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Sample records for lines responded differentially

  1. Product Line Rivalry with Brand Differentiation

    OpenAIRE

    Gilbert, Richard J.; Matutes, Carmen

    1989-01-01

    Competition with product rivalry is examined in a model where products are differentiated by both quality and brand name. With no commitment, firms produce a full product line. When firms can commit to restrict their product offerings, firms specialize if the degree of brand-specific differentiation is small and they produce a full product line if brand-specific differentiation is large relative to intrafirm differentiation. Firms may crowd a product space when all competitors would be better...

  2. Thirty-seven transcription factor genes differentially respond to a ...

    Indian Academy of Sciences (India)

    Plant transcription factors and insect defence si. Thirty-seven transcription factor genes differentially respond to a harpin protein and affect resistance to the green peach aphid in Arabidopsis. HUNLIN. PIN. RUOXUE LIŲ, BEIBEI LÜ, XIAOMENG WANG, CHUNLING ZHANG, SHUPING ZHANG, JUN QIAN, LEI CHEN,.

  3. Understanding and responding the students in learning mathematics through the differentiated instruction

    Science.gov (United States)

    Hapsari, T.; Darhim; Dahlan, J. A.

    2018-05-01

    This research discusses the differentiated instruction, a mathematic learning which is as expected by the students in connection with the differentiated instruction itself, its implementation, and the students’ responses. This research employs a survey method which involves 62 students as the research respondents. The mathematics learning types required by the students and their responses to the differentiated instruction are examined through questionnaire and interview. The mathematics learning types in orderly required by the students, from the highest frequency cover the easily understood instructions, slowly/not rushing teaching, fun, not complicated, interspersed with humour, various question practices, not too serious, and conducive class atmosphere for the instructions. Implementing the differentiated instruction is not easy. The teacher should be able to constantly assess the students, s/he should have good knowledge of relevant materials and instructions, and properly prepare the instructions, although it is time-consuming. The differentiated instruction is implemented on the instructions of numerical pattern materials. The strategies implemented are flexible grouping, tiered assignment, and compacting. The students positively respond the differentiated learning instruction that they become more motivated and involved in the instruction.

  4. A Line-Tau Collocation Method for Partial Differential Equations ...

    African Journals Online (AJOL)

    This paper deals with the numerical solution of second order linear partial differential equations with the use of the method of lines coupled with the tau collocation method. The method of lines is used to convert the partial differential equation (PDE) to a sequence of ordinary differential equations (ODEs) which is then ...

  5. Adipose gene expression prior to weight loss can differentiate and weakly predict dietary responders.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: The ability to identify obese individuals who will successfully lose weight in response to dietary intervention will revolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight during dietary intervention using only a single gene expression snapshot. METHODOLOGY/PRINCIPAL FINDINGS: The present study involved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines (NUGENOB trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss prior to the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expression profiles of responders (8-12 kgs weight loss could always be differentiated from non-responders (<4 kgs weight loss. We also assessed whether this differentiation was sufficient for prediction. Using a bottom-up (i.e. black-box approach, standard class prediction algorithms were able to predict dietary responders with up to 61.1%+/-8.1% accuracy. Using a top-down approach (i.e. using differentially expressed genes to build a classifier improved prediction accuracy to 80.9%+/-2.2%. CONCLUSION: Adipose gene expression profiling prior to the consumption of a low-fat diet is able to differentiate responders from non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of prediction accuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that the comprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition.

  6. Infant differential behavioral responding to discrete emotions.

    Science.gov (United States)

    Walle, Eric A; Reschke, Peter J; Camras, Linda A; Campos, Joseph J

    2017-10-01

    Emotional communication regulates the behaviors of social partners. Research on individuals' responding to others' emotions typically compares responses to a single negative emotion compared with responses to a neutral or positive emotion. Furthermore, coding of such responses routinely measure surface level features of the behavior (e.g., approach vs. avoidance) rather than its underlying function (e.g., the goal of the approach or avoidant behavior). This investigation examined infants' responding to others' emotional displays across 5 discrete emotions: joy, sadness, fear, anger, and disgust. Specifically, 16-, 19-, and 24-month-old infants observed an adult communicate a discrete emotion toward a stimulus during a naturalistic interaction. Infants' responses were coded to capture the function of their behaviors (e.g., exploration, prosocial behavior, and security seeking). The results revealed a number of instances indicating that infants use different functional behaviors in response to discrete emotions. Differences in behaviors across emotions were clearest in the 24-month-old infants, though younger infants also demonstrated some differential use of behaviors in response to discrete emotions. This is the first comprehensive study to identify differences in how infants respond with goal-directed behaviors to discrete emotions. Additionally, the inclusion of a function-based coding scheme and interpersonal paradigms may be informative for future emotion research with children and adults. Possible developmental accounts for the observed behaviors and the benefits of coding techniques emphasizing the function of social behavior over their form are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Line pressure effects on differential pressure measurements

    International Nuclear Information System (INIS)

    Neff, G.G.; Evans, R.P.

    1982-01-01

    The performance of differential pressure transducers in experimental pressurized water reactor (PWR) systems was evaluated. Transient differential pressure measurements made using a simple calibration proportionality relating differential pressure to output voltage could have large measurement uncertainties. A more sophisticated calibration equation was derived to incorporate the effects of zero shifts and sensitivity shifts as pressure in the pressure sensing line changes with time. A comparison made between the original calibration proportionality equation and the derived compensation equation indicates that potential measurement uncertainties can be reduced

  8. Adipose Gene Expression Prior to Weight Loss Can Differentiate and Weakly Predict Dietary Responders

    Science.gov (United States)

    Mutch, David M.; Temanni, M. Ramzi; Henegar, Corneliu; Combes, Florence; Pelloux, Véronique; Holst, Claus; Sørensen, Thorkild I. A.; Astrup, Arne; Martinez, J. Alfredo; Saris, Wim H. M.; Viguerie, Nathalie; Langin, Dominique; Zucker, Jean-Daniel; Clément, Karine

    2007-01-01

    Background The ability to identify obese individuals who will successfully lose weight in response to dietary intervention will revolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight during dietary intervention using only a single gene expression snapshot. Methodology/Principal Findings The present study involved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines (NUGENOB) trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss prior to the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expression profiles of responders (8–12 kgs weight loss) could always be differentiated from non-responders (diet is able to differentiate responders from non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of prediction accuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that the comprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition. PMID:18094752

  9. Sensing line effects on PWR-based differential pressure measurements

    International Nuclear Information System (INIS)

    Evans, R.P.; Neff, G.G.

    1982-01-01

    An incorrrect configuration of the fluid-filled pressure sensing lines connecting differential pressure transducers to the pressure taps in a pressurized water reactor system can cause errors in the measurement and, during rapid pressure transients, could cause the transducer to fail. Testing was performed in both static and dynamic modes to experimentally determine the effects of sensing lines of various lengths, diameters, and materials. Testing was performed at ambient temperature with absolute line pressures at about 17 MPa using water as the pressure transmission fluid

  10. Survey of Differentially Methylated Promoters in Prostate Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yipeng Wang

    2005-08-01

    Full Text Available DNA methylation, copy number in the genomes of three immortalized prostate epithelial, five cancer cell lines (LNCaP, PC3, PC3M, PC3M-Pro4, PC3MLN4 were compared using a microarray-based technique. Genomic DNA is cut with a methylation-sensitive enzyme Hpall, followed by linker ligation, polymerase chain reaction (PCR amplification, labeling, hybridization to an array of promoter sequences. Only those parts of the genomic DNA that have unmethylated restriction sites within a few hundred base pairs generate PCR products detectable on an array. Of 2732 promoter sequences on a test array, 504 (18.5% showed differential hybridization between immortalized prostate epithelial, cancer cell lines. Among candidate hypermethylated genes in cancer-derived lines, there were eight (CD44, CDKN1A, ESR1, PLAU, RARB, SFN, TNFRSF6, TSPY previously observed in prostate cancer, 13 previously known methylation targets in other cancers (ARHI, bcl-2, BRCA1, CDKN2C, GADD45A, MTAP, PGR, SLC26A4, SPARC, SYK, TJP2, UCHL1, WIT-1. The majority of genes that appear to be both differentially methylated, differentially regulated between prostate epithelial, cancer cell lines are novel methylation targets, including PAK6, RAD50, TLX3, PIR51, MAP2K5, INSR, FBN1, GG2-1, representing a rich new source of candidate genes used to study the role of DNA methylation in prostate tumors.

  11. CBT for childhood anxiety disorders: differential changes in selective attention between treatment responders and non-responders.

    Science.gov (United States)

    Legerstee, Jeroen S; Tulen, Joke H M; Dierckx, Bram; Treffers, Philip D A; Verhulst, Frank C; Utens, Elisabeth M W J

    2010-02-01

    This study examined whether treatment response to stepped-care cognitive-behavioural treatment (CBT) is associated with changes in threat-related selective attention and its specific components in a large clinical sample of anxiety-disordered children. Ninety-one children with an anxiety disorder were included in the present study. Children received a standardized stepped-care CBT. Three treatment response groups were distinguished: initial responders (anxiety disorder free after phase one: child-focused CBT), secondary responders (anxiety disorder free after phase two: child-parent-focused CBT), and treatment non-responders. Treatment response was determined using a semi-structured clinical interview. Children performed a pictorial dot-probe task before and after stepped-care CBT (i.e., before phase one and after phase two CBT). Changes in selective attention to severely threatening pictures, but not to mildly threatening pictures, were significantly associated with treatment success. At pre-treatment assessment, initial responders selectively attended away from severely threatening pictures, whereas secondary responders selectively attended toward severely threatening pictures. After stepped-care CBT, initial and secondary responders did not show any selectivity in the attentional processing of severely threatening pictures. Treatment non-responders did not show any changes in selective attention due to CBT. Initial and secondary treatment responders showed a reduction of their predisposition to selectively attend away or toward severely threatening pictures, respectively. Treatment non-responders did not show any changes in selective attention. The pictorial dot-probe task can be considered a potentially valuable tool in assigning children to appropriate treatment formats as well as for monitoring changes in selective attention during the course of CBT.

  12. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    International Nuclear Information System (INIS)

    Goupille, Olivier; Penglong, Tipparat; Lefèvre, Carine; Granger, Marine; Kadri, Zahra; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

    2012-01-01

    Highlights: ► UT7 erythroleukemia cells are known to be refractory to differentiate. ► Brief JQ1 treatment initiates the first steps of erythroid differentiation program. ► Engaged UT7 cells then maturate in the presence of erythropoietin. ► Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  13. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    Energy Technology Data Exchange (ETDEWEB)

    Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  14. Self-renewal and differentiation capabilities are variable between human embryonic stem cell lines I3, I6 and BG01V

    Directory of Open Access Journals (Sweden)

    Rao Mahendra S

    2009-06-01

    Full Text Available Abstract Background A unique and essential property of embryonic stem cells is the ability to self-renew and differentiate into multiple cell lineages. However, the possible differences in proliferation and differentiation capabilities among independently-derived human embryonic stem cells (hESCs are not well known because of insufficient characterization. To address this question, a side-by-side comparison of 1 the ability to maintain an undifferentiated state and to self-renew under standard conditions; 2 the ability to spontaneously differentiate into three primary embryonic germ lineages in differentiating embryoid bodies; and 3 the responses to directed neural differentiation was made between three NIH registered hES cell lines I3 (TE03, I6 (TE06 and BG01V. Lines I3 and I6 possess normal XX and a normal XY karyotype while BG01V is a variant cell line with an abnormal karyotype derived from the karyotypically normal cell line BG01. Results Using immunocytochemistry, flow cytometry, qRT-PCR and MPSS, we found that all three cell lines actively proliferated and expressed similar "stemness" markers including transcription factors POU5F1/Oct3/4 and NANOG, glycolipids SSEA4 and TRA-1-81, and alkaline phosphatase activity. All cell lines differentiated into three embryonic germ lineages in embryoid bodies and into neural cell lineages when cultured in neural differentiation medium. However, a profound variation in colony morphology, growth rate, BrdU incorporation, and relative abundance of gene expression in undifferentiated and differentiated states of the cell lines was observed. Undifferentiated I3 cells grew significantly slower but their differentiation potential was greater than I6 and BG01V. Under the same neural differentiation-promoting conditions, the ability of each cell line to differentiate into neural progenitors varied. Conclusion Our comparative analysis provides further evidence for similarities and differences between three h

  15. Differential cisplatin responses in human carcinoma cell lines pre-exposed to fractionated X-irradiation

    International Nuclear Information System (INIS)

    Dempke, W.C.M.; Hosking, L.K.; Shellard, S.A.; Hill, B.T.

    1991-01-01

    These results suggest that cells exposed to X-irradiation may respond differently to subsequent cisplatin (CDDP) treatment. Initial studies of possible mechanisms responsible for these differential sensitivities indicate that they may differ according to whether resistance or hypersensitivity is expressed. (author)

  16. Transcriptome variations among human embryonic stem cell lines are associated with their differentiation propensity.

    Directory of Open Access Journals (Sweden)

    Changbin Sun

    Full Text Available Human embryonic stem cells (hESCs have the potential to form any cell type in the body, making them attractive cell sources in drug screening, regenerative medicine, disease and developmental processes modeling. However, not all hESC lines have the equal potency to generate desired cell types in vitro. Significant variations have been observed for the differentiation efficiency of various human ESC lines. The precise underpinning molecular mechanisms are still unclear. In this work, we compared transcriptome variations of four hESC lines H7, HUES1, HUES8 and HUES9. We found that hESC lines have different gene expression profiles, and these differentially expressed genes (DEGs are significantly enriched in developmental processes, such as ectodermal, mesodermal and endodermal development. The enrichment difference between hESC lines was consistent with its lineage bias. Among these DEGs, some pluripotency factors and genes involved in signaling transduction showed great variations as well. The pleiotropic functions of these genes in controlling hESC identity and early lineage specification, implicated that different hESC lines may utilize distinct balance mechanisms to maintain pluripotent state. When the balance is broken in a certain environment, gene expression variation between them could impact on their different lineage specification behavior.

  17. Differential BPFs with Multiple Transmission Zeros Based on Terminated Coupled Lines

    Science.gov (United States)

    Niu, Yiming; Yang, Guo; Wu, Wen

    2018-04-01

    Differential bandpass filters (BPFs) named Filter A and Filter B based on Terminated Coupled Lines (TCLs) are proposed in this letter. The TCLs contributes to not only three poles in differential-mode (DM) for wideband filtering response but also multiple zeros in both DM and common-mode (CM) offering wide DM out-of-band rejection and good CM suppression. Fabricated filters centred at 3.5 GHz with wide DM passband and wideband CM suppression have been designed and measured. The filters improved the noise suppression capability of the communication and radiometer systems. The simulated and measured results are in good agreement.

  18. Plasmodium species differentiation by non-expert on-line volunteers for remote malaria field diagnosis.

    Science.gov (United States)

    Ortiz-Ruiz, Alejandra; Postigo, María; Gil-Casanova, Sara; Cuadrado, Daniel; Bautista, José M; Rubio, José Miguel; Luengo-Oroz, Miguel; Linares, María

    2018-01-30

    Routine field diagnosis of malaria is a considerable challenge in rural and low resources endemic areas mainly due to lack of personnel, training and sample processing capacity. In addition, differential diagnosis of Plasmodium species has a high level of misdiagnosis. Real time remote microscopical diagnosis through on-line crowdsourcing platforms could be converted into an agile network to support diagnosis-based treatment and malaria control in low resources areas. This study explores whether accurate Plasmodium species identification-a critical step during the diagnosis protocol in order to choose the appropriate medication-is possible through the information provided by non-trained on-line volunteers. 88 volunteers have performed a series of questionnaires over 110 images to differentiate species (Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, Plasmodium knowlesi) and parasite staging from thin blood smear images digitalized with a smartphone camera adapted to the ocular of a conventional light microscope. Visual cues evaluated in the surveys include texture and colour, parasite shape and red blood size. On-line volunteers are able to discriminate Plasmodium species (P. falciparum, P. malariae, P. vivax, P. ovale, P. knowlesi) and stages in thin-blood smears according to visual cues observed on digitalized images of parasitized red blood cells. Friendly textual descriptions of the visual cues and specialized malaria terminology is key for volunteers learning and efficiency. On-line volunteers with short-training are able to differentiate malaria parasite species and parasite stages from digitalized thin smears based on simple visual cues (shape, size, texture and colour). While the accuracy of a single on-line expert is far from perfect, a single parasite classification obtained by combining the opinions of multiple on-line volunteers over the same smear, could improve accuracy and reliability of Plasmodium species

  19. Genetics and biochemistry of collagen binding-triggered glandular differentiation in a human colon carcinoma cell line

    International Nuclear Information System (INIS)

    Pignatelli, M.; Bodmer, W.F.

    1988-01-01

    The authors have examined the interaction between collagen binding and epithelial differentiation by using a human colon carcinoma cell line (SW1222) that can differentiate structurally when grown in a three-dimensional collagen gel to form glandular structures. As much as 66% inhibition of glandular differentiation can be achieved by addition to the culture of a synthetic peptide containing the Arg-Gly-Asp-Thr (RGDT) sequence, which is a cell recognition site found in collagen. Arg-Gly-Asp-Thr also inhibited the cell attachment to collagen-coated plates. Chromosome 15 was found in all human-mouse hybrid clones that could differentiate in the collagen gel and bind collagen. Both binding to collagen and glandular differentiation of the hybrid cells were also inhibited by Arg-Gly-Asp-Thr as for the parent cell line SW1222. The ability of SW1222 cells to express the differentiated phenotype appears, therefore, to be determined by an Arg-Gly-Asp-directed collagen receptor on the cell surface that is controlled by a gene on chromosome 15

  20. Neurotrophic effects of growth/differentiation factor 5 in a neuronal cell line.

    Science.gov (United States)

    Toulouse, André; Collins, Grace C; Sullivan, Aideen M

    2012-04-01

    The neurotrophin growth/differentiation factor 5 (GDF5) is studied as a potential therapeutic agent for Parkinson's disease as it is believed to play a role in the development and maintenance of the nigrostriatal system. Progress in understanding the effects of GDF5 on dopaminergic neurones has been hindered by the use of mixed cell populations derived from primary cultures or in vivo experiments, making it difficult to differentiate between direct and indirect effects of GDF5 treatment on neurones. In an attempt to establish an useful model to study the direct neuronal influence of GDF5, we have characterised the effects of GDF5 on a human neuronal cell line, SH-SY5Y. Our results show that GDF5 has the capability to promote neuronal but not dopaminergic differentiation. We also show that it promotes neuronal survival in vitro following a 6-hydroxydopamine insult. Our results show that application of GDF5 to SH-SY5Y cultures induces the SMAD pathway which could potentially be implicated in the intracellular transmission of GDF5's neurotrophic effects. Overall, our study shows that the SH-SY5Y neuroblastoma cell line provides an excellent neuronal model to study the neurotrophic effects of GDF5.

  1. X-ray differential phase-contrast tomographic reconstruction with a phase line integral retrieval filter

    International Nuclear Information System (INIS)

    Fu, Jian; Hu, Xinhua; Li, Chen

    2015-01-01

    We report an alternative reconstruction technique for x-ray differential phase-contrast computed tomography (DPC-CT). This approach is based on a new phase line integral projection retrieval filter, which is rooted in the derivative property of the Fourier transform and counteracts the differential nature of the DPC-CT projections. It first retrieves the phase line integral from the DPC-CT projections. Then the standard filtered back-projection (FBP) algorithms popular in x-ray absorption-contrast CT are directly applied to the retrieved phase line integrals to reconstruct the DPC-CT images. Compared with the conventional DPC-CT reconstruction algorithms, the proposed method removes the Hilbert imaginary filter and allows for the direct use of absorption-contrast FBP algorithms. Consequently, FBP-oriented image processing techniques and reconstruction acceleration softwares that have already been successfully used in absorption-contrast CT can be directly adopted to improve the DPC-CT image quality and speed up the reconstruction

  2. Studies for the application of boron neutron capture therapy to the treatment of differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Dagrosa, A.; Carpano, M.; Perona, M.; Thomasz, L.; Nievas, S.; Cabrini, R.; Juvenal, G.; Pisarev, M.

