69-74. Damasco, O.P., Smith, M.K. and Adkins, S.W.. 1996. Gibberellic acid detection of dwarf offtypes in micropropagated Cavendish bananas. Australian Journal of Experimental.

  13. Initiation, proliferation and development of micro-propagation ...

    African Journals Online (AJOL)

    ... rooting medium with an average root length of 2.4 cm. 100% hardening response was obtained in Peat moss after 21 days of transplantation in glass house. The experiments were designed in completely randomized pattern. Key words: Murashige and skoog's medium, proliferation, banana, micro propagation system.

  14. Baicalein and U0126 suppress bladder cancer proliferation via ...

    African Journals Online (AJOL)

    Results: Baicalein and U0126 suppressed bladder cancer cell T24 proliferation by blocking cell cycle in G0~G1 phase. TUNEL and Annexin V/PI detection showed both baicalein and U0126 induced T24 cell apoptosis. Baicalein and U0126 significantly down-regulated MAPK signaling pathway related molecule activity in ...

  15. Proliferation of Genetically Modified Human Cells on Electrospun Nanofiber Scaffolds

    Directory of Open Access Journals (Sweden)

    Mandula Borjigin

    2012-01-01

    Full Text Available Gene editing is a process by which single base mutations can be corrected, in the context of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs. The survival and proliferation of the corrected cells bearing modified genes, however, are impeded by a phenomenon known as reduced proliferation phenotype (RPP; this is a barrier to practical implementation. To overcome the RPP problem, we utilized nanofiber scaffolds as templates on which modified cells were allowed to recover, grow, and expand after gene editing. Here, we present evidence that some HCT116-19, bearing an integrated, mutated enhanced green fluorescent protein (eGFP gene and corrected by gene editing, proliferate on polylysine or fibronectin-coated polycaprolactone (PCL nanofiber scaffolds. In contrast, no cells from the same reaction protocol plated on both regular dish surfaces and polylysine (or fibronectin-coated dish surfaces proliferate. Therefore, growing genetically modified (edited cells on electrospun nanofiber scaffolds promotes the reversal of the RPP and increases the potential of gene editing as an ex vivo gene therapy application.

  16. Effect of yeast extract and chitosan on shoot proliferation ...

    African Journals Online (AJOL)

    This paper reported the effect of yeast extract and chitosan with combination of yeast extract on the growth and morphological changes and production of phenolics in the in vitro plantlets of Curcuma mangga. Yeast extract did not show any effect on the biomass and shoot proliferation of in vitro plantlets. However, the ...

  17. Estimation of Cell Proliferation Dynamics Using CFSE Data

    Science.gov (United States)

    Banks, H.T.; Sutton, Karyn L.; Thompson, W. Clayton; Bocharov, Gennady; Roose, Dirk; Schenkel, Tim; Meyerhans, Andreas

    2010-01-01

    Advances in fluorescent labeling of cells as measured by flow cytometry have allowed for quantitative studies of proliferating populations of cells. The investigations (Luzyanina et al. in J. Math. Biol. 54:57–89, 2007; J. Math. Biol., 2009; Theor. Biol. Med. Model. 4:1–26, 2007) contain a mathematical model with fluorescence intensity as a structure variable to describe the evolution in time of proliferating cells labeled by carboxyfluorescein succinimidyl ester (CFSE). Here, this model and several extensions/modifications are discussed. Suggestions for improvements are presented and analyzed with respect to statistical significance for better agreement between model solutions and experimental data. These investigations suggest that the new decay/label loss and time dependent effective proliferation and death rates do indeed provide improved fits of the model to data. Statistical models for the observed variability/noise in the data are discussed with implications for uncertainty quantification. The resulting new cell dynamics model should prove useful in proliferation assay tracking and modeling, with numerous applications in the biomedical sciences. PMID:20195910

  18. Cholesterol induces proliferation of chicken primordial germ cells.

    Science.gov (United States)

    Chen, Dongyang; Chen, Meijuan; Lu, Zhenping; Yang, Mengmeng; Xie, Long; Zhang, Wenxin; Xu, Huiyan; Lu, Kehuan; Lu, Yangqing

    2016-08-01

    Primordial germ cells (PGCs) are the precursors of sperm and eggs and may serve as suitable cells for use in research in developmental biology and transgenic animals. However, the long-term propagation of PGCs in vitro has so far been plagued by the loss of their germ cell characteristics. This is largely because of the scarcity of knowledge concerning cell division and proliferation in these cells and the poor optimization of the culture medium. The sonic hedgehog (SHH) signaling pathway is involved in proliferation of many types of cells, but little is known about its role in chicken PGCs. The results of the current study indicate that the proliferation of chicken PGCs increases significantly when cholesterol, a molecule that facilitates the trafficking of HH ligands, is supplemented in the culture medium. This effect was attenuated when an SHH antagonist, cyclopamine was added, suggesting the involvement of SHH signaling in this process. The characterization of PGCs treated with cholesterol has shown that these cells express germ-cell-related markers and retain their capability to colonize the embryonic gonad after re-introduction to vasculature of stage-15 HH embryos, indicating that proliferation of PGCs induced by cholesterol does not alter the germ cell characteristics of these cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Effects of growth-promoting factors on proliferation of mouse ...

    African Journals Online (AJOL)

    AJL

    2012-02-16

    Feb 16, 2012 ... Homeostatic regulation of germinal stem cell proliferation by the. GDNF/FSH pathway. Mech. Dev. 113: 29-39. Takeshi M, Chiemi M (2001). A Model for Analysis of Spermatogenesis. Zool. Sci. 18: 1055-1063. Temple S, Qian X (1995). bFGF, neurotrophins, and the control or cortical neurogenesis. Neuron.

  20. Stimulation of cell proliferation by calcium and a calcimimetic compound

    NARCIS (Netherlands)

    Mailland, M; Waelchli, R; Ruat, M; Boddeke, HGWM; Seuwen, K

    Some mesenchymal cells respond to stimulation by specific cations with increased cell proliferation. In the present study we have investigated whether the parathyroid/kidney/brain calcium-sensing receptor (PCaR) can mediate such mitogenic responses. We have expressed the recombinant rat PCaR in

  1. Crude extract of Nigella sativa inhibits proliferation and induces ...

    African Journals Online (AJOL)

    Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells. ... African Journal of Biotechnology ... Cervical cancer is a major cause of morbidity in women worldwide and chemotherapy for this cancer seems unsatisfactory, which demands exploring new therapeutic ...

  2. TLR4 as a negative regulator of keratinocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Guergana Iotzova-Weiss

    Full Text Available TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.

  3. TLR4 as a negative regulator of keratinocyte proliferation.

    Science.gov (United States)

    Iotzova-Weiss, Guergana; Freiberger, Sandra N; Johansen, Pål; Kamarachev, Jivko; Guenova, Emmanuella; Dziunycz, Piotr J; Roux, Guillaume A; Neu, Johannes; Hofbauer, Günther F L

    2017-01-01

    TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC) of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.

  4. The peroxisome proliferators-ativated receptor gamma (PPARG ...

    African Journals Online (AJOL)

    Peroxisome proliferators-activated receptor gamma (PPARG) is an important regulator in the regulation of adipose differentiation and development. The mutations of the PPARG in human had been shown to be associated with type II diabetes, fat distribution and body weight. The functional importance of the PPARG makes ...

  5. Withaferin A promotes proliferation and migration of brain ...

    African Journals Online (AJOL)

    Trop J Pharm Res, July 2016; 15(7): 1488 assumed to be indispensable in the postnatal development of neovessels. Therefore the proliferation and migration ability of endothelial cells is vital for the recovery of vascular diseases, including cardiovascular diseases and stroke. Withaferin A [1], a steroidal lactone is isolated.

  6. CSFV proliferation is associated with GBF1 and Rab2

    Indian Academy of Sciences (India)

    Fulltext. Click here to view fulltext PDF. Permanent link: ... after BFA and GCA treatment. CSFV multiplication dynamics were retarded in cells transfected withGBF1 and Rab2 shRNA. ... Hence, Golgi function is important for CSFV multiplication, and GBF1 and Rab2 participate inCSFV proliferation. Further studies must ...

  7. Neonatal pancreatic pericytes support β-cell proliferation

    Directory of Open Access Journals (Sweden)

    Alona Epshtein

    2017-10-01

    Conclusions: This study introduces pancreatic pericytes as regulators of neonatal β-cell proliferation. In addition to advancing current understanding of the physiological β-cell replication process, these findings could facilitate the development of protocols aimed at expending these cells as a potential cure for diabetes.

  8. Electrospun fiber membranes enable proliferation of genetically modified cells

    Science.gov (United States)

    Borjigin, Mandula; Eskridge, Chris; Niamat, Rohina; Strouse, Bryan; Bialk, Pawel; Kmiec, Eric B

    2013-01-01

    Polycaprolactone (PCL) and its blended composites (chitosan, gelatin, and lecithin) are well-established biomaterials that can enrich cell growth and enable tissue engineering. However, their application in the recovery and proliferation of genetically modified cells has not been studied. In the study reported here, we fabricated PCL-biomaterial blended fiber membranes, characterized them using physicochemical techniques, and used them as templates for the growth of genetically modified HCT116-19 colon cancer cells. Our data show that the blended polymers are highly miscible and form homogenous electrospun fiber membranes of uniform texture. The aligned PCL nanofibers support robust cell growth, yielding a 2.5-fold higher proliferation rate than cells plated on standard plastic plate surfaces. PCL-lecithin fiber membranes yielded a 2.7-fold higher rate of proliferation, while PCL-chitosan supported a more modest growth rate (1.5-fold higher). Surprisingly, PCL-gelatin did not enhance cell proliferation when compared to the rate of cell growth on plastic surfaces. PMID:23467983

  9. Serotonin regulates osteoblast proliferation and function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dai, S.Q.; Yu, L.P. [Department of Orthopedic Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Shi, X. [Department of Obstetrics and Gynecology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Wu, H. [Emergency Department, The First Affiliated Hospital, Soochow University, Suzhou (China); Shao, P.; Yin, G.Y.; Wei, Y.Z. [Department of Orthopedic Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China)

    2014-08-01

    The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT{sub 1A}, 5-HT{sub 1B}, 5-HT{sub 1D}, 5-HT{sub 2A}, 5-HT{sub 2B}, and 5-HT{sub 2C}) were found to exist in rat osteoblasts. Of these, 5-HT{sub 2A} and 5-HT{sub 1B} receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

  10. Microglial recruitment, activation, and proliferation in response to primary demyelination

    DEFF Research Database (Denmark)

    Remington, Leah T; Babcock, Alicia A; Zehntner, Simone P

    2007-01-01

    antigen-presenting cells in vitro. T cells were recruited to the demyelinated corpus callosum but did not appear to be activated. Our study highlights the role of microglia as a heterogeneous population of cells in primary demyelination, with the capacity to present antigen, proliferate, and migrate...

  11. Apigenin inhibits proliferation and migratory properties of Barrett's ...

    African Journals Online (AJOL)

    Methods: Proliferation index of OE33 in the absence and presence of apigenin was determined by methyl-thiazolyl-tetrazolium (MTT) assay and apoptosis was determined by enzyme-linked immunosorbent assay (ELISA) method. Boyden Chamber's assay was applied to determine the migration and invasion of control and ...

  12. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Goldston

    2011-04-28

    Integrated energy, environment and economics modeling suggests that worldwide electrical energy use will increase from 2.4 TWe today to ~12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources derived from natural energy flows. Thus nuclear power may be needed to provide ~30%, 3600 GWe, by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century global nuclear proliferation risks are much greater, and more resistant to mitigation. Fusion energy, if successfully demonstrated to be economically competitive, would provide a source of nuclear power with much lower proliferation risks than fission.

  13. Addressing Information Proliferation: Applications of Information Extraction and Text Mining

    Science.gov (United States)

    Li, Jingjing

    2013-01-01

    The advent of the Internet and the ever-increasing capacity of storage media have made it easy to store, deliver, and share enormous volumes of data, leading to a proliferation of information on the Web, in online libraries, on news wires, and almost everywhere in our daily lives. Since our ability to process and absorb this information remains…

  14. Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ...

    African Journals Online (AJOL)

    Purpose: To demonstrate the role of chloroquinone (CQ) in inducing apoptosis in HONE-1 and HNE-1, nasopharyngeal carcinoma (NPC) cell lines. Methods: Water-soluble tetrazolium salt (WST)-1 assay was used for the determination of cell proliferation while an inverted microscope was employed for the analysis of ...

  15. Inhibition of proliferation, migration and invasion of human non ...

    African Journals Online (AJOL)

    Purpose: To determine the effect of phlomisoside F (PMF) on the proliferation, migration and invasion of human non-small cell lung cancer cell line A549 and explore the possible mechanisms. Methods: The anti-proliferative effect of PMF on A549 cells was determined by CCK-8. Subsequently, migration and invasion were ...

  16. Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

    Directory of Open Access Journals (Sweden)

    Khadijeh Khosravi

    2016-05-01

    Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

  17. Bryostatin I inhibits growth and proliferation of pancreatic cancer ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of bryostatin I on proliferation of pancreatic cancer cells as well as tumor growth in mice tumor xenograft model. Methods: Activation of NF-κB was evaluated by preparing nuclear material extract using nuclear extract kit (Carlsbad, CA, USA) followed by enzyme-linked immunosorbent assay ...

  18. Proliferation and Shoot Recovery among the East African Highland ...

    African Journals Online (AJOL)

    The study demonstrates the potential of in vitro approach for production of banana planting materials. In vitro proliferation ability and in particualr efficiency to produce recoverable shoots of the different EA-AAA banana cultivars could be improved by varying the culture conditions during the subsequent subculture cycles.

  19. Knockdown of Cripto-1 inhibits the proliferation, migration, invasion ...

    Indian Academy of Sciences (India)

    We performed Cell Counting Kit-8, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and flowcytometry to detect the cellular proliferation and cycle. The transwell assay was used to observe cellular migration andinvasion. The ability of angiogenesis was evaluated by tube formation assay. Our results showed that CR-1 ...

  20. Contribution of mesenchymal proliferation in tooth root morphogenesis.

    Science.gov (United States)

    Sohn, W-J; Choi, M-A; Yamamoto, H; Lee, S; Lee, Y; Jung, J-K; Jin, M-U; An, C-H; Jung, H-S; Suh, J-Y; Shin, H-I; Kim, J-Y

    2014-01-01

    In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig's epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.

  1. Rapid scenarios and observed intensities

    OpenAIRE

    Franco Pettenati; Livio Sirovich

    2012-01-01

    After a destructive earthquake, national Governments need to know the approximate amount of damage, the number of casualties, and the financial losses as soon as possible. Rapid scenarios are also used to inform the general public; see the widely used Shakemap package [Wald et al. 1999, 2006] of the US Geological Survey (USGS) and the one modified by the Istituto Nazionale di Geofisica e Vulcanologia (INGV; National Institute of Geophysics and Volcanology), which is reproduced for Figure 1. T...

  2. Rapid synthesis of beta zeolites

    Science.gov (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  3. [Effect of reduced oxygen concentrations and hydrogen sulfide on the amino acid metabolism and mesenchymal cells proliferation].

    Science.gov (United States)

    Plotnikova, L N; Berezovskii, V A; Veselskii, S P

    2015-01-01

    We investigated the effect of hydrogen sulfide donor (10(-12) mol/l NaHS--I group) alone and together with the reduced oxygen concentrations (5% O2--II group, 3% O2--III group, 24 h) on the biological processes of human stem cells culture. It was shown that the cells proliferation by the third day of cultivation in I, II and III group decreased 1,7; 2,8 and 4,2 times. On the 4th day of culture proliferation inhibited in I, II and III group by 29; 33 and 54% compared to the control. Thus, adverse effects NaHS enhanced by reducing the oxygen concentration. It was established that in all experimental versions rapidly absorbed from the culture medium amino acids: cysteine and cystine, serine and aspartic acid, valine and tryptophan, proline and hydroxyproline, which are involved in the synthesis of proteins, in particular collagen. In the culture medium increased the concentration of free amino acids of the three factions: arginine, histidine and taurine; glycine and methionine; alanine and glutamine. We believe that in the applied concentration of hydrogen sulfide donor in conditions of low oxygen in a gaseous medium incubation inhibits the proliferation and alters the amino acid metabolism of human cells line 4BL.

  4. Inactivating the spindle checkpoint kinase Bub1 during embryonic development results in a global shutdown of proliferation

    Directory of Open Access Journals (Sweden)

    Taylor Stephen S

    2009-09-01

    Full Text Available Abstract Background Bub1 is a component of the spindle assembly checkpoint, a surveillance mechanism that maintains chromosome stability during M-phase. Bub1 is essential during the early stages of embryogenesis, with homozygous BUB1-null mice dying shortly after day E3.5. Bub1 is also required later during embryogenesis; inactivation of BUB1 on day E10.5 appears to rapidly block all further development. However, the mechanism(s responsible for this phenotype remain unclear. Findings Here we show that inactivating BUB1 on day E10.5 stalls embryogenesis within 48 hours. This is accompanied by a global shutdown of proliferation, widespread apoptosis and haemorrhaging. Conclusion Our results suggest that Bub1 is required throughout the developing embryo for cellular proliferation. Therefore, Bub1 has been shown to be essential in all scenarios analyzed thus far in mice: proliferation of cultured fibroblasts, spermatogenesis, oogenesis and both early and late embryonic development. This likely reflects the fact that Bub1 has dual functions during mitosis, being required for both SAC function and chromosome alignment.

  5. TNF-related apoptosis-inducing ligand promotes human preadipocyte proliferation via ERK1/2 activation.

    Science.gov (United States)

    Funcke, Jan-Bernd; Zoller, Verena; El Hay, Muad Abd; Debatin, Klaus-Michael; Wabitsch, Martin; Fischer-Posovszky, Pamela

    2015-07-01

    Upon obesity, adipose tissue is excessively expanded and characterized by pathologic processes like hypoxia, fibrosis, and inflammation. Death ligands belonging to the TNF superfamily such as TNF-α are important contributors to these derangements and exert a pronounced influence on the metabolic and cellular homeostasis of adipose tissue. Here, we sought to identify the effect of the death ligand TNF-related apoptosis-inducing ligand (TRAIL) on the adipose tissue precursor cell pool and therefore investigated its influence on preadipocyte proliferation. Treatment of human preadipocytes with TRAIL resulted in a time- and dose-dependent increase in proliferation (EC50 3.4 ng/ml) comparable to IGF-1. Although no apoptosis was observed, TRAIL triggered a rapid cleavage of caspase-8 and -3. Neither inhibition of caspase activity by zVAD.fmk (20 µM) nor ablation of caspase-8 expression by lentivirus-delivered small hairpin RNA (shRNA) abolished the proliferative response. TRAIL triggered a delayed and sustained activation of ERK1/2, leaving Akt, p38, JNK, and NF-κB unaffected. Importantly, inhibition of ERK1/2 activation by PD0325901 (300 nM) or AZD6244 (5 or 10 µM) completely abolished the proliferative response. We thus reveal a hitherto unknown function of TRAIL in regulating adipose tissue homeostasis by promoting the proliferation of tissue-resident precursor cells. © FASEB.