    2011-01-01

    The aim of these studies was to evaluate the possibility of treating differentiated thyroid cancer by BNCT. These carcinomas are well controlled with surgery followed by therapy with 131 I; however, some patients do not respond to this treatment. BPA uptake was analyzed both in vitro and in nude mice implanted with cell lines of differentiated thyroid carcinoma. The boron intracellular concentration in the different cell lines and the biodistribution studies showed the selectivity of the BPA uptake by this kind of tumor.

  3. Differential resistances to anthracnose in Capsicum baccatum as responding to two Colletotrichum pathotypes and inoculation methods.

    Science.gov (United States)

    Mahasuk, Pitchayapa; Chinthaisong, Jittima; Mongkolporn, Orarat

    2013-09-01

    Chili anthracnose, caused by Colletotrichum spp., is one of the major diseases to chili production in the tropics and subtropics worldwide. Breeding for durable anthracnose resistance requires a good understanding of the resistance mechanisms to different pathotypes and inoculation methods. This study aimed to investigate the inheritances of differential resistances as responding to two different Colletotrichum pathotypes, PCa2 and PCa3 and as by two different inoculation methods, microinjection (MI) and high pressure spray (HP). Detached ripe fruit of Capsicum baccatum 'PBC80' derived F2 and BC1s populations was assessed for anthracnose resistance. Two dominant genes were identified responsible for the differential resistance to anthracnose. One was responsible for the resistance to PCa2 and PCa3 by MI and the other was responsible for the resistance to PCa3 by HP. The two genes were linked with 16.7 cM distance.

  4. Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

    NARCIS (Netherlands)

    Dihal, A.A.; Woutersen, R.A.; Ommen, B.v.; Rietjens, I.M.C.M.; Stierum, R.H.

    2006-01-01

    The effect of the dietary flavonoid quercetin was investigated on proliferation and differentiation of the human colon cancer cell line Caco-2. Confluent Caco-2 monolayers exposed to quercetin showed a biphasic effect on cell proliferation and a decrease in cell differentiation (0.001

  5. Resilience among first responders | Pietrantoni | African Health ...

    African Journals Online (AJOL)

    Nine hundred and sixty-one first responders filled out an on-line questionnaire, containing measure of sense of community, collective efficacy, self-efficacy and work-related mental health outcomes (compassion fatigue, burnout and compassion satisfaction). Results. First responders reported high level of compassion ...

  6. Convergence of method of lines approximations to partial differential equations

    International Nuclear Information System (INIS)

    Verwer, J.G.; Sanz-Serna, J.M.

    1984-01-01

    Many existing numerical schemes for evolutionary problems in partial differential equations (PDEs) can be viewed as method of lines (MOL) schemes. This paper treats the convergence of one-step MOL schemes. The main purpose is to set up a general framework for a convergence analysis applicable to nonlinear problems. The stability materials for this framework are taken from the field of nonlinear stiff ODEs. In this connection, important concepts are the logarithmic matrix norm and C-stability. A nonlinear parabolic equation and the cubic Schroedinger equation are used for illustrating the ideas. (Auth.)

  7. Crossing the invisible line: De-differentiation of wake, sleep and dreaming may engender both creative insight and psychopathology.

    Science.gov (United States)

    Llewellyn, Sue

    2016-11-01

    Writing about dreaming, the poet Raymond Carver said "I feel as if I've crossed some kind of invisible line". In creative people, the "line" between wake, dreaming and psychopathology may be porous, engendering a de-differentiated, super-critical, hybrid state. Evidence exists for a relationship between creativity and psychopathology but its nature has been elusive. De-differentiation between wake, sleep and dreaming may be the common substrate, as dream-like cognition pervades wake and wake-like neurophysiology suffuses sleep. Chaos theory posits brain states as inherently labile, transient and dynamically unstable. Over and above transient dissociations, an enduring and, sometimes, progressive, de-differentiation may be possible. Evidence indicates that sleep and dreaming facilitate creative insight. In consequence, a mild to moderate form of de-differentiation may enhance creativity but if wake-like neurobiology permeates sleep this may disrupt sleep-dependent memory processing and emotional regulation. If de-differentiation is progressive and enduring, various forms of psychopathology may result. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A rank-based algorithm of differential expression analysis for small cell line data with statistical control.

    Science.gov (United States)

    Li, Xiangyu; Cai, Hao; Wang, Xianlong; Ao, Lu; Guo, You; He, Jun; Gu, Yunyan; Qi, Lishuang; Guan, Qingzhou; Lin, Xu; Guo, Zheng

    2017-10-13

    To detect differentially expressed genes (DEGs) in small-scale cell line experiments, usually with only two or three technical replicates for each state, the commonly used statistical methods such as significance analysis of microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold change method lacks any statistical control. In this study, we demonstrated that the within-sample relative expression orderings (REOs) of gene pairs were highly stable among technical replicates of a cell line but often widely disrupted after certain treatments such like gene knockdown, gene transfection and drug treatment. Based on this finding, we customized the RankComp algorithm, previously designed for individualized differential expression analysis through REO comparison, to identify DEGs with certain statistical control for small-scale cell line data. In both simulated and real data, the new algorithm, named CellComp, exhibited high precision with much higher sensitivity than the original RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient tool for analyzing small-scale cell line data. © The Author 2017. Published by Oxford University Press.

  9. Simulation of longitudinal differential protection of transmission lines with additional stabilization and APU system

    Directory of Open Access Journals (Sweden)

    Rajić Tomislav D.

    2016-01-01

    Full Text Available This paper explains the algorithm for the longitudinal differential protection of transmission lines with automatic reclosing. Classic stabilization is not sufficient for avoiding of unnecessary operations caused by saturation of current transformer. This problem can occur during the fault plased outside of the protected zone of the transmission line. It is shown how unnecessary operation can occur during the outside fault whithout using of additional stabilization. The different types of faults were simulated and comparison of relay operations with and without additional stabilization is presented. The simulations were performed on the three-phase model of the transmission line formed by using of MATLAB/Simulink program.

  10. Spectral function for a nonsymmetric differential operator on the half line

    Directory of Open Access Journals (Sweden)

    Wuqing Ning

    2017-05-01

    Full Text Available In this article we study the spectral function for a nonsymmetric differential operator on the half line. Two cases of the coefficient matrix are considered, and for each case we prove by Marchenko's method that, to the boundary value problem, there corresponds a spectral function related to which a Marchenko-Parseval equality and an expansion formula are established. Our results extend the classical spectral theory for self-adjoint Sturm-Liouville operators and Dirac operators.

  11. A Modified Generalized Laguerre-Gauss Collocation Method for Fractional Neutral Functional-Differential Equations on the Half-Line

    Directory of Open Access Journals (Sweden)

    Ali H. Bhrawy

    2014-01-01

    Full Text Available The modified generalized Laguerre-Gauss collocation (MGLC method is applied to obtain an approximate solution of fractional neutral functional-differential equations with proportional delays on the half-line. The proposed technique is based on modified generalized Laguerre polynomials and Gauss quadrature integration of such polynomials. The main advantage of the present method is to reduce the solution of fractional neutral functional-differential equations into a system of algebraic equations. Reasonable numerical results are achieved by choosing few modified generalized Laguerre-Gauss collocation points. Numerical results demonstrate the accuracy, efficiency, and versatility of the proposed method on the half-line.

  12. Differential acceleration in the final beam lines of a Heavy Ion Fusion driver

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, Alex, E-mail: af@llnl.gov [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); The Virtual National Laboratory for Heavy Ion Fusion Science (United States)

    2014-01-01

    A long-standing challenge in the design of a Heavy Ion Fusion power plant is that the ion beams entering the target chamber, which number of order a hundred, all need to be routed from one or two multi-beam accelerators through a set of transport lines. The beams are divided into groups, each of which has a unique arrival time and may have a unique kinetic energy. It is also necessary to arrange for each beam to enter the target chamber from a prescribed location on the periphery of that chamber. Furthermore, it has generally been assumed that additional constraints must be obeyed: that the path lengths of the beams in a group must be equal, and that any delay of “main-pulse” beams relative to “foot-pulse” beams must be provided by the insertion of large delay-arcs in the main beam transport lines. Here we introduce the notion of applying “differential acceleration” to individual beams or sets of beams at strategic stages of the transport lines. That is, by accelerating some beams “sooner” and others “later,” it is possible to simplify the beam line configuration in a number of cases. For example, the time delay between the foot and main pulses can be generated without resorting to large arcs in the main-pulse beam lines. It is also possible to use differential acceleration to effect the simultaneous arrival on target of a set of beams (e.g., for the foot-pulse) without requiring that their path lengths be precisely equal. We illustrate the technique for two model configurations, one corresponding to a typical indirect-drive scenario requiring distinct foot and main energies, and the other to an ion-driven fast-ignition scenario wherein the foot and main beams share a common energy.

  13. Differential acceleration in the final beam lines of a Heavy Ion Fusion driver

    International Nuclear Information System (INIS)

    Friedman, Alex

    2014-01-01

    A long-standing challenge in the design of a Heavy Ion Fusion power plant is that the ion beams entering the target chamber, which number of order a hundred, all need to be routed from one or two multi-beam accelerators through a set of transport lines. The beams are divided into groups, each of which has a unique arrival time and may have a unique kinetic energy. It is also necessary to arrange for each beam to enter the target chamber from a prescribed location on the periphery of that chamber. Furthermore, it has generally been assumed that additional constraints must be obeyed: that the path lengths of the beams in a group must be equal, and that any delay of “main-pulse” beams relative to “foot-pulse” beams must be provided by the insertion of large delay-arcs in the main beam transport lines. Here we introduce the notion of applying “differential acceleration” to individual beams or sets of beams at strategic stages of the transport lines. That is, by accelerating some beams “sooner” and others “later,” it is possible to simplify the beam line configuration in a number of cases. For example, the time delay between the foot and main pulses can be generated without resorting to large arcs in the main-pulse beam lines. It is also possible to use differential acceleration to effect the simultaneous arrival on target of a set of beams (e.g., for the foot-pulse) without requiring that their path lengths be precisely equal. We illustrate the technique for two model configurations, one corresponding to a typical indirect-drive scenario requiring distinct foot and main energies, and the other to an ion-driven fast-ignition scenario wherein the foot and main beams share a common energy

  14. Cytotoxicity of Vitex agnus-castus fruit extract and its major component, casticin, correlates with differentiation status in leukemia cell lines.

    Science.gov (United States)

    Kikuchi, Hidetomo; Yuan, Bo; Nishimura, Yoshio; Imai, Masahiko; Furutani, Ryota; Kamoi, Saki; Seno, Misako; Fukushima, Shin; Hazama, Shingo; Hirobe, Chieko; Ohyama, Kunio; Hu, Xiao-Mei; Takagi, Norio; Hirano, Toshihiko; Toyoda, Hiroo

    2013-12-01

    We have demonstrated that an extract from the ripe fruit of Vitex agnus-castus (Vitex) exhibits cytotoxic activities against various types of solid tumor cells, whereas its effects on leukemia cells has not been evaluated to date. In this study, the effects of Vitex and its major component, casticin, on leukemia cell lines, HL-60 and U-937, were investigated by focusing on proliferation, induction of apoptosis and differentiation. Identification and quantitation by NMR spectroscopy showed that casticin accounted for approximate 1% weight of Vitex. Dose-dependent cytotoxicity of Vitex and casticin was observed in both cell lines, and HL-60 cells were more sensitive to the cytotoxicity of Vitex/casticin compared to U-937 cells. Furthermore, compared to unstimulated HL-60 cells, phorbol 12-myristate 13-acetate (PMA)- and 1,25-dihydroxyvitamin D₃ (VD₃)-differentiated HL-60 cells acquired resistance to Vitex/casticin based on the results from cell viability and apoptosis induction analysis. Since the HL-60 cell line is more immature than the U-937 cell line, these results suggested that the levels of cytotoxicity of Vitex/casticin were largely attributed to the degree of differentiation of leukemia cells; that is, cell lines with less differentiated phenotype were more susceptible than the differentiated ones. RT-PCR analysis demonstrated that PMA upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) in HL-60 cells, and that anti-ICAM-1 monoclonal antibody not only abrogated PMA-induced aggregation and adhesion of the cells but also restored its sensitivity to Vitex. These results suggested that ICAM-1 plays a crucial role in the acquired resistance in PMA-differentiated HL-60 cells by contributing to cell adhesion. These findings provide fundamental insights into the clinical application of Vitex/casticin for hematopoietic malignancy.

  15. Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line.

    Science.gov (United States)

    Shipley, Mackenzie M; Mangold, Colleen A; Szpara, Moriah L

    2016-02-17

    Having appropriate in vivo and in vitro systems that provide translational models for human disease is an integral aspect of research in neurobiology and the neurosciences. Traditional in vitro experimental models used in neurobiology include primary neuronal cultures from rats and mice, neuroblastoma cell lines including rat B35 and mouse Neuro-2A cells, rat PC12 cells, and short-term slice cultures. While many researchers rely on these models, they lack a human component and observed experimental effects could be exclusive to the respective species and may not occur identically in humans. Additionally, although these cells are neurons, they may have unstable karyotypes, making their use problematic for studies of gene expression and reproducible studies of cell signaling. It is therefore important to develop more consistent models of human neurological disease. The following procedure describes an easy-to-follow, reproducible method to obtain homogenous and viable human neuronal cultures, by differentiating the chromosomally stable human neuroblastoma cell line, SH-SY5Y. This method integrates several previously described methods(1-4) and is based on sequential removal of serum from media. The timeline includes gradual serum-starvation, with introduction of extracellular matrix proteins and neurotrophic factors. This allows neurons to differentiate, while epithelial cells are selected against, resulting in a homogeneous neuronal culture. Representative results demonstrate the successful differentiation of SH-SY5Y neuroblastoma cells from an initial epithelial-like cell phenotype into a more expansive and branched neuronal phenotype. This protocol offers a reliable way to generate homogeneous populations of neuronal cultures that can be used for subsequent biochemical and molecular analyses, which provides researchers with a more accurate translational model of human infection and disease.

  16. Dishonest responding or true virtue?

    DEFF Research Database (Denmark)

    Zettler, Ingo; Hilbig, Benjamin E.; Moshagen, Morten

    2015-01-01

    but troubling proposition that high scores in impression management scales actually reflect honesty rather than dishonest responding. In line with findings indicating that respondents answer to personality questionnaires rather accurately in typical low demand situations, we herein suggest that high impression...... management scores indeed reflect true virtues rather than dishonesty under such conditions. We found support for this idea by replicating previous correlations between impression management scores and virtue-related basic personality traits (including honesty-humility), and additionally provided conclusive...

  17. Cell kinetics of differentiation of Na+-dependent hexose transport in a cultured renal epithelial cell line

    International Nuclear Information System (INIS)

    Cook, J.S.; Weiss, E.R.

    1985-01-01

    Fully differentiated cells of the renal proximal tubule have the capability of taking up hexoses across their apical borders by transport coupled to the Na + -electrochemical gradient. This property is also found in postconfluent cultures of the cloned cell line LLC-PK 1 , a morphologically polarized line of renal cells. Postconfluent cells develop the Na + -dependent capacity to transport hexoses at their apical surface. This function is not observable during the growth phase of the cultures. To analyze the developmental process at the cellular level a method has been derived to separate transporting cells, expressing the differentiated function, from nontransporting cells. The method is based on the swelling of the cells accompanying the uptake of the nonmetabolizable glucose analog alpha methylglucoside. The swollen cells have a lower buoyant density than the undifferentiated cells and may be separated from them on density gradients. Analysis of the distribution of cells on such gradients shows that after the cells reach confluence the undifferentiated subpopulation is recruited onto the differentiation pathway with a rate constant of 0.2 per day, that 5 to 7 days are required for a cell to traverse this pathway to the fully differentiated state, and that once the maximum uptake capacity is achieved the cells do not develop further

  18. Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y.

    Science.gov (United States)

    Constantinescu, R; Constantinescu, A T; Reichmann, H; Janetzky, B

    2007-01-01

    Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in industrialized countries. Present cell culture models for PD rely on either primary cells or immortal cell lines, neither of which allow for long-term experiments on a constant population, a crucial requisite for a realistic model of slowly progressing neurodegenerative diseases. We differentiated SH-SY5Y human dopaminergic neuroblastoma cells to a neuronal-like state in a perfusion culture system using a combination of retinoic acid and mitotic inhibitors. The cells could be cultivated for two months without the need for passage. We show, by various means, that the differentiated cells exhibit, at the molecular level, many neuronal properties not characteristic to the starting line. This approach opens the possibility to develop chronic models, in which the effect of perturbations and putative counteracting strategies can be monitored over long periods of time in a quasi-stable cell population.

  19. Identification of differentially expressed proteins between human esophageal immortalized and carcinomatous cell lines by two-dimensional electrophoresis and MALDI-TOF-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Xing-Dong Xiong; Li-Yan Xu; Zhong-Ying Shen; Wei-Jia Cai; Jian-Min Luo; Ya-Li Han; En-Min Li

    2002-01-01

    AIM: To identify the differentially expressed proteins between the human immortalized esophageal epithelial cell line (SHEE) and the malignant transformed esophageal carcinoma cell line (SHEEC), and to explore new ways for studying esophageal carcinoma associated genes. METHODS: SHEE and SHEEC cell lines were used to separate differentially expressed proteins by two-dimensional electrophoresis/The silver-stained 2-D gels was scanned with EDAS290 digital camera system and analyzed with the PDQuest 6.2 Software. Six spots in which the differentially expressed protein was more obvious were selected and analyzed with matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS).RESULTS: There were 107±4.58 and 115±9.91 protein spots observed in SHEE and SHEEC respectively, and the majority of these spots between the two cell lines matched each other (r=-0.772), only a few were expressed differentially. After analyzed by MALDI-TOF-MS and database search for the six differentially expressed proteins, One new protein as well as other five sequence-known proteins including RNPEP-like protein, human rRNA gene upstream sequence binding transcription factor, uracil DNA glycosylase,Annexin A2 and p300/CBP-associated factor were preliminarily identified.CONCLUSION: These differentially expressed proteins might play an importance role during malignant transformation of SHEEC from SHEE. The identification of these proteins may serve as a new way for studying esophageal carcinoma associated genes.

  20. Value of diffusion-weighted images in differentiating mid-course responders to chemotherapy for osteosarcoma compared to the histological response: preliminary results

    International Nuclear Information System (INIS)

    Baunin, C.; Schmidt, G.; Aschero, A.; Ruocco, A.; Bourliere, B.; Gorincour, G.; Desvignes, C.; Colavolpe, N.; Petit, P.; Baumstarck, K.; Auqier, P.; Bouvier, C.; Gentet, J.C.; Bollini, G.

    2012-01-01

    Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy. (orig.)

  1. Value of diffusion-weighted images in differentiating mid-course responders to chemotherapy for osteosarcoma compared to the histological response: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Baunin, C.; Schmidt, G.; Aschero, A.; Ruocco, A.; Bourliere, B.; Gorincour, G.; Desvignes, C.; Colavolpe, N.; Petit, P. [Hopital Timone Enfants, Service d' Imagerie Pediatrique et Prenatale, Marseille Cedex 05 (France); Baumstarck, K.; Auqier, P. [Faculte de Medecine de Marseille, Service de Sante Publique, Marseille Cedex 05 (France); Bouvier, C. [Hopital Timone, Service d' Anatomopathologie, Marseille Cedex 05 (France); Gentet, J.C. [Hopital Timone Enfants, Service d' Oncologie Pediatrique, Marseille Cedex 05 (France); Bollini, G. [Hopital Timone Enfants, Service d' Orthopedie Pediatrique, Marseille Cedex 05 (France)

    2012-09-15

    Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy. (orig.)

  2. Effects of reinforcer magnitude on responding under differential-reinforcement-of-low-rate schedules of rats and pigeons.