  6. Programmed Cell Death, Proliferating Cell Nuclear Antigen and p53 Expression in Mouse Colon Mucosa during Diet-Induced Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Mauro Risio

    2000-01-01

    Full Text Available Western‐style diets (WDs trigger and sustain the early phases of tumorigenesis in mouse colon, and when continued throughout the life span lead to the development of dysplastic crypts. In order to evaluate the roles both of cell proliferation and programmed cell death (PCD in WD‐induced tumorigenesis, immunohistochemical detection of proliferating nuclear antigen (PCNA, in situ end labeling (TUNEL of DNA breaks, and p53 protein were carried out in mouse colonic mucosa during prolonged feeding of two WDs. PCNA Labeling Index of colonic crypts was significantly higher in WD‐treated animals than in controls only at the beginning of the nutritional study, the gap rapidly bridged by increased cell proliferation spontaneously occurring in the colonic mucosa during aging. A transient early homeostatic activation of PCD at the base of the crypt also was observed in WD groups. No changes in PCD were seen in the upper third of the crypt or in surface epithelium throughout the study, indicating that PCD in that colonic crypt segment produces a constant flux of cell loss, uninfluenced by homeostatic fluctuations. A major finding was an irreversible, progressive, age‐related decline of PCD at the crypt base in both control and treated animals that occurred during the second half of the rodents  life span. p53 protein was not immunohistochemically detected, suggesting that neither overexpression of wild‐type nor mutated forms of the protein are involved in the above mentioned changes.

  7. Rapid scenarios and observed intensities

    Directory of Open Access Journals (Sweden)

    Franco Pettenati

    2012-10-01

    Full Text Available After a destructive earthquake, national Governments need to know the approximate amount of damage, the number of casualties, and the financial losses as soon as possible. Rapid scenarios are also used to inform the general public; see the widely used Shakemap package [Wald et al. 1999, 2006] of the US Geological Survey (USGS and the one modified by the Istituto Nazionale di Geofisica e Vulcanologia (INGV; National Institute of Geophysics and Volcanology, which is reproduced for Figure 1. The general matter of the use of intensities in damage scenarios was discussed in a special session at the 2008 Annual Meeting of the Seismological Society of America (http://www.seismosoc.org/meetings/2008/specialsessions.html, and was also discussed in the NIS-1 session of the European Congress in Moscow, in August 2012 (http://www.esc2012-moscow.org/esc_thematicareas.html. The purposes of the present report are to: (i compare different types of intensities; (ii check two rapid scenarios of intensity; and (iii understand whether the KF formula [Sirovich 1996, Sirovich et al. 2009] can be used as a new 'attenuation' relationship to improve rapid scenarios. […

  8. Rapid diagnosis of mycobacterial infections

    Directory of Open Access Journals (Sweden)

    Michel Drancourt

    2015-01-01

    Full Text Available While pulmonary tuberculosis (PTB remains an important public health issue worldwide, there is an emerging interest in non-tuberculous mycobacteria (NTM which is responsible for opportunistic infections of the respiratory tract as well as other anatomical sites in both developed and developing countries. In this context the one goal of the clinical mycobacteriology laboratories is to provide physicians with an accurate identification of the mycobacterium as rapidly as possible. During the last ten years, several lines of laboratory tools have been developed in order to speed the isolation and identification of mycobacteria from clinical specimens. Chiefly, the composition of culture medium was renewed along with the protocol of incubation in order to recover Mycobacterium tuberculosis (MTB micro-colonies as soon as 48 h after the inoculation of the specimen. MALDI-TOF rapid identification is clearly the tool to be implemented in the laboratory for the rapid identification of the micro-colonies. Also, molecular tools and genomics are necessary in order to depict new mycobacteria species, including those of the Mycobacterium abscessus complex and the Mycobacterium avium complex. All these tools and their connections will be presented during this conference.

  9. Arachidonoyl-Phospholipid Remodeling in Proliferating Murine T Cells

    Directory of Open Access Journals (Sweden)

    Ando Soichiro

    2004-01-01

    Full Text Available Abstract Backgound Previous studies have shown that the functional capacity of T cells may be modulated by the composition of fatty acids within, and the release of fatty acids from membrane phospholipids, particulary containing arachidonic acid (AA. The remodeling of AA within membrane phospholipids of resting and proliferating CD4+ and CD8+ T cells is examined in this study. Results Splenic T cells were cultured in the presence or absence of anti-CD3 mAb for 48 h then labeled with [3H]AA for 20 min. In unstimulated cells, labeled AA was preferentially incorporated into the phosphoglycerides, phosphatidylcholine (PC followed by phosphatidylinositol (PI and phosphatidylethanolamine (PE. During a subsequent chase in unlabeled medium unstimulated CD4+ and CD8+ T cells demonstrated a significant and highly selective transfer of free, labeled AA into the PC pool. In contrast, proliferating CD4+ and CD8+ T cells distributed labeled [3H]AA predominantly into PI followed by PC and PE. Following a chase in AA-free medium, a decline in the content of [3H]AA-PC was observed in association with a comparable increase in [3H]AA-PE. Subsequent studies revealed that the cold AA content of all PE species was increased in proliferating T cells compared with that in non-cycling cells, but that enrichment in AA was observed only in the ether lipid fractions. Finally, proliferating T cells preincubated with [3H]AA exhibited a significant loss of labeled arachidonate in the PC fraction and an equivalent gain in labeled AA in 1-alk-1'-enyl-2-arachidonoyl-PE during a chase in unlabeled medium. Conclusion This apparent unidirectional transfer of AA from PC to ether-containing PE suggests the existence of a CoA-independent transacylase system in T cells and supports the hypothesis that arachidonoyl phospholipid remodeling may play a role in the regulation of cellular proliferation.

  10. Simvastatin Modulates Mesenchymal Stromal Cell Proliferation and Gene Expression

    Science.gov (United States)

    Zanette, Dalila Lucíola; Lorenzi, Julio Cesar Cetrulo; Panepucci, Rodrigo Alexandre; Palma, Patricia Vianna Bonini; dos Santos, Daiane Fernanda; Prata, Karen Lima; Silva, Wilson Araújo

    2015-01-01

    Statins are widely used hypocholesterolemic drugs that block the mevalonate pathway, responsible for the biosysnthesis of cholesterol. However, statins also have pleiotropic effects that interfere with several signaling pathways. Mesenchymal stromal cells (MSC) are a heterogeneous mixture of cells that can be isolated from a variety of tissues and are identified by the expression of a panel of surface markers and by their ability to differentiate in vitro into osteocytes, adipocytes and chondrocytes. MSC were isolated from amniotic membranes and bone marrows and characterized based on ISCT (International Society for Cell Therapy) minimal criteria. Simvastatin-treated cells and controls were directly assayed by CFSE (Carboxyfluorescein diacetate succinimidyl ester) staining to assess their cell proliferation and their RNA was used for microarray analyses and quantitative PCR (qPCR). These MSC were also evaluated for their ability to inhibit PBMC (peripheral blood mononuclear cells) proliferation. We show here that simvastatin negatively modulates MSC proliferation in a dose-dependent way and regulates the expression of proliferation-related genes. Importantly, we observed that simvastatin increased the percentage of a subset of smaller MSC, which also were actively proliferating. The association of MSC decreased size with increased pluripotency and the accumulating evidence that statins may prevent cellular senescence led us to hypothesize that simvastatin induces a smaller subpopulation that may have increased ability to maintain the entire pool of MSC and also to protect them from cellular senescence induced by long-term cultures/passages in vitro. These results may be important to better understand the pleiotropic effects of statins and its effects on the biology of cells with regenerative potential. PMID:25874574

  11. Molecular signatures of proliferation and quiescence in hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Teresa A Venezia

    2004-10-01

    Full Text Available Stem cells resident in adult tissues are principally quiescent, yet harbor enormous capacity for proliferation to achieve self renewal and to replenish their tissue constituents. Although a single hematopoietic stem cell (HSC can generate sufficient primitive progeny to repopulate many recipients, little is known about the molecular mechanisms that maintain their potency or regulate their self renewal. Here we have examined the gene expression changes that occur over a time course when HSCs are induced to proliferate and return to quiescence in vivo. These data were compared to data representing differences between naturally proliferating fetal HSCs and their quiescent adult counterparts. Bioinformatic strategies were used to group time-ordered gene expression profiles generated from microarrays into signatures of quiescent and dividing stem cells. A novel method for calculating statistically significant enrichments in Gene Ontology groupings for our gene lists revealed elemental subgroups within the signatures that underlie HSC behavior, and allowed us to build a molecular model of the HSC activation cycle. Initially, quiescent HSCs evince a state of readiness. The proliferative signal induces a preparative state, which is followed by active proliferation divisible into early and late phases. Re-induction of quiescence involves changes in migratory molecule expression, prior to reestablishment of homeostasis. We also identified two genes that increase in both gene and protein expression during activation, and potentially represent new markers for proliferating stem cells. These data will be of use in attempts to recapitulate the HSC self renewal process for therapeutic expansion of stem cells, and our model may correlate with acquisition of self renewal characteristics by cancer stem cells.

  12. Nuclear proliferation and civilian nuclear power: report of the Nonproliferation Alternative Systems Assessment Program. Volume II. Proliferation resistance

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Volume II assesses proliferation resistance. Chapters are devoted to: assessment of civilian nuclear systems (once-through fuel-cycle systems, closed fuel cycle systems, research reactors and critical facilities); assessment of associated sensitive materials and facilities (enrichment, problems with storage of spent fuel and plutonium content, and reprocessing and refabrication facilities); and safeguards for alternative fuel cycles.

  13. Extracts of proliferating and non-proliferating human cells display different base excision pathways and repair fidelity

    DEFF Research Database (Denmark)

    Akbari, Mansour; Pena Diaz, Javier; Andersen, Sonja

    2009-01-01

    Base excision repair (BER) of damaged or inappropriate bases in DNA has been reported to take place by single nucleotide insertion or through incorporation of several nucleotides, termed short-patch and long-patch repair, respectively. We found that extracts from proliferating and non-proliferati...

  14. Hepatocellular proliferation in response to agonists of peroxisome proliferator-activated receptor alpha: a role for kupffer cells?

    Directory of Open Access Journals (Sweden)

    Alsarra Ibrahim A

    2006-11-01

    Full Text Available Abstract Background It has been proposed that PPARα agonists stimulate Kupffer cells in rodents which in turn, release mitogenic factors leading to hepatic hyperplasia, and eventually cancer. However, Kupffer cells do not express PPARα receptors, and PPARα agonists stimulate hepatocellular proliferation in both TNFα- and TNFα receptor-null mice, casting doubt on the involvement of Kupffer cells in the mitogenic response to PPARα agonists. This study was therefore designed to investigate whether the PPARα agonist PFOA and the Kupffer cell inhibitor methylpalmitate produce opposing effects on hepatocellular proliferation and Kupffer cell activity in vivo, in a manner that would implicate these cells in the mitogenic effects of PPARα agonists. Methods Male Sprague-Dawley rats were treated intravenously via the tail vein with methylpalmitate 24 hrs prior to perfluorooctanoic acid (PFOA, and were sacrificed 24 hrs later, one hr after an intraperitoneal injection of bromodeoxyuridine (BrdU. Sera were analyzed for TNFα and IL-1β. Liver sections were stained immunohistochemically and quantified for BrdU incorporated into DNA. Results Data show that PFOA remarkably stimulated hepatocellular proliferation in the absence of significant changes in the serum levels of either TNFα or IL-1β. In addition, methylpalmitate did not alter the levels of these mitogens in PFOA-treated animals, despite the fact that it significantly blocked the hepatocellular proliferative effect of PFOA. Correlation between hepatocellular proliferation and serum levels of TNFα or IL-1β was extremely poor. Conclusion It is unlikely that mechanisms involving Kupffer cells play an eminent role in the hepatic hyperplasia, and consequently hepatocarcinogenicity attributed to PPARα agonists. This conclusion is based on the above mentioned published data and the current findings showing animals treated with PFOA alone or in combination with methylpalmitate to have similar

  15. MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice.

    Science.gov (United States)

    Risal, Sanjiv; Zhang, Jingjing; Adhikari, Deepak; Liu, Xiaoman; Shao, Jingchen; Hu, Mengwen; Busayavalasa, Kiran; Tu, Zhaowei; Chen, Zijiang; Kaldis, Philipp; Liu, Kui

    2017-01-01

    In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death of Mastl -null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl -null PGCs was rescued by simultaneous deletion of Ppp2r1a (α subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis.

  16. Effect of seaweed proliferation on benthic habitat quality assessed by Sediment Profile Imaging

    Science.gov (United States)

    Bona, Francesca

    2006-10-01

    Changes in sediment quality, with special reference to benthic habitat conditions resulting from macroalgae overgrowth, were studied in the Venice Lagoon, Italy. Data were collected biweekly in spring and summer from 1993 to 1998 and from 2001 to 2002, as part of the macroalgae growth control strategies managed by the Venice Water Authority-Consorzio Venezia Nuova. Benthic habitat conditions were studied by means of Sediment Profile Imaging, which allowed the collection of several variables: aRPD (apparent redox potential discontinuity), prism penetration depth, presence of anoxia on the surface of the sediment, presence of reduced gas bubbles, stage of benthic colonization. All these variables led to the calculation of an environmental index (Organism-Sediment Index, OSI), which was then related to physical variables and macroalgae abundance. Until 1996, the overall benthic habitat of the Venice Lagoon showed almost stressed conditions; from 1997, the seaweed biomass rapidly declined and the OSI increased significantly. The OSI seemed to be affected by seaweed biomass, sediment compactness and water depth. Macroalgae biomass greater than 4.5 kg/m 2 led to the complete disappearance of stage III of benthic colonization; values as low as 0.70 kg m 2 already had a severe impact on recolonization. SPI attributes indicated the main mechanisms that could have contributed to the benthic quality: seaweed proliferation is often followed by rapid decay of macroalgae biomass, especially when present in large amounts. The decrease in seaweed biomass often results in oxygen depletion in the water column and thus in the sediment, preventing complete benthic colonization. This research confirms the importance of in situ rapid reconnaissance surveys to assess the impact of eutrophication on the benthic habitat.

  17. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Deng, Wei [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072 (China); Han, Hui; Wang, Hao [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Chen, Yuguo [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Li, Yu, E-mail: qlliyu@126.com [Department of Respiratory, Qilu Hospital of Shandong University, Jinan 250012 (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2014-07-18

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  18. CD98 regulates vascular smooth muscle cell proliferation in atherosclerosis.

    Science.gov (United States)

    Baumer, Yvonne; McCurdy, Sara; Alcala, Martin; Mehta, Nehal; Lee, Bog-Hieu; Ginsberg, Mark H; Boisvert, William A

    2017-01-01

    Vascular smooth muscle cells (VSMC) migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. CD98 is a transmembrane protein made of two subunits, CD98 heavy chain (CD98hc) and one of six light chains, and is known to be involved in cell proliferation and survival. Because the influence of CD98hc on atherosclerosis development is unknown, our aim was to determine if CD98hc expressed on VSMC plays a role in shaping the morphology of atherosclerotic plaques by regulating VSMC function. In addition to determining the role of CD98hc in VSMC proliferation and apoptosis, we utilized mice with SMC-specific deletion of CD98hc (CD98hc(fl/fl)SM22αCre(+)) to determine the effects of CD98hc deficiency on VSMC function in atherosclerotic plaque. After culturing for 5 days in vitro, CD98hc(-/-) VSMC displayed dramatically reduced cell counts, reduced proliferation, as well as reduced migration compared to control VSMC. Analysis of aortic VSCM after 8 weeks of HFD showed a reduction in CD98hc(-/-) VSMC proliferation as well as increased apoptosis compared to controls. A long-term atherosclerosis study using SMC-CD98hc(-/-)/ldlr(-/-) mice was performed. Although total plaque area was unchanged, CD98hc(-/-) mice showed reduced presence of VSMC within the plaque (2.1 ± 0.4% vs. 4.3 ± 0.4% SM22α-positive area per plaque area, p < 0.05), decreased collagen content, as well as increased necrotic core area (25.8 ± 1.9% vs. 10.9 ± 1.6%, p < 0.05) compared to control ldlr(-/-) mice. We conclude that CD98hc is required for VSMC proliferation, and that its deficiency leads to significantly reduced presence of VSMC in the neointima. Thus, CD98hc expression in VSMC contributes to the formation of plaques that are morphologically more stable, and thereby protects against atherothrombosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. [Tissue culture and rapid propogation of seeds of Uyghur traditional herbal Capparis spinosa].

    Science.gov (United States)

    Ma, Sheng-Jun; Lu, Ting; Zhang, Ai-Qin; Wang, Ying; Zhou, Ling

    2010-12-01

    To optimize the tissue culture and rapid proliferation techniques of seeds of Capparis spinosa for producing large scale seedlings. The seeds of Capparis spinosa were collected as explants and cultivated in different MS media, which were from Turpan in Xinjiang. The optimum media were selected by adjusting the combinations of different hormone and concentration. The best on institution of asepsis explants was rinsing for 8 hours and 0.1% HgCl2 for 12 minutes. The medium MS + 6-BA 0.6 mg/L + NAA 0.1 mg/L was suitable for primary and second culture. The medium MS + 6-BA 0.6 mg/L + 2,4-D 1.0 mg/L was suitable for proliferation, and the optimum medium of rooting was MS + IBA 0.8 mg / L + 300 mg/L activated carbon. The rapid proliferation technique of seeds of Capparis spinosa can be used for producing large scale seedlings.

  20. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Melcher, Cynthia P.

    2015-08-28

    The Wyoming Basin Rapid Ecoregional Assessment was conducted in partnership with the Bureau of Land Management (BLM). The overall goals of the BLM Rapid Ecoregional Assessments (REAs) are to identify important ecosystems and wildlife habitats at broad spatial scales; identify where these resources are at risk from Change Agents, including development, wildfire, invasive species, disease and climate change; quantify cumulative effects of anthropogenic stressors; and assess current levels of risk to ecological resources across a range of spatial scales and jurisdictional boundaries by assessing all lands within an ecoregion. There are several components of the REAs. Management Questions, developed by the BLM and stakeholders for the ecoregion, identify the regionally significant information needed for addressing land-management responsibilities. Conservation Elements represent regionally significant species and ecological communities that are of management concern. Change Agents that currently affect or are likely to affect the condition of species and communities in the future are identified and assessed. REAs also identify areas that have high conservation potential that are referred to as “large intact areas.” At the ecoregion level, the ecological value of large intact areas is based on the assumption that because these areas have not been greatly altered by human activities (such as development), they are more likely to contain a variety of plant and animal communities and to be resilient and resistant to changes resulting from natural disturbances such as fire, insect outbreaks, and disease.

  1. Rapid self-healing hydrogels

    Science.gov (United States)

    Phadke, Ameya; Zhang, Chao; Arman, Bedri; Hsu, Cheng-Chih; Mashelkar, Raghunath A.; Lele, Ashish K.; Tauber, Michael J.; Arya, Gaurav; Varghese, Shyni

    2012-01-01

    Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically cross-linked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels. PMID:22392977

  2. Rapid generalization in phonotactic learning

    Directory of Open Access Journals (Sweden)

    Tal Linzen

    2017-10-01

    Full Text Available Speakers judge novel strings to be better potential words of their language if those strings consist of sound sequences that are attested in the language. These intuitions are often generalized to new sequences that share some properties with attested ones: Participants exposed to an artificial language where all words start with the voiced stops [b] and [d] will prefer words that start with other voiced stops (e.g., [g] to words that start with vowels or nasals. The current study tracks the evolution of generalization across sounds during the early stages of artificial language learning. In Experiments 1 and 2, participants received varying amounts of exposure to an artificial language. Learners rapidly generalized to new sounds: In fact, following short exposure to the language, attested patterns were not distinguished from unattested patterns that were similar in their phonological properties to the attested ones. Following additional exposure, participants showed an increasing preference for attested sounds, alongside sustained generalization to unattested ones. Finally, Experiment 3 tested whether participants can rapidly generalize to new sounds based on a single type of sound. We discuss the implications of our results for computational models of phonotactic learning.