    Science.gov (United States)

    Doughty, Adam H; Richards, Jerry B

    2002-07-01

    Experiment I investigated the effects of reinforcer magnitude on differential-reinforcement-of-low-rate (DRL) schedule performance in three phases. In Phase 1, two groups of rats (n = 6 and 5) responded under a DRI. 72-s schedule with reinforcer magnitudes of either 30 or 300 microl of water. After acquisition, the water amounts were reversed for each rat. In Phase 2, the effects of the same reinforcer magnitudes on DRL 18-s schedule performance were examined across conditions. In Phase 3, each rat responded unider a DR1. 18-s schedule in which the water amotnts alternated between 30 and 300 microl daily. Throughout each phase of Experiment 1, the larger reinforcer magnitude resulted in higher response rates and lower reinforcement rates. The peak of the interresponse-time distributions was at a lower value tinder the larger reinforcer magnitude. In Experiment 2, 3 pigeons responded under a DRL 20-s schedule in which reinforcer magnitude (1-s or 6-s access to grain) varied iron session to session. Higher response rates and lower reinforcement rates occurred tinder the longer hopper duration. These results demonstrate that larger reinforcer magnitudes engender less efficient DRL schedule performance in both rats and pigeons, and when reinforcer magnitude was held constant between sessions or was varied daily. The present results are consistent with previous research demonstrating a decrease in efficiency as a function of increased reinforcer magnituide tinder procedures that require a period of time without a specified response. These findings also support the claim that DRI. schedule performance is not governed solely by a timing process.

  3. Transcriptome-based differentiation of closely-related Miscanthus lines.

    Directory of Open Access Journals (Sweden)

    Philippe Chouvarine

    Full Text Available BACKGROUND: Distinguishing between individuals is critical to those conducting animal/plant breeding, food safety/quality research, diagnostic and clinical testing, and evolutionary biology studies. Classical genetic identification studies are based on marker polymorphisms, but polymorphism-based techniques are time and labor intensive and often cannot distinguish between closely related individuals. Illumina sequencing technologies provide the detailed sequence data required for rapid and efficient differentiation of related species, lines/cultivars, and individuals in a cost-effective manner. Here we describe the use of Illumina high-throughput exome sequencing, coupled with SNP mapping, as a rapid means of distinguishing between related cultivars of the lignocellulosic bioenergy crop giant miscanthus (Miscanthus × giganteus. We provide the first exome sequence database for Miscanthus species complete with Gene Ontology (GO functional annotations. RESULTS: A SNP comparative analysis of rhizome-derived cDNA sequences was successfully utilized to distinguish three Miscanthus × giganteus cultivars from each other and from other Miscanthus species. Moreover, the resulting phylogenetic tree generated from SNP frequency data parallels the known breeding history of the plants examined. Some of the giant miscanthus plants exhibit considerable sequence divergence. CONCLUSIONS: Here we describe an analysis of Miscanthus in which high-throughput exome sequencing was utilized to differentiate between closely related genotypes despite the current lack of a reference genome sequence. We functionally annotated the exome sequences and provide resources to support Miscanthus systems biology. In addition, we demonstrate the use of the commercial high-performance cloud computing to do computational GO annotation.

  4. Paracrine and autocrine signals promoting full chondrogenic differentiation of a mesoblastic cell line.

    Science.gov (United States)

    Locker, Morgane; Kellermann, Odile; Boucquey, Marie; Khun, Huot; Huerre, Michel; Poliard, Anne

    2004-01-01

    The pluripotent mesoblastic C1 cell line was used under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to drive chondrogenesis. Sequential addition of two systemic hormones, dexamethasone and triiodothyronine, permits full chondrogenic differentiation. The cell intrinsic activation of the BMP signaling pathway and Sox9 expression occurring on mesoblastic condensation is insufficient for recruitment of the progenitors. Dexamethasone-dependent Sox9 upregulation is essential for chondrogenesis. Differentiation of lineage stem cells relies on cell autonomous regulations modulated by external signals. We used the pluripotent mesoblastic C1 cell line under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to induce differentiation of a precursor clone along the chondrogenic lineage. C1 cells, cultured as aggregates, were induced toward chondrogenesis by addition of 10(-7) M dexamethasone in serum-free medium. After 30 days, dexamethasone was replaced by 10 nM triiodothyronine to promote final hypertrophic conversion. Mature and hypertrophic phenotypes were characterized by immunocytochemistry using specific antibodies against types II and X collagens, respectively. Type II collagen, bone morphogenetic proteins (BMPs), BMP receptors, Smads, and Sox9 expression were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot, and/or Western blot analysis. Once C1 cells have formed nodules, sequential addition of two systemic hormones is sufficient to promote full chondrogenic differentiation. In response to dexamethasone, nearly 100% of the C1 precursors engage in chondrogenesis and convert within 30 days into mature chondrocytes, which triggers a typical cartilage matrix. On day 25, a switch in type II procollagen mRNA splicing acted as a limiting step in the acquisition of the mature chondrocyte phenotype. On day 30, substitution of dexamethasone with

  5. Mouse DRG Cell Line with Properties of Nociceptors.

    Science.gov (United States)

    Doran, Ciara; Chetrit, Jonathan; Holley, Matthew C; Grundy, David; Nassar, Mohammed A

    2015-01-01

    In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons.

  6. Veterans Crisis Line

    Data.gov (United States)

    Department of Veterans Affairs — The caring responders at the Veterans Crisis Line are specially trained and experienced in helping Veterans of all ages and circumstances. Some of the responders are...

  7. Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor chimeric transgenes for terminal differentiation coupled to growth arrest and apoptosis.

    Science.gov (United States)

    Selvakumaran, M; Liebermann, D; Hoffman-Liebermann, B

    1993-05-01

    Conditional mutants of the myeloblastic leukemic M1 cell line, expressing the chimeric mycer transgene, have been established. It is shown that M1 mycer cells, like M1, undergo terminal differentiation coupled to growth arrest and programmed cell death (apoptosis) after treatment with the physiologic differentiation inducer interleukin-6. However, when beta-estradiol is included in the culture medium, M1 mycer cells respond to differentiation inducers like M1 myc cell lines, where the differentiation program is blocked at an intermediate stage. By manipulating the function of the mycer transgene product, it is shown that there is a 10-hour window during myeloid differentiation, from 30 to 40 hours after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, where activation of c-myc has no apparent effect on mature macrophages. M1 mycer cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal myelopoiesis and in leukemogenesis, also providing a strategy to clone c-myc target genes.

  8. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2-M17 Neuroblastoma Cell Lines upon Differentiation.

    Directory of Open Access Journals (Sweden)

    Roberta Filograna

    Full Text Available Human cell lines are often used to investigate cellular pathways relevant for physiological or pathological processes or to evaluate cell toxicity or protection induced by different compounds, including potential drugs. In this study, we analyzed and compared the differentiating activities of three agents (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate on the human neuroblastoma SH-SY5Y and BE(2-M17 cell lines; the first cell line is largely used in the field of neuroscience, while the second is still poorly characterized. After evaluating their effects in terms of cell proliferation and morphology, we investigated their catecholaminergic properties by assessing the expression profiles of the major genes involved in catecholamine synthesis and storage and the cellular concentrations of the neurotransmitters dopamine and noradrenaline. Our results demonstrate that the two cell lines possess similar abilities to differentiate and acquire a neuron-like morphology. The most evident effects in SH-SY5Y cells were observed in the presence of staurosporine, while in BE(2-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH-SY5Y and BE(2-M17 cells are characterized by the production of both NA and DA, but their levels are considerably higher in BE(2-M17 cells. Moreover, the NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2-M17 cells have a more prominent DAergic phenotype. Finally, the catecholamine concentration strongly increases upon differentiation induced by staurosporine in both cell lines. In conclusion, in this work the catecholaminergic phenotype of the human BE(2-M17 cell line upon differentiation was characterized for the first time. Our data suggest that SH-SY5Y and BE(2-M17 represent two alternative cell models for the neuroscience field.

  9. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2)-M17 Neuroblastoma Cell Lines upon Differentiation.

    Science.gov (United States)

    Filograna, Roberta; Civiero, Laura; Ferrari, Vanni; Codolo, Gaia; Greggio, Elisa; Bubacco, Luigi; Beltramini, Mariano; Bisaglia, Marco

    2015-01-01

    Human cell lines are often used to investigate cellular pathways relevant for physiological or pathological processes or to evaluate cell toxicity or protection induced by different compounds, including potential drugs. In this study, we analyzed and compared the differentiating activities of three agents (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate) on the human neuroblastoma SH-SY5Y and BE(2)-M17 cell lines; the first cell line is largely used in the field of neuroscience, while the second is still poorly characterized. After evaluating their effects in terms of cell proliferation and morphology, we investigated their catecholaminergic properties by assessing the expression profiles of the major genes involved in catecholamine synthesis and storage and the cellular concentrations of the neurotransmitters dopamine and noradrenaline. Our results demonstrate that the two cell lines possess similar abilities to differentiate and acquire a neuron-like morphology. The most evident effects in SH-SY5Y cells were observed in the presence of staurosporine, while in BE(2)-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH-SY5Y and BE(2)-M17 cells are characterized by the production of both NA and DA, but their levels are considerably higher in BE(2)-M17 cells. Moreover, the NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2)-M17 cells have a more prominent DAergic phenotype. Finally, the catecholamine concentration strongly increases upon differentiation induced by staurosporine in both cell lines. In conclusion, in this work the catecholaminergic phenotype of the human BE(2)-M17 cell line upon differentiation was characterized for the first time. Our data suggest that SH-SY5Y and BE(2)-M17 represent two alternative cell models for the neuroscience field.

  10. Conference Session I: Mitigating Risk at the Front Lines: The Copyright First Responders Program. Presented by Kyle Courtney, Copyright Advisor, the Office for Scholarly Communication, Harvard University.

    Directory of Open Access Journals (Sweden)

    Sara R. Benson

    2018-02-01

    Full Text Available This is a summary of Kyle Courtney's Invited Presentation at the 2017 Kraemer Copyright Conference titled "Mitigating Risk at the Front Lines:  The Copyright First Responders Program."  After reading this article you will better understand the method and purpose of the First Responders Program and, hopefully, like me, you will be ready to volunteer your institution to add to the growing list of libraries engaged in this hub-and-spoke model of copyright information system.

  11. Cellular Glycolysis and The Differential Survival of Lung Fibroblast and Lung Carcinoma Cell Lines.

    Science.gov (United States)

    Farah, Ibrahim O

    2016-04-01

    Tumor growth and abnormal cell survival were shown to be associated with a number of cellular metabolic abnormalities revealed by impaired oral glucose tolerance, depressed lipoprotein lipase activity leading to hypertriglyceridemia, and changes in amino acid profile as evidenced by increased plasma free tryptophan levels in patients with breast, lung, colon, stomach, and other cancers from various origins. The above findings seem to relate to or indicate a shift to non-oxidative metabolic pathways in cancer. In contrast to normal cells, cancer cells may lose the ability to utilize aerobic respiration due to either defective mitochondria or hypoxia within the tumor microenvironments. Glucose was shown to be the major energy source in cancer cells where it utilizes aerobic /anaerobic glycolysis with the resultant lactic acid formation. The role of energetic modulations and use of glycolytic inhibitors on cancer/normal cell survival is not clearly established in the literature. We hypothesize that natural intermediates of glycolysis and the citric acid cycle will differentially and negatively impact the cancer phenotype in contrast to their no effects on the normal cell phenotype. Therefore, the purpose of this study was to evaluate six potential glycolytic modulators namely, Pyruvic acid, oxalic acid, Zn acetate, sodium citrate, fructose diphosphate (FDP) and sodium bicarbonate at μM concentrations on growing A549 (lung cancer) and MRC-5 (normal; human lung fibroblast) cell lines with the objective of determining their influence on visual impact, cell metabolic activity, cell viability and end-point cell survival. Exposed and non-exposed cells were tested with phase-contrast micro-scanning, survival/death and metabolic activity trends through MTT-assays, as well as death end-point determinations by testing re-growth on complete media and T4 cellometer counts. Results showed that oxalic acid and Zn acetate both influenced the pH of the medium and resulted in

  12. Dysfunctions at human intestinal barrier by water-borne protozoan parasites: lessons from cultured human fully differentiated colon cancer cell lines.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa

    2013-06-01

    Some water-borne protozoan parasites induce diseases through their membrane-associated functional structures and virulence factors that hijack the host cellular molecules and signalling pathways leading to structural and functional lesions in the intestinal barrier. In this Microreview we analyse the insights on the mechanisms of pathogenesis of Entamoeba intestinalis, Giardia and Cryptosporidium observed in the human colon carcinoma fully differentiated colon cancer cell lines, cell subpopulations and clones expressing the structural and functional characteristics of highly specialized fully differentiated epithelial cells lining the intestinal epithelium and mimicking structurally and functionally an intestinal barrier. © 2013 John Wiley & Sons Ltd.

  13. Differential Responding by Rhesus Monkeys (Macaca mulatta and Humans (Homo sapiens to Variable Outcomes in the Assurance Game

    Directory of Open Access Journals (Sweden)

    Audrey E. Parrish

    2014-08-01

    Full Text Available Behavioral flexibility in how one responds to variable partner play can be examined using economic coordination games in which subjects play against a variety of partners and therefore may need to alter their behavior to produce the highest payoff. But how do we study this behavioral flexibility once players have settled on a response? Here, we investigated how responding by rhesus monkeys (Macaca mulatta and humans (Homo sapiens playing a computerized single-player version of a coordination game, the Assurance game, changed as a function of the variable responses (Stag/Hare generated by multiple simulations (SIMs. We were interested in whether individuals could track and differentially respond to changing frequencies of Stag and Hare play by the SIMs, especially with regard to the payoff dominant (Stag-Stag outcome, something that could not be done with real partners as they quickly settled on the Stag response. For both monkeys and humans, there was a linear relationship between proportion of Stag play by the subject and the likelihood of the Stag choice by the SIM such that both species increased their use of Stag as the SIM increased its use of the Stag response. However, humans more closely matched their proportion of Stag responses to that of the SIM, whereas monkeys adopted a different, but equally effective, strategy of exploiting the higher-paying Stag alternative. These results suggest that monkeys and humans demonstrate sensitivity to a dynamic game environment in which they encounter variable contingencies for the same response options, although they may employ different strategies to maximize reward.

  14. A family history of Type 1 alcoholism differentiates alcohol consumption in high cortisol responders to stress.

    Science.gov (United States)

    Brkic, Sejla; Söderpalm, Bo; Söderpalm Gordh, Anna

    2015-03-01

    The differentiation between high and low cortisol responders to stress is of interest in determining the risk factors which may, along with genetic vulnerability, influence alcohol intake. Thirty-two healthy volunteers, family history positive to alcoholism (FHP, n = 16) and family history negative (FHN, n = 16) attended two laboratory sessions during which alcohol or placebo was offered. There were no differences in consumption of alcohol or placebo between FHP and FHN subjects. STUDY 2: Fifty-eight healthy social drinkers, FHP (n = 27) and FHN (n = 31) attended two laboratory sessions. They were administered either alcohol or placebo in both sessions they attended. All subjects underwent either a stress task (the Trier Social Stress Test, TSST) or a stress-free period, at two separate occasions, before being offered beverage. After the salivary cortisol analysis, subjects in each group were divided into high (HCR) or low (LCR) cortisol responders. After stress, subjects who were FHP-HCR consumed more alcohol than FHN-HCR. There were no differences in the placebo intake between FHP and FHN subjects regardless of their cortisol response. This result indicates that stress promotes alcohol consumption only in subjects with a family history of Type 1 alcoholism who show an increase in cortisol response to stress. This behaviour is similar to that previously observed in alcohol dependent individuals after stress and thus could represent an endophenotype posing a risk for future development of alcohol use disorders. Copyright © 2015. Published by Elsevier Inc.

  15. Differential responses to radiation and hyperthermia of cloned cell lines derived from a single human melanoma xenograft

    International Nuclear Information System (INIS)

    Rofstad, E.K.; Brustad, T.

    1984-01-01

    One uncloned and five cloned cell lines were derived from a single human melanoma xenograft. Cells from passages 7-12 were exposed to either radiation or hyperthermia (42.5 0 C, pH = 7.4) under aerobic conditions and the colony forming ability of the cells was assayed in soft agar. The five cloned lines showed individual and characteristic responses to radiation as well as to hyperthermia. The variation in the response to radiation was mainly reflected in the size of the shoulders of the survival curves rather than in the D 0 -values. The variation in the response to hyperthermia was mainly reflected in the terminal slopes of the survival curves. The survival curve of cells from the uncloned line, both when exposed to radiation and hyperthermia, was positioned in the midst of those of the cloned lines. The response of the cloned lines to radiation did not correlate with the response to hyperthermia, indicating that tumor cell subpopulations which are resistant to radiation may respond well to hyperthermia

  16. Responding to Mechanical Antigravity

    Science.gov (United States)

    Millis, Marc G.; Thomas, Nicholas E.

    2006-01-01

    Based on the experiences of the NASA Breakthrough Propulsion Physics Project, suggestions are offered for constructively responding to proposals that purport breakthrough propulsion using mechanical devices. Because of the relatively large number of unsolicited submissions received (about 1 per workday) and because many of these involve similar concepts, this report is offered to help the would-be submitters make genuine progress as well as to help reviewers respond to such submissions. Devices that use oscillating masses or gyroscope falsely appear to create net thrust through differential friction or by misinterpreting torques as linear forces. To cover both the possibility of an errant claim and a genuine discovery, reviews should require that submitters meet minimal thresholds of proof before engaging in further correspondence; such as achieving sustained deflection of a level-platform pendulum in the case of mechanical thrusters.

  17. American marten respond to seismic lines in northern Canada at two spatial scales.

    Directory of Open Access Journals (Sweden)

    Jesse Tigner

    Full Text Available Development of hydrocarbon resources across northwest Canada has spurred economic prosperity and generated concerns over impacts to biodiversity. To balance these interests, numerous jurisdictions have adopted management thresholds that allow for limited energy development but minimize undesirable impacts to wildlife. Used for exploration, seismic lines are the most abundant linear feature in the boreal forest and exist at a variety of widths and recovery states. We used American marten (Martes americana as a model species to measure how line attributes influence species' response to seismic lines, and asked whether responses to individual lines trigger population impacts. Marten response to seismic lines was strongly influenced by line width and recovery state. Compared to forest interiors, marten used open seismic lines ≥ 3 m wide less often, but used open lines ≤ 2 m wide and partially recovered lines ≥ 6 m wide similarly. Marten response to individual line types appeared to trigger population impacts. The probability of occurrence at the home range scale declined with increasing seismic line density, and the inclusion of behavioral response to line density calculations improved model fit. In our top performing model, we excluded seismic lines ≤ 2 m from our calculation of line density, and the probability of occurrence declined > 80% between home ranges with the lowest and highest line densities. Models that excluded seismic lines did not strongly explain occurrence. We show how wildlife-derived metrics can inform regulatory guidelines to increase the likelihood those guidelines meet intended management objectives. With respect to marten, not all seismic lines constitute disturbances, but avoidance of certain line types scales to population impacts. This approach provides the ecological context required to understand cause and effect relationships among socio-economic and ecological conservation goals.

  18. A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Coexpressing Neuronal and Glial Markers

    Directory of Open Access Journals (Sweden)

    Anjali Shiras

    2003-11-01

    Full Text Available The molecular mechanisms involved in tumor progression from a low-grade astrocytoma to the most malignant glioblastoma multiforme (GBM have been hampered due to lack of suitable experimental models. We have established a model of tumor progression comprising of two cell lines derived from the same astrocytoma tumor with a set of features corresponding to low-grade glioma (as in HNGC-1 and high-grade GBM (as in HNGC-2. The HNGC-1 cell line is slowgrowing, contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly proliferating, anchorage-independent, highly tumorigenic, and invasive cell line. The proliferation of cell lines is independent of the addition of exogenous growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid karyotype except for a disomy of chromosome 2. The two cell lines express the neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as well as glial differentiation protein S100μ. The HNGC-1 cell line also expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic differentiation marker, hence contributing toward a more morphologically differentiated phenotype with a propensity for neural differentiation in vitro. Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and loss of fibronectin were observed only in the HNGC-2 cell line, implicating the significance of these pathways in tumor progression. This in vitro model system assumes importance in unraveling the cellular and molecular mechanisms in differentiation, transformation, and gliomagenesis.

  19. Fearing shades of grey: individual differences in fear responding towards generalisation stimuli.

    Science.gov (United States)

    Arnaudova, Inna; Krypotos, Angelos-Miltiadis; Effting, Marieke; Kindt, Merel; Beckers, Tom

    2017-09-01

    Individual differences in fear generalisation have been proposed to play a role in the aetiology and/or maintenance of anxiety disorders, but few data are available to directly support that claim. The research that is available has focused mostly on generalisation of peripheral and central physiological fear responses. Far less is known about the generalisation of avoidance, the behavioural component of fear. In two experiments, we evaluated how neuroticism, a known vulnerability factor for anxiety, modulates an array of fear responses, including avoidance tendencies, towards generalisation stimuli (GS). Participants underwent differential fear conditioning, in which one conditioned stimulus (CS+) was repeatedly paired with an aversive outcome (shock; unconditioned stimulus, US), whereas another was not (CS-). Fear generalisation was observed across measures in Experiment 1 (US expectancy and evaluative ratings) and Experiment 2 (US expectancy, evaluative ratings, skin conductance, startle responses, safety behaviours), with overall highest responding to the CS+, lowest to the CS- and intermediate responding to the GSs. Neuroticism had very little impact on fear generalisation (but did affect GS recognition rates in Experiment 1), in line with the idea that fear generalisation is largely an adaptive process.

  20. Geriatric Respondents and Non-Respondents To Probiotic Intervention Can Be Differentiated By Inherent Gut Microbiome Composition

    Directory of Open Access Journals (Sweden)

    Suja eSenan

    2015-09-01

    Full Text Available Scope: Probiotic interventions are known to have been shown to influence the composition of the intestinal microbiota in geriatrics. The growing concern is the apparent variation in response to identical strain dosage among human volunteers. One factor that governs this variation is the host gut microbiome. In this study, we attempted to define a core gut metagenome which could act as a predisposition signature marker of inherent bacterial community that can help predict the success of a probiotic intervention. Methods and Results: To characterize the geriatric gut microbiome we designed primers targeting the 16S rRNA hypervariable region V2-V3 followed by semiconductor sequencing using Ion Torrent PGM. Among respondents and non- respondents the chief genera of phylum Firmicutes that showed significant differences are Lactobacillus, Clostridium, Eubacterium, and Blautia (q< 0.002 while in the genera of phylum Proteobacteria included Shigella, Escherichia, Burkholderia and Camphylobacter (q <0.002. Conclusion: We have identified potential microbial biomarkers and taxonomic patterns that correlate with a positive response to probiotic intervention in geriatric volunteers. Future work with larger cohorts of geriatrics with diverse dietary influences could reveal the potential of the signature patterns of microbiota for personalized nutrition.

  1. [Biologically active fragment of the differentiation factor from HL-60 cell line. Identification and properties].

    Science.gov (United States)

    Kostanian, I A; Astapova, M V; Navolotskaia, E V; Lepikhova, T N; Dranitsyna, S M; Telegin, G B; Rodionov, I L; Baĭdakova, L K; Zolotarev, Iu A; Molotkovskaia, I M; Lipkin, V M

    2000-07-01

    Six-membered peptide fragment TGENHR (HLDF-6) was identified in the HL-60 cell culture of human promyelocyte leukemia treated with retinoic acid when studying the differentiation factor HLDF of this cell line. HLDF-6 retains the ability of the full-size factor to induce the differentiation and arrest the proliferation of the starting HL-60 cells. It was shown that the synthetic peptide HLDF-6 has no specific receptors on the surface of the HL-60 cells but can affect the binding of interleukin IL-1 beta, a cytokine involved in proliferation, to the cell surface. It was found on a model of transplantable NSO myeloma that HLDF-6 has an antitumor activity.

  2. Dissociating indifferent, directional, and extreme responding in personality data

    DEFF Research Database (Denmark)

    Zettler, Ingo; Lang, Jonas W B; Hülsheger, Ute R

    2015-01-01

    - and observer reports of personality traits. The three-process model captures indifferent, directional, and extreme responding. Substantively, we hypothesize that, and test whether, trait Honesty-Humility is negatively linked to extreme responding. METHOD: We applied the three-process model to personality data......-process model. Second, we show that the various response processes show a pattern of correlations across traits and rating sources which is in line with the idea that indifferent and extreme responding are person-specific tendencies, whereas directional responding is content-specific. Third, we report findings...... of N = 577 dyads (self- and observer reports of the HEXACO Personality Inventory-Revised) of Dutch and German respondents. RESULTS: First, we provide evidence that indifferent, directional, and extreme responding can be separated from each other in personality data through the use of the three...

  3. Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration.

    Science.gov (United States)

    Maier, Oliver; Böhm, Julia; Dahm, Michael; Brück, Stefan; Beyer, Cordian; Johann, Sonja

    2013-06-01

    Alpha-motoneurons appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Morphological and physiological degeneration of this neuronal phenotype is typically characterized by a marked decrease of neuronal markers and by alterations of cholinergic metabolism such as reduced choline acetyltransferase (ChAT) expression. The motoneuron-like cell line NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells. In order to further establish this cell line as a valid model system to investigate cholinergic neurodegeneration, NSC-34 cells were differentiated by serum deprivation and additional treatment with all-trans retinoic acid (atRA). Cell maturation was characterized by neurite outgrowth and increased expression of neuronal and cholinergic markers, including MAP2, GAP-43 and ChAT. Subsequently, we used differentiated NSC-34 cells to study early degenerative responses following exposure to various neurotoxins (H2O2, TNF-α, and glutamate). Susceptibility to toxin-induced cell death was determined by means of morphological changes, expression of neuronal marker proteins, and the ratio of pro-(Bax) to anti-(Bcl-2) apoptotic proteins. NSC-34 cells respond to low doses of neurotoxins with increased cell death of remaining undifferentiated cells with no obvious adverse effects on differentiated cells. Thus, the different vulnerability of differentiated and undifferentiated NSC-34 cells to neurotoxins is a key characteristic of NSC-34 cells and has to be considered in neurotoxic studies. Nonetheless, application of atRA induced differentiation of NSC-34 cells and provides a suitable model to investigate molecular events linked to neurodegeneration of differentiated neurons. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Nanotopography induced contact guidance of the F11 cell line during neuronal differentiation: a neuronal model cell line for tissue scaffold development

    International Nuclear Information System (INIS)

    Wieringa, Paul; Micera, Silvestro; Tonazzini, Ilaria; Cecchini, Marco

    2012-01-01

    The F11 hybridoma, a dorsal root ganglion-derived cell line, was used to investigate the response of nociceptive sensory neurons to nanotopographical guidance cues. This established this cell line as a model of peripheral sensory neuron growth for tissue scaffold design. Cells were seeded on substrates of cyclic olefin copolymer (COC) films imprinted via nanoimprint lithography (NIL) with a grating pattern of nano-scale grooves and ridges. Different ridge widths were employed to alter the focal adhesion formation, thereby changing the cell/substrate interaction. Differentiation was stimulated with forskolin in culture medium consisting of either 1 or 10% fetal bovine serum (FBS). Per medium condition, similar neurite alignment was achieved over the four day period, with the 1% serum condition exhibiting longer, more aligned neurites. Immunostaining for focal adhesions found the 1% FBS condition to also have fewer, less developed focal adhesions. The robust response of the F11 to guidance cues further builds on the utility of this cell line as a sensory neuron model, representing a useful tool to explore the design of regenerative guidance tissue scaffolds. (paper)

  5. Liver Progenitor Cell Line HepaRG Differentiated in a Bioartificial Liver Effectively Supplies Liver Support to Rats with Acute Liver Failure

    NARCIS (Netherlands)

    Nibourg, Geert A. A.; Chamuleau, Robert A. F. M.; van der Hoeven, Tessa V.; Maas, Martinus A. W.; Ruiter, An F. C.; Lamers, Wouter H.; Oude Elferink, Ronald P. J.; van Gulik, Thomas M.; Hoekstra, Ruurdtje

    2012-01-01

    A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into

  6. In Vitro Differentiation and Propagation of Urothelium from Pluripotent Stem Cell Lines.

    Science.gov (United States)

    Osborn, Stephanie L; Kurzrock, Eric A

    2018-01-01

    Bioengineering of bladder tissue, particularly for those patients who have advanced bladder disease, requires a source of urothelium that is healthy, capable of significant proliferation in vitro and immunologically tolerated upon transplant. As pluripotent stem cells have the potential to fulfill such criteria, they provide a critical cell source from which urothelium might be derived in vitro and used clinically. Herein, we describe the in vitro differentiation of urothelium from the H9 human embryonic stem cell (hESC) line through the definitive endoderm (DE) phase via selective culture techniques. The protocol can be used to derive urothelium from other hESCs or human-induced pluripotent stem cells.

  7. Directed Differentiation of Human Pluripotent Stem Cells to Microglia

    Directory of Open Access Journals (Sweden)

    Panagiotis Douvaras

    2017-06-01

    Full Text Available Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs. Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell lines.

  8. Line probe assay for differentiation within Mycobacterium tuberculosis complex. Evaluation on clinical specimens and isolates including Mycobacterium pinnipedii

    DEFF Research Database (Denmark)

    Kjeldsen, Marianne Kirstine; Bek, Dorte; Rasmussen, Erik Michael

    2009-01-01

    A line probe assay (GenoType MTBC) was evaluated for species differentiation within the Mycobacterium tuberculosis complex (MTBC). We included 387 MTBC isolates, 43 IS6110 low-copy MTBC isolates, 28 clinical specimens with varying microscopy grade, and 30 isolates of non-tuberculous mycobacteria...

  9. TRIM32 promotes retinoic acid receptor α-mediated differentiation in human promyelogenous leukemic cell line HL60

    International Nuclear Information System (INIS)

    Sato, Tomonobu; Okumura, Fumihiko; Iguchi, Akihiro; Ariga, Tadashi; Hatakeyama, Shigetsugu

    2012-01-01

    Highlights: ► TRIM32 enhanced RARα-mediated transcriptional activity even in the absence of RA. ► TRIM32 stabilized RARα in the human promyelogenous leukemic cell line HL60. ► Overexpression of TRIM32 in HL60 cells induced granulocytic differentiation. ► TRIM32 may function as a coactivator for RARα-mediated transcription in APL cells. -- Abstract: Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor α (RARα). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RARα and enhances transcriptional activity of RARα in mouse neuroblastoma cells and embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RARα, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RARα-mediated transcriptional activity even in the absence of RA and stabilizes RARα in the human promyelogenous leukemic cell line HL60. Moreover, we found that overexpression of TRIM32 in HL60 cells suppresses cellular proliferation and induces granulocytic differentiation even in the absence of RA. These findings suggest that TRIM32 functions as one of the coactivators for RARα-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL.

  10. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

    DEFF Research Database (Denmark)

    Suzuki, Harukazu; Forrest, Alistair R R; van Nimwegen, Erik

    2009-01-01

    , we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks......Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites...... involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process....

  11. Effects of Pulsed Electromagnetic Field on Differentiation of HUES-17 Human Embryonic Stem Cell Line

    Directory of Open Access Journals (Sweden)

    Yi-Lin Wu

    2014-08-01

    Full Text Available Electromagnetic fields are considered to potentially affect embryonic development, but the mechanism is still unknown. In this study, human embryonic stem cell (hESC line HUES-17 was applied to explore the mechanism of exposure on embryonic development to pulsed electromagnetic field (PEMF for 400 pulses at different electric field intensities and the differentiation of HUES-17 cells was observed after PEMF exposure. The expression of alkaline phosphatase (AP, stage-specific embryonic antigen-3 (SSEA-3, SSEA-4 and the mRNA level and protein level of Oct4, Sox2 and Nanog in HUES-17 cells remained unchanged after PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m. Four hundred pulses PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m did not affect the differentiation of HUES-17 cells. The reason why electromagnetic fields affect embryonic development may be due to other mechanisms rather than affecting the differentiation of embryonic stem cells.

  12. Face and voice as social stimuli enhance differential physiological responding in a Concealed Information Test

    Directory of Open Access Journals (Sweden)

    Wolfgang eAmbach

    2012-11-01

    Full Text Available Attentional, intentional, and motivational factors are known to influence the physiological responses in a Concealed Information Test (CIT. Although concealing information is essentially a social action closely related to motivation, CIT studies typically rely on testing participants in an environment lacking of social stimuli: Subjects interact with a computer while sitting alone in an experimental room. To address this gap, we examined the influence of social stimuli on the physiological responses in a CIT.Seventy-one participants underwent a mock-crime experiment with a modified CIT. In a between-subjects design, subjects were either questioned acoustically by a pre-recorded male voice presented together with a virtual male experimenter’s uniform face or by a text field on the screen, which displayed the question devoid of face and voice. Electrodermal activity (EDA, respiration line length (RLL, phasic heart rate (pHR, and finger pulse waveform length (FPWL were registered. The Psychopathic Personality Inventory - Revised (PPI-R was administered in addition. The differential responses of RLL, pHR, and FPWL to probe vs. irrelevant items were greater in the condition with social stimuli than in the text condition; interestingly, the differential responses of EDA did not differ between conditions. No modulatory influence of the PPI-R sum or subscale scores was found.The results emphasize the relevance of social aspects in the process of concealing information and in its detection. Attentional demands as well as the participants’ motivation to avoid detection might be the important links between social stimuli and physiological responses in the CIT.

  13. [SP600125-induced polyploidization of megakaryocytic leukemia cell lines by ribosomal protein S6 kinase 1 depends on the degree of cell differentiation].

    Science.gov (United States)

    Wang, Lili; Yang, Jingang; Li, Changling; Xing, Sining; Yu, Ying; Liu, Shuo; Zhao, Song; Ma, Dongchu

    2016-10-01

    Objective To investigate regulatory role of ribosomal protein S6 kinase 1 (S6K1) in the polyploidization of different megakaryocytic leukemia cell lines at the different differentiation stages. Methods Megakaryocytic leukemia cell lines (Dami, Meg-01 and HEL cells) were induced towards polyploidization by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. The SP600125-inducing process was blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor. The phenotype (CD41a, CD42a and CD42b) and DNA ploidy were detected by flow cytometry. The expression and phosphorylation of S6K1 and related proteins were detected by Western blotting. Results SP600125 induced polyploidization and increased the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) in Dami, Meg-01 and HEL cells. However, the effect of SP600125 on polyploidization of the three cell lines was different, with the strongest effect on Dami cells and the weakest on Meg-01 cells. Moreover, SP600125 increased the phosphorylation of S6K1 Thr421/Ser424 and decreased the phosphorylation of Thr389 in Dami cells. However, it only increased the phosphorylation of Thr389 in HEL cells and had no effect on the phosphorylation of S6K1 in Meg-01 cells. Interestingly, H-89 only partially blocked the polyploidization of Dami cells, although it decreased the phosphorylation of 4E-BP1 in all SP600125-induced three cell lines. Noticeably, H-89 decreased the phosphorylation of S6K1 Thr421/Ser424 and increased the phosphorylation of Thr389 in Dami cells. However, H-89 had no effect on the phosphorylation of Thr421/Ser424, although it increased the phosphorylation of Thr389 in Meg-01 and HEL cells. Phenotypic analysis showed that the three cell lines were at different levels of differentiation in megakaryocytic lineage, with the highest differentiation in Dami and the lowest in Meg-01 cells. Conclusion SP600125-induced polyploidization of megakaryocytic leukemia cell lines is dependent on the effect

  14. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Science.gov (United States)

    Faggi, Fiorella; Codenotti, Silvia; Poliani, Pietro Luigi; Cominelli, Manuela; Chiarelli, Nicola; Colombi, Marina; Vezzoli, Marika; Monti, Eugenio; Bono, Federica; Tulipano, Giovanni; Fiorentini, Chiara; Zanola, Alessandra; Lo, Harriet P; Parton, Robert G; Keller, Charles; Fanzani, Alessandro

    2015-01-01

    The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3) in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS), an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC) expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  15. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Directory of Open Access Journals (Sweden)

    Fiorella Faggi

    Full Text Available The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3 in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS, an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  16. Mischievous responding in Internet Gaming Disorder research.

    Science.gov (United States)

    Przybylski, Andrew K

    2016-01-01

    The most recent update to the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included Internet Gaming Disorder as a new potential psychiatric condition that merited further scientific study. The present research was conducted in response to the APA Substance-Related Disorders Working Group's research call to estimate the extent to which mischievous responding-a known problematic pattern of participant self-report responding in questionnaires-is relevant to Internet Gaming Disorder research. In line with a registered sampling and analysis plan, findings from two studies (n tot = 11,908) provide clear evidence that mischievous responding is positively associated with the number of Internet Gaming Disorder indicators participants report. Results are discussed in the context of ongoing problem gaming research and the discussion provides recommendations for improving the quality of scientific practice in this area.

  17. Anti-proliferative and differentiation-inducing activities of the green tea catechin epigallocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line.

    Science.gov (United States)

    Lung, H L; Ip, W K; Wong, C K; Mak, N K; Chen, Z Y; Leung, K N

    2002-12-06

    A novel approach for the treatment of leukemia is the differentiation therapy in which immature leukemia cells are induced to attain a mature phenotype when exposed to differentiation inducers, either alone or in combinations with other chemotherapeutic or chemopreventive drugs. Over the past decade, numerous studies indicated that green tea catechins (GTC) could suppress the growth and induce apoptosis on a number of human cancer cell lines. However, the differentiation-inducing activity of GTC on human tumors remains poorly understood. In the present study, the effect of the major GTC epigallocatechin-3-gallate (EGCG) on the proliferation and differentiation of a human eosinophilc leukemic cell line, EoL-1, was examined. Our results showed that EGCG suppressed the proliferation of the EoL-1 cells in a dose-dependent manner, with an estimated IC(50) value of 31.5 microM. On the other hand, EGCG at a concentration of 40 microM could trigger the EoL-1 cells to undergo morphological differentiation into mature eosinophil-like cells. Using RT-PCR and flow cytometry, it was found that EGCG upregulated the gene and protein expression of two eosinophil-specific granule proteins, the major basic protein (MBP) and eosinophil peroxidase (EPO), in EoL-1 cells. Taken together, our findings suggest that EGCG can exhibit anti-leukemic activity on a human eosinophilic cell line EoL-1 by suppressing the proliferation and by inducing the differentiation of the leukemia cells.

  18. Differential-interference-contrast digital in-line holography microscopy based on a single-optical-element.

    Science.gov (United States)

    Zhang, Yuchao; Xie, Changqing

    2015-11-01

    Both digital in-line holography (DIH) and zone plate-based microscopy have received considerable interest as powerful imaging tools. However, the former suffers from a twin-image noise problem. The latter suffers from low efficiency and difficulty in fabrication. Here, we present an effective and efficient phase-contrast imaging approach, named differential-interference-contrast digital in-line holography (DIC-DIH), by using a single optical element to split the incident light into a plane wave and a converging spherical wave and generate a two-dimensional (2D) DIC effect simultaneously. Specifically, to improve image contrast, we present a new single optical element, termed 2D DIC compound photon sieves, by combining two overlaid binary gratings and a compound photon sieve through two logical XOR operations. The proof-of-concept experiments demonstrate that the proposed technique can eliminate the twin-image noise problem and improve image contrast with high efficiency. Additionally, we present an example of the phase-contrast imaging nonuniform thick photoresist development process.

  19. Differentiation in Stem Cell Lineages and in Life: Explorations in the Male Germ Line Stem Cell Lineage.

    Science.gov (United States)

    Fuller, Margaret T

    2016-01-01

    I have been privileged to work on cellular differentiation during a great surge of discovery that has revealed the molecular mechanisms and genetic regulatory circuitry that control embryonic development and adult tissue maintenance and repair. Studying the regulation of proliferation and differentiation in the male germ line stem cell lineage has allowed us investigate how the developmental program imposes layers of additional controls on fundamental cellular processes like cell cycle progression and gene expression to give rise to the huge variety of specialized cell types in our bodies. We are beginning to understand how local signals from somatic support cells specify self-renewal versus differentiation in the stem cell niche at the apical tip of the testis. We are discovering the molecular events that block cell proliferation and initiate terminal differentiation at the switch from mitosis to meiosis-a signature event of the germ cell program. Our work is beginning to reveal how the developmental program that sets up the dramatic new cell type-specific transcription program that prepares germ cells for meiotic division and spermatid differentiation is turned on when cells become spermatocytes. I have had the privilege of working with incredible students, postdocs, and colleagues who have discovered, brainstormed, challenged, and refined our science and our ideas of how developmental pathways and cellular mechanisms work together to drive differentiation. © 2016 Elsevier Inc. All rights reserved.