  3. Rapid ISS Power Availability Simulator

    Science.gov (United States)

    Downing, Nicholas

    2011-01-01

    The ISS (International Space Station) Power Resource Officers (PROs) needed a tool to automate the calculation of thousands of ISS power availability simulations used to generate power constraint matrices. Each matrix contains 864 cells, and each cell represents a single power simulation that must be run. The tools available to the flight controllers were very operator intensive and not conducive to rapidly running the thousands of simulations necessary to generate the power constraint data. SOLAR is a Java-based tool that leverages commercial-off-the-shelf software (Satellite Toolkit) and an existing in-house ISS EPS model (SPEED) to rapidly perform thousands of power availability simulations. SOLAR has a very modular architecture and consists of a series of plug-ins that are loosely coupled. The modular architecture of the software allows for the easy replacement of the ISS power system model simulator, re-use of the Satellite Toolkit integration code, and separation of the user interface from the core logic. Satellite Toolkit (STK) is used to generate ISS eclipse and insulation times, solar beta angle, position of the solar arrays over time, and the amount of shadowing on the solar arrays, which is then provided to SPEED to calculate power generation forecasts. The power planning turn-around time is reduced from three months to two weeks (83-percent decrease) using SOLAR, and the amount of PRO power planning support effort is reduced by an estimated 30 percent.

  4. KEPLER RAPIDLY ROTATING GIANT STARS

    Energy Technology Data Exchange (ETDEWEB)

    Costa, A. D.; Martins, B. L. Canto; Bravo, J. P.; Paz-Chinchón, F.; Chagas, M. L. das; Leão, I. C.; Oliveira, G. Pereira de; Silva, R. Rodrigues da; Roque, S.; Oliveira, L. L. A. de; Silva, D. Freire da; De Medeiros, J. R., E-mail: renan@dfte.ufrn.br [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Campus Universitário, Natal RN (Brazil)

    2015-07-10

    Rapidly rotating giant stars are relatively rare and may represent important stages of stellar evolution, resulting from stellar coalescence of close binary systems or accretion of substellar companions by their hosting stars. In the present Letter, we report 17 giant stars observed in the scope of the Kepler space mission exhibiting rapid rotation behavior. For the first time, the abnormal rotational behavior for this puzzling family of stars is revealed by direct measurements of rotation, namely from photometric rotation period, exhibiting a very short rotation period with values ranging from 13 to 55 days. This finding points to remarkable surface rotation rates, up to 18 times the rotation of the Sun. These giants are combined with six others recently listed in the literature for mid-infrared (IR) diagnostics based on Wide-field Infrared Survey Explorer information, from which a trend for an IR excess is revealed for at least one-half of the stars, but at a level far lower than the dust excess emission shown by planet-bearing main-sequence stars.

  5. Rapid starting methanol reactor system

    Science.gov (United States)

    Chludzinski, Paul J.; Dantowitz, Philip; McElroy, James F.

    1984-01-01

    The invention relates to a methanol-to-hydrogen cracking reactor for use with a fuel cell vehicular power plant. The system is particularly designed for rapid start-up of the catalytic methanol cracking reactor after an extended shut-down period, i.e., after the vehicular fuel cell power plant has been inoperative overnight. Rapid system start-up is accomplished by a combination of direct and indirect heating of the cracking catalyst. Initially, liquid methanol is burned with a stoichiometric or slightly lean air mixture in the combustion chamber of the reactor assembly. The hot combustion gas travels down a flue gas chamber in heat exchange relationship with the catalytic cracking chamber transferring heat across the catalyst chamber wall to heat the catalyst indirectly. The combustion gas is then diverted back through the catalyst bed to heat the catalyst pellets directly. When the cracking reactor temperature reaches operating temperature, methanol combustion is stopped and a hot gas valve is switched to route the flue gas overboard, with methanol being fed directly to the catalytic cracking reactor. Thereafter, the burner operates on excess hydrogen from the fuel cells.

  6. Rapidly Developing Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Viktoria Oline Barrios Poulsen

    2013-01-01

    Full Text Available Severe cutaneous reactions with potentially fatal outcomes can have many different causes. The Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are rare. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated. Urgent active therapy is required. Prompt recognition and withdrawal of suspect drug and rapid intervention can result in favourable outcome. No further international guidelines for treatment exist, and much of the treatment relies on old or experimental concepts with no scientific evidence. We report on a 54-year-old man experiencing rapidly developing drug-induced severe TEN and presented multiorgan failure involving the respiratory and circulatory system, coagulopathy, and renal insufficiency. Detachment counted 30% of total body surface area (TBSA. SCORTEN = 5, indicating a mortality rate >90%. The patient was sedated and mechanically ventilated, supported with fluids and inotropes to maintain a stable circulation. Component therapy was guided by thromboelastography (TEG. The patient received plasmapheresis, and shock reversal treatment was initiated. He was transferred to a specialized intensive care burn unit within 24 hours from admittance. The initial care was continued, and hemodialysis was started. Pulmonary, circulatory, and renal sequelae resolved with intensive care, and re-epithelialization progressed slowly. The patient was discharged home on hospital day 19.

  7. Unicystic ameloblastoma with diverse mural proliferation - a hybrid lesion

    Energy Technology Data Exchange (ETDEWEB)

    Mahadesh, Jyothi [Sri Siddhartha Dental College and Hospital, (India); Rayapati, Dilip Kumar; Maligi, Prathima M; Ramachandra, Prashanth [Dayananda Sagar College of Dental Sciences, Bengaluru (India)

    2011-03-15

    A 46-year-old man was referred to our hospital for treatment, complaining of swelling on the right mandibular molar region. Radiographic examination revealed a well defined multilocular radiolucent lesion with root resorption of right lower anteriors and molars. Following biopsy, a diagnosis of unicystic ameloblastoma of mural type was made and hemimandibulectomy was performed under general anesthesia. Histopathological examination of the surgical specimen exhibited a unicystic ameloblastoma of luminal, intraluminal, and mural type. Intraluminal proliferation was of plexiform pattern and mural proliferation showed unusual histopathological findings, which revealed follicular, acanthomatous areas coexisted with desmoplastic areas. This mural picture was similar to the so-called 'hybrid lesion of ameloblastoma', whose biological profile is not elicited due to the lack of adequate published reports. Two years follow up till date has not revealed any signs of recurrence.

  8. Prognostic value of proliferation in pleomorphic soft tissue sarcomas

    DEFF Research Database (Denmark)

    Seinen, Jojanneke M; Jönsson, Mats; Bendahl, Pär-Ola O

    2012-01-01

    = 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification...... of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently...... to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy....

  9. Small molecule mediated proliferation of primary retinal pigment epithelial cells.

    Science.gov (United States)

    Swoboda, Jonathan G; Elliott, Jimmy; Deshmukh, Vishal; de Lichtervelde, Lorenzo; Shen, Weijun; Tremblay, Matthew S; Peters, Eric C; Cho, Charles Y; Lu, Bin; Girman, Sergej; Wang, Shaomei; Schultz, Peter G

    2013-07-19

    Retinal pigment epithelial (RPE) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle. Degeneration of RPE cells results in retinal disorders such as age-related macular degeneration. Cell transplant strategies have potential therapeutic value for such disorders; however, risks associated with an inadequate supply of donor cells limit their therapeutic success. The identification of factors that proliferate RPE cells ex vivo could provide a renewable source of cells for transplantation. Here, we report that a small molecule (WS3) can reversibly proliferate primary RPE cells isolated from fetal and adult human donors. Following withdrawal of WS3, RPE cells differentiate into a functional monolayer, as exhibited by their expression of mature RPE genes and phagocytosis of photoreceptor outer segments. Furthermore, chemically expanded RPE cells preserve vision when transplanted into dystrophic Royal College of Surgeons (RCS) rats, a well-established model of retinal degeneration.

  10. Stimulation of Cellular Proliferation by Hepatitis B Virus X Protein

    Directory of Open Access Journals (Sweden)

    Charles R. Madden

    2001-01-01

    Full Text Available Chronic infection with the hepatitis B virus (HBV is a known risk factor in the development of human hepatocellular carcinoma (HCC. The HBV-encoded X protein, HBx, has been investigated for properties that may explain its cancer cofactor role in transgenic mouse lines. We discuss here recent data showing that HBx is able to induce hepatocellular proliferation in vitro and in vivo. This property of HBx is predicted to sensitize hepatocytes to other HCC cofactors, including exposure to carcinogens and to other hepatitis viruses. Cellular proliferation is intimately linked to the mechanism(s by which most tumor-associated viruses transform virus-infected cells. The HBx alteration of the cell cycle provides an additional mechanism by which chronic HBV infection may contribute to HCC.

  11. Petasites japonicus Stimulates the Proliferation of Mouse Spermatogonial Stem Cells.

    Directory of Open Access Journals (Sweden)

    Hye-Ryun Kang

    Full Text Available Oriental natural plants have been used as medical herbs for the treatment of various diseases for over 2,000 years. In this study, we evaluated the effect of several natural plants on the preservation of male fertility by assessing the ability of plant extracts to stimulate spermatogonial stem cell (SSC proliferation by using a serum-free culture method. In vitro assays showed that Petasites japonicus extracts, especially the butanol fraction, have a significant effect on germ cells proliferation including SSCs. The activity of SSCs cultured in the presence of the Petasites japonicus butanol fraction was confirmed by normal colony formation and spermatogenesis following germ cell transplantation of the treated SSCs. Our findings could lead to the discovery of novel factors that activate SSCs and could be useful for the development of technologies for the prevention of male infertility.

  12. Eroding market stability by proliferation of financial instruments

    Science.gov (United States)

    Caccioli, F.; Marsili, M.; Vivo, P.

    2009-10-01

    We contrast Arbitrage Pricing Theory (APT), the theoretical basis for the development of financial instruments, with a dynamical picture of an interacting market, in a simple setting. The proliferation of financial instruments apparently provides more means for risk diversification, making the market more efficient and complete. In the simple market of interacting traders discussed here, the proliferation of financial instruments erodes systemic stability and it drives the market to a critical state characterized by large susceptibility, strong fluctuations and enhanced correlations among risks. This suggests that the hypothesis of APT may not be compatible with a stable market dynamics. In this perspective, market stability acquires the properties of a common good, which suggests that appropriate measures should be introduced in derivative markets, to preserve stability. in here

  13. Simulated Hypergravity Alters Vascular Smooth Muscle Cell Proliferation and Motility

    Science.gov (United States)

    Hunt, Shameka; Bettis, Barika; Harris-Hooker, Sandra; Sanford, Gary L.

    1997-01-01

    The cellular effects of gravity are poorly understood due to its constancy and nonavailability of altered gravitational models. Such an understanding is crucial for prolonged space flights. In these studies, we assessed the influence of centrifugation at 6G (HGrav) on vascular smooth muscle (SMC) mobility and proliferation. Cells were: (a) plated at low density and subjected to HGrav for 24-72 hr for proliferation studies, or (b) grown to confluency, subjected to HGrav, mechanically denuded and monitored for cell movement into the denuded area. Controls were maintained under normogravity. SMC showed a 50% inhibition of growth under HGrav and 10% serum; HGrav and low serum resulted in greater growth inhibition. The rate of movement of SMC into the denuded area was 2-3-fold higher under HGrav in low serum compared to controls, but similar in 10% serum. These studies show that HGrav has significant effects on SMC growth and mobility, which are dependent on serum levels.

  14. An Introduction to Nuclear Non-Proliferation and Safeguards

    Energy Technology Data Exchange (ETDEWEB)

    Haakansson, Ane; Jonter, Thomas

    2007-06-15

    The purpose of this project was to compile a course material that covers how the nuclear safeguards system has emerged and how it works today. The produced compendium is directed to both university students and people concerned by safeguards from the industry. The primary aim of the first part of this paper is to describe the historical development of this global non-proliferation system and its central tasks. A second purpose is to discuss the advantages and disadvantages of its current design in order to answer the following question: Can we today say that we have a functioning global non-proliferation system? Does it require further strengthening, and, if so, how can this be achieved? In the second section we review the verification regime within nuclear safeguards, i. e. describe the methods and techniques that are available to reassure the world community that concluded treaties are adhered to

  15. Proliferation resistance assessment of high temperature gas reactors

    Energy Technology Data Exchange (ETDEWEB)

    Chikamatsu N, M. A. [Instituto Tecnologico y de Estudios Superiores de Monterrey, Campus Santa Fe, Av. Carlos Lazo No. 100, Santa Fe, 01389 Mexico D. F. (Mexico); Puente E, F., E-mail: midori.chika@gmail.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2014-10-15

    The Generation IV International Forum has established different objectives for the new generation of reactors to accomplish. These objectives are focused on sustain ability, safety, economics and proliferation resistance. This paper is focused on how the proliferation resistance of the High Temperature Gas Reactors (HTGR) is assessed and the advantages that these reactors present currently. In this paper, the focus will be on explaining why such reactors, HTGR, can achieve the goals established by the GIF and can present a viable option in terms of proliferation resistance, which is an issue of great importance in the field of nuclear energy generation. The reason why the HTGR are being targeted in this writing is that these reactors are versatile, and present different options from modular reactors to reactors with the same size as the ones that are being operated today. Besides their versatility, the HTGR has designed features that might improve on the overall sustain ability of the nuclear reactors. This is because the type of safety features and materials that are used open up options for industrial processes to be carried out; cogeneration for instance. There is a small section that mentions how HTGR s are being developed in the international sector in order to present the current world view in this type of technology and the further developments that are being sought. For the proliferation resistance section, the focus is on both the intrinsic and the extrinsic features of the nuclear systems. The paper presents a comparison between the features of Light Water Reactors (LWR) and the HTGR in order to be able to properly compare the most used technology today and one that is gaining international interest. (Author)

  16. Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

    OpenAIRE

    Jihan Youssef; Mostafa Badr

    2004-01-01

    Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes...

  17. Proliferation of Weapons of Mass Destruction: Assessing and Risks

    Science.gov (United States)

    1993-10-01

    Endowment for Director Harvard University International Peace Office of National Security Technology Stephen M. Meyer Sergio C. Trindade Pacific Northwest...addition to produc- people as one delivered by intercontinental ballis- ing acute illness or death at considerable dis- tic missile; a given quantity of...the field, par- nity, either because it cannot be publicly ticularly if the proliferant has been produc- released or because public allegations of ing

  18. Chemopreventive effects of metformin on obesity-associated endometrial proliferation.

    Science.gov (United States)

    Zhang, Qian; Celestino, Joseph; Schmandt, Rosemarie; McCampbell, Adrienne S; Urbauer, Diana L; Meyer, Larissa A; Burzawa, Jennifer K; Huang, Marilyn; Yates, Melinda S; Iglesias, David; Broaddus, Russell R; Lu, Karen H

    2013-07-01

    Obesity is a significant contributing factor to endometrial cancer risk. We previously demonstrated that estrogen-induced endometrial proliferation is enhanced in the context of hyperinsulinemia and insulin resistance. In this study, we investigate whether pharmacologic agents that modulate insulin sensitivity or normalize insulin levels will diminish the proliferative response to estrogen. Zucker fa/fa obese rats and lean controls were used as models of hyperinsulinemia and insulin resistance. Insulin levels were depleted in ovariectomized rats following treatment with streptozotocin, or modulated by metformin treatment. The number of BrdU-incorporated cells, estrogen-dependent proliferative and antiproliferative gene expression, and activation of mTOR and ERK1/2 MAPK signaling were studied. A rat normal endometrial cell line RENE1 was used to evaluate the direct effects of metformin on endometrial cell proliferation and gene expression in vitro. Streptozotocin lowered circulating insulin levels in obese rats and decreased the number of BrdU-labeled endometrial cells even in the presence of exogenous estrogen. Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRβ/IGF1R) and ERK1/2. In vitro studies indicated metformin inhibited RENE1 proliferation in a dose-dependent manner. These findings suggest that drugs that modulate insulin sensitivity, such as metformin, hinder estrogen-mediated endometrial proliferation. Therefore, these drugs may be clinically useful for the prevention of endometrial cancer in obese women. Copyright © 2013 Mosby, Inc. All rights reserved.

  19. Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

    DEFF Research Database (Denmark)

    Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina

    2015-01-01

    diet (r(2)=0.33, Pinflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients...... with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta. CONCLUSIONS: (18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis....

  20. Enterocyte Proliferation and Signaling Are Constitutively Altered in Celiac Disease

    Science.gov (United States)

    Maglio, Mariantonia; Kosova, Roberta; Sarno, Marco; Gaito, Alessandra; Discepolo, Valentina; Troncone, Riccardo; Auricchio, Salvatore

    2013-01-01

    Celiac disease (CD) occurs frequently, and is caused by ingestion of prolamins from cereals in subjects with a genetic predisposition. The small intestinal damage depends on an intestinal stress/innate immune response to certain gliadin peptides (e.g., A-gliadin P31-43) in association with an adaptive immune response to other gliadin peptides (e.g., A-gliadin P57-68). Gliadin and peptide P31-43 affect epithelial growth factor receptor (EGFR) signaling and CD enterocyte proliferation. The reason why the stress/innate immune and proliferative responses to certain gliadin peptides are present in CD and not in control intestine is so far unknown. The aim of this work is to investigate if, in CD, a constitutive alteration of enterocyte proliferation and signaling exists that may represent a predisposing condition to the damaging effects of gliadin. Immunofluorescence and immunohistochemistry were used to study signaling in CD fibroblasts and intestinal biopsies. Western blot (WB) analysis, immunoprecipitation, and quantitative PCR were also used. We found in CD enterocytes enhancement of both proliferation and Epidermal Growth Factor Receptor (EGFR)/ligand system. In CD enterocytes and fibroblasts we found increase of the phosphorylated downstream signaling molecule Extracellular Signal Regulated Kinase (ERK); block of the ERK activation normalizes enterocytes proliferation in CD mucosa. In conclusion the same pathway, which gliadin and gliadin peptide P31-43 can interfere with, is constitutively altered in CD cells. This observation potentially explains the specificity of the damaging effects of certain gliadin peptides on CD intestine. PMID:24204586

  1. Enterocyte proliferation and signaling are constitutively altered in celiac disease.

    Directory of Open Access Journals (Sweden)

    Merlin Nanayakkara

    Full Text Available Celiac disease (CD occurs frequently, and is caused by ingestion of prolamins from cereals in subjects with a genetic predisposition. The small intestinal damage depends on an intestinal stress/innate immune response to certain gliadin peptides (e.g., A-gliadin P31-43 in association with an adaptive immune response to other gliadin peptides (e.g., A-gliadin P57-68. Gliadin and peptide P31-43 affect epithelial growth factor receptor (EGFR signaling and CD enterocyte proliferation. The reason why the stress/innate immune and proliferative responses to certain gliadin peptides are present in CD and not in control intestine is so far unknown. The aim of this work is to investigate if, in CD, a constitutive alteration of enterocyte proliferation and signaling exists that may represent a predisposing condition to the damaging effects of gliadin. Immunofluorescence and immunohistochemistry were used to study signaling in CD fibroblasts and intestinal biopsies. Western blot (WB analysis, immunoprecipitation, and quantitative PCR were also used. We found in CD enterocytes enhancement of both proliferation and Epidermal Growth Factor Receptor (EGFR/ligand system. In CD enterocytes and fibroblasts we found increase of the phosphorylated downstream signaling molecule Extracellular Signal Regulated Kinase (ERK; block of the ERK activation normalizes enterocytes proliferation in CD mucosa. In conclusion the same pathway, which gliadin and gliadin peptide P31-43 can interfere with, is constitutively altered in CD cells. This observation potentially explains the specificity of the damaging effects of certain gliadin peptides on CD intestine.

  2. Learning and adult neurogenesis: survival with or without proliferation?

    Science.gov (United States)

    Prickaerts, Jos; Koopmans, Guido; Blokland, Arjan; Scheepens, Arjan

    2004-01-01

    Recent high quality papers have renewed interest in the phenomenon of neurogenesis within the adult mammalian brain. Many studies now show that neurogenesis can be modulated by environmental factors including physical activity, stress, and learning. These findings have considerable implications for neuroscience in general, including the study of learning and memory, neural network plasticity, aging, neurodegeneration, and the recovery from brain injury. Although new light has been shed on this field, many contradictory findings have been reported. Here we propose two principle issues which underlie these inconsistencies, with particular focus on the interaction between learning and neurogenesis. The first issue relates to the basic methodology of measuring the generation of new brain cells, i.e., proliferation, as compared to survival of the newly made cells. Mostly, measures of neurogenesis reported are a combination of proliferation and survival, making it impossible to distinguish between these separate processes. The second aspect is in regards to the role of environmental factors which can affect both proliferation and survival independently. Especially the interaction between stress and learning is of importance since these might counteract each other in some circumstances. Reviewing the literature while taking these issues into account indicates that, in contrast to some findings, cell proliferation in the dentate gyrus of the hippocampus as a result of learning cannot be ruled out yet. On the other hand, increased survival of granule cells in the dentate gyrus as a result of hippocampal-dependent learning has been clearly demonstrated. Moreover, this learning-induced survival of granule cells, which were born before the actual learning experience, might provide a molecular mechanism for the 'use it or lose it' principle.

  3. The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians.

    Science.gov (United States)

    Zhu, Shu Jun; Pearson, Bret J

    2013-01-15

    Freshwater planarians are flatworms of the Lophotrochozoan superphylum and are well known for their regenerative abilities, which rely on a large population of pluripotent adult stem cells. However, the mechanisms by which planarians maintain a precise population of adult stem cells while balancing proliferation and cell death, remain to be elucidated. Here we have identified, characterized, and functionally tested the core Retinoblastoma (Rb) pathway components in planarian adult stem cell biology. The Rb pathway is an ancient and conserved mechanism of proliferation control from plants to animals and is composed of three core components: an Rb protein, and a transcription factor heterodimer of E2F and DP proteins. Although the planarian genome contains all components of the Rb pathway, we found that they have undergone gene loss from the ancestral state, similar to other species in their phylum. The single Rb homolog (Smed-Rb) was highly expressed in planarian stem cells and was required for stem cell maintenance, similar to the Rb-homologs p107 and p130 in vertebrates. We show that planarians and their phylum have undergone the most severe reduction in E2F genes observed thus far, and the single remaining E2F was predicted to be a repressive-type E2F (Smed-E2F4-1). Knockdown of either Smed-E2F4-1 or its dimerization partner Dp (Smed-Dp) by RNAi resulted in temporary hyper-proliferation. Finally, we showed that known Rb-interacting genes in other systems, histone deacetylase 1 and cyclinD (Smed-HDAC1; Smed-cycD), were similar to Rb in expression and phenotypes when knocked down by RNAi, suggesting that these established interactions with Rb may also be conserved in planarians. Together, these results showed that planarians use the conserved components of the Rb tumor suppressor pathway to control proliferation and cell survival. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Zag Expression during Aging Suppresses Proliferation after Kidney Injury

    OpenAIRE

    Schmitt, Roland; Marlier, Arnaud; Cantley, Lloyd G.

    2008-01-01

    Recovery after acute kidney injury is impaired in the elderly, but mechanistic information regarding why this occurs is limited. In this study, aged mouse kidneys displayed a reduced epithelial proliferative reserve in vivo and in vitro. Microarray analysis identified increased expression of zinc-α (2)-glycoprotein (Zag) in aged proximal tubular cells. The addition of recombinant Zag to primary renal epithelial cell cultures decreased proliferation, whereas knockdown of Zag increased prolifer...

  5. Inhibition of tracheal smooth muscle cell proliferation by phosphodiesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Kazuko Masu

    1999-01-01

    Full Text Available Agents that increase intracellular cyclic 3',5'-adenosine monophosphate (cAMP, such as forskolin, prostaglandin (PGE2, salbutamol and 8-bromo-cAMP, have been shownto inhibit the proliferation of airway smooth-muscle (ASM cells in vitro. However, it has not yet been determined whether selective inhibitors of phosphodiesterase (PDE isoenzymes III and IV that catalyze cAMPto 5'-adenosine monophosphate have the ability to inhibit ASM cell proliferation. To evaluate the effectsof PDE inhibitors on ASM cell proliferation, ASM cells isolated from bovine tracheae were cultured in the presence of fetal bovine serum (FBS, with or without a non-selective PDE inhibitor (theophylline, a selective PDE III inhibitor (cilostazol, and a selective PDE IV inhibitor (rolipram. The number of ASM cells cultured with 5% FBS was significantly reduced by the presence of theophylline at 10−3 and 3 × 10−4 mol/L, cilostazol at 10−5, 10−6 and 10−7 mol/L, and rolipram at 10−4 and 10−5 mol/L. The release of lactic dehydrogenase from ASM cells cultured with any concentration of these agents was not significantly different from that with medium alone. Inhibitors of PDE III and IV were demonstrated to have an inhibitory effect on ASM cell proliferation induced by FBS. Our results suggest the value of the further development of PDE inhibitors for the treatment of hyperplasia of ASM cells characteristic of airway remodeling, in addition to bronchospasm and airway inflammation, in bronchial asthma.

  6. Assessment of cell proliferation with resazurin-based fluorescent dye.

    Science.gov (United States)

    Czekanska, Ewa M

    2011-01-01

    The Alamar Blue assay is based on enzymatic reduction of indicator dye by viable cells and serves as an effective tool for assessing cell proliferation and as a screening technique. It can be applied in studies concentrating on animal, plant, yeast, and bacteria cells. Among the various methods for cell viability and cytotoxicity, it utilises all features of ideal and reliable test; it is one-step, sensitive, safe, non-toxic for cells, and cost-effective.

  7. Effects of BIO on proliferation and chondrogenic differentiation of mouse marrow derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Nasrin Fallah

    2013-06-01

    Full Text Available In vitroexpansion of mesenchymal stem cell (MSCs into large number is necessary fortheir application in cell-based treatment of articular cartilage defects. On the other hand,some studies have indicated that BIO (6-Bromoindirubin-3-Oxime possesses mitogeniceffects on cell culture. The objective of the present study was to examine the effect of BIO onin vitro expansion and chondrogenic differentiation of mouse marrow-derived MSCs. Theculture was established using bone marrow tissue obtained from 10 NMRI mice. MSC natureof the isolated cells was verified according to the minimal criteria proposed for MSC.Passaged-3 cells were seeded in 24-well culture plates and treated by 0.05, 0.01, 0.1, 1.0 and1.5 μM BIO forsevendays. The culture without BIO was taken as the control. At the end ofcultivation period, the cultures were examinedfor viable cell number which was then used tocalculate population doubling time (PDT. The BIO with higher proliferation-promoting effectwas investigated for its chondrogenic effect on MSC culture. There was significantly moreviable cells at the cultures treated by 0.1 μM BIO. At this culture the cells tended to doubletheir population in rapid rate (each 43.07 hr than the cells treated with the other BIOconcentrations (p< 0.05. Interestingly treatment of MSC chondrogenic culture with 0.1 μMBIO ledto the up-regulation of cartilage specific genes including aggrecan, collagen II andSox9. In conclusion BIO at 0.1 μM could enhance mouse MSC in vitro proliferation as well astheir chondrogenic differentiation. These findings would be of great importance for the fieldof regenerative medicine.

  8. The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation

    Directory of Open Access Journals (Sweden)

    Pavan Rajanahalli

    2015-01-01

    Full Text Available Silver nanoparticles (AgNPs are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.

  9. An alkylphenol mix promotes seminoma derived cell proliferation through an ERalpha36-mediated mechanism.

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    Hussein Ajj

    Full Text Available Long chain alkylphenols are man-made compounds still present in industrial and agricultural processes. Their main use is domestic and they are widespread in household products, cleansers and cosmetics, leading to a global environmental and human contamination. These molecules are known to exert estrogen-like activities through binding to classical estrogen receptors. In vitro, they can also interact with the G-protein coupled estrogen receptor. Testicular germ cell tumor etiology and progression are proposed to be stimulated by lifelong estrogeno-mimetic exposure. We studied the transduction signaling pathways through which an alkyphenol mixture triggers testicular cancer cell proliferation in vitro and in vivo. Proliferation assays were monitored after exposure to a realistic mixture of 4-tert-octylphenol and 4-nonylphenol of either TCam-2 seminoma derived cells, NT2/D1 embryonal carcinoma cells or testis tumor in xenografted nude mice. Specific pharmacological inhibitors and gene-silencing strategies were used in TCam-2 cells in order to demonstrate that the alkylphenol mix triggers CREB-phosphorylation through a rapid, ERα36-PI3kinase non genomic pathway. Microarray analysis of the mixture target genes revealed that this pathway can modulate the expression of the DNA-methyltransferase-3 (Dnmt3 gene family which is involved in DNA methylation control. Our results highlight a key role for ERα36 in alkylphenol non genomic signaling in testicular germ cell tumors. Hence, ERα36-dependent control of the epigenetic status opens the way for the understanding of the link between endocrine disruptor exposure and the burden of hormone sensitive cancers.

  10. Transforming growth factor alpha (TGFα regulates granulosa cell tumor (GCT cell proliferation and migration through activation of multiple pathways.

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    Cheng Wang

    Full Text Available Granulosa cell tumors (GCTs are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

  11. Micropatterning topology on soft substrates affects myoblast proliferation and differentiation.

    Science.gov (United States)

    Zatti, Susi; Zoso, Alice; Serena, Elena; Luni, Camilla; Cimetta, Elisa; Elvassore, Nicola

    2012-02-07

    Micropatterning techniques and substrate engineering are becoming useful tools to investigate several aspects of cell-cell interaction biology. In this work, we rationally study how different micropatterning geometries can affect myoblast behavior in the early stage of in vitro myogenesis. Soft hydrogels with physiological elastic modulus (E = 15 kPa) were micropatterned in parallel lanes (100, 300, and 500 μm width) resulting in different local and global myoblast densities. Proliferation and differentiation into multinucleated myotubes were evaluated for murine and human myoblasts. Wider lanes showed a decrease in murine myoblast proliferation: (69 ± 8)% in 100 μm wide lanes compared to (39 ± 7)% in 500 μm lanes. Conversely, fusion index increased in wider lanes: from (46 ± 7)% to (66 ± 7)% for murine myoblasts, and from (15 ± 3)% to (36 ± 2)% for human primary myoblasts, using a patterning width of 100 and 500 μm, respectively. These results are consistent with both computational modeling data and conditioned medium experiments, which demonstrated that wider lanes favor the accumulation of endogenous secreted factors. Interestingly, human primary myoblast proliferation is not affected by patterning width, which may be because the high serum content of their culture medium overrides the effect of secreted factors. These data highlight the role of micropatterning in shaping the cellular niche through secreted factor accumulation, and are of paramount importance in rationally understanding myogenesis in vitro for the correct design of in vitro skeletal muscle models.

  12. Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells.

    Science.gov (United States)

    Kotake, Yojiro; Goto, Taiki; Naemura, Madoka; Inoue, Yasutoshi; Okamoto, Haruna; Tahara, Keiichiro

    2017-01-01

    A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G1 phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G1 phase arrest. These results suggest that PANDA promotes G1-S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Crucial Role for Membrane Fluidity in Proliferation of Primitive Cells

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    Romain Mercier

    2012-05-01

    Full Text Available The cell wall is a defining structural feature of the bacterial subkingdom. However, most bacteria are capable of mutating into a cell-wall-deficient “L-form” state, requiring remarkable physiological and structural adaptations. L-forms proliferate by an unusual membrane deformation and scission process that is independent of the conserved and normally essential FtsZ based division machinery, and which may provide a model for the replication of primitive cells. Candidate gene screening revealed no requirement for the cytoskeletal systems that might actively drive membrane deformation or scission. Instead, we uncovered a crucial role for branched-chain fatty acid (BCFA synthesis. BCFA-deficient mutants grow and undergo pulsating shape changes, but membrane scission fails, abolishing the separation of progeny cells. The failure in scission is associated with a reduction in membrane fluidity. The results identify a step in L-form proliferation and demonstrate that purely biophysical processes may have been sufficient for proliferation of primitive cells.

  14. Click Chemistry for Analysis of Cell Proliferation in Flow Cytometry.

    Science.gov (United States)

    Clarke, Scott T; Calderon, Veronica; Bradford, Jolene A

    2017-10-02

    The measurement of cellular proliferation is fundamental to the assessment of cellular health, genotoxicity, and the evaluation of drug efficacy. Labeling, detection, and quantification of cells in the synthesis phase of cell cycle progression are not only important for characterizing basic biology, but also in defining cellular responses to drug treatments. Changes in DNA replication during S-phase can provide valuable insights into mechanisms of cell growth, cell cycle kinetics, and cytotoxicity. A common method for detection of cell proliferation is the incorporation of a thymidine analog during DNA synthesis. This chapter presents a pulse labeling method using the thymidine analog, 5-ethynyl-2'-deoxyuridine (EdU), with subsequent detection by click chemistry. EdU detection using click chemistry is bio-orthogonal to most living systems and does not non-specifically label other biomolecules. Live cells are first pulsed with EdU. After antibody labeling cell surface markers, fixation, and permeabilization, the incorporated EdU is covalently labeled using click chemistry thereby identifying proliferating cells. Improvements in click chemistry allow for labeling in the presence of fluorescent proteins and phycobiliproteins without quenching due to copper. Measuring DNA replication during cell cycle progression has cell health applications in flow cytometry, fluorescence microscopy, and high content imaging. This protocol has been developed and optimized for research use only and is not suitable for use in diagnostic procedures. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  15. Promotion of stem cell proliferation by vegetable peptone.

    Science.gov (United States)

    Lee, J; Lee, J; Hwang, H; Jung, E; Huh, S; Hyun, J; Park, D

    2009-10-01

    Technical limitations and evolution of therapeutic applications for cell culture-derived products have accelerated elimination of animal-derived constituents from such products to minimize inadvertent introduction of microbial contaminants, such as fungi, bacteria or viruses. The study described here was conducted to investigate the proliferative effect of vegetable peptone on adult stem cells in the absence of serum, and its possible mechanisms of action. Cell viability and proliferation were determined using the MTT assay and Click-iT EdU flow cytometry, respectively. In addition, changes in expression of cytokine genes were analysed using MILLIPLEX human cytokine enzyme-linked immunosorbent assay kit. Viability of cord blood-derived mesenchymal stem cells (CB-MSC) and adipose tissue-derived stem cells (ADSC) increased significantly when treated with the peptone. In addition, median value of the group treated with peptone shifted to the right when compared to the untreated control group. Furthermore, quantitative analysis of the cytokines revealed that production of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and interleukin-6 (IL-6) increased significantly in response to treatment with our vegetable peptone in both CB-MSCs and ADSCs. Our findings revealed that the vegetable peptone promotes proliferation of CB-MSCs and ADSCs. In addition, results of this study suggest that induction of stem cell proliferation by vegetable peptone is likely to be related to its induction of VEGF, TGF-beta1, and IL-6 expression.

  16. Retrotransposon Proliferation Coincident with the Evolution of Dioecy in Asparagus

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    Alex Harkess

    2016-09-01

    Full Text Available Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus. Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion, or to retrotransposon proliferation in dioecious species. We first estimate genome sizes, or use published values, for four hermaphrodites and four dioecious species distributed across the phylogeny, and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach, we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication (WGD event predating the diversification of the Asparagus genus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing, and common elements were annotated. Across our broad phylogenetic sampling, Ty-1 Copia retroelements, in particular, have undergone a marked proliferation in dioecious species. In the absence of a detectable WGD event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioecious Asparagus species.

  17. Retrotransposon Proliferation Coincident with the Evolution of Dioecy in Asparagus.

    Science.gov (United States)

    Harkess, Alex; Mercati, Francesco; Abbate, Loredana; McKain, Michael; Pires, J Chris; Sala, Tea; Sunseri, Francesco; Falavigna, Agostino; Leebens-Mack, Jim

    2016-09-08

    Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion, or to retrotransposon proliferation in dioecious species. We first estimate genome sizes, or use published values, for four hermaphrodites and four dioecious species distributed across the phylogeny, and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach, we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication (WGD) event predating the diversification of the Asparagus genus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing, and common elements were annotated. Across our broad phylogenetic sampling, Ty-1 Copia retroelements, in particular, have undergone a marked proliferation in dioecious species. In the absence of a detectable WGD event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioecious Asparagus species. Copyright © 2016 Harkess et al.

  18. Nifedipine promotes the proliferation and migration of breast cancer cells.

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    Dong-Qing Guo

    Full Text Available Nifedipine is widely used as a calcium channel blocker (CCB to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3. Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.

  19. Development of bioengineering system for stem cell proliferation

    Science.gov (United States)

    Park, H. S.; Shah, R.; Shah, C.

    2016-08-01

    From last decades, intensive research in the field of stem cells proliferation had been promoted due to the unique property of stem cells to self-renew themselves into multiples and has potential to replicate into an organ or tissues and so it's highly demanding though challenging. Bioreactor, a mechanical device, works as a womb for stem cell proliferation by providing nutritious environment for the proper growth of stem cells. Various factors affecting stem cells growth are the bioreactor mechanism, feeding of continuous nutrients, healthy environment, etc., but it always remains a challenge for controlling biological parameters. The present paper unveils the design of mechanical device commonly known as bioreactor in tissues engineering and biotech field, use for proliferation of stem cells and imparts the proper growing condition for stem cells. This high functional bioreactor provides automation mixing of cell culture and stem cells. This design operates in conjunction with mechanism of reciprocating motion. Compare to commercial bioreactors, this proposed design is more convenient, easy to operate and less maintenance is required as bioreactor culture bag is made of polyethylene which is single use purpose. Development of this bioengineering system will be beneficial for better growth and expansion of stem cell

  20. Cell cycles and proliferation patterns in Haematococcus pluvialis

    Science.gov (United States)

    Zhang, Chunhui; Liu, Jianguo; Zhang, Litao

    2017-09-01

    Most studies on Haematococcus pluvialis have been focused on cell growth and astaxanthin accumulation; far less attention has been paid to cell cycles and proliferation patterns. The purpose of this study was to clarify cell cycles and proliferation patterns in H. pluvialis microscopically using a camera and video recorder system. The complicated life history of H. pluvialis can be divided into two stages: the motile stage and the non-motile stage. All the cells can be classified into forms as follows: motile cell, nonmotile cell, zoospore and aplanospore. The main cell proliferation, both in the motile phase and non-motile phase in H. pluvialis, is by asexual reproduction. Under normal growth conditions, a motile cell usually produces two, sometimes four, and exceptionally eight zoospores. Under unfavorable conditions, the motile cell loses its flagella and transforms into a non-motile cell, and the non-motile cell usually produces 2, 4 or 8 aplanospores, and occasionally 20-32 aplanospores, which further develop into non-motile cells. Under suitable conditions, the non-motile cell is also able to release zoospores. The larger non-motile cells produce more than 16 zoospores, and the smaller ones produce 4 or 8 zoospores. Vegetative reproduction is by direct cell division in the motile phase and by occasional cell budding in the non-motile phase. There is, as yet, no convincing direct evidence for sexual reproduction.

  1. Long-term proliferation and safeguards issues in future technologies

    Energy Technology Data Exchange (ETDEWEB)

    Keisch, B.; Auerbach, C.; Fainberg, A.; Fiarman, S.; Fishbone, L.G.; Higinbotham, W.A.; Lemley, J.R.; O' Brien, J.