  20. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Marilyn Carrier

    Full Text Available Retinoic acid (RA, the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα, which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

  1. Over-expression and siRNA of a novel environmental lipopolysaccharide-responding gene on the cell cycle of the human hepatoma-derived cell line HepG2

    International Nuclear Information System (INIS)

    Du Kejun; Chai Yubo; Hou Lichao; Chang Wenhui; Chen Suming; Luo Wenjing; Cai Tongjian; Zhang Xiaonan; Chen Nanchun; Chen Yaoming; Chen Jingyuan

    2008-01-01

    Lipopolysaccharide (LPS) is the toxic determinant for Gram-negative bacterium infection. The individual response to LPS was related to its gene background. It is necessary to identify new molecules and signaling transduction pathways about LPS. The present study was undertaken to evaluate the effects of a novel environmental lipopolysaccharide-responding (Elrg) gene on the regulation of proliferation and cell cycle of the hepatoma-derived cell line, HepG2. By means of RT-PCR, the new molecule of Elrg was generated from a human dental pulp cell cDNA library. Expression level of Elrg in HepG2 cells was remarkably upgraded by the irritation of LPS. Localization of Elrg in HepG2 cells was positioned mainly in cytoplasm. HepG2 cells were markedly arrested in the G1 phase by over-expressing Elrg. The percentage of HepG2 cells in G1 phase partly decreased after Elrg-siRNA. In conclusion, Elrg is probably correlative with LPS responding. Elrg is probably a new protein in cytoplasm which plays an important role in regulating cell cycle. The results will deepen our understanding about the potential effects of Elrg on the human hepatoma-derived cell line HepG2

  2. Melatonin receptor genes (mel-1a, mel-1b, mel-1c) are differentially expressed in the avian germ line.

    Science.gov (United States)

    Kawashima, Takaharu; Stepińska, Urszula; Kuwana, Takashi; Olszańska, Bozenna

    2008-09-01

    The presence of melatonin receptor transcripts (mel-1a, mel-1b and mel-1c) was investigated in primordial germ cells (PGCs), immature and mature oocytes, and sperm of Japanese quail by reverse transcription--polymerase chain reaction (RT-PCR). The mel-1a transcript was detected in as few as in a thousand PGCs. Significant differences in the expression of melatonin receptor genes were found in differentiating germ cells: in PGCs only the mel-1a receptor was expressed, in blastoderms and immature oocytes all three transcripts (mel-1a, mel-1b, mel-1c) were present, while in mature ovulated oocytes the predominant transcript was mel-1c (with sporadic occurrence of mel-1a and mel-1b). In sperm, mel-1a and mel-1c were present but mel-1b was absent. This indicates that the expression of melatonin receptor genes changes throughout the differentiation of PGCs into adult gametes: during oocyte differentiation two additional transcripts, mel-1b and mel-1c, are synthesized in addition to mel-1a, but at oocyte maturation, mel-1a and mel-1b are degraded and only mel-1c remains. During male line (spermatozoa) differentiation mel-1c is transcribed in addition to mel-1a, with mel-1b being completely absent. Since melatonin and the activities of enzymes participating in melatonin synthesis are present in the avian yolk, it is reasonable to suggest a role for this molecule in early avian development and germ line differentiation. We propose that melatonin may act as a signaling molecule regulating some differentiation processes (e.g., cell proliferation, migration, etc.) before the formation of neural and hormonal systems.

  3. Transcriptome profiling of differentially expressed genes in floral buds and flowers of male sterile and fertile lines in watermelon.

    Science.gov (United States)

    Rhee, Sun-Ju; Seo, Minseok; Jang, Yoon-Jeong; Cho, Seoae; Lee, Gung Pyo

    2015-11-09

    Male sterility is an important mechanism for the production of hybrid seeds in watermelon. Although fruit development has been studied extensively in watermelon, there are no reports on gene expression in floral organs. In this study, RNA-sequencing (RNA-seq) was performed in two near-isogenic watermelon lines (genic male sterile [GMS] line, DAH3615-MS and male fertile line, DAH3615) to identify the differentially expressed genes (DEGs) related to male sterility. DEG analysis showed that 1259 genes were significantly associated with male sterility at a FDR P-value of watermelon. This analysis revealed essential genes responsible for stamen development, including pollen development and pollen tube elongation, and allowed their functional classification. These results provided new information on global mechanisms related to male sterility in watermelon.

  4. Tissue transglutaminase (TG2 activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

    Directory of Open Access Journals (Sweden)

    Xiaoxue Yin

    2012-08-01

    Full Text Available Tissue transglutaminase (type II, TG2 has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14 to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC mRNA, bone morphogenetic protein-2 (BMP-2 and collagen I, significantly high alkaline phosphatase (ALP activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

  5. Physiological response and productivity of safflower lines under water deficit and rehydration.

    Science.gov (United States)

    Bortolheiro, Fernanda P A P; Silva, Marcelo A

    2017-01-01

    Water deficit is one of the major stresses affecting plant growth and productivity worldwide. Plants induce various morphological, physiological, biochemical and molecular changes to adapt to the changing environment. Safflower (Carthamus tinctorius L.), a potential oil producer, is highly adaptable to various environmental conditions, such as lack of rainfall and temperatures. The objective of this work was to study the physiological and production characteristics of six safflower lines in response to water deficit followed by rehydration. The experiment was conducted in a protected environment and consisted of 30 days of water deficit followed by 18 days of rehydration. A differential response in terms of photosynthetic pigments, electrolyte leakage, water potential, relative water content, grain yield, oil content, oil yield and water use efficiency was observed in the six lines under water stress. Lines IMA 04, IMA 10, IMA 14 showed physiological characteristics of drought tolerance, with IMA 14 and IMA 16 being the most productive after water deficit. IMA 02 and IMA 21 lines displayed intermediate characteristics of drought tolerance. It was concluded that the lines responded differently to water deficit stress, showing considerable genetic variation and influence to the environment.

  6. Physiological response and productivity of safflower lines under water deficit and rehydration

    Directory of Open Access Journals (Sweden)

    FERNANDA P.A.P. BORTOLHEIRO

    2017-12-01

    Full Text Available ABSTRACT Water deficit is one of the major stresses affecting plant growth and productivity worldwide. Plants induce various morphological, physiological, biochemical and molecular changes to adapt to the changing environment. Safflower (Carthamus tinctorius L., a potential oil producer, is highly adaptable to various environmental conditions, such as lack of rainfall and temperatures. The objective of this work was to study the physiological and production characteristics of six safflower lines in response to water deficit followed by rehydration. The experiment was conducted in a protected environment and consisted of 30 days of water deficit followed by 18 days of rehydration. A differential response in terms of photosynthetic pigments, electrolyte leakage, water potential, relative water content, grain yield, oil content, oil yield and water use efficiency was observed in the six lines under water stress. Lines IMA 04, IMA 10, IMA 14 showed physiological characteristics of drought tolerance, with IMA 14 and IMA 16 being the most productive after water deficit. IMA 02 and IMA 21 lines displayed intermediate characteristics of drought tolerance. It was concluded that the lines responded differently to water deficit stress, showing considerable genetic variation and influence to the environment.

  7. How front-line healthcare workers respond to stock-outs of essential medicines in the Eastern Cape Province of South Africa.

    Science.gov (United States)

    Hodes, R; Price, I; Bungane, N; Toska, E; Cluver, L

    2017-08-25

    Shortages of essential medicines are a daily occurrence in many of South Africa (SA)'s public health facilities. This study focuses on the responses of healthcare workers to stock-outs, investigating how actors at the 'front line' of public health delivery understand, experience and respond to shortages of essential medicines and equipment in their facilities. Findings are based on focus groups, observations and interviews with healthcare workers and patients at healthcare facilities in the Eastern Cape Province of SA, conducted as part of the Mzantsi Wakho study. The research revealed a discrepancy between 'informal' definitions of stock-outs and their reporting through formal stock-out management channels. Front-line healthcare workers had designed their own systems for classifying the severity of stock-outs, based on the product in question, and on their potential to access stocks from other facilities. Beyond formal systems of procurement and supply, healthcare workers had established vast networks of alternative communication and action, often using personal resources to procure medical supplies. Stock-outs were only reported when informal methods of stock-sharing did not secure top-up supplies. These findings have implications for understanding the frequency and severity of stock-outs, and for taking action to prevent and manage stock-outs effectively.

  8. A comparison of physical and psychological features of responders and non-responders to cervical facet blocks in chronic whiplash

    Science.gov (United States)

    2013-01-01

    Background Cervical facet block (FB) procedures are often used as a diagnostic precursor to radiofrequency neurotomies (RFN) in the management of chronic whiplash associated disorders (WAD). Some individuals will respond to the FB procedures and others will not respond. Such responders and non-responders provided a sample of convenience to question whether there were differences in their physical and psychological features. This information may inform future predictive studies and ultimately the clinical selection of patients for FB procedures. Methods This cross-sectional study involved 58 individuals with chronic WAD who responded to cervical FB procedures (WAD_R); 32 who did not respond (WAD_NR) and 30 Healthy Controls (HC)s. Measures included: quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test); nociceptive flexion reflex (NFR); motor function (cervical range of movement (ROM); activity of the superficial neck flexors during the cranio-cervical flexion test (CCFT). Self-reported measures were gained from the following questionnaires: neuropathic pain (s-LANSS); psychological distress (General Health Questionnaire-28), post-traumatic stress (PDS) and pain catastrophization (PCS). Individuals with chronic whiplash attended the laboratory once the effects of the blocks had abated and symptoms had returned. Results Following FB procedures, both WAD groups demonstrated generalized hypersensitivity to all sensory tests, decreased neck ROM and increased superficial muscle activity with the CCFT compared to controls (p 0.05). Both WAD groups demonstrated psychological distress (GHQ-28; p < 0.05), moderate post-traumatic stress symptoms and pain catastrophization. The WAD_NR group also demonstrated increased medication intake and elevated PCS scores compared to the WAD_R group (p < 0.05). Conclusions Chronic WAD responders and non-responders to FB procedures demonstrate a similar presentation of sensory disturbance, motor

  9. Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Dana M. Cairns

    2016-09-01

    Full Text Available Limited availability of human neurons poses a significant barrier to progress in biological and preclinical studies of the human nervous system. Current stem cell-based approaches of neuron generation are still hindered by prolonged culture requirements, protocol complexity, and variability in neuronal differentiation. Here we establish stable human induced neural stem cell (hiNSC lines through the direct reprogramming of neonatal fibroblasts and adult adipose-derived stem cells. These hiNSCs can be passaged indefinitely and cryopreserved as colonies. Independently of media composition, hiNSCs robustly differentiate into TUJ1-positive neurons within 4 days, making them ideal for innervated co-cultures. In vivo, hiNSCs migrate, engraft, and contribute to both central and peripheral nervous systems. Lastly, we demonstrate utility of hiNSCs in a 3D human brain model. This method provides a valuable interdisciplinary tool that could be used to develop drug screening applications as well as patient-specific disease models related to disorders of innervation and the brain.

  10. Do people with and without medical conditions respond similarly to the short health anxiety inventory? An assessment of differential item functioning using item response theory.

    Science.gov (United States)

    LeBouthillier, Daniel M; Thibodeau, Michel A; Alberts, Nicole M; Hadjistavropoulos, Heather D; Asmundson, Gordon J G

    2015-04-01

    Individuals with medical conditions are likely to have elevated health anxiety; however, research has not demonstrated how medical status impacts response patterns on health anxiety measures. Measurement bias can undermine the validity of a questionnaire by overestimating or underestimating scores in groups of individuals. We investigated whether the Short Health Anxiety Inventory (SHAI), a widely-used measure of health anxiety, exhibits medical condition-based bias on item and subscale levels, and whether the SHAI subscales adequately assess the health anxiety continuum. Data were from 963 individuals with diabetes, breast cancer, or multiple sclerosis, and 372 healthy individuals. Mantel-Haenszel tests and item characteristic curves were used to classify the severity of item-level differential item functioning in all three medical groups compared to the healthy group. Test characteristic curves were used to assess scale-level differential item functioning and whether the SHAI subscales adequately assess the health anxiety continuum. Nine out of 14 items exhibited differential item functioning. Two items exhibited differential item functioning in all medical groups compared to the healthy group. In both Thought Intrusion and Fear of Illness subscales, differential item functioning was associated with mildly deflated scores in medical groups with very high levels of the latent traits. Fear of Illness items poorly discriminated between individuals with low and very low levels of the latent trait. While individuals with medical conditions may respond differentially to some items, clinicians and researchers can confidently use the SHAI with a variety of medical populations without concern of significant bias. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.

    Science.gov (United States)

    Sato, Eiichi; Ando, Takashi; Ichikawa, Jiro; Okita, Genki; Sato, Nobutaka; Wako, Masanori; Ohba, Tetsuro; Ochiai, Satoshi; Hagino, Tetsuo; Jacobson, Richard; Haro, Hirotaka

    2014-12-01

    Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  12. Effect of human granulocyte macrophage-colony stimulating factor on differentiation and apoptosis of the human osteosarcoma cell line SaOS-2

    Directory of Open Access Journals (Sweden)

    L Postiglione

    2009-06-01

    Full Text Available We investigated the effects of human granulocyte macrophage- colony stimulating factor (GM-CSF on the relation between differentiation and apoptosis in SaOS-2 cells, an osteoblast-like cell line. To determine the relationship between these cellular processes, SaOS-2 cells were treated in vitro for 1, 7 and 14 days with 200 ng/mL GM-CSF and compared with untreated cells. Five nM insulin-like growth factor (IGF-I and 30 nM okadaic acid were used as negative and positive controls of apoptosis, respectively. Effects on cell differentiation were determined by ECM (extracellular matrix mineralization, morphology of some typical mature osteoblast differentiation markers, such as osteopontin and sialoprotein II (BSP-II, and production of bone ECM components such as collagen I. The results showed that treatment with GM-CSF caused cell differentiation accompanied by increased production of osteopontin and BSP-II, together with increased ECM deposition and mineralization. Flow cytometric analysis of annexin V and propidium iodide incorporation showed that GM-CSF up-regulated apoptotic cell death of SaOS-2 cells after 14 days of culture in contrast to okadaic acid, which stimulated SaOS-2 apoptosis only during the early period of culture. Endonucleolytic cleavage of genomic DNA, detected by “laddering analysis”, confirmed these data. The results suggest that GM-CSF induces osteoblastic differentiation and long-term apoptotic cell death of the SaOS-2 human osteosarcoma cell line, which in turn suggests a possible in vivo physiological role for GM-CSF on human osteoblast cells.

  13. Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.

    Science.gov (United States)

    Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne

    2010-10-01

    We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

  14. The effects of diazinon and cypermethrin on the differentiation of neuronal and glial cell lines

    International Nuclear Information System (INIS)

    Flaskos, J.; Harris, W.; Sachana, M.; Munoz, D.; Tack, J.; Hargreaves, A.J.

    2007-01-01

    Diazinon and cypermethrin are pesticides extensively used in sheep dipping. Diazinon is a known anti-cholinesterase, but there is limited information regarding its molecular mechanism of action. This paper describes the effects of diazinon and cypermethrin at a morphological and molecular level on differentiating mouse N2a neuroblastoma and rat C6 glioma cell lines. Concentrations up to 10 μM of both compounds and their mixture had no effect on the viability of either cell line, as determined by methyl blue tetrazolium reduction and total protein assays. Microscopic analysis revealed that 1 μM and 10 μM diazinon but not cypermethrin inhibited the outgrowth of axon-like processes in N2a cells after a 24-h exposure but neither compound affected process outgrowth by differentiating C6 cells at these concentrations. Under these conditions, 10 μM diazinon inhibited AChE slightly compared to the control after a 4-h exposure but not after 24 h. Western blotting analysis showed that morphological changes were associated with reduced cross-reactivity with antibodies that recognize the neurofilament heavy chain (NFH), microtubule associated protein MAP 1B and HSP-70 compared to control cell extracts, whereas reactivity with anti-α-tubulin antibodies was unchanged. Aggregation of NFH was observed in cell bodies of diazinon-treated N2a cells, as determined by indirect immunofluorescence staining. These data demonstrate that diazinon specifically targets neurite outgrowth in neuronal cells and that this effect is associated with disruption of axonal cytoskeleton proteins, whereas cypermethrin has no effect on the same parameters

  15. Ultrastructural characteristics of three undifferentiated mouse embryonic stem cell lines and their differentiated three-dimensional derivatives: a comparative study.

    Science.gov (United States)

    Alharbi, Suzan; Elsafadi, Mona; Mobarak, Mohammed; Alrwili, Ali; Vishnubalaji, Radhakrishnan; Manikandan, Muthurangan; Al-Qudsi, Fatma; Karim, Saleh; Al-Nabaheen, May; Aldahmash, Abdullah; Mahmood, Amer

    2014-04-01

    The fine structures of mouse embryonic stem cells (mESCs) grown as colonies and differentiated in three-dimensional (3D) culture as embryoid bodies (EBs) were analyzed by transmission electron microscopy. Undifferentiated mESCs expressed markers that proved their pluripotency. Differentiated EBs expressed different differentiation marker proteins from the three germ layers. The ultrastructure of mESCs revealed the presence of microvilli on the cell surfaces, large and deep infolded nuclei, low cytoplasm-to-nuclear ratios, frequent lipid droplets, nonprominent Golgi apparatus, and smooth endoplasmic reticulum. In addition, we found prominent juvenile mitochondria and free ribosomes-rich cytoplasm in mESCs. Ultrastructure of the differentiated mESCs as EBs showed different cell arrangements, which indicate the different stages of EB development and differentiation. The morphologies of BALB/c and 129 W9.5 EBs were very similar at day 4, whereas C57BL/6 EBs were distinct from the others at day 4. This finding suggested that differentiation of EBs from different cell lines occurs in the same pattern but not at the same rate. Conversely, the ultrastructure results of BALB/c and 129 W9.5 ESCs revealed differentiating features, such as the dilated profile of a rough endoplasmic reticulum. In addition, we found low expression levels of undifferentiated markers on the outer cells of BALB/c and 129 W9.5 mESC colonies, which suggests a faster differentiation potential.

  16. Numerical differential protection

    CERN Document Server

    Ziegler, Gerhard

    2012-01-01

    Differential protection is a fast and selective method of protection against short-circuits. It is applied in many variants for electrical machines, trans?formers, busbars, and electric lines.Initially this book covers the theory and fundamentals of analog and numerical differential protection. Current transformers are treated in detail including transient behaviour, impact on protection performance, and practical dimensioning. An extended chapter is dedicated to signal transmission for line protection, in particular, modern digital communication and GPS timing.The emphasis is then pla

  17. Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

    Science.gov (United States)

    Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

    2014-09-01

    For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

  18. Downregulation of rRNA transcription triggers cell differentiation.

    Directory of Open Access Journals (Sweden)

    Yuki Hayashi

    Full Text Available Responding to various stimuli is indispensable for the maintenance of homeostasis. The downregulation of ribosomal RNA (rRNA transcription is one of the mechanisms involved in the response to stimuli by various cellular processes, such as cell cycle arrest and apoptosis. Cell differentiation is caused by intra- and extracellular stimuli and is associated with the downregulation of rRNA transcription as well as reduced cell growth. The downregulation of rRNA transcription during differentiation is considered to contribute to reduced cell growth. However, the downregulation of rRNA transcription can induce various cellular processes; therefore, it may positively regulate cell differentiation. To test this possibility, we specifically downregulated rRNA transcription using actinomycin D or a siRNA for Pol I-specific transcription factor IA (TIF-IA in HL-60 and THP-1 cells, both of which have differentiation potential. The inhibition of rRNA transcription induced cell differentiation in both cell lines, which was demonstrated by the expression of the common differentiation marker CD11b. Furthermore, TIF-IA knockdown in an ex vivo culture of mouse hematopoietic stem cells increased the percentage of myeloid cells and reduced the percentage of immature cells. We also evaluated whether differentiation was induced via the inhibition of cell cycle progression because rRNA transcription is tightly coupled to cell growth. We found that cell cycle arrest without affecting rRNA transcription did not induce differentiation. To the best of our knowledge, our results demonstrate the first time that the downregulation of rRNA levels could be a trigger for the induction of differentiation in mammalian cells. Furthermore, this phenomenon was not simply a reflection of cell cycle arrest. Our results provide a novel insight into the relationship between rRNA transcription and cell differentiation.