    1986-02-01

    The purpose of the task was to assess the effect of potential new technologies, nuclear and non-nuclear, on safeguards needs and non-proliferation policies, and to explore possible solutions to some of the problems envisaged. Eight subdivisions were considered: New Enrichment Technologies; Non-Aqueous Reprocessing Technologies; Fusion; Accelerator-Driven Reactor Systems; New Reactor Types; Heavy Water and Deuterium; Long-Term Storage of Spent Fuel; and Other Future Technologies (Non-Nuclear). For each of these subdivisions, a careful review of the current world-wide effort in the field provided a means of subjectively estimating the viability and qualitative probability of fruition of promising technologies. Technologies for which safeguards and non-proliferation requirements have been thoroughly considered by others were not restudied here (e.g., the Fast Breeder Reactor). The time scale considered was 5 to 40 years for possible initial demonstration although, in some cases, a somewhat optimistic viewpoint was embraced. Conventional nuclear-material safeguards are only part of the overall non-proliferation regime. Other aspects are international agreements, export controls on sensitive technologies, classification of information, intelligence gathering, and diplomatic initiatives. The focus here is on safeguards, export controls, and classification.

  2. Homocysteine inhibits hepatocyte proliferation via endoplasmic reticulum stress.

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    Xue Yu

    Full Text Available Homocysteine is an independent risk factor for coronary, cerebral, and peripheral vascular diseases. Recent studies have shown that levels of homocysteine are elevated in patients with impaired hepatic function, but the precise role of homocysteine in the development of hepatic dysfunction is unclear. In this study, we examined the effect of homocysteine on hepatocyte proliferation in vitro. Our results demonstrated that homocysteine inhibited hepatocyte proliferation by up-regulating protein levels of p53 as well as mRNA and protein levels of p21(Cip1 in primary cultured hepatocytes. Homocysteine induced cell growth arrest in p53-positive hepatocarcinoma cell line HepG2, but not in p53-null hepatocarcinoma cell line Hep3B. A p53 inhibitor pifithrin-α inhibited the expression of p21(Cip1 and attenuated homocysteine-induced cell growth arrest. Homocysteine induced TRB3 expression via endoplasmic reticulum stress pathway, resulting in Akt dephosphorylation. Knock-down of endogenous TRB3 significantly suppressed the inhibitory effect of homocysteine on cell proliferation and the phosphorylation of Akt. LiCl reversed homocysteine-mediated cell growth arrest by inhibiting TRB3-mediated Akt dephosphorylation. These results demonstrate that both TRB3 and p21(Cip1 are critical molecules in the homocysteine signaling cascade and provide a mechanistic explanation for impairment of liver regeneration in hyperhomocysteinemia.

  3. Emdogain-gel stimulates proliferation of odontoblasts and osteoblasts.

    Science.gov (United States)

    Jiang, Jin; Goodarzi, Golnaz; He, Jianing; Li, Haitao; Safavi, Kamran E; Spångberg, Larz S W; Zhu, Qiang

    2006-11-01

    The purpose of this study was to determine whether a premixed form of enamel matrix derivative (EMD), Emdogain-gel, has the same property as the original formula of EMD in stimulating the proliferation of osteoblasts and odontoblasts. Osteoblast cell line (MC3T3) and odontoblast cell line (MDPC) were cultured in the 6-well culture plates and treated in 4 different groups: (1) culture medium control, (2) 100 microg/mL Emdogain-gel directly added to the culture medium, (3) culture medium with a culture plate insert, and (4) 100 microg/mL Emdogain-gel added onto a culture plate insert. The culture plate insert prevented direct contact between Emdogain-gel and the cells. After 3-day incubation, cell morphology was examined and the total cell number per well was counted. Data were analyzed using 1-way ANOVA. Emdogain-gel significantly increased cell number of both osteoblasts and odontoblasts regardless the presence of the culture plate insert. Emdogain-gel stimulates cell proliferation of odontoblasts and osteoblasts. The direct contact between Emdogain-gel and cells is not required. Heat treatment of EMD and premix with propylene glycol alginate did not change its property of releasing bioactive molecules for promoting cell proliferation.

  4. Sustained proliferation in cancer: mechanisms and novel therapeutic targets

    Science.gov (United States)

    Arzumanyan, Alla; Kulathinal, Rob J.; Blain, Stacy W.; Holcombe, Randall F.; Mahajna, Jamal; Marino, Maria; Martinez-Chantar, Maria L.; Nawroth, Roman; Sanchez-Garcia, Isidro; Sharma, Dipali; Saxena, Neeraj K.; Singh, Neetu; Vlachostergios, Panagiotis J.; Guo, Shanchun; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Nowsheen, Somaira

    2016-01-01

    Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). This data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression. PMID:25892662

  5. Heparin-binding EGF-like growth factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas.

    Science.gov (United States)

    Todd, Levi; Volkov, Leo I; Zelinka, Chris; Squires, Natalie; Fischer, Andy J

    2015-11-01

    Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, heparin-binding EGF-like growth factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF not only stimulated MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators.

    Science.gov (United States)

    Reddy, J K; Goel, S K; Nemali, M R; Carrino, J J; Laffler, T G; Reddy, M K; Sperbeck, S J; Osumi, T; Hashimoto, T; Lalwani, N D

    1986-01-01

    The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate [(EtHx)2 greater than Pht] increase the activities of hepatic catalase and peroxisomal fatty acid beta-oxidation enzymes in conjunction with profound proliferation of peroxisomes in hepatocytes. In order to delineate the level at which these enzymes are induced in the liver, the transcriptional activity of specific genes for fatty acyl-CoA oxidase (FAOxase) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme (PBE), the first two enzymes of the peroxisomal beta-oxidation system, and for catalase were measured in isolated hepatocyte nuclei obtained from male rats following a single intragastric dose of ciprofibrate, clofibrate, or (EtHx)2 greater than Pht. All three peroxisome proliferators rapidly increased the rate of FAOxase and PBE gene transcription in liver, with near maximal rates (9-15 times control) reached by 1 hr and persisting until at least 16 hr after administration of the compound. FAOxase and PBE mRNA levels, measured by blot-hybridization analysis and FAOxase and PBE protein content, analyzed by immunoblotting, increased concurrently up to at least 16 hr following a single dose of peroxisome proliferator. The catalase mRNA level increased about 1.4-fold, but the transcription rate of the catalase gene was not significantly affected. The results show that the peroxisome proliferators clofibrate, ciprofibrate, and (EtHx)2 greater than Pht selectively increase the rate of transcription of peroxisomal fatty acid beta-oxidation enzyme genes. Whether the transcriptional effects are mediated by peroxisome proliferator-receptor complexes remains to be elucidated. Images PMID:3456610

  7. A Comparison of Proliferation Resistance Measures of Misuse Scenarios Using a Markov Approach

    Energy Technology Data Exchange (ETDEWEB)

    Yue,M.; Cheng, L.-Y.; Bari, R.

    2008-05-11

    Misuse of declared nuclear facilities is one of the important proliferation threats. The robustness of a facility against these threats is characterized by a number of proliferation resistance (PR) measures. This paper evaluates and compares PR measures for several misuse scenarios using a Markov model approach to implement the pathway analysis methodology being developed by the PR&PP (Proliferation Resistance and Physical Protection) Expert Group. Different misue strategies can be adopted by a proliferator and each strategy is expected to have different impacts on the proliferator's success. Selected as the probabilistic measure to represent proliferation resistance, the probabilities of the proliferator's success of misusing a hypothetical ESFR (Example Sodium Fast Reactor) facility system are calculated using the Markov model based on the pathways constructed for individual misuse scenarios. Insights from a comparison of strategies that are likely to be adopted by the proliferator are discussed in this paper.

  8. Liver cell proliferation after partial hepatectomy in rats with liver metastases

    NARCIS (Netherlands)

    de Jong, KP; Brouwers, MAM; Huls, GA; Bun, JCAM; Wubbena, AS; Nieuwenhuis, P; Slooff, MJH; Dam, A.

    OBJECTIVE: To validate proliferating cell nuclear antigen (PCNA) expression and flow cytometry as proliferation markers in regenerating rat liver containing metastases. STUDY DESIGN: Rats containing colorectal liver metastases were killed at various days after 70% partial hepatectomy or a sham

  9. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells.

    Directory of Open Access Journals (Sweden)

    Kavita S Subramaniam

    Full Text Available Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin and hormonal (estrogen and progesterone receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175% when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51% (P<0.0001. These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001, suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR, also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP-1, interleukin (IL-6, IL-8, RANTES and vascular

  10. Enhancing BWR proliferation resistance fuel with minor actinides

    Science.gov (United States)

    Chang, Gray S.

    2009-03-01

    To reduce spent fuel for storage and enhance the proliferation resistance for the intermediate-term, there are two major approaches (a) increase the discharged spent fuel burnup in the advanced light water reactor- LWR (Gen-III Plus), which not only can reduce the spent fuel for storage, but also increase the 238Pu isotopes ratio to enhance the proliferation resistance, and (b) use of transuranic nuclides ( 237Np and 241Am) in the high burnup fuel, which can drastically increase the proliferation resistance isotope ratio of 238Pu/Pu. For future advanced nuclear systems, minor actinides (MA) are viewed more as a resource to be recycled, and transmuted to less hazardous and possibly more useful forms, rather than simply disposed of as a waste stream in an expensive repository facility. As a result, MAs play a much larger part in the design of advanced systems and fuel cycles, not only as additional sources of useful energy, but also as direct contributors to the reactivity control of the systems into which they are incorporated. In the study, a typical boiling water reactor (BWR) fuel unit lattice cell model with UO 2 fuel pins will be used to investigate the effectiveness of minor actinide reduction approach (MARA) for enhancing proliferation resistance and improving the fuel cycle performance in the intermediate-term goal for future nuclear energy systems. To account for the water coolant density variation from the bottom (0.76 g/cm 3) to the top (0.35 g/cm 3) of the core, the axial coolant channel and fuel pin were divided to 24 nodes. The MA transmutation characteristics at different elevations were compared and their impact on neutronics criticality discussed. The concept of MARA, which involves the use of transuranic nuclides ( 237Np and/or 241Am), significantly increases the 238Pu/Pu ratio for proliferation resistance, as well as serves as a burnable absorber to hold-down the initial excess reactivity. It is believed that MARA can play an important role in

  11. Rapid Adaptation in Digital Transformation

    DEFF Research Database (Denmark)

    Hansen, Anne Mette; Kræmmergaard, Pernille; Mathiassen, Lars

    2011-01-01

    the organization’s digitization approach. We demonstrate in detail how the leaders within these two organizations were engaged and offer recommendations for how other organizations can use the PPM to rapidly adapt their approaches to digital transformation through more effective IS leadership roles.......In today’s highly dynamic environments, organizational leaders need to quickly adapt existing approaches to digital transformation. However, without a shared mindset between IS and business leaders, it is difficult to adopt new approaches in response to changes in the competitive and technology...... landscape. In this article, we share insights gained from two public sector organizations in which IS and business leaders used the Participatory Process Model (PPM) designed by the authors to share their assumptions about IS leadership, challenge existing IT strategies and collaboration patterns and adapt...

  12. Moved by a Rapid Transit

    Science.gov (United States)

    Bueter, C.

    2013-04-01

    Enticing by virtue of its predictability, historical utility, and spectacle, the transit of Venus is a niche event among astronomical phenomena. Though the value of a transit for scientific purposes is now diminished, the brief appearance of Venus silhouetted against the background of the Sun in 2004 moved the artistic community to celebrate the rare alignment. Artists of all ages combined old traditions with fresh technology to create a 21st-century tapestry of music, sculpture, paintings, glasswork, quilts, sky shows, and digital imagery. A full catalog of transit-related art generated over the centuries would feature the sampling of entries presented here and at the Moved by a Rapid Transit website.

  13. [Rapid diagnostic test for malaria].

    Science.gov (United States)

    Houzé, S

    2017-02-01

    The rapid diagnostic tests (RDTs) whose main interest lies in their implementation without special equipment by unskilled personnel have grown significantly over the past fifteen years to diagnose malaria. They rely on the detection of specific Plasmodium proteins, PfHRP2, pLDH and aldolase. If the detection of PfHRP2 has very good sensitivity for the diagnosis of Plasmodium falciparum malaria, the detection of pLDH or aldolase is less efficient for other species, leaving its place to the reference microscopic diagnosis. RDT could not generally be used to monitor therapeutic efficacy because they can remain positive after clinical and parasitological cure. Furthermore, the development of the use of these tests has highlighted the need for quality assurance programs to monitor their production as their use.

  14. Rapid Solidification of Magnetic Oxides

    Science.gov (United States)

    Kalonji, G.; Deguire, M. R.

    1985-01-01

    The enhanced control over microstructural evolution inherent in rapid solidification processing techniques are exploited to create novel ceramic magnetic materials. The great sensitivity of magnetic properties to local structure provides a powerful probe both for the study of structure and of microscopic solidification mechanisms. The first system studied is the SrO-Fe2O3 binary, which contains the commercially important hard magnetic compound strontium hexaferrite. The products were analyzed by transmission electron microscopy, Mossbauer spectroscopy, magnetic measurements, and differential thermal analysis. As-quenched ribbons contain high concentrations of super-paramagnetic particles, 80 to 250 Angstroms in diameter, in a glassy matrix. This suggests the possibility of crystallizing monodomain strontium hexaferrite during subsequent heat treatment, with a resulting increase in coercivity over conventionally processed ferrite magnets. That magnetic properties can be controlled in solidification processing by varying the quench rate is demonstrated.

  15. Dying endothelial cells stimulate proliferation of malignant glioma cells via a caspase 3-mediated pathway

    OpenAIRE

    Mao, Ping; Smith, Luke; XIE, WANFU; Wang, Maode

    2013-01-01

    Emerging evidence has indicated that apoptotic cells have a compensatory effect on the proliferation of neighboring cells. However, the potential role of dying vascular endothelial cells (ECs) in glioma tumor proliferation remains unclear. In the present study, three glioma cell lines were cocultured with dying ECs under various conditions to evaluate the effect of dying ECs on tumor proliferation using alamarBlue and trypan blue assays to assess cell proliferation and viability, respectively...

  16. Ceramic microfabrication by rapid prototyping process chains

    Indian Academy of Sciences (India)

    To avoid high tooling costs in product development, a rapid prototyping process chain has been established that enables rapid manufacturing of ceramic microcomponents from functional models to small lot series within a short time. This process chain combines the fast and inexpensive supply of master models by rapid ...

  17. Rapid Prototyping in Instructional Design: Creating Competencies

    Science.gov (United States)

    Fulton, Carolyn D.

    2010-01-01

    Instructional designers working in rapid prototyping environments currently do not have a list of competencies that help to identify the knowledge, skills, and attitudes (KSAs) required in these workplaces. This qualitative case study used multiple cases in an attempt to identify rapid prototyping competencies required in a rapid prototyping…

  18. Rapid Tooling via Investment Casting and Rapid Prototype Patterns

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Michael D.

    1999-06-01

    The objective of this work to develop the materials processing and design technologies required to reduce the die development time for metal mold processes from 12 months to 3 months, using die casting of Al and Mg as the example process. Sandia demonstrated that investment casting, using rapid prototype patterns produced from Stereo lithography or Selective laser Sintering, was a viable alternative/supplement to the current technology of machining form wrought stock. A demonstration die insert (ejector halt) was investment cast and subsequently tested in the die casting environment. The stationary half of the die insert was machined from wrought material to benchmark the cast half. The two inserts were run in a die casting machine for 3,100 shots of aluminum and at the end of the run no visible difference could be detected between the cast and machined inserts. Inspection concluded that the cast insert performed identically to the machined insert. Both inserts had no indications of heat checking or degradation.

  19. Rapid prototyping of nano- and micro-patterned substrates for the control of cell neuritogenesis by topographic and chemical cues

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Ajay V.; Gailite, Lasma; Vyas, Varun [European School of Molecular Medicine (SEMM), IFOM-IEO Campus, Via Adamello 16, I-20139 Milano (Italy); CIMAINA and Dipartimento di Fisica, Universita di Milano, via Celoria 16, I-20133 Milano (Italy); Lenardi, Cristina, E-mail: cristina.lenardi@mi.infn.it [CIMAINA and Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Universita di Milano, via Trentacoste 2, I-20134 Milano (Italy); Fondazione Filarete, viale Ortles 22/4, I-20139 Milano (Italy); Forti, Stefania [CIMAINA and Dipartimento di Fisica, Universita di Milano, via Celoria 16, I-20133 Milano (Italy); Matteoli, Michela [Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, Universita di Milano, via Vanvitelli 32, I-20139 Milano (Italy); Fondazione Filarete, viale Ortles 22/4, I-20139 Milano (Italy); Milani, Paolo, E-mail: paolo.milani@mi.infn.it [CIMAINA and Dipartimento di Fisica, Universita di Milano, via Celoria 16, I-20133 Milano (Italy); Fondazione Filarete, viale Ortles 22/4, I-20139 Milano (Italy)

    2011-07-20

    Rapid prototyping of titania substrates with micro and nanofeatures is obtained by combining nanosphere lithography with supersonic cluster beam deposition on protein-functionalized glass supports. The proliferation and differentiation of PC12 cells were studied on these substrates. The facile control and modification of the substrate structure at the micro- and nanoscale allowed us to characterize the role of functional and structural features on neuritogenesis and to control this phenomenon by identifying the optimal topography.

  20. Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway

    Directory of Open Access Journals (Sweden)

    Daya M

    2018-01-01

    Full Text Available Minerva Daya,1–3 Watcharin Loilome,1,3 Anchalee Techasen,3,4 Malinee Thanee,3 Prakasit Sa-Ngiamwibool,4,5 Attapol Titapun,5,6 Puangrat Yongvanit,3 Nisana Namwat1,31Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 2Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Sampaloc, Manila, Philippines; 3Cholangiocarcinoma Research Institute, 4Faculty of Associated Medical Science, 5Department of Pathology, 6Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Abstract: Progranulin (PGRN is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA. However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K and phosphorylated Akt (pAkt proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial–mesenchymal transition (EMT revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In

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

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

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

  2. Prostate progenitor cells proliferate in response to castration

    Directory of Open Access Journals (Sweden)

    Xudong Shi

    2014-07-01

    Full Text Available Androgen-deprivation is a mainstay of therapy for advanced prostate cancer but tumor regression is usually incomplete and temporary because of androgen-independent cells in the tumor. It has been speculated that these tumor cells resemble the stem/progenitor cells of the normal prostate. The purpose of this study was to examine the response of slow-cycling progenitor cells in the adult mouse prostate to castration. Proliferating cells in the E16 urogenital sinus were pulse labeled by BrdU administration or by doxycycline-controlled labeling of the histone-H2B GFP mouse. A small population of labeled epithelial cells in the adult prostate localized at the junction of the prostatic ducts and urethra. Fluorescence-activated cell sorting (FACS showed that GFP label-retaining cells were enriched for cells co-expressing stem cell markers Sca-1, CD133, CD44 and CD117 (4- marker cells; 60-fold enrichment. FACS showed, additionally, that 4-marker cells were androgen receptor positive. Castration induced proliferation and dispersal of E16 labeled cells into more distal ductal segments. When naïve adult mice were administered BrdU daily for 2 weeks after castration, 16% of 4-marker cells exhibited BrdU label in contrast to only 6% of all epithelial cells (P < 0.01. In sham-castrated controls less than 4% of 4-marker cells were BrdU labeled (P < 0.01. The unexpected and admittedly counter-intuitive finding that castration induced progenitor cell proliferation suggests that androgen deprivation therapy in men with advanced prostate cancer could not only exert pleiotrophic effects on tumor sub-populations but may induce inadvertent expansion of tumor stem cells.

  3. Gastrokine 1 inhibits gastrin-induced cell proliferation.

    Science.gov (United States)

    Kim, Olga; Yoon, Jung Hwan; Choi, Won Suk; Ashktorab, Hassan; Smoot, Duane T; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

    2016-04-01

    Gastrokine 1 (GKN1) acts as a gastric tumor suppressor. Here, we investigated whether GKN1 contributes to the maintenance of gastric mucosal homeostasis by regulating gastrin-induced gastric epithelial cell growth. We assessed the effects of gastrin and GKN1 on cell proliferation in stable AGS(GKN1) and MKN1(GKN1) gastric cancer cell lines and HFE-145 nonneoplastic epithelial cells. Cell viability and proliferation were analyzed by MTT and BrdU incorporation assays, respectively. Cell cycle and expression of growth factor receptors were examined by flow cytometry and Western blot analyses. Gastrin treatment stimulated a significant time-dependent increase in cell viability and proliferation in AGS(mock) and MKN1(mock), but not in HFE-145, AGS(GKN1), and MKN1(GKN1), cells, which stably expressed GKN1. Additionally, gastrin markedly increased the S-phase cell population, whereas GKN1 significantly inhibited the effect of gastrin by regulating the expression of G1/S cell-cycle regulators. Furthermore, gastrin induced activation of the NF-kB and β-catenin signaling pathways and increased the expression of CCKBR, EGFR, and c-Met in AGS and MKN1 cells. However, GKN1 completely suppressed these effects of gastrin via downregulation of gastrin/CCKBR/growth factor receptor expression. Moreover, GKN1 reduced gastrin and CCKBR mRNA expression in AGS and MKN1 cells, and there was an inverse correlation between GKN1 and gastrin, as well as between GKN1 and CCKBR mRNA expression in noncancerous gastric mucosae. These data suggest that GKN1 may contribute to the maintenance of gastric epithelial homeostasis and inhibit gastric carcinogenesis by downregulating the gastrin-CCKBR signaling pathway.

  4. Hemopoietic stem cells: stochastic differentiation and humoral control of proliferation.

    Science.gov (United States)

    Ogawa, M

    1989-03-01

    The central feature of hemopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The entry into cell cycle of the dormant stem cells may be promoted by such factors as interleukin-1, interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). Once the stem cells leave G0 and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. While several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a random (stochastic) process. The proliferation of early hemopoietic progenitors requires the presence of interleukin-3 (IL-3), and the intermediate process appears to be supported by granulocyte/macrophage colony-stimulating factor (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin and G-CSF. Synthesis of a hemopoietic factor may take place in different cell types and is regulated by multiple factors. The physiological regulator of erythropoiesis is erythropoietin, which, by a feedback mechanism, provides fine control of erythrocyte production. Feedback mechanisms for leukocyte production have not been identified. It is possible that there is no feedback regulator of leukopoiesis. In this model, leukocyte production in the steady state is maintained at a genetically determined level. When an infection occurs, the bacterial lipopolysaccharides may augment the production of interleukin 1 alpha and beta, tumor necrosis factor, macrophage colony-stimulating factor, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration.

    Directory of Open Access Journals (Sweden)

    Erika Costa de Alvarenga

    Full Text Available The angiotensin-I converting enzyme (ACE plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II. More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet.Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration.We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC, and experimental results in CHO cells, demonstrated that the β3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5 showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein.ACE activation regulates melanoma cell proliferation and migration.

  6. GLUT1 regulates cell glycolysis and proliferation in prostate cancer.

    Science.gov (United States)

    Xiao, Hengjun; Wang, Jun; Yan, Weixin; Cui, Yubin; Chen, Zheng; Gao, Xin; Wen, Xingqiao; Chen, Jun

    2018-02-01

    Glucose transporter 1 (GLUT1) plays a critical role in tumorigenesis and tumor progression in multiple cancer types. However, the specific function and clinical significance of GLUT1 in prostate cancer (PCa) are still unclear. Therefore, in this study, we investigated the role of GLUT1 in PCa. GLUT1 protein levels in prostate cancer tissue and tumor-adjacent normal tissues were measured and compared. Furthermore, real-time PCR and Western blot analysis were both used to detect GLUT1 expression levels in different PCa cell lines. Flow cytometry and cell-based assays, such as a glucose uptake and lactate secretion assay, CCK-8 assay, and transwell migration and wound healing assay, were used to monitor cancer cell cycle distribution, glycolysis, proliferation, and motility, respectively. Moreover, a mouse tumor xenograft model was used to investigate the role of GLUT1 in tumor progression in vivo. GLUT1 expression levels are higher in PCa tissues than in tumor-adjacent normal tissues. The results from real-time PCR and Western blot analysis revealed a similar increase in the GLUT1 expression levels in PCa cell lines. Moreover, knockdown of GLUT1 inhibits cell glycolysis and proliferation and leads to cell cycle arrest at G2/M phase in the 22RV1 cell line but not in the PC3 cell line. In vivo experiments further confirmed that GLUT1 knockdown inhibits the growth of tumors derived from the 22RV1 cell line. In addition, we also showed that GLUT1 knockdown has no effect on cell migration in vitro. GLUT1 may play an important role in PCa progression via mediating glycolysis and proliferation. Our study also indicated a potential crosstalk between GLUT1-mediated glycolysis and androgen sensitivity in PCa. © 2017 Wiley Periodicals, Inc.

  7. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Jeong, Jieun; Wi, Anjin; Park, Whoashig [Jeollanamdo Forest Resources Research Institute, Naju 520-833 (Korea, Republic of); Han, Ho-jae [College of Veterinary Medicine, Seoul National University, Seoul 151-741 (Korea, Republic of); Park, Soo-hyun, E-mail: parksh@chonnam.ac.kr [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

    2015-06-05

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.

  8. Phospholipase Cβ interacts with cytosolic partners to regulate cell proliferation.

    Science.gov (United States)

    Scarlata, Suzanne; Singla, Ashima; Garwain, Osama

    2018-01-01

    Phospholipase Cβ (PLCβ) is the main effector of the Gαq signaling pathway relaying different extracellular sensory information to generate intracellular calcium signals. Besides this classic function, we have found that PLCβ plays an important but unknown role in regulating PC12 cell differentiation by interacting with components in the RNA-induced silencing machinery. In trying to understand the role of PLCβ in PC12 cell differentiation, we find that over-expressing PLCβ reduces PC12 cell proliferation while down-regulating PLCβ increases the rate of cell proliferation. However, this behavior is not seen in other cancerous cell lines. To determine the underlying mechanism, we carried out mass spectrometry analysis of PLCβ complexes in PC12 cells. We find that in unsynchronized cells, PLCβ primarily binds cyclin-dependent kinase (CDK)16 whose activity plays a key role in cell proliferation. In vitro studies show a direct association between the two proteins that result in loss in CDK16 activity. When cells are arrested in the G2/M phase, a large population of PLCβ is bound to Ago2 in a complex that contains C3PO and proteins commonly found in stress granules. Additionally, another population of PLCβ complexes with CDK18 and cyclin B1. Fluorescence lifetime imaging microscopy (FLIM) confirms cell cycle dependent associations between PLCβ and these other protein binding partners. Taken together, our studies suggest that PLCβ may play an active role in mediating interactions required to move through the cell cycle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. MicroRNAs Inducing Proliferation of Quiescent Adult Cardiomyocytes.

    Science.gov (United States)

    Pandey, Raghav; Ahmed, Rafeeq P H

    In the United States, each year over 700,000 people suffer from a heart attack and over 25% of deaths are related to heart disease, making it the leading cause of death. Following ischemic injury a part of the heart muscle is replaced by a scar tissue, reducing its functioning capacity. Recent advancements in surgical intervention and pharmacotherapy only provide symptomatic relief and do not address the root cause of the problem which is the massive loss of cardiomyocytes (CM). Therefore, the development of novel therapeutic intervention for the repair and regeneration of ischemic myocardium remains an area of intense research. While existing CM in zebra fish and neonatal mice are known to proliferate and replenish the infarcted heart, it has been shown that adult mammalian CM lose this ability, thus preventing regeneration of the scar tissue. There have been many attempts to facilitate regeneration of ischemic heart but have met with limited success. Micro-RNAs (miRNAs) are one of the promising candidates towards this goal as they are known to play important regulatory roles during differentiation and tissue regeneration, and regulate genetic information by post-transcriptional modification as well as regulation of other miRNAs. While previous work by Eulalio et al., showed miRNAs inducing proliferation in neonatal CM (NCM), we here identify miRNAs inducing proliferation of rat adult-CM (ACM). This commentary while analyses recent work by Eulalio et al[1] also shows some new data with microRNAs in rat adult-CMs. Further work into the mechanism of these miRNAs can determine their therapeutic potential towards regenerating cardiac tissue post ischemic injury.

  10. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  11. Cyclooxygenase 2 plays a role in Emdogain-induced proliferation.

    Science.gov (United States)

    Khedmat, S; Seyedabadi, M; Ghahremani, M H; Ostad, S N

    2011-02-01

    Enamel matrix proteins are involved in the development and regeneration of root cementum and in its attachment to dentin; however, the mechanisms through which this occurs have yet to be elucidated. The present study was therefore carried out to evaluate the mitogenic and proliferative responses of human periodontal fibroblast (HPLF) cells to Emdogain (EMD), and the potential role of cyclooxygenase 2 (COX-2) in this process. We investigated the effects of EMD on 5-bromo-2'-deoxyuridine (BrdU) incorporation, colchicine freezing of mitosis, XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and Trypan Blue dye exclusion, with or without celecoxibe, a selective cyclooxygenase-2 (COX-2) inhibitor; we also evaluated the expression of COX-2 mRNA and COX-2 protein in response to EMD. EMD significantly enhanced mitosis in, and proliferation of, human periodontal ligament fibroblasts in a dose-dependent manner; however, there was a small increase of DNA synthesis only in response to a high dose of EMD (200 μg/mL). EMD (100 and 200 μg/mL) elicited an increase in COX-2 expression (p ≤ 0.05). Celecoxibe (20 μm) diminished the EMD-induced mitosis and proliferation of HPLF cells (p ≤ 0.05). Celecoxibe hampered EMD-induced mitosis and proliferation, which, in association with EMD-increased COX-2 expression, indicates that COX-2 may be involved in the proliferative response of HPLF cells to EMD. © 2010 John Wiley & Sons A/S.

  12. Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation

    OpenAIRE

    Phillips Jonathan E; Bakthavatsalam Deenadayalan; Choe Jonathan M; Gomer Richard H

    2009-01-01

    Abstract Background Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the...

  13. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Means, Robert E.

    2013-01-01

    The overall goal of the Wyoming Basin Rapid Ecoregional Assessment (REA) is to provide information that supports regional planning and analysis for the management of ecological resources. The REA provides an assessment of baseline ecological conditions, an evaluation of current risks from drivers of ecosystem change (including energy development, fire, and invasive species), and a predictive capacity for evaluating future risks (including climate change). Additionally, the REA may be used for identifying priority areas for conservation or restoration and for assessing cumulative effects of multiple land uses. The Wyoming Basin REA will address Management Questions developed by the Bureau of Land Management and other agency partners for 8 major biomes and 19 species or species assemblages. The maps developed for addressing Management Questions will be integrated into overall maps of landscape-level ecological values and risks. The maps can be used to address the goals of the REA at a number of levels: for individual species, species assemblages, aquatic and terrestrial systems, and for the entire ecoregion. This allows flexibility in how the products of the REA are compiled to inform planning and management actions across a broad range of spatial scales.

  14. Rapid purification of recombinant histones.

    Directory of Open Access Journals (Sweden)

    Henrike Klinker

    Full Text Available The development of methods to assemble nucleosomes from recombinant histones decades ago has transformed chromatin research. Nevertheless, nucleosome reconstitution remains time consuming to this day, not least because the four individual histones must be purified first. Here, we present a streamlined purification protocol of recombinant histones from bacteria. We termed this method "rapid histone purification" (RHP as it circumvents isolation of inclusion bodies and thereby cuts out the most time-consuming step of traditional purification protocols. Instead of inclusion body isolation, whole cell extracts are prepared under strongly denaturing conditions that directly solubilize inclusion bodies. By ion exchange chromatography, the histones are purified from the extracts. The protocol has been successfully applied to all four canonical Drosophila and human histones. RHP histones and histones that were purified from isolated inclusion bodies had similar purities. The different purification strategies also did not impact the quality of octamers reconstituted from these histones. We expect that the RHP protocol can be readily applied to the purification of canonical histones from other species as well as the numerous histone variants.

  15. Rapid typing of Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Heidie M Hornstra

    Full Text Available Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels among multispacer sequence typing (MST loci and designed 14 SNP-based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies.

  16. Rapid Response Flood Water Mapping

    Science.gov (United States)

    Policelli, Fritz; Brakenridge, G. R.; Coplin, A.; Bunnell, M.; Wu, L.; Habib, Shahid; Farah, H.

    2010-01-01

    Since the beginning of operation of the MODIS instrument on the NASA Terra satellite at the end of 1999, an exceptionally useful sensor and public data stream have been available for many applications including the rapid and precise characterization of terrestrial surface water changes. One practical application of such capability is the near-real time mapping of river flood inundation. We have developed a surface water mapping methodology based on using only bands 1 (620-672 nm) and 2 (841-890 nm). These are the two bands at 250 m, and the use of only these bands maximizes the resulting map detail. In this regard, most water bodies are strong absorbers of incoming solar radiation at the band 2 wavelength: it could be used alone, via a thresholding procedure, to separate water (dark, low radiance or reflectance pixels) from land (much brighter pixels) (1, 2). Some previous water mapping procedures have in fact used such single band data from this and other sensors that include similar wavelength channels. Adding the second channel of data (band 1), however, allows a band ratio approach which permits sediment-laden water, often relatively light at band 2 wavelengths, to still be discriminated, and, as well, provides some removal of error by reducing the number of cloud shadow pixels that would otherwise be misclassified as water.

  17. PROLIFERATION RESISTANCE AND PHYSICAL PROTECTION WORKING GROUP: METHODOLOGY AND APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Bari R. A.; Whitlock, J.; Therios, I.U.; Peterson, P.F.

    2012-11-14

    We summarize the technical progress and accomplishments on the evaluation methodology for proliferation resistance and physical protection (PR and PP) of Generation IV nuclear energy systems. We intend the results of the evaluations performed with the methodology for three types of users: system designers, program policy makers, and external stakeholders. The PR and PP Working Group developed the methodology through a series of demonstration and case studies. Over the past few years various national and international groups have applied the methodology to nuclear energy system designs as well as to developing approaches to advanced safeguards.

  18. Strengthening the nuclear-reactor fuel cycle against proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Travelli, A.; Snelgrove, J.; Persiani, P. [Argonne National Lab., IL (United States). Arms Control and Nonproliferation Program

    1992-12-31

    Argonne National Laboratory (ANL) conducts several research programs that serve to reduce the risks of fissile-material diversion from the nuclear-reactor fuel cycle. The objectives are to provide economical and efficient neutron or power generation with the minimum of inherent risks, and to further minimize risks by utilizing sophisticated techniques to detect attempts at material diversion. This paper will discuss the Reduced Enrichment Research and Test Reactor (RERTR) Program, the Isotope Correlation Technique (ICT), and Proliferation-Resistant Closed-Cycle Reactors. The first two are sponsored by the DOE Office of Arms Control and Nonproliferation.

  19. Proliferation Potential of Accelerator-Drive Systems: Feasibility Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Riendeau, C.D.; Moses, D.L.; Olson, A.P.

    1998-11-01

    Accelerator-driven systems for fissile materials production have been proposed and studied since the early 1950s. Recent advances in beam power levels for small accelerators have raised the possibility that such use could be feasible for a potential proliferator. The objective of this study is to review the state of technology development for accelerator-driven spallation neutron sources and subcritical reactors. Energy and power requirements were calculated for a proton accelerator-driven neutron spallation source and subcritical reactors to produce a significant amount of fissile material--plutonium.

  20. Bizarre parosteal osteochondromatous proliferation of the proximal humerus: case report

    Energy Technology Data Exchange (ETDEWEB)

    Bush, J.B.; Meyer, Mark S. [Ochsner Clinic Foundation, Department of Orthopedics, New Orleans, LA (United States); Reith, John D. [University of Florida College of Medicine, Departments of Pathology, Immunology and Laboratory Medicine and Orthopaedics and Rehabilitation, Gainesville, Florida (United States)

    2007-06-15

    Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare lesion of bone occurring predominantly in the long bones of the hands and feet. It exists as a puzzling clinical entity of uncertain origins and high recurrence rates after surgical resection. To our knowledge, this clinical entity has not been reported in the proximal aspect of the humerus. An interesting report of a lesion occurring in the proximal humerus, which initially was misinterpreted as a parosteal osteosarcoma, is discussed outlining the clinical, radiographic and pathologic features of the BPOP lesion. (orig.)

  1. Niclosamide suppresses hepatoma cell proliferation via the Wnt pathway

    Directory of Open Access Journals (Sweden)

    Tomizawa M

    2013-11-01

    Full Text Available Minoru Tomizawa,1 Fuminobu Shinozaki,2 Yasufumi Motoyoshi,3 Takao Sugiyama,4 Shigenori Yamamoto,5 Makoto Sueishi,4 Takanobu Yoshida6 1Department of Gastroenterology, 2Department of Radiology, 3Department of Neurology, 4Department of Rheumatology, 5Department of Pediatrics, 6Department of Internal Medicine, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba, Japan Background: The Wnt pathway plays an important role in hepatocarcinogenesis. We analyzed the association of the Wnt pathway with the proliferation of hepatoma cells using Wnt3a and niclosamide, a drug used to treat tapeworm infection. Methods: We performed an MTS assay to determine whether Wnt3a stimulated proliferation of Huh-6 and Hep3B human hepatoma cell lines after 72 hours of incubation with Wnt3a in serum-free medium. The cells were subjected to hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL after 48 hours of incubation. RNA was isolated 48 hours after addition of Wnt3a or niclosamide, and cyclin D1 expression levels were analyzed by real-time quantitative polymerase chain reaction. The promoter activity of T-cell factor was analyzed by luciferase assay 48 hours after transfection of TOPflash. Western blot analysis was performed with antibodies against β-catenin, dishevelled 2, and cyclin D1. Results: Cell proliferation increased with Wnt3a. Niclosamide suppressed proliferation with or without Wnt3a. Hematoxylin and eosin and TUNEL staining suggested that apoptosis occurred in cells with niclosamide. Cyclin D1 was upregulated in the presence of Wnt3a and downregulated with addition of niclosamide. The promoter activity of T-cell factor increased with Wnt3a, whereas T-cell factor promoter activity decreased with niclosamide. Western blot analysis showed that Wnt3a upregulated β-catenin, dishevelled 2, and cyclin D1, while niclosamide downregulated them. Conclusion: Niclosamide is a potential

  2. Preliminary analysis of alternative fuel cycles for proliferation evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Steindler, M. J.; Ripfel, H. C.F.; Rainey, R. H.

    1977-01-01

    The ERDA Division of Nuclear Research and Applications proposed 67 nuclear fuel cycles for assessment as to their nonproliferation potential. The object of the assessment was to determine which fuel cycles pose inherently low risk for nuclear weapon proliferation while retaining the major benefits of nuclear energy. This report is a preliminary analysis of these fuel cycles to develop the fuel-recycle data that will complement reactor data, environmental data, and political considerations, which must be included in the overall evaluation. This report presents the preliminary evaluations from ANL, HEDL, ORNL, and SRL and is the basis for a continuing in-depth study. (DLC)

  3. Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells.

    Science.gov (United States)

    Sullivan, Lucas B; Gui, Dan Y; Hosios, Aaron M; Bush, Lauren N; Freinkman, Elizaveta; Vander Heiden, Matthew G

    2015-07-30

    Mitochondrial respiration is important for cell proliferation; however, the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here, we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Plant root proliferation in nitrogen-rich patches confers competitive advantage

    Science.gov (United States)

    Robinson, D.; Hodge, A.; Griffiths, B. S.; Fitter, A. H.