  19. Epitopes recognized by CBV4 responding T cells: effect of type 1 diabetes and associated HLA-DR-DQ haplotypes

    International Nuclear Information System (INIS)

    Marttila, Jane; Hyoety, Heikki; Naentoe-Salonen, Kirsti; Simell, Olli; Ilonen, Jorma

    2004-01-01

    The present study aimed at characterizing the epitopes recognized by coxsackievirus B4 (CBV4)-specific T-cell lines established from 23 children with type 1 diabetes (T1D) and 29 healthy children with T1D risk-associated HLA genotypes. Responsiveness to VP1 region was dependent on the specific infection history as 55% of the T-cell lines from donors with neutralizing antibodies to CBV serotypes responded to VP1 peptides compared to none of the T-cell lines from other donors (P = 0.01). The pattern of recognized peptides was dependent of the HLA genotype. Forty-two percent of the T-cell lines from donors carrying the HLA-(DR4)-DQB1*0302 haplotype responded to VP1 peptides 71-80 compared to none of the T-cell lines from donors without this haplotype (P = 0.02). No evidence for the existence of diabetes-specific epitopes was found. Only few epitopes were exclusive recognized by T cells from diabetic children, and in each case only one or two T-cell lines were responding

  20. Differential performance and parasitism of caterpillars on maize inbred lines with distinctly different herbivore-induced volatile emissions.

    Directory of Open Access Journals (Sweden)

    Thomas Degen

    Full Text Available Plant volatiles induced by insect feeding are known to attract natural enemies of the herbivores. Six maize inbred lines that showed distinctly different patterns of volatile emission in laboratory assays were planted in randomized plots in the Central Mexican Highlands to test their ability to recruit parasitic wasps under field conditions. The plants were artificially infested with neonate larvae of the fall armyworm Spodoptera frugiperda, and two of its main endoparasitoids, Campoletis sonorensis and Cotesia marginiventris, were released in the plots. Volatiles were collected from equally treated reference plants in the neighbourhood of the experimental field. The cumulative amount of 36 quantified volatile compounds determined for each line was in good accordance with findings from the laboratory; there was an almost 15-fold difference in total emission between the two extreme lines. We found significant differences among the lines with respect to the numbers of armyworms recovered from the plants, their average weight gain and parasitism rates. Average weight of the caterpillars was negatively correlated with the average total amount of volatiles released by the six inbred lines. However, neither total volatile emission nor any specific single compound within the blend could explain the differential parasitism rates among the lines, with the possible exception of (E-2-hexenal for Campoletis sonorensis and methyl salicylate for Cotesia marginiventris. Herbivore-induced plant volatiles and/or correlates thereof contribute to reducing insect damage of maize plants through direct plant defence and enhanced attraction of parasitoids, alleged indirect defence. The potential to exploit these volatiles for pest control deserves to be further evaluated.

  1. Effect of graphene oxide on undifferentiated and retinoic acid-differentiated SH-SY5Y cells line

    Science.gov (United States)

    Lv, Min; Zhang, Yujie; Liang, Le; Wei, Min; Hu, Wenbing; Li, Xiaoming; Huang, Qing

    2012-06-01

    Graphene oxide (GO), has created an unprecedented opportunity for development and application in biology, due to its abundant functional groups and well water solubility. Recently, the potential toxicity of GO in the environment and in humans has garnered more and more attention. In this paper, we systematically studied the cytotoxicity of GO nanosheets via examining the effect of GO on the morphology, viability and differentiation of a human neuroblastoma SH-SY5Y cell line, which was an ideal model used to study neuronal disease in vitro. The results suggested that GO had no obvious cytotoxicity at low concentration (cells exhibited dose- and time-dependent decreases at high concentration (>=80 μg mL-1). Moreover, GO did not induce apoptosis. Very interestingly, GO significantly enhanced the differentiation of SH-SY5Y induced-retinoic acid (RA) by evaluating neurite length and the expression of neuronal marker MAP2. These data provide a promising application for neurodegenerative diseases.

  2. The Conscientious Responders Scale Helps Researchers Verify the Integrity of Personality Questionnaire Data.

    Science.gov (United States)

    Marjanovic, Zdravko; Bajkov, Lisa; MacDonald, Jennifer

    2018-01-01

    The Conscientious Responders Scale is a five-item embeddable validity scale that differentiates between conscientious and indiscriminate responding in personality-questionnaire data (CR & IR). This investigation presents further evidence of its validity and generalizability across two experiments. Study 1 tests its sensitivity to questionnaire length, a known cause of IR, and tries to provoke IR by manipulating psychological reactance. As expected, short questionnaires produced higher Conscientious Responders Scale scores than long questionnaires, and Conscientious Responders Scale scores were unaffected by reactance manipulations. Study 2 tests concerns that the Conscientious Responders Scale's unusual item content could potentially irritate and baffle responders, ironically increasing rates of IR. We administered two nearly identical questionnaires: one with an embedded Conscientious Responders Scale and one without the Conscientious Responders Scale. Psychometric comparisons revealed no differences across questionnaires' means, variances, interitem response consistencies, and Cronbach's alphas. In sum, the Conscientious Responders Scale is highly sensitive to questionnaire length-a known correlate of IR-and can be embedded harmlessly in questionnaires without provoking IR or changing the psychometrics of other measures.

  3. Bursal transcriptome profiling of different inbred chicken lines reveals key differentially expressed genes at 3 days post-infection with very virulent infectious bursal disease virus.

    Science.gov (United States)

    Farhanah, Mohd Isa; Yasmin, Abd Rahaman; Mat Isa, Nurulfiza; Hair-Bejo, Mohd; Ideris, Aini; Powers, Claire; Oladapo, Omobolanle; Nair, Venugopal; Khoo, Jia-Shiun; Ghazali, Ahmad-Kamal; Yee, Wai-Yan; Omar, Abdul Rahman

    2018-01-01

    Infectious bursal disease is a highly contagious disease in the poultry industry and causes immunosuppression in chickens. Genome-wide regulations of immune response genes of inbred chickens with different genetic backgrounds, following very virulent infectious bursal disease virus (vvIBDV) infection are poorly characterized. Therefore, this study aims to analyse the bursal tissue transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following infection with vvIBDV strain UK661 using strand-specific next-generation sequencing, by highlighting important genes and pathways involved in the infected chicken during peak infection at 3 days post-infection. All infected chickens succumbed to the infection without major variations among the different lines. However, based on the viral loads and bursal lesion scoring, lines P and 6 can be considered as the most susceptible lines, while lines 15 and N were regarded as the least affected lines. Transcriptome profiling of the bursa identified 4588 genes to be differentially expressed, with 2985 upregulated and 1642 downregulated genes, in which these genes were commonly or uniquely detected in all or several infected lines. Genes that were upregulated are primarily pro-inflammatory cytokines, chemokines and IFN-related. Various genes that are associated with B-cell functions and genes related to apoptosis were downregulated, together with the genes involved in p53 signalling. In conclusion, bursal transcriptome profiles of different inbred lines showed differential expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT signalling genes, MAPK signalling genes, and their related pathways following vvIBDV infection.

  4. Mischievous responding in Internet Gaming Disorder research

    Directory of Open Access Journals (Sweden)

    Andrew K. Przybylski

    2016-09-01

    Full Text Available The most recent update to the American Psychiatric Association’s (APA Diagnostic and Statistical Manual of Mental Disorders (DSM-5 included Internet Gaming Disorder as a new potential psychiatric condition that merited further scientific study. The present research was conducted in response to the APA Substance-Related Disorders Working Group’s research call to estimate the extent to which mischievous responding—a known problematic pattern of participant self-report responding in questionnaires—is relevant to Internet Gaming Disorder research. In line with a registered sampling and analysis plan, findings from two studies (ntot = 11,908 provide clear evidence that mischievous responding is positively associated with the number of Internet Gaming Disorder indicators participants report. Results are discussed in the context of ongoing problem gaming research and the discussion provides recommendations for improving the quality of scientific practice in this area.

  5. New Stokes' line in WKB theory

    International Nuclear Information System (INIS)

    Berk, H.L.; Nevins, W.M.; Roberts, K.V.

    1982-01-01

    The WKB theory for differential equations of arbitrary order or integral equations in one dimension is investigated. The rules previously stated for the construction of Stokes' lines for Nth-order differential equations, N> or =3, or integral equations are found to be incomplete because these rules lead to asymptotic forms of the solutions that depend on path. This paradox is resolved by the demonstration that new Stokes' lines can arise when previously defined Stokes' lines cross. A new formulation of the WKB problem is given to justify the new Stokes' lines. With the new Stokes' lines, the asymptotic forms can be shown to be independent of path. In addition, the WKB eigenvalue problem is formulated, and the global dispersion relation is shown to be a functional of loop integrals of the action

  6. Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

    Directory of Open Access Journals (Sweden)

    Faten Merhi

    2008-08-01

    Full Text Available Faten Merhi1, Jacques Auger2, Francine Rendu1, Brigitte Bauvois11UMR 7131 UPMC Paris Universitas/CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France; 2University F. Rabelais, IRBI, UPRESA CNRS 6035, Tours, FranceAbstract: Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS, diallyl TS (All2TS, dipropyl TS (Pr2TS and dimethyl TS (Me2TS, are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6 in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide. As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1 inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2 induced macrophage maturation, and 3 inhibited the levels of secreted MMP-9 (protein and activity and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.Keywords: acute myeloid leukemia, thiosulfinate, proliferation, differentiation, matrix metalloproteinase-9

  7. Differences in change in coping styles between good responders, moderate responders and non-responders to pulmonary rehabilitation.

    Science.gov (United States)

    Stoilkova-Hartmann, Ana; Janssen, Daisy J A; Franssen, Frits M E; Wouters, Emiel F M

    2015-12-01

    Pulmonary rehabilitation (PR) improves exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). Data on the effects of PR on coping styles are limited. Aim of the present study was to compare changes in coping styles between patients who had a good, moderate and no improvement in either exercise tolerance or health status after PR. Coping styles of 439 COPD patients undergoing PR were assessed by the Utrecht Coping List (UCL) at baseline and after PR. Patients' pulmonary function, six-minute walking distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) and Hospital Anxiety and Depression Scale (HADS-A and HADS-D) were recorded. Good, moderate and non-responders were defined on the basis of minimally clinically important difference (MCID) for SGRQ total score and/or 6MWD. Overall, 54.0% of the patients fulfilled the criteria for good responders, while 22.1% were moderate responders. Change in passive reaction pattern coping style differed significantly between good responders and non-responders following PR (p styles after PR occurred among the good responders, whereas the majority of moderate responders' and non-responders' coping styles were not significantly influenced by PR. Good responders decreased their passive reaction pattern coping style in contrast to non-responders after PR. In general, PR did not change the coping among moderate and non-responders. Further research is warranted to determine whether including interventions targeting coping styles may modify coping behaviour of COPD patients, as well as improvement in exercise tolerance or health status after PR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Activation of Group II Metabotropic Glutamate Receptors Increases Proliferation but does not Influence Neuronal Differentiation of a Human Neural Stem Cell Line

    DEFF Research Database (Denmark)

    Dindler, Anne; Blaabjerg, Morten; Kamand, Morad

    2018-01-01

    of pharmacological activation and inhibition of mGluR2/3 on proliferation, differentiation and viability of a human neural stem cell line. Immunofluorescence staining revealed the presence of mGluR2/3 receptors on both proliferating and differentiating stem cells, including cells differentiated into β-tubulin III....... Western blot analysis revealed that the active, dimeric form of mGluR2/3 was mainly present on the proliferating cells, which may explain our findings. The present study emphasises the importance of glutamate and mGluRs on regulation of human neural stem cells and suggests a significant role of mGluR2....../3 during cell proliferation. This article is protected by copyright. All rights reserved....

  9. Drug use among complete responders, partial responders and non-responders in a longitudinal survey of nonagenarians

    DEFF Research Database (Denmark)

    Wastesson, Jonas W; Rasmussen, Lotte; Oksuzyan, Anna

    2017-01-01

    PURPOSE: In observational studies, non-response can limit representativity and introduce bias. We aimed to investigate the longitudinal changes in the number of used drugs among complete responders, partial responders, and non-responders in a whole birth cohort of Danish nonagenarians participati...

  10. Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study.

    Science.gov (United States)

    Li, Wenhua; Zhao, Xiaoying; Wang, Huijie; Liu, Xin; Zhao, Xinmin; Huang, Mingzhu; Qiu, Lixin; Zhang, Wen; Chen, Zhiyu; Guo, Weijian; Li, Jin; Zhu, Xiaodong

    2017-06-06

    Maintenance therapy proves to be effective in advanced lung and breast cancer after initial chemotherapy. The purpose of this phase II study was to evaluate the efficacy and safety of Uracil and Tegafur (UFT) maintenance in metastatic gastric cancer patients following the first-line fluorouracil-based chemotherapy. Metastatic gastric cancer patients with stable disease or a better response after the completion of first-line chemotherapy were randomized to oral UFT (360mg/m2 × 2 weeks) every 3 weeks until disease progression/intolerable toxicity or to observation (OBS). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS) and safety. The trial was closed after the interim analysis of the 58 enrolled (120 planned) patients. Median PFS was not improved in the UFT group compared with the OBS group (3.2 months versus 3.6 months, P = 0.752), as well as the median OS (14.2 months for both, P = 0.983). However, subgroup analysis showed that low baseline hemoglobin (maintenance therapy (P = 0.032), while the normal hemoglobin patients benefit from the UFT treatment (P = 0.008). Grade 3 to 4 toxicities in the UFT group were anemia (3.4%), thrombocytopenia (3.4%) and diarrhea (6.9%). This trial did not show superiority of UFT maintenance in non-selected patients responding to fluorouracil-based first-line chemotherapy. The normal hemoglobin level at baseline is a predictive biomarker for favorable patient subsets from the maintenance treatment.

  11. Bufalin inhibits the differentiation and proliferation of human osteosarcoma cell line hMG63-derived cancer stem cells.

    Science.gov (United States)

    Chang, Yuewen; Zhao, Yongfang; Zhan, Hongsheng; Wei, Xiaoen; Liu, Tianjin; Zheng, Bo

    2014-02-01

    Cancer stem cells (CSCs) play an important role in drug resistance of tumor and are responsible for high recurrence rates. Agents that can suppress the proliferation and differentiation of CSCs would provide new opportunity to fight against tumor recurrence. In this study, we developed a new strategy to enrich CSCs in human osteosarcoma cell line hMG63. Using these CSCs as model, we tested the effect of bufalin, a traditional Chinese medicine, on the proliferation and differentiation of CSCs. hMG63 cells were cultured in poly-HEMA-treated dish and cancer stem cell-specific medium. In this nonadhesive culture system, hMG63 formed spheres, which were then collected and injected into the immunodeficient mice. Cisplatin was administered every 3 days for five times. The enriched xenograft tumors were cultured in cancer stem cell-specific medium again to form tumor spheres. Expression of cancer stem cell markers of these cells was measured by flow cytometry. These cells were then treated with bufalin, and the proliferation and differentiation ability were indicated by the expression level of molecular markers and the formation of sphere again in vitro. We obtained a low CD133+/CD44 cell population with high-level stem cell marker. When treated with bufalin, the sphere could not get attached to the flask and failed to differentiate, which was indicated by the stable expression of stem cell marker CD133 and OCT-4 in the condition permissive to differentiation. Treatment of bufalin also suppressed the single cells isolated from the sphere to form sphere again in the nonadhesive culture system, and a decreased expression of proliferation marker Ki67 was also detected in these cells. Sphere-formed and chemoresistant colon xenograft tumors in immunodeficient mice could enrich cancer stem cell population. Bufalin could inhibit proliferation and differentiation of CSCs.

  12. Comprehensive transcriptome-based characterization of differentially expressed genes involved in microsporogenesis of radish CMS line and its maintainer.

    Science.gov (United States)

    Xie, Yang; Zhang, Wei; Wang, Yan; Xu, Liang; Zhu, Xianwen; Muleke, Everlyne M; Liu, Liwang

    2016-09-01

    Microsporogenesis is an indispensable period for investigating microspore development and cytoplasmic male sterility (CMS) occurrence. Radish CMS line plays a critical role in elite F1 hybrid seed production and heterosis utilization. However, the molecular mechanisms of microspore development and CMS occurrence have not been thoroughly uncovered in radish. In this study, a comparative analysis of radish floral buds from a CMS line (NAU-WA) and its maintainer (NAU-WB) was conducted using next generation sequencing (NGS) technology. Digital gene expression (DGE) profiling revealed that 3504 genes were significantly differentially expressed between NAU-WA and NAU-WB library, among which 1910 were upregulated and 1594 were downregulated. Gene ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly enriched in extracellular region, catalytic activity, and response to stimulus. KEGG enrichment analysis revealed that the DEGs were predominantly associated with flavonoid biosynthesis, glycolysis, and biosynthesis of secondary metabolites. Real-time quantitative PCR analysis showed that the expression profiles of 13 randomly selected DEGs were in high agreement with results from Illumina sequencing. Several candidate genes encoding ATP synthase, auxin response factor (ARF), transcription factors (TFs), chalcone synthase (CHS), and male sterility (MS) were responsible for microsporogenesis. Furthermore, a schematic diagram for functional interaction of DEGs from NAU-WA vs. NAU-WB library in radish plants was proposed. These results could provide new information on the dissection of the molecular mechanisms underlying microspore development and CMS occurrence in radish.

  13. Value correlates of the motivations to respond without prejudice / Correlatos valorativos das motivações para responder sem preconceito

    Directory of Open Access Journals (Sweden)

    Valdiney V. Gouveia

    2006-01-01

    Full Text Available The current study aimed at establishing to what extent both internal and external motivations to respond without prejudice towards Blacks would correlate with human values. As many as 308 subjects from João Pessoa – comprising high school and university students as well as individuals from the community as a whole – were considered. The Basic Values Questionnaire, the Impression Management Scale and the Scale of Internal and External Motivation to Respond without Prejudice, and also demographic questions were applied. Results showed that the internal motivation was positively correlated with the suprapersonal values, specifically maturity, beauty and knowledge. Moreover, the external motivation did correlate, predominantly, with the achievement values, specifically those of prestige and privacy. Such results are in line with those found in the literature, which indicate the opposition between egalitarianism (suprapersonal vs. protestant ethic (achievement values so as to explicate the prejudice and the motivations that would prevent such attitude.

  14. Product line design

    Czech Academy of Sciences Publication Activity Database

    Anderson, S. P.; Celik, Levent

    2015-01-01

    Roč. 157, May (2015), s. 517-526 ISSN 0022-0531 Institutional support: RVO:67985998 Keywords : product line design * product differentiation * second-degree price discrimination Subject RIV: AH - Economics Impact factor: 1.097, year: 2015

  15. Identification of differentially expressed genes in the oviduct of two rabbit lines divergently selected for uterine capacity using suppression subtractive hybridization.