    1999-01-01

    Plants respond strongly to environmental heterogeneity, particularly below ground, where spectacular root proliferations in nutrient-rich patches may occur. Such 'foraging' responses apparently maximize nutrient uptake and are now prominent in plant ecological theory. Proliferations in nitrogen-rich patches are difficult to explain adaptively, however. The high mobility of soil nitrate should limit the contribution of proliferation to N capture. Many experiments on isolated plants show only a weak relation between proliferation and N uptake. We show that N capture is associated strongly with proliferation during interspecific competition for finite, locally available, mixed N sources, precisely the conditions under which N becomes available to plants on generally infertile soils. This explains why N-induced root proliferation is an important resource-capture mechanism in N-limited plant communities and suggests that increasing proliferation by crop breeding or genetic manipulation will have a limited impact on N capture by well-fertilized monocultures.

  5. Auxin induces cell proliferation in an experimental model of mammalian renal tubular epithelial cells.

    Science.gov (United States)

    Cernaro, Valeria; Medici, Maria Antonietta; Leonello, Giuseppa; Buemi, Antoine; Kohnke, Franz Heinrich; Villari, Antonino; Santoro, Domenico; Buemi, Michele

    2015-06-01

    Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration.

  6. Extracellular matrix stiffness causes systematic variations in proliferation and chemosensitivity in myeloid leukemias

    Science.gov (United States)

    Shin, Jae-Won; Mooney, David J.

    2016-01-01

    Extracellular matrix stiffness influences biological functions of some tumors. However, it remains unclear how cancer subtypes with different oncogenic mutations respond to matrix stiffness. In addition, the relevance of matrix stiffness to in vivo tumor growth kinetics and drug efficacy remains elusive. Here, we designed 3D hydrogels with physical parameters relevant to hematopoietic tissues and adapted them to a quantitative high-throughput screening format to facilitate mechanistic investigations into the role of matrix stiffness on myeloid leukemias. Matrix stiffness regulates proliferation of some acute myeloid leukemia types, including MLL-AF9+ MOLM-14 cells, in a biphasic manner by autocrine regulation, whereas it decreases that of chronic myeloid leukemia BCR-ABL+ K-562 cells. Although Arg-Gly-Asp (RGD) integrin ligand and matrix softening confer resistance to a number of drugs, cells become sensitive to drugs against protein kinase B (PKB or AKT) and rapidly accelerated fibrosarcoma (RAF) proteins regardless of matrix stiffness when MLL-AF9 and BCR-ABL are overexpressed in K-562 and MOLM-14 cells, respectively. By adapting the same hydrogels to a xenograft model of extramedullary leukemias, we confirm the pathological relevance of matrix stiffness in growth kinetics and drug sensitivity against standard chemotherapy in vivo. The results thus demonstrate the importance of incorporating 3D mechanical cues into screening for anticancer drugs. PMID:27790998

  7. 2D ratiometric fluorescent pH sensor for tracking of cells proliferation and metabolism.

    Science.gov (United States)

    Ma, Jun; Ding, Changqin; Zhou, Jie; Tian, Yang

    2015-08-15

    Extracellular pH plays a vital role no matter in physiological or pathological studies. In this work, a hydrogel, CD@Nile-FITC@Gel (Gel sensor), entrapping the ratiometric fluorescent probe CD@Nile-FITC was developed. The Gel sensor was successfully used for real-time extracellular pH monitoring. In the case of CD@Nile-FITC, pH-sensitive fluorescent dye fluorescein isothiocyanate (FITC) was chosen as the response signal for H(+) and Nile blue chloride (Nile) as the reference signal. The developed fluorescent probe exhibited high selectivity for pH over other metal ions and amino acids. Meanwhile, the carbon-dots-based inorganic-organic probe demonstrated excellent photostability against long-term light illumination. In order to study the extracellular pH change in processes of cell proliferation and metabolism, CD@Nile-FITC probe was entrapped in sodium alginate gel and consequently formed CD@Nile-FITC@Gel. The MTT assay showed low cytotoxicity of the Gel and the pH titration indicated that it could monitor the pH fluctuations linearly and rapidly within the pH range of 6.0-9.0, which is valuable for physiological pH determination. As expected, the real-time bioimaging of the probe was successfully achieved. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Cell proliferation is necessary for the regeneration of oral structures in the anthozoan cnidarian Nematostella vectensis

    Directory of Open Access Journals (Sweden)

    Passamaneck Yale J

    2012-12-01

    Full Text Available Abstract Background The contribution of cell proliferation to regeneration varies greatly between different metazoan models. Planarians rely on pluripotent neoblasts and amphibian limb regeneration depends upon formation of a proliferative blastema, while regeneration in Hydra can occur in the absence of cell proliferation. Recently, the cnidarian Nematostella vectensis has shown potential as a model for studies of regeneration because of the ability to conduct comparative studies of patterning during embryonic development, asexual reproduction, and regeneration. The present study investigates the pattern of cell proliferation during the regeneration of oral structures and the role of cell proliferation in this process. Results In intact polyps, cell proliferation is observed in both ectodermal and endodermal tissues throughout the entire oral-aboral axis, including in the tentacles and physa. Following bisection, there is initially little change in proliferation at the wound site of the aboral fragment, however, beginning 18 to 24 hours after amputation there is a dramatic increase in cell proliferation at the wound site in the aboral fragment. This elevated level of proliferation is maintained throughout the course or regeneration of oral structures, including the tentacles, the mouth, and the pharynx. Treatments with the cell proliferation inhibitors hydroxyurea and nocodazole demonstrate that cell proliferation is indispensable for the regeneration of oral structures. Although inhibition of regeneration by nocodazole was generally irreversible, secondary amputation reinitiates cell proliferation and regeneration. Conclusions The study has found that high levels of cell proliferation characterize the regeneration of oral structures in Nematostella, and that this cell proliferation is necessary for the proper progression of regeneration. Thus, while cell proliferation contributes to regeneration of oral structures in both Nematostella and

  9. Serglycin in Quiescent and Proliferating Primary Endothelial Cells

    Science.gov (United States)

    Reine, Trine M.; Vuong, Tram T.; Rutkovskiy, Arkady; Meen, Astri J.; Vaage, Jarle; Jenssen, Trond G.; Kolset, Svein O.

    2015-01-01

    Proteoglycans are fundamental components of the endothelial barrier, but the functions of the proteoglycan serglycin in endothelium are less described. Our aim was to describe the roles of serglycin in processes relevant for endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVEC) were cultured in vitro and the expression of proteoglycans was investigated. Dense cell cultures representing the quiescent endothelium coating the vasculature was compared to sparse activated cell cultures, relevant for diabetes, cancer and cardiovascular disease. Secretion of 35S- proteoglycans increased in sparse cultures, and we showed that serglycin is a major component of the cell-density sensitive proteoglycan population. In contrast to the other proteoglycans, serglycin expression and secretion was higher in proliferating compared to quiescent HUVEC. RNAi silencing of serglycin inhibited proliferation and wound healing, and serglycin expression and secretion was augmented by hypoxia, mechanical strain and IL-1β induced inflammation. Notably, the secretion of the angiogenic chemokine CCL2 resulting from IL-1β activation, was increased in serglycin knockdown cells, while angiopoietin was not affected. Both serglycin and CCL2 were secreted predominantly to the apical side of polarized HUVEC, and serglycin and CCL2 co-localized both in perinuclear areas and in vesicles. These results suggest functions for serglycin in endothelial cells trough interactions with partner molecules, in biological processes with relevance for diabetic complications, cardiovascular disease and cancer development. PMID:26694746

  10. Cell topology, geometry, and morphogenesis in proliferating epithelia.

    Science.gov (United States)

    Gibson, William T; Gibson, Matthew C

    2009-01-01

    Epithelia are sheets of tightly adherent cells that line both internal and external surfaces in a vast array of metazoans. During development, an intrinsic consequence of coupling tight adhesion with cellular proliferation is the emergence of an epithelial form characterized by a stereotyped distribution of polygonal cell shapes. Despite the near universality of this constraint on cell shape and tissue organization, very little is known about the possible implications of cell pattern geometry for mechanical properties of tissues or key biological processes, such as planar polarization, tissue remodeling, and cell division. In this chapter, through an examination of increasingly complex models, we highlight what is known about the role of mitotic proliferation in the emergence of epithelial cell geometry, and examine some possible implications for tissue morphogenesis. Ideally, continued progress in this area will address a major conceptual challenge in biology, which is to understand aspects of morphogenesis that are not explicitly directed by genetic control, but instead emerge from the complex interactions between geometric and biomechanical properties of epithelial tissues.

  11. Rnd3 regulates lung cancer cell proliferation through notch signaling.

    Directory of Open Access Journals (Sweden)

    Yongjun Tang

    Full Text Available Rnd3/RhoE is a small Rho GTPase involved in the regulation of different cell behaviors. Dysregulation of Rnd3 has been linked to tumorigenesis and metastasis. Lung cancers are the leading cause of cancer-related death in the West and around the world. The expression of Rnd3 and its ectopic role in non-small cell lung cancer (NSCLC remain to be explored. Here, we reported that Rnd3 was down-regulated in three NSCLC cell lines: H358, H520 and A549. The down-regulation of Rnd3 led to hyper-activation of Rho Kinase and Notch signaling. The reintroduction of Rnd3 or selective inhibition of Notch signaling, but not Rho Kinase signaling, blocked the proliferation of H358 and H520 cells. Mechanistically, Notch intracellular domain (NICD protein abundance in H358 cells was regulated by Rnd3-mediated NICD proteasome degradation. Rnd3 regulated H358 and H520 cell proliferation through a Notch1/NICD/Hes1 signaling axis independent of Rho Kinase.

  12. Effect of Ultrasonic Vibration on Proliferation and Differentiation of Cells

    Directory of Open Access Journals (Sweden)

    Haruka Hino

    2016-12-01

    Full Text Available The effect of mechanical stimulation of vibration on proliferation and differentiation of cells has been studied in vitro. To apply the vibration on the cells, a piezoelectric element was attached on the outside surface of the bottom of the culture plate of six wells. The piezoelectric element was vibrated by sinusoidally alternating voltage at 1.0 MHz generated by a function generator. Five kinds of cells were used in the experiment: C2C12 (mouse myoblast cell, L929 (fibroblast connective tissue of mouse, Hepa1-6 (mouse hepatoma cell, HUVEC (human umbilical vein endothelial cell, and Neuro-2a (mouse neural crest-derived cell line. After the incubation for 24 hours, cells were exposed to the ultrasonic vibration intermittently for three days: for thirty minutes per day. At the end of the experiment, the number of cells was counted by colorimetric method with a microplate photometer. In the case of Neuro-2a, the total length of the neurite was calculated at the microscopic image. The experimental study shows following results. Cells are exfoliated by the strong vibration. Proliferation and differentiation of cells are accelerated with mild vibration. The optimum intensity of vibration depends on the kind of cells.

  13. A perspective on the proliferation risks of plutonium mines

    Energy Technology Data Exchange (ETDEWEB)

    Lyman, E.S. [Nuclear Control Institute, Washington, DC (United States)

    1996-05-01

    The program of geologic disposal of spent fuel and other plutonium-containing materials is increasingly becoming the target of criticism by individuals who argue that in the future, repositories may become low-cost sources of fissile material for nuclear weapons. This paper attempts to outline a consistent framework for analyzing the proliferation risks of these so-called {open_quotes}plutonium mines{close_quotes} and putting them into perspective. First, it is emphasized that the attractiveness of plutonium in a repository as a source of weapons material depends on its accessibility relative to other sources of fissile material. Then, the notion of a {open_quotes}material production standard{close_quotes} (MPS) is proposed: namely, that the proliferation risks posed by geologic disposal will be acceptable if one can demonstrate, under a number of reasonable scenarios, that the recovery of plutonium from a repository is likely to be as difficult as new production of fissile material. A preliminary analysis suggests that the range of circumstances under which current mined repository concepts would fail to meet this standard is fairly narrow. Nevertheless, a broad application of the MPS may impose severe restrictions on repository design. In this context, the relationship of repository design parameters to easy of recovery is discussed.

  14. Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.

    Directory of Open Access Journals (Sweden)

    Xuming Jia

    Full Text Available Methylglyoxal (MG is a highly reactive metabolite physiologically presented in all biological systems. The effects of MG on diabetes and hypertension have been long recognized. In the present study, we investigated the potential role of MG in obesity, one of the most important factors to cause metabolic syndrome. An increased MG accumulation was observed in the adipose tissue of obese Zucker rats. Cell proliferation assay showed that 5-20 µM of MG stimulated the proliferation of 3T3-L1 cells. Further study suggested that accumulated-MG stimulated the phosphorylation of Akt1 and its targets including p21 and p27. The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells. The effects of MG were efficiently reversed by advanced glycation end product (AGE breaker alagebrium and Akt inhibitor SH-6. In summary, our study revealed a previously unrecognized effect of MG in stimulating adipogenesis by up-regulation of Akt signaling pathway and this mechanism might offer a new approach to explain the development of obesity.

  15. PDGFs regulate tooth germ proliferation and ameloblast differentiation.

    Science.gov (United States)

    Wu, Nan; Iwamoto, Tsutomu; Sugawara, Yu; Futaki, Masaharu; Yoshizaki, Keigo; Yamamoto, Shinya; Yamada, Aya; Nakamura, Takashi; Nonaka, Kazuaki; Fukumoto, Satoshi

    2010-06-01

    The purpose of this study was to elucidate the effects of platelet-derived growth factors (PDGFs) during tooth development, as well as the mechanisms underlying the interactions of growth factors with PDGF signalling during odontogenesis. We used an ex vivo tooth germ organ culture system and two dental cell lines, SF2 cells and mDP cells, as models of odontogenesis. AG17, a tyrosine kinase inhibitor, was utilised for blocking PDGF receptor signalling. To analyse the expressions of PDGFs, reverse transcriptase (RT)-PCR and immunohistochemistry were performed. Proliferation was examined using a BrdU incorporation assay for the organ cultures and a cell counting kit for the cell lines. The expressions of Fgf2 and ameloblastin were analysed by real-time RT-PCR. The PDGF ligands PDGF-A and PDGF-B, and their receptors, PDGFRalpha and PDGFRbeta, were expressed throughout the initial stages of tooth development. In the tooth germ organ cultures, PDGF-AA, but not PDGF-BB, accelerated cusp formation. Conversely, AG17 suppressed both growth and cusp formation of tooth germs. Exogenous PDGF-BB promoted mDP cell proliferation. Furthermore, PDGF-AA decreased Fgf2 expression and increased that of ameloblastin, a marker of differentiated ameloblasts. Our results indicate that PDGFs are involved in initial tooth development and regulate tooth size and shape, as well as ameloblast differentiation. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. β-Escin Effectively Modulates HUVECS Proliferation and Tube Formation

    Directory of Open Access Journals (Sweden)

    Lenka Varinská

    2018-01-01

    Full Text Available In the present study we evaluated the anti-angiogenic activities of β-escin (the major active compound of Aesculus hippocastanum L. seeds. Human umbilical-vein endothelial cells (HUVECs were used as an in vitro model for studying the molecular mechanism underlying the anti-angiogenic effect of β-escin. We investigated the in vitro effects on proliferation, migration, and tube formation of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM angiogenesis assay. Moreover, the effect on gene expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It was found that β-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF-induced proliferation, migration and tube formation, as well as CAM angiogenesis in vivo. The inhibition of critical steps of angiogenic process observed with β-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of β-escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells. In conclusion, β-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action.

  17. Lysyl Oxidase Propeptide Inhibits Smooth Muscle Cell Signaling and Proliferation

    Science.gov (United States)

    Hurtado, Paola A.; Vora, Siddharth; Sume, Siddika Selva; Yang, Dan; St. Hilaire, Cynthia; Guo, Ying; Palamakumbura, Amitha H.; Schreiber, Barbara M.; Ravid, Katya; Trackman, Philip C.

    2008-01-01

    Lysyl oxidase is required for the normal biosynthesis and maturation of collagen and elastin. It is expressed by vascular smooth muscle cells, and its increased expression has been previously found in atherosclerosis and in models of balloon angioplasty. The lysyl oxidase propeptide (LOX-PP) has more recently been found to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map kinase activation. We reasoned that LOX-PP may have functions in normal non-transformed cells. We, therefore, investigated its effects on smooth muscle cells, focusing on important biological processes mediated by Erk1/2-dependent signaling pathways including proliferation and matrix metalloproteinase-9 (MMP-9) expression. In addition, we investigated whether evidence for accumulation of LOX-PP could be found in vivo in a femoral artery injury model. Recombinant LOX-PP was expressed and purified, and was found to inhibit primary rat aorta smooth muscle cell proliferation and DNA synthesis by more than 50%. TNF-α-stimulated MMP-9 expression and Erk1/2 activation were both significantly inhibited by LOX-PP. Immunohistochemistry studies carried out with affinity purified anti-LOX-PP antibody showed that LOX-PP epitopes were expressed at elevated levels in vascular lesions of injured arteries. These novel data suggest that LOX-PP may provide a feedback control mechanism that serves to inhibit properties associated with the development of vascular pathology. PMID:18060869

  18. Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA

    Directory of Open Access Journals (Sweden)

    Jui-Lung Shen

    2011-01-01

    Full Text Available This study evaluates the proliferative effects of danshen and its monomer extract, tanshinone IIA, on Schwann cell proliferation. A piece of silicone rubber was guided across a 15-mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of danshen (0–100 mg/mL. The results showed that danshen increased the expressions of uPA, cyclin D1, E and ERK, JNK, and P38 MAP kinases via the FGF-2 signaling pathway in a dose-dependent manner. RSC96, Schwann cells were also administered with danshen (0, 20, 40, 60, 80, and 100 μg/mL and tanshinone IIA (0, 2, 4, 6, 8, and 10 μg/mL. In lower concentrations, danshen and tanshinone IIA exhibited an apparent effect on Schwann cells. Similar effects were also demonstrated in the FGF-2-uPA regulating cascade and cell cycle proliferative protein results. Schwann cell migration was elevated as well. We used MAPK-signaling chemical inhibitors and identified the proliferative effects of danshen and tanshinone IIA as MAPK-signaling dependent. The results from the in vitro systems indicate that danshen and tanshinone IIA can be used to induce Schwann cell proliferation, and in vivo results potentially suggest that danshen and tanshinone IIA might enhance neuron regeneration.

  19. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  20. Cannabinoids attenuate cancer pain and proliferation in a mouse model.

    Science.gov (United States)

    Saghafi, Negin; Lam, David K; Schmidt, Brian L

    2011-01-25

    We investigated the effects of cannabinoid receptor agonists on (1) oral cancer cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse cancer model. We utilized immunohistochemistry and Western blot to show that human oral cancer cells express CBr1 and CBr2. When treated with WIN55,212-2 (non-selective), ACEA (CBr1-selective) or AM1241 (CBr2-selective) agonists in vitro, oral cancer cell proliferation was significantly attenuated in a dose-dependent manner. In vivo, systemic administration (0.013M) of WIN55,212-2, ACEA, or AM1241 significantly attenuated cancer-induced mechanical allodynia. Tumor growth was also significantly attenuated with systemic AM1241 administration. Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation. The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Amniotic Fluid Cells Proliferation in Normal and Down Syndrome Subjects

    Directory of Open Access Journals (Sweden)

    Honcea Adina

    2016-02-01

    Full Text Available Down Syndrome/Trisomy 21 is the most common chromosomal anomaly, and it represents the most common congenital cause of infants’ intellectual disability. Subjects with this syndrome are affected by degenerative processes caused by accelerated aging or unknown ethyologies. In recent years, accumulating evidence revealed increased potential of amniotic fluid-derived stem cells to be used in regenerative therapy. Our aim was to assess differences in immunophenotype, cell morphology and proliferation of amniotic fluid cells from normal and Down Syndrome pregnancies using a quantitative cytometry approach. Results revealed the emergence of a population of small sized cells in Down Syndrome derived amniotic fluid cells that are readily visible upon microscopic inspection. Hence, the fluorescence–based quantitative image cytometry determinations showed a tendency of decrease in both cell and nuclei size in trisomy, with no significant modification in nuclei circularity, as measured following actin cytoskeleton and nuclei labeling. The propensity of Ki67 positive cells was found to be increased in Down Syndrome derived cells (48.92% as compared to normal specimens (28.68%. However, cells in S and G2/M cell cycle phases decreased from 32.91% to 4.49% in diseased cells. Further studies are devoted to understanding the molecular basis of the observed differences in the proliferation ability of Down Syndrome amniotic cells, in order to evaluate the potential therapeutic effect of amniotic fluid stem cells for tissue regeneration in subjects with trisomy and to find correlations between amniotic cells phenotype and patient prognosis.