    Science.gov (United States)

    Ballester, M; Castelló, A; Peiró, R; Argente, M J; Santacreu, M A; Folch, J M

    2013-06-01

    Suppressive subtractive hybridization libraries from oviduct at 62 h post-mating of two lines of rabbits divergently selected for uterine capacity were generated to identify differentially expressed genes. A total of 438 singletons and 126 contigs were obtained by cluster assembly and sequence alignment of 704 expressed sequence tags (ESTs), of which 54% showed homology to known proteins of the non-redundant NCBI databases. Differential screening by dot blot validated 71 ESTs, of which 47 showed similarity to known genes. Transcripts of genes were functionally annotated in the molecular function and the biological process gene ontology categories using the BLAST2GO software and were assigned to reproductive developmental process, immune response, amino acid metabolism and degradation, response to stress and apoptosis terms. Finally, three interesting genes, PGR, HSD17B4 and ERO1L, were identified as overexpressed in the low line using RT-qPCR. Our study provides a list of candidate genes that can be useful to understanding the molecular mechanisms underlying the phenotypic differences observed in early embryo survival and development traits. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

  16. Cloning of a glutathione S-transferase decreasing during differentiation of HL60 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Chul; Park, In Kyu; Lee, Kyu Bo; Sohn, Sang Kyun; Kim, Moo Kyu; Kim, Jung Chul [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of)

    1999-06-01

    By sequencing the Expressed Sequence Tags of human dermal papilla cDNA library, we identified a clone named K872 of which the expression decreased during differentiation of HL60 cell line. K872 plasmid DNA was isolated according to QIA plasmid extraction kit (Qiagen GmbH, Germany). The nucleotide sequencing was performed by Sanger's method with K872 plasmid DNA. The most updated GenBank EMBL necleic acid banks were searched through the internet by using BLAST (Basic Local Alignment Search Tools) program. Northern bots were performed using RNA isolated from various human tissues and cancer cell lines. The gene expression of the fusion protein was achieved by His-Patch Thiofusion expression system and the protein product was identified on SDS-PAGE. K872 clone is 1006 nucleotides long, and has a coding region of 675 nucleotides and a 3' non-coding region of 280 nucleotides. The presumed open reading frame starting at the 5' terminus of K872 encodes 226 amino acids, including the initiation methionine residue. The amino acid sequence deduced from the open reading frame of K872 shares 70% identity with that of rat glutathione S-transferase kappa 1 (rGSTK1). The transcripts were expressed inh a variety of human tissues and cancer cells. The levels of transcript were relatively high in those tissues such as heart, skeletal muscle, and peripheral blood leukocyte. It is noteworthy that K872 was found to be abundantly expressed in colorectal cancer and melanoma cell lines. Homology search result suggests that K872 clone is the human homolog of the rGSTK1 which is known to be involved in the resistance of cytotoxic therapy. We propose that meticulous functional analysis should be followed to confirm that.

  17. Pseudo-differentiation syndrome

    Directory of Open Access Journals (Sweden)

    Fathi Jehani

    2011-01-01

    Full Text Available

    line-height: 200%; text-indent: 0.5in; margin: 12pt 0in 10pt;">line-height: 200%;">A patient with relapsed acute myeloid leukemia (AML (M2 FAB classification developed a differentiating syndrome upon receiving Decitabine therapy given with palliative intent. The patient presented with high grade fever, constitutional symptoms and severe chest symptoms with no underlying lung condition. Chest x-ray (CXR showed diffuse pulmonary infiltrates. Septic work up followed by intravenous broad spectrum antimicrobials did not improve his condition. Pan cultures’ results were repeatedly negative. Treatment with high dose Dexamethasone (DXM resulted in marked clinical and radiological improvement.

    line-height: 200%; text-indent: 0.5in; margin: 12pt 0in 10pt;">line-height: 200%;">Our patient initially presented with relapsed AML (M2 Fab classification with t (8; 21; negative line-height: 200%;" lang="EN">FMS-like tyrosine kinaseline-height: 200%;" lang="EN"> line-height: 200%;">-internal tandem duplication (FLT3-ITD which are all good prognostic factors, yet the patient had an atypical clinical course with early frequent relapses, differentiation syndrome associated with Decitabine therapy and late in his disease, he developed a granulocytic sarcoma.

  18. On-line transmission electron microscopic image analysis of chromatin texture for differentiation of thyroid gland tumors.

    Science.gov (United States)

    Kriete, A; Schäffer, R; Harms, H; Aus, H M

    1987-06-01

    Nuclei of the cells from the thyroid gland were analyzed in a transmission electron microscope by direct TV scanning and on-line image processing. The method uses the advantages of a visual-perception model to detect structures in noisy and low-contrast images. The features analyzed include area, a form factor and texture parameters from the second derivative stage. Three tumor-free thyroid tissues, three follicular adenomas, three follicular carcinomas and three papillary carcinomas were studied. The computer-aided cytophotometric method showed that the most significant differences were the statistics of the chromatin texture features of homogeneity and regularity. These findings document the possibility of an automated differentiation of tumors at the ultrastructural level.

  19. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    International Nuclear Information System (INIS)

    Seriwatanachai, Dutmanee; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-01-01

    Highlights: ► Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. ► Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. ► Higher PRL concentrations (⩾100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of ⩾100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  20. Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Helena Carén

    2015-11-01

    Full Text Available Glioblastoma (GBM is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM.

  1. Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells.

    Science.gov (United States)

    Silva, Patrícia Benites Gonçalves da; Rodini, Carolina Oliveira; Kaid, Carolini; Nakahata, Adriana Miti; Pereira, Márcia Cristina Leite; Matushita, Hamilton; Costa, Silvia Souza da; Okamoto, Oswaldo Keith

    2016-08-01

    Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

  2. A theoretical framework to study variations in workplace violence experienced by emergency responders

    NARCIS (Netherlands)

    L. van Reemst (Lisa)

    2016-01-01

    markdownabstractEmergency responders are often sent to the front line and are often confronted with aggression and violence in interaction with citizens. According to previous studies, some professionals experience more workplace violence than others. In this article, the theoretical framework to

  3. Effect of TH-lines and clones on the growth and differentiation of B cell clones in microculture.

    Science.gov (United States)

    Kotloff, D B; Cebra, J J

    1988-02-01

    Antibody isotype expression by B cell clones was analyzed using in vitro microcultures containing low numbers of hapten-gelatin-enriched B cells and higher numbers of hemocyanin-specific helper T cell lines or clones. Twenty-eight to sixty-three percent of clones grown in microculture with haptenated hemocyanin and T cells from established lines expressed IgG and/or IgA isotypes in random mixtures, almost always accompanied by IgM. Helper T cells from hemocyanin-specific clones also supported the expression of non-IgM isotypes by the B cell clones, suggesting that a single specificity of T cell can provide sufficient growth and differentiation factors for the display of isotype switching. A positive correlation between the antibody output of clones and the expression of non-IgM isotypes indicated that the switching process may be associated with cell division. Although memory B cells that give clones expressing IgG and/or IgA in the absence of IgM are also enriched on haptenated gelatin, they are not stimulable under conditions of this microculture assay.

  4. Effect of ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in human lung cancer cell lines

    International Nuclear Information System (INIS)

    He Pengfei; Borland, Michael G.; Zhu Bokai; Sharma, Arun K.; Amin, Shantu; El-Bayoumy, Karam; Gonzalez, Frank J.; Peters, Jeffrey M.

    2008-01-01

    There is compelling evidence that peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) mediates terminal differentiation and is associated with inhibition of cell growth. However, it was recently suggested that growth of two human lung cancer cell lines is enhanced by PPARβ/δ. The goal of the present study was to provide insight in resolving this controversy. Therefore, the effect of ligand activation of PPARβ/δ in A549 and H1838 human lung cancer cell lines was examined using two high affinity PPARβ/δ ligands. Ligand activation of PPARβ/δ caused up-regulation of a known PPARβ/δ target gene, angiopoietin-like 4 (Angptl4) but did not influence expression of phosphatase and tensin homolog (PTEN) or phosphorylation of protein kinase B (Akt), and did not affect cell growth. Results from this study demonstrate that two human lung cancer cell lines respond to ligand activation of PPARβ/δ by modulation of target gene expression (Angptl4), but fail to exhibit significant modulation of cell proliferation

  5. Effects of IGFBP-2 on proliferation and differentiation in neural stem cell line C17.2

    Directory of Open Access Journals (Sweden)

    Deng Y

    2017-07-01

    Full Text Available Yujia Deng,1 Lei Wang,1,2 Lite Ge,1,3 Da Duan,1 Yi Zhuo,1 Ting Yuan,1 Weiping Yan,1 Peiqi Huang,1 Xiaohua Teng,1 Ming Lu1,3 1Department of Neurosurgery, The Second Affiliated Hospital of Hunan Normal University (163 Hospital of the People’s Liberation Army, Changsha, 2Department of Neurosurgery, Affiliated Haikou Hospital, Xiangya School of Central South University, Haikou, 3Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China Objective: Insulin-like growth factor binding protein-2 (IGFBP-2, a member of a highly conserved family of six insulin-like growth factor binding proteins (IGFBPs, can regulate several cellular processes through IGF-dependent or IGF-independent pathway. Recent studies have provided solid evidence for the importance to delineate that olfactory ensheathing cells (OEC-conditioned medium (OCM can not only facilitate the differentiation of neural stem cell line (C17.2 into neurons, but also promote the survival and proliferation. We have previously reported that IGFBP-2 was detected in OCM. This study is designed to investigate the roles of IGFBP-2 for the regulation of C17.2 differentiation and proliferation.Methods and results: IGFBP-2 was identified and upregulated in OCM to compare with astrocytes-conditioned medium by shotgun proteomics and semiquantitative proteomic analysis. In order to investigate whether exogenous IGFBP-2 could stimulate proliferation in C17.2 cells and differentiate it into glia or neuron, we used various concentrations of IGFBP-2 to induce C17.2 cells which were cultured in DMEM/F12. The results showed that exogenous IGFBP-2 can promote proliferation in C17.2 cells, but had little effect on differentiation. Interestingly, we also found that IGFBP-2 could induce C17.2 cells to differentiate into astrocytes, while inhibiting their differentiation into neurons in a dose

  6. Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders

    Directory of Open Access Journals (Sweden)

    Wu Yan-Ting

    2012-12-01

    Full Text Available Abstract Background The counselling of poor ovarian responders about the probability of pregnancy remains a puzzle for gynaecologists. The aim of this study was to optimise the management of poor responders by investigating the role of the oocyte-derived factor bone morphogenetic protein-15 (BMP-15 combined with chronological age in the prediction of the outcome of in-vitro fertilisation-embryo transfer (IVF-ET in poor responders. Methods A retrospective study conducted in a university hospital. A total of 207 poor ovarian responders who reached the ovum pick-up stage undergoing IVF/intracytoplasmic sperm injection (ICSI with three or fewer follicles no less than 14 mm on the day of oocyte retrieval were recruited from July 1, 2008 to December 31, 2009. Another 215 coinstantaneous cycles with normal responses were selected as controls. The BMP-15 levels in the follicular fluid (FF of the 207 poor responders were analysed by western blot. Based on the FF BMP-15 level and age, poor responders were sub-divided into four groups. The main outcome measures were the FF BMP-15 level, implantation rate, pregnancy rate, and live birth rate. Results The implantation rate (24.2% vs. 15.3%, chemical pregnancy rate (40% vs. 23.7%, clinical pregnancy rate (36.5% vs. 20.4% and live birth rate (29.4% vs. 15.1% in the high BMP-15 group were significantly higher than those in the low BMP-15 group. Furthermore, poor responders aged less than or equal to 35 years with a higher FF BMP-15 level had the best implantation, pregnancy and live birth rates, which were comparable with those of normal responders. Conclusions Our study suggests a potential role of BMP-15 in the prediction of the IVF outcome. A high FF BMP-15 combined with an age less than or equal to 35 years may be used as a potential indicator for repeating IVF cycles in poor ovarian responders.

  7. A Theoretical Framework to Study Variations in Workplace Violence Experienced by Emergency Responders

    NARCIS (Netherlands)

    L. van Reemst (Lisa)

    2016-01-01

    textabstractEmergency responders are often sent to the front line and are often confronted with aggression and violence in inter- action with citizens. According to previous studies, some professionals experience more workplace violence than others. In this article, the theoretical framework to

  8. Advantages and disadvantages of straight-lined and nonstraight-lined organizations at the airway facilities training division of the Federal Aviation Administration Academy

    Science.gov (United States)

    McMullen, Jessie L.

    Scope and method of study. This study describes the advantages and the disadvantages of straight-lined and nonstraight-lined organizations at the MMAC FAA Academy. The primary focus will be on the AF division within the FAA Academy. This study will assist in making sound decisions about which structure is better at the present time. Others who read this research will gain an awareness of advantages and disadvantages of each structure. The reason for focusing primarily on individuals from the FAA is because of their experience in straight-line and nonstraight-line organizations. Data were collected during the study and analyzed to determine what the majority of the candidates thought about the structure. Findings and conclusions. Many of the respondents believe the FAA Academy AF Division should be straight-lined to the AFZ organization in Headquarters. Most of the respondents still see the FAA organization as a closed-type structure with a top-down management style. Another important outcome of the findings was many of the respondents believed, regardless of the structure, employees should be empowered more and allowed to participate in the decision-making process. Based on the findings some of the advantages of straight-lined organizations were: it brings the parent organization in and gives them a first hand view of its operations, there is no middle person involved, and there is a direct line to parent organization. The disadvantages of straight-lined organizations based on the findings were: there is no middle management to speak to headquarters as an intermediator on training issues/concerns, it requires more resources and funding that may not be forthcoming, and it compels a parent organization to acquire more resources to handle its own business.

  9. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B; Olsen, Jørgen

    2002-01-01

    The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transc......The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change...... cells by performing reverse transcriptase-polymerase chain reaction on RNA extracted from laser dissected intestinal crypt and villi. In a screen of eight transcripts one - SART3 - was identified as a marker for human colonic crypts....

  10. Academics respond

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2015-01-01

    Contribution to the article "Academics respond: Brexit would weaken UK university research and funding", Guardian Witness, The Guardian, UK......Contribution to the article "Academics respond: Brexit would weaken UK university research and funding", Guardian Witness, The Guardian, UK...

  11. Survey of transmission line corridors. [Data on delays in transmission line construction

    Energy Technology Data Exchange (ETDEWEB)

    1979-01-05

    The intent of this study is to determine the extent of delays experienced in planning and constructing transmission lines in the continental United States. The reasons for the delays are identified for each line studied and their effect on the total electrical system is sought. Data was collected for 136 different lines either recently built or currently under study. Statistics were developed for each line in several categories and comparisons of lines delayed were made by company, area served and generation capacity. From the study presented here it was found that: right-of-way acquisition procedures including condemnation and easement negotiation practices delay more projects than local, state and federal regulatory requirements combined; load growth reductions particularly in the east have reduced the impact of regulatory delays; the south, southeast and southwestern areas of the country experience fewer delays in constructing transmission lines than the more populated states, and the cost for corridor delays was responded to for only 17 of the 142 projects surveyed. By far the most costly delay is the expense of condemning land for transmission right-of-way.

  12. SOLAR CYCLE VARIABILITY AND SURFACE DIFFERENTIAL ROTATION FROM Ca II K-LINE TIME SERIES DATA

    Energy Technology Data Exchange (ETDEWEB)

    Scargle, Jeffrey D.; Worden, Simon P. [NASA Ames Research Center, Moffett Field, CA, 94035 (United States); Keil, Stephen L. [National Solar Observatory, P.O. Box 57, Sunspot, NM 88349 (United States)

    2013-07-01

    Analysis of over 36 yr of time series data from the NSO/AFRL/Sac Peak K-line monitoring program elucidates 5 components of the variation of the 7 measured chromospheric parameters: (a) the solar cycle (period {approx} 11 yr), (b) quasi-periodic variations (periods {approx} 100 days), (c) a broadband stochastic process (wide range of periods), (d) rotational modulation, and (e) random observational errors, independent of (a)-(d). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these parameters. Time-frequency analysis illuminates periodic and quasi-periodic signals, details of frequency modulation due to differential rotation, and in particular elucidates the rather complex harmonic structure (a) and (b) at timescales in the range {approx}0.1-10 yr. These results using only full-disk data suggest that similar analyses will be useful for detecting and characterizing differential rotation in stars from stellar light curves such as those being produced by NASA's Kepler observatory. Component (c) consists of variations over a range of timescales, in the manner of a 1/f random process with a power-law slope index that varies in a systematic way. A time-dependent Wilson-Bappu effect appears to be present in the solar cycle variations (a), but not in the more rapid variations of the stochastic process (c). Component (d) characterizes differential rotation of the active regions. Component (e) is of course not characteristic of solar variability, but the fact that the observational errors are quite small greatly facilitates the analysis of the other components. The data analyzed in this paper can be found at the National Solar Observatory Web site http://nsosp.nso.edu/cak{sub m}on/, or by file transfer protocol at ftp://ftp.nso.edu/idl/cak.parameters.

  13. Advanced high-speed protection for transmission lines with different configurations

    Energy Technology Data Exchange (ETDEWEB)

    Tholomier, D.; Naisani, P. [Areva T and D Automation Canada Inc., Monteal, PQ (Canada); Apostolov, A. [Omicron Electronics, Houston, TX (United States)

    2008-07-01

    Power substations and transmission lines require intelligent (microprocessor-based) electronic devices (IED) for data acquisition, protection, metering, and control. This paper presented a universal transmission line protection relay with segregated phase differential protection as the main function and multiple backup protection functions, including 3 zone distance protection. It described features allowing the application of the IED to multi-terminal lines, mutual coupled lines, charging current compensation, transformer inrush current detection, breaker and a half and ring bus substation configurations. GPS synchronized current differential protection offers reliable protection for transmission and distribution circuits. The security of the protection relay can be improved significantly by combining it with fallback techniques to cover loss of GPS synchronizing, and by including non-differential elements as back-up during route switching and channel failures. 7 figs.

  14. Train-the-trainer training for EV first responders

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2011-11-15

    This paper presents Electrical Line magazine. The magazine covers new product releases, provides expert opinion on solving problems posted by readers, has updated industry news and posts event calendars, among other features. This paper discusses industry news and various topics on electric vehicles. Nova Scotia Power is researching the convenience of electric charging and the readiness of the provincial electric grid to support electric vehicles as well as their cost effectiveness and performance. The paper describes how Hydro-Quebec is supporting the use of such vehicles through the selection of ten Boucherville businesses to participate in an electric vehicles trial program. The ten company names are listed. Recently, the national alternative fuels training consortium (NAFTC) conducted a safety-training workshop for electric drive vehicle first responders at the Tesla Motors headquarters in California. The aim was to ensure that first responders had the opportunity to enhance their knowledge of electric drive vehicle accident response procedures.

  15. Differential gene expression by 1,25(OH)2D3 in an endometriosis stromal cell line.

    Science.gov (United States)

    Ingles, Sue Ann; Wu, Liang; Liu, Benjamin T; Chen, Yibu; Wang, Chun-Yeh; Templeman, Claire; Brueggmann, Doerthe

    2017-10-01

    Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH) 2 D 3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH) 2 D 3 , and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH) 2 D 3 . Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH) 2 D 3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    Energy Technology Data Exchange (ETDEWEB)

    Seriwatanachai, Dutmanee [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Krishnamra, Nateetip [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand); Charoenphandhu, Narattaphol, E-mail: naratt@narattsys.com [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. Black-Right-Pointing-Pointer Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. Black-Right-Pointing-Pointer Higher PRL concentrations ( Greater-Than-Or-Slanted-Equal-To 100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of Greater-Than-Or-Slanted-Equal-To 100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  17. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    DEFF Research Database (Denmark)

    Sustarsic, Elahu G; Junnila, Riia K; Kopchick, John J.

    2013-01-01

    cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found...

  18. IK channel activation increases tumor growth and induces differential behavioral responses in two breast epithelial cell lines.