  2. Plant retinoblastoma homologues control nuclear proliferation in the female gametophyte.

    Science.gov (United States)

    Ebel, Chantal; Mariconti, Luisa; Gruissem, Wilhelm

    2004-06-17

    Haploid spores of plants divide mitotically to form multicellular gametophytes. The female spore (megaspore) of most flowering plants develops by means of a well-defined programme into the mature megagametophyte consisting of the egg apparatus and a central cell. We investigated the role of the Arabidopsis retinoblastoma protein homologue and its function as a negative regulator of cell proliferation during megagametophyte development. Here we show that three mutant alleles of the gene for the Arabidopsis retinoblastoma-related protein, RBR1 (ref. 4), are gametophytic lethal. In heterozygous plants 50% of the ovules are aborted when the mutant allele is maternally inherited. The mature unfertilized mutant megagametophyte fails to arrest mitosis and undergoes excessive nuclear proliferation in the embryo sac. Supernumerary nuclei are present at the micropylar end of the megagametophyte, which develops into the egg apparatus and central cell. The central cell nucleus, which gives rise to the endosperm after fertilization, initiates autonomous endosperm development reminiscent of fertilization-independent seed (fis) mutants. Thus, RBR1 has a novel and previously unrecognized function in cell cycle control during gametogenesis and in the repression of autonomous endosperm development.

  3. Effects of drinking desalinated seawater on cell viability and proliferation.

    Science.gov (United States)

    Macarrão, Camila Longhi; Bachi, André Luis Lacerda; Mariano, Mario; Abel, Lucia Jamli

    2017-06-01

    Desalination of seawater is becoming an important means to address the increasing scarcity of freshwater resources in the world. Seawater has been used as drinking water in the health, food, and medical fields and various beneficial effects have been suggested, although not confirmed. Given the presence of 63 minerals and trace elements in drinking desalinated seawater (63 DSW), we evaluated their effects on the behavior of tumorigenic and nontumorigenic cells through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and annexin-V-fluorescein isothiocyanate/propidium iodide staining. Our results showed that cell viability and proliferation in the presence of 63 DSW were significantly greater than in mineral water and in the presence of fetal bovine serum in a dose-dependent manner. Furthermore, 63 DSW showed no toxic effect on murine embryonic fibroblast (NIH-3T3) and murine melanoma (B16-F10) cells. In another assay, we also showed that pre-treatment of non-adherent THP-1 cells with 63 DSW reduces apoptosis incidence, suggesting a protective effect against cell death. We conclude that cell viability and proliferation were improved by the mineral components of 63 DSW and this effect can guide further studies on health effects associated with DSW consumption.

  4. Unremitting Cell Proliferation in the Secretory Phase of Eutopic Endometriosis

    Science.gov (United States)

    Franco-Murillo, Yanira; Miranda-Rodríguez, José Antonio; Rendón-Huerta, Erika; Montaño, Luis F.; Cornejo, Gerardo Velázquez; Gómez, Lucila Poblano; Valdez-Morales, Francisco Javier; Gonzalez-Sanchez, Ignacio

    2014-01-01

    Objective: Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium. Design: Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle. Results: Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis. Conclusion: Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways. PMID:25194152

  5. Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial proliferation, arterial relaxation, vascular permeability and angiogenesis by dobesilate.

    Science.gov (United States)

    Angulo, Javier; Peiró, Concepción; Romacho, Tania; Fernández, Argentina; Cuevas, Begoña; González-Corrochano, Rocío; Giménez-Gallego, Guillermo; de Tejada, Iñigo Sáenz; Sánchez-Ferrer, Carlos F; Cuevas, Pedro

    2011-09-30

    Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and vascular permeability which is associated with many pathological processes. 2,5-hydroxybenzene sulfonate (DHBS; dobesilate) is a small molecule with anti-angiogenic activity that has been described as an inhibitor of fibroblast growth factors (FGF). The aim of the present study was to evaluate the effects of DHBS on VEGF-induced actions. The effects of DHBS were evaluated on VEGF-induced proliferation in human umbilical vein endothelial cells (HUVEC) and rat aorta relaxation, as well as on in vivo VEGF-induced skin vascular permeability and neovascularization in rats. DHBS at 50 and 100 μM concentration significantly inhibited the proliferation of HUVEC induced by VEGF (10 ng/ml), without significantly affecting HUVEC proliferation in the absence of VEGF. Rapid VEGF-induced activation of Akt in HUVEC was also prevented by DHBS (100 μM). Additionally, DHBS (2 μM) specifically inhibited the relaxation of rat aorta induced by VEGF (0.1 to 30 ng/ml), but not endothelium-dependent relaxation to acetylcholine (1 nM to 10 μM). The in vivo enhancement of vascular permeability caused by VEGF injection (50 μl at 10 ng/ml) in rat skin was also inhibited by DHBS co-administration (200 μM) (74.8±3.8% inhibition of dye extravasation). Administration of DHBS (200 mg/kg/day; i.p.) also reduced VEGF-induced angiogenesis in vivo. DHBS inhibits main responses elicited in vitro and in vivo by VEGF. As a dual antagonist of VEGF and FGF activities, DHBS could be of therapeutic interest in the treatment of diseases related to VEGF/FGF overproduction and excessive angiogenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro

    Science.gov (United States)

    Rathinasamy, Vignesh; Toet, Hayley; McCammick, Erin; O’Connor, Anna; Marks, Nikki J.; Mousley, Angela; Brennan, Gerard P.; Halton, David W.; Spithill, Terry W.; Maule, Aaron G.

    2016-01-01

    Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving ‘molecular toolbox’ for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the “neoblast” stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in

  7. The Application Trends of Rapid Prototyping Manufacturing

    Directory of Open Access Journals (Sweden)

    Qiu Xiao Lin

    2016-01-01

    characteristics of laser stero lithography (LSL selective laser sintering (SLS, three-dimensional printing (DP, fused deposition modeling (FDM, computer numerical control (CNC and other rapid prototyping technologies. After discussed these five rapid prototyping technology materials, we presented the hotspot and direction of rapid prototyping technology and look forward to the development of its technique, the expansion of its field and the progress of its academic ideology.

  8. The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation

    Directory of Open Access Journals (Sweden)

    Sunnerhagen Per

    2009-11-01

    Full Text Available Abstract The ataxia telangiectasia mutated (ATM and the ATM- related (ATR kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets, since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM (KU55933 or ATM and ATR (CGK733 have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p21 expression required for the survival of these cells. The precise molecular pharmacology of these agents however, is not well characterized. Herein, we report that caffeine, CGK733, and to a lesser extent KU55933, inhibit the proliferation of otherwise untreated human cancer and non-transformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and CGK733 was associated with a rapid decline in cyclin D1 protein levels and a reduction in the levels of both phosphorylated and total retinoblastoma protein (RB. Our studies suggest that observations based on the effects of these compounds on cell proliferation and survival must be interpreted with caution. The differential effects of caffeine/CGK733 and KU55933 on cyclin D1 protein levels suggest that these agents will exhibit dissimilar molecular pharmacological profiles.

  9. Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

    Directory of Open Access Journals (Sweden)

    Mathieu Dalvai

    Full Text Available Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7 the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.

  10. Induction of suppressive allogeneic regulatory T cells via rabbit antithymocyte polyclonal globulin during homeostatic proliferation in rat kidney transplantation.

    Science.gov (United States)

    Valdez-Ortiz, Rafael; Bestard, Oriol; Llaudó, Inés; Franquesa, Marcella; Cerezo, Gema; Torras, Joan; Herrero-Fresneda, Inmaculada; Correa-Rotter, Ricardo; Grinyó, Josep M

    2015-01-01

    Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4+CD25++Foxp3+ cells (Tregs). We investigated the major biological effects of a self-manufactured rabbit polyclonal anti-rat thymoglobulin (rATG) in vitro, as well as its effects on different peripheral T-cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of rATG-induced Tregs in an experimental rat renal transplant model. Our results show that rATG has the capacity to induce apoptosis in T lymphocyte lymphocytes as a primary mechanism of T-cell depletion. Our in vivo studies demonstrated a rapid but transient cellular depletion of the main T cell subsets, directly proportional to the rATG dose used, but not of the effector memory T cells, which required significantly higher rATG doses. After rATG administration, we observed a significant proliferation of Tregs in the peripheral blood of transplanted rats, leading to an increase in the Treg/T effector ratio. Importantly, rATG-induced Tregs displayed a strong donor-specific suppressive capacity when assessed in an antigen-specific allogeneic co-culture. All of these results were associated with better renal graft function in rats that received rATG. Our study shows that rATG has the biological capacity immunomodulatory to promote a regulatory alloimmune milieu during post-transplant homeostatic proliferation. © 2014 Steunstichting ESOT.

  11. Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

    Directory of Open Access Journals (Sweden)

    Marie Strand

    Full Text Available Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs of the acidic copper cell region (CCR, which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

  12. Flow-systems analysis and characterization of protein contents and proliferating kinetics in ascites and solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Crissman, H.A.; Kissane, R.J.; Wanek, P.L.; Oka, M.S.; Steinkamp, J.A.

    1976-01-01

    Flow microfluorometric analysis of the DNA and protein content of mouse ascites and solid tumor cell populations grown in vivo has provided information on protein distribution of cells in various phases of the cell cycle, as well as age-associated changes in proliferation kinetics of these tumor systems. L1210 ascites cells and solid Lewis lung carcinomas were dispersed, fixed, and stained for both DNA and protein, respectively, using the fluorochromes propidium iodide (red) and fluorescein isothiocyanate (green). Simultaneous DNA and protein determinations were performed using a flow system in which rapid two-color analysis of stained cells was achieved at approximately 10/sup 3/ cells/second. Analysis of the DNA distributions of L1210 cells on days three, four, six, and seven following implantation of 10/sup 5/ cells revealed changes in cycle kinetic patterns concomitant with increased cell density or tumor age. DNA distribution patterns for Lewis lung tumors showed a 2C peak and a cell proliferation pattern extending between the 4C and 8C peaks. Cells sorted electronically from the 2C and 4C-8C contents of the DNA spectrum were identified morphologically as normal and tumor cells, respectively. Tumor cells exhibited elevated protein distributions compared to normal cells; however, tumor cells were quite heterogeneous in cell size and morphology.

  13. WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation.

    Science.gov (United States)

    Banerjee, Snigdha; Saxena, Neela; Sengupta, Krishanu; Tawfik, Ossama; Mayo, Matthew S; Banerjee, Sushanta K

    2003-01-01

    WISP-2 mRNA and protein was overexpressed in preneoplastic and cancerous cells of human breast. Statistical analyses show a significant association between WISP-2 expression and estrogen receptor (ER) positivity. In normal breast, the expression was virtually undetected. The studies showed that WISP-2 is an estrogen-induced early response gene in MCF-7 cells and the expression was continuously increased to reach a maximum level at 24 h. The estrogen effect was inhibited by a pure antiestrogen (ICI 182,780). Human mammary epithelial cells, in which WISP-2 expression was undetected or minimally detected, responded to 17beta-estradiol by upregulating the WISP-2 gene after transfection with ER-alpha, providing further evidences that WISP-2 expression is mediated through ER-alpha. Overexpression of WISP-2 mRNA by estrogen may be accomplished by both transcriptional activation and stabilization. MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction. In combination with estradiol, progesterone acted as an antagonist inhibiting the expression of WISP-2 mRNA. Moreover, disruption of WISP-2 signaling in MCF-7 cells by use of antisense oligomers caused a significant reduction in tumor cell proliferation. The results are consistent with the conclusion that WISP-2 expression is a requirement for breast tumor cells proliferation.

  14. WISP-2 Gene in Human Breast Cancer: Estrogen and Progesterone Inducible Expression and Regulation of Tumor Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Snigdha Banerjee

    2003-01-01

    Full Text Available WISP-2 mRNA and protein was overexpressed in preneoplastic and cancerous cells of human breast. Statistical analyses show a significant association between WISP-2 expression and estrogen receptor (ER positivity. In normal breast, the expression was virtually undetected. The studies showed that WISP-2 is an estrogen-induced early response gene in MCF-7 cells and the expression was continuously increased to reach a maximum level at 24 h. The estrogen effect was inhibited by a pure antiestrogen (ICI 182,780. Human mammary epithelial cells, in which WISP-2 expression was undetected or minimally detected, responded to 17β-estradiol by upregulating the WISP-2 gene after transfection with ER-α, providing further evidences that WISP-2 expression is mediated through ER-α. Overexpression of WISP-2 mRNA by estrogen may be accomplished by both transcriptional activation and stabilization. MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction. In combination with estradiol, progesterone acted as an antagonist inhibiting the expression of WISP-2 mRNA. Moreover, disruption of WISP-2 signaling in MCF-7 cells by use of antisense oligomers caused a significant reduction in tumor cell proliferation. The results are consistent with the conclusion that WISP-2 expression is a requirement for breast tumor cells proliferation.

  15. WISP-2 Gene in Human Breast Cancer: Estrogen and Progesterone Inducible Expression and Regulation of Tumor Cell Proliferation1

    Science.gov (United States)

    Banerjee, Snigdha; Saxena, Neela; Sengupta, Krishanu; Tawfik, Ossama; Mayo, Matthew S; Banerjee, Sushanta K

    2003-01-01

    Abstract WISP-2 mRNA and protein was overexpressed in preneoplastic and cancerous cells of human breast. Statistical analyses show a significant association between WISP-2 expression and estrogen receptor (ER) positivity. In normal breast, the expression was virtually undetected. The studies showed that WISP-2 is an estrogen-induced early response gene in MCF-7 cells and the expression was continuously increased to reach a maximum level at 24 h. The estrogen effect was inhibited by a pure antiestrogen (ICI 182,780). Human mammary epithelial cells, in which WISP-2 expression was undetected or minimally detected, responded to 17β-estradiol by upregulating the WISP-2 gene after transfection with ER-α, providing further evidences that WISP-2 expression is mediated through ER-α. Overexpression of WISP-2 mRNA by estrogen may be accomplished by both transcriptional activation and stabilization. MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction. In combination with estradiol, progesterone acted as an antagonist inhibiting the expression of WISP-2 mRNA. Moreover, disruption of WISP-2 signaling in MCF-7 cells by use of antisense oligomers caused a significant reduction in tumor cell proliferation. The results are consistent with the conclusion that WISP-2 expression is a requirement for breast tumor cells proliferation. PMID:12659671

  16. Rapid Automated Mission Planning System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is an automated UAS mission planning system that will rapidly identify emergency (contingency) landing sites, manage contingency routing, and...

  17. WIST: toolkit for rapid, customized LIMS development

    National Research Council Canada - National Science Library

    Huang, Y Wayne; Arkin, Adam P; Chandonia, John-Marc

    2011-01-01

    Workflow Information Storage Toolkit (WIST) is a set of application programming interfaces and web applications that allow for the rapid development of customized laboratory information management systems (LIMS...

  18. JIEDDO Experience Provides Rapid Acquisition Insights

    National Research Council Canada - National Science Library

    James P Craft

    2015-01-01

    .... JIDA's rapid acquisition capabilities were preserved by transitioning the expedient organization that received supplemental funding into the Defense Department's newest combat support agency (CSA...

  19. Basic fibroblast growth factor/vascular endothelial growth factor in the serum from severe burn patients stimulates the proliferation of cultured human umbilical cord mesenchymal stem cells via activation of Notch signaling pathways.

    Science.gov (United States)

    Liu, Ling-Ying; Hou, Yu-Sen; Chai, Jia-Ke; Hu, Quan; Duan, Hong-Jie; Yu, Yong-Hui; Yin, Hui-Nan; Hao, Dai-Feng; Feng, Guang; Li, Tao; Du, Jun-Dong

    2013-11-01

    Mesenchymal stem cells (MSCs) are the leading cellular constituents used in regenerative medicine. MSCs repair and reconstruct wounds of acute traumata and radiation-induced burns through proliferation, differentiation, and trophic activity. However, repair effect of MSCs on severe burn wounds remain to be clarified because severe burns are much more complex traumata than radiation-induced burns. Survival and proliferation of MSCs in microenvironments affected by severe burns are very important for improving wound repair/regeneration. This study aimed to elucidate the survival and proliferation effects and the potential proliferation mechanism of serum from severe burn patients (BPS) on human umbilical cord MSCs (hUCMSCs) in vitro. The hUCMSCs were isolated, cultured, and identified. Next, we evaluated the effects of BPS on cell numbers, cell cycle progression, cyclin D expression, and key proteins and genes of the Notch signaling pathway. Putative mechanisms underlying the proliferation of hUCMSCs were investigated. BPS markedly increased the number of hUCMSCs, and the results of the cell cycle studies indicated that BPS induced cell cycle progression into the M phase. Cyclin D expression was higher with BPS than in the control group. Moreover, Notch-1, a key determinant of hUCMSC activation and proliferation, and its target gene Hes-1 were overexpressed after BPS treatment. Proliferation numbers of hUCMSC, rate of proliferation period (G2/M+S), and the expression of cyclin D, Notch-1, and Hes-1 were markedly decreased by Notch signaling inhibitors (DAPT/GSI). In the case of BPS, basic fibroblast growth factor and vascular endothelial growth factor were the key factors that promoted hUCMSC proliferation. This study provides novel evidence for the role of BPS in the survival and rapid proliferation of hUCMSCs and suggests that these cells could be used for cell therapy-based clinical applications for treating severe burns. Furthermore, hUCMSC proliferation was

  20. The bomb black market - Inquiry about nuclear proliferation; Le marche noir de la bombe - Enquete sur la proliferation nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Tertrais, B

    2009-07-01

    Nuclear weapons remain for a long time in the hands of the five big powers: USA, Soviet Union, Great Britain, France and China. Things started to change when Israel, and then India acquired the atomic bomb as well. Pakistan took up the race too but Abdul Qadeer Khan, one of the nuclear program maker of the country, took profit of the situation to set up a huge international proliferation network for the spreading of the technologies, tools and materials necessary for weapons fabrication. He offered his services not only to Iran and North Korea, but to Iraq and Libya as well and probably to some other countries. Today, the Iranian nuclear program generates both envy and fear in the Middle East. Who is going to be the next domino of the nuclear game? Egypt, Saudi Arabia, Algeria and Turkey are potential candidates. But while Pakistan sinks into crisis, the terrorists are taking interest in nukes. The author of this book has worked for more than 10 years on this dossier. He has had access to the most sensible documents and to essential testimonies. He now lifts the curtain on the secrets of nuclear proliferation. In this book, where reality sometimes surpasses fiction, he explains how the CIA finally succeeded in infiltrating the 'Khan ring' after having closed its eyes on his deals for a long time. He describes the branches of the Pakistani atomic complex and analyses with lucidity the nuclear terrorism risk.