    Science.gov (United States)

    Thurber, Amy E; Nelson, Michaela; Frost, Crystal L; Levin, Michael; Brackenbury, William J; Kaplan, David L

    2017-06-27

    Many potassium channel families are over-expressed in cancer, but their mechanistic role in disease progression is poorly understood. Potassium channels modulate membrane potential (Vmem) and thereby influence calcium ion dynamics and other voltage-sensitive signaling mechanisms, potentially acting as transcriptional regulators. This study investigated the differential response to over-expression and activation of a cancer-associated potassium channel, the intermediate conductance calcium-activated potassium channel (IK), on aggressive behaviors in mammary epithelial and breast cancer cell lines. IK was over-expressed in the highly metastatic breast cancer cell line MDA-MB-231 and the spontaneously immortalized breast epithelial cell line MCF-10A, and the effect on cancer-associated behaviors was assessed. IK over-expression increased primary tumor growth and metastasis of MDA-MB-231 in orthotopic xenografts, demonstrating for the first time in any cancer type that increased IK is sufficient to promote cancer aggression. The primary tumors had similar vascularization as determined by CD31 staining and similar histological characteristics. Interestingly, despite the increased in vivo growth and metastasis, neither IK over-expression nor activation with agonist had a significant effect on MDA-MB-231 proliferation, invasion, or migration in vitro. In contrast, IK decreased MCF-10A proliferation and invasion through Matrigel but had no effect on migration in a scratch-wound assay. We conclude that IK activity is sufficient to promote cell aggression in vivo. Our data provide novel evidence supporting IK and downstream signaling networks as potential targets for cancer therapies.

  19. Super differential forms on super Riemann surfaces

    International Nuclear Information System (INIS)

    Konisi, Gaku; Takahasi, Wataru; Saito, Takesi.

    1994-01-01

    Line integral on the super Riemann surface is discussed. A 'super differential operator' which possesses both properties of differential and of differential operator is proposed. With this 'super differential operator' a new theory of differential form on the super Riemann surface is constructed. We call 'the new differentials on the super Riemann surface' 'the super differentials'. As the applications of our theory, the existency theorems of singular 'super differentials' such as 'super abelian differentials of the 3rd kind' and of a super projective connection are examined. (author)

  20. Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

    Directory of Open Access Journals (Sweden)

    Zahra Moinfar

    Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

  1. Anti-proliferative effect of 20-hydroxyecdysone in a lepidopteran cell line.

    Science.gov (United States)

    Auzoux-Bordenave, Stéphanie; Hatt, Philippe-Jacques; Porcheron, Patrick

    2002-02-01

    Ecdysteroids are steroid hormones involved in the epidermal growth of arthropods, controlling cell proliferation and further differentiation of target cells. The epidermal cell line IAL-PID2, established from imaginal discs of the Indian meal moth Plodia interpunctella kept its sensitivity to ecdysteroids in vitro, cells being able to respond to them by cytological and biochemical changes. When added to the culture medium, 20-hydroxyecdysone (20E) stopped cell proliferation and induced formation of epithelial-like aggregates. In order to better understand the cellular sequence of ecdysteroids signalling in epidermal cells we used the IAL-PID2 cell line for in vitro investigations of cytological events induced by the moulting hormone. After a 40 h serum deprivation, formazan assay (XTT) was routinely used to evaluate anti-proliferative effects of 20E during cell cycle. We established a more precise timing of the period of cell sensitivity to the hormone during the cell cycle, by the use of the mitotic index and the BrdU incorporation test. These in vitro assays were performed in parallel with the description of some hormone dependant cytological events, using immunofluorescent labelling with anti-beta tubulin/FITC antibodies and DNA staining.

  2. Product line design

    Czech Academy of Sciences Publication Activity Database

    Anderson, S. P.; Celik, Levent

    2015-01-01

    Roč. 157, May (2015), s. 517-526 ISSN 0022-0531 R&D Projects: GA ČR(CZ) GA15-22540S Institutional support: PRVOUK-P23 Keywords : product line design * product differentiation * second-degree price discrimination Subject RIV: AH - Economics Impact factor: 1.097, year: 2015

  3. MICROLENSING OF QUASAR BROAD EMISSION LINES: CONSTRAINTS ON BROAD LINE REGION SIZE

    Energy Technology Data Exchange (ETDEWEB)

    Guerras, E.; Mediavilla, E. [Instituto de Astrofisica de Canarias, Via Lactea S/N, La Laguna E-38200, Tenerife (Spain); Jimenez-Vicente, J. [Departamento de Fisica Teorica y del Cosmos, Universidad de Granada, Campus de Fuentenueva, E-18071 Granada (Spain); Kochanek, C. S. [Department of Astronomy and the Center for Cosmology and Astroparticle Physics, The Ohio State University, 4055 McPherson Lab, 140 West 18th Avenue, Columbus, OH 43221 (United States); Munoz, J. A. [Departamento de Astronomia y Astrofisica, Universidad de Valencia, E-46100 Burjassot, Valencia (Spain); Falco, E. [Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Motta, V. [Departamento de Fisica y Astronomia, Universidad de Valparaiso, Avda. Gran Bretana 1111, Valparaiso (Chile)

    2013-02-20

    We measure the differential microlensing of the broad emission lines between 18 quasar image pairs in 16 gravitational lenses. We find that the broad emission lines are in general weakly microlensed. The results show, at a modest level of confidence (1.8{sigma}), that high ionization lines such as C IV are more strongly microlensed than low ionization lines such as H{beta}, indicating that the high ionization line emission regions are more compact. If we statistically model the distribution of microlensing magnifications, we obtain estimates for the broad line region size of r{sub s} = 24{sup +22} {sub -15} and r{sub s} = 55{sup +150} {sub -35} lt-day (90% confidence) for the high and low ionization lines, respectively. When the samples are divided into higher and lower luminosity quasars, we find that the line emission regions of more luminous quasars are larger, with a slope consistent with the expected scaling from photoionization models. Our estimates also agree well with the results from local reveberation mapping studies.

  4. Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation

    DEFF Research Database (Denmark)

    Emdal, Kristina B; Pedersen, Anna-Kathrine; Bekker-Jensen, Dorte B

    2015-01-01

    SH-SY5Y neuroblastoma cells respond to nerve growth factor (NGF)-mediated activation of the tropomyosin-related kinase A (TrkA) with neurite outgrowth, thereby providing a model to study neuronal differentiation. We performed a time-resolved analysis of NGF-TrkA signaling in neuroblastoma cells...... then becomes phosphorylated and ubiquitylated and decreases in abundance. We also found that recruitment of Cbl-b promotes TrkA ubiquitylation and degradation. Furthermore, the amount of phosphorylation of the kinase ERK and neurite outgrowth increased upon Cbl-b depletion in several neuroblastoma cell lines...

  5. Coping on the Front-line

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum; Lønsmann, Dorte

    language boundaries in their everyday work. Despite official English language policies in the three companies, our findings show that employees face a number of different language boundaries, and that ad hoc and informal solutions in many cases are vital for successful cross-language communication. Drawing......This article investigates how front-line employees respond to English language policies implemented by the management of three multinational corporations (MNCs) headquartered in Scandinavia. Based on interview and document data the article examines the ways in which front-line employees cross...

  6. Differential profiles of crack users in respondent-driven and institutional samples: a three-site comparison

    NARCIS (Netherlands)

    Oteo Pérez, A.; Benschop, A.; Korf, D.J.

    2012-01-01

    Background/Aim: Respondent-driven sampling (RDS) is increasingly applied in social epidemiological surveys among ‘hidden populations’ of hard drug users. The objective of the present study was to assess whether the profile of frequent crack users recruited through RDS differed from those surveyed in

  7. Conditioned Media from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Umbilical Cord-Derived Mesenchymal Stem Cells Efficiently Induced the Apoptosis and Differentiation in Human Glioma Cell Lines In Vitro

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2014-01-01

    Full Text Available Human mesenchymal stem cells (MSCs have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs. We found (1 MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2 MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3 real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4 furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.

  8. Yellow Rust Resistance in Advanced Lines and Commercial ...

    African Journals Online (AJOL)

    The objective of this study was to characterize seedling yellow rust resistance in 21 advanced bread wheat lines and 20 cultivars from Ethiopia. Yellow rust infection types (ITs) produced on test wheat lines and cultivars from nine yellow rust races were compared with ITs produced on standard differential lines that differed ...

  9. Solving Differential Equations in R: Package deSolve

    Science.gov (United States)

    In this paper we present the R package deSolve to solve initial value problems (IVP) written as ordinary differential equations (ODE), differential algebraic equations (DAE) of index 0 or 1 and partial differential equations (PDE), the latter solved using the method of lines appr...

  10. Field study of age-differentiated strain for assembly line workers in the automotive industry.

    Science.gov (United States)

    Börner, Kerstin; Scherf, Christian; Leitner-Mai, Bianca; Spanner-Ulmer, Birgit

    2012-01-01

    A field study in an automotive supply industry company was conducted to explore age-differentiated strain of assembly line workers. Subjective and objective data from 23 female workers aged between 27 and 57 years were collected at the workplace belt buckle assembly during morning shifts. Subjects with medication or chronic diseases affecting heart rate and breath rate were excluded. For subjective data generation different questionnaires were used. Before the Work Ability Index and the Munich Chronotype Questionnaire were completed by the subjects. Short questionnaires (strain-ratings, NASA-TLX) directly at begin and end of the work were used for obtaining shift-related data. During the whole shift (6 a.m. - 2.45 p.m.) bodily functions were logged with a wireless chest strap. In addition, the motion of the hand-arm-system was recorded for 30 times, 3 minutes each after a fixed time-schedule. First results show that younger subjects need significant less time for assembly (mean = 14.940 s) compared to older subjects (mean = 17.040 s; t(472.026) = -9.278 , p < 0.01).

  11. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sustarsic, Elahu G. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Junnila, Riia K. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Kopchick, John J., E-mail: kopchick@ohio.edu [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH (United States)

    2013-11-08

    Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on

  12. Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

    Science.gov (United States)

    Freeman, Joshua T; Elinder-Camburn, Anna; McClymont, Catherine; Anderson, Deverick J; Bilkey, Mary; Williamson, Deborah A; Berkahn, Leanne; Roberts, Sally A

    2013-01-01

    We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

  13. Gene expression profiling of the local cecal response of genetic chicken lines that differ in their susceptibility to Campylobacter jejuni colonization.

    Directory of Open Access Journals (Sweden)

    Xianyao Li

    Full Text Available Campylobacter jejuni (C. jejuni is one of the most common causes of human bacterial enteritis worldwide primarily due to contaminated poultry products. Previously, we found a significant difference in C. jejuni colonization in the ceca between two genetically distinct broiler lines (Line A (resistant has less colony than line B (susceptible on day 7 post inoculation. We hypothesize that different mechanisms between these two genetic lines may affect their ability to resist C. jejuni colonization in chickens. The molecular mechanisms of the local host response to C. jejuni colonization in chickens have not been well understood. In the present study, to profile the cecal gene expression in the response to C. jejuni colonization and to compare differences between two lines at the molecular level, RNA of ceca from two genetic lines of chickens (A and B were applied to a chicken whole genome microarray for a pair-comparison between inoculated (I and non-inoculated (N chickens within each line and between lines. Our results demonstrated that metabolism process and insulin receptor signaling pathways are key contributors to the different response to C. jejuni colonization between lines A and B. With C. jejuni inoculation, lymphocyte activation and lymphoid organ development functions are important for line A host defenses, while cell differentiation, communication and signaling pathways are important for line B. Interestingly, circadian rhythm appears play a critical role in host response of the more resistant A line to C. jejuni colonization. A dramatic differential host response was observed between these two lines of chickens. The more susceptible line B chickens responded to C. jejuni inoculation with a dramatic up-regulation in lipid, glucose, and amino acid metabolism, which is undoubtedly for use in the response to the colonization with little or no change in immune host defenses. However, in more resistant line A birds the host defense

  14. Solving Differential Equations in R: Package deSolve

    NARCIS (Netherlands)

    Soetaert, K.E.R.; Petzoldt, T.; Setzer, R.W.

    2010-01-01

    In this paper we present the R package deSolve to solve initial value problems (IVP) written as ordinary differential equations (ODE), differential algebraic equations (DAE) of index 0 or 1 and partial differential equations (PDE), the latter solved using the method of lines approach. The

  15. Differentiation Therapy of Acute Myeloid Leukemia

    International Nuclear Information System (INIS)

    Gocek, Elzbieta; Marcinkowska, Ewa

    2011-01-01

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

  16. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-05-16

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

  17. Respiratory Epithelium Lined Cyst of the Maxilla: Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    C. P. Martinelli-Kläy

    2017-01-01

    Full Text Available Maxillary cysts, including the cysts lined by respiratory epithelium, can present a diagnostic challenge. We report an unusual case of a maxillary cyst on an endodontically treated tooth #16, in which the cavity was totally lined by a respiratory epithelium. The patient, a 35-year-old male, presented with a generalized chronic periodontitis and complained of a pain in the tooth #16 region. A periodontal pocket extending to the root apices with pus coming out from the gingival was found. A combined endodontic periodontal was observed on a panoramic radiography. CBCT-scan revealed a well-circumscribed radiolucent lesion at the apices of the distobuccal root of the 16. A communication with the right maxillary sinus cavity and a maxillary and ethmoidal sinusitis were also observed. The lesion was removed and histological examination revealed a cyst lined exclusively by respiratory epithelium. Ciliated and rare mucous cells were also observed. The diagnosis could evoke a surgical ciliated cyst mimicking the radicular cyst but the patient has no previous history of trauma or surgery in the maxillofacial region. It could also be an unusual radicular cyst in which the stratified squamous epithelium was destroyed by inflammation and replaced by a respiratory epithelium of the maxillary sinus.

  18. MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors.

    Science.gov (United States)

    Gradiz, Rui; Silva, Henriqueta C; Carvalho, Lina; Botelho, Maria Filomena; Mota-Pinto, Anabela

    2016-02-17

    Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24(-), CD44(+/++), CD326(-/+) and CD133/1(-), while PANC-1 is CD24(-/+), CD44(+), CD326(-/+) and CD133/1(-). Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16(INK4A), but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.

  19. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B; Olsen, Jørgen Lillelund

    2002-01-01

    The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transc...

  20. How did the Turkish Industry Respond to Increased Competitive Pressures, 1998-2007?

    OpenAIRE

    Gokhan Yilmaz; Rauf Gonenc

    2008-01-01

    This study examines how Turkish manufacturing industry responded to increased competitive pressures that it has faced over the past decade. Pressures arose both from growing trade competition from low-cost countries which have similar trade specialisation patterns to Turkey’s, and from strong trend real currency appreciation that Turkey has experienced during this period. In response, Turkish manufacturers increased their productivity, differentiated products, moderated wage growth and drew o...

  1. A differentiated plane wave: its passage through a slab

    International Nuclear Information System (INIS)

    Hannay, J H; Nye, J F

    2013-01-01

    Differentiating a monochromatic uniform plane electromagnetic wavefield with respect to its direction produces, from a field that is completely lacking in localized specific features, one that contains a straight vortex-like line, a ‘C-line’ of defined circular polarization. There is also a second separate C-line of opposite handedness; indeed, in a sense, a straight line of every polarization is realized. Because of its primitive construction it is analytically simple to study the passage of a differentiated wave obliquely through a plane interface into a medium of different refractive index, to trace its C-line. This was done in an earlier paper. Here we extend the method to passage through a parallel-sided transparent slab. There are multiple reflections within the slab, as in a Fabry–Pérot interferometer. The exiting wave, as a single differentiated plane wave, has a straight oblique C-line. Inside the slab, and in front of it, there is wave interference. The result is a coiled, helix-like, C-line in front of the slab and another inside it. The two coils wrap around separate hyperboloids of one sheet, like cooling towers. The emerging straight C-line is shifted (with respect to a C-line in a notional undisturbed incident plane wave) both in the plane of incidence and transversely to it, and the second C-line behaves similarly. The analysis is exact and could be extended in a straightforward way to a general stratified medium. (paper)

  2. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    International Nuclear Information System (INIS)

    Rangwala, Fatima; Williams, Kevin P; Smith, Ginger R; Thomas, Zainab; Allensworth, Jennifer L; Lyerly, H Kim; Diehl, Anna Mae; Morse, Michael A; Devi, Gayathri R

    2012-01-01

    Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC 50 : 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC 50 : 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC)

  3. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    Directory of Open Access Journals (Sweden)

    Rangwala Fatima

    2012-09-01

    Full Text Available Abstract Background Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO in combination with sorafenib or fluorouracil (5-FU, in both hepatic tumor cells and stromal cells. Methods Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Results Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2. In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. Conclusions ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC.

  4. Errorless discrimination established by differential autoshaping.

    Science.gov (United States)

    Wilkie, D M; Ramer, D G

    1974-09-01

    In Experiment I, pigeons exposed to a differential autoshaping procedure pecked a key in the presence of the stimulus associated with reinforcement but did not peck, or pecked infrequently, in the presence of the stimulus associated with nonreinforcement. In Experiment II, pigeons were exposed to a differential autoshaping procedure in which one stimulus was associated with reinforcement and two stimuli were associated with nonreinforcement. The birds initially responded in the presence of one stimulus associated with nonreinforcement but never responded in the presence of the second stimulus associated with nonreinforcement. They were subsequently exposed to an autoshaping procedure in which reinforcement followed both these stimuli. The number of stimulus-reinforcement pairings required to establish pecking in the presence of the stimulus during which responses had not previously occurred suggested that such stimuli are inhibitory. These findings have implications for autoshaping, errorless discrimination, inhibition, and theories of discrimination byproducts.

  5. An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

    Science.gov (United States)

    Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

    2013-01-01

    The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

  6. Effects of Feeder Cells on Dopaminergic Differentiation of Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Zhenqiang Zhao

    2016-12-01

    Full Text Available Mouse embryonic fibroblasts (MEFs and human foreskin fibroblasts (HFFs are used for the culture of human embryonic stem cells (hESCs. MEFs and HFFs differed in their capacity to support the proliferation and pluripotency of hESCs and could affect cardiac differentiation potential of hESCs. The aim of this study was to evaluate the effect of MEFs and HFFs feeders on dopaminergic differentiation of hESCs lines. To minimize the impact of culture condition variation, two hESCs lines were cultured on mixed feeder cells (MFCs, MEFs: HFFs =1:1 and HFFs feeder respectively, and then were differentiated into DA neurons under the identical protocol. Dopaminergic differentiation was evaluated by immunocytochemistry, quantitative fluorescent real-time PCR (qRT-PCR, transmission and scanning electron microscopy, and patch clamp. Our results demonstrated that these hESCs-derived neurons were genuine and functional DA neurons. However, compared to hESCs line on MFCs feeder, hESCs line on HFFs feeder had a higher proportion of TH positive cells and expressed higher levels of FOXA2, PITX3, NURR1 and TH genes. In addition, the values of threshold intensity and threshold membrane potential of DA neurons from hESCs line on HFFs feeder were lower than those of DA neurons from hESCs line on the MFCs feeder. In conclusion, HFFs feeder not only facilitated the differentiation of hESCs cells into dopaminergic neurons, but also induced hESCs-derived DA neurons to express higher electrophysiological excitability. Therefore, feeder cells could affect not only dopaminergic differentiation potential of different hESCs lines, but also electrophysiological properties of hESCs-derived DA neurons.

  7. The effect of Zhangfei/CREBZF on cell growth, differentiation, apoptosis, migration, and the unfolded protein response in several canine osteosarcoma cell lines.

    Science.gov (United States)

    Zhang, Rui; Thamm, Douglas H; Misra, Vikram

    2015-02-07

    We had previously shown that the bLZip domain-containing transcription factor, Zhangfei/CREBZF inhibits the growth and the unfolded protein response (UPR) in cells of the D-17 canine osteosarcoma (OS) line and that the effects of Zhangfei are mediated by it stabilizing the tumour suppressor protein p53. To determine if our observations with D-17 cells applied more universally to canine OS, we examined three other independently isolated canine OS cell lines--Abrams, McKinley and Gracie. Like D-17, the three cell lines expressed p53 proteins that were capable of activating promoters with p53 response elements on their own, and synergistically with Zhangfei. Furthermore, as with D-17 cells, Zhangfei suppressed the growth and UPR-related transcripts in the OS cell lines. Zhangfei also induced the activation of osteocalcin expression, a marker of osteoblast differentiation and triggered programmed cell death. Osteosarcomas are common malignancies in large breeds of dogs. Although there has been dramatic progress in their treatment, these therapies often fail, leading to recurrence of the tumour and metastatic spread. Our results indicate that induction of the expression of Zhangfei in OS, where p53 is functional, may be an effective modality for the treatment of OS.

  8. HLXB9 gene expression, and nuclear location during in vitro neuronal differentiation in the SK-N-BE neuroblastoma cell line.

    Directory of Open Access Journals (Sweden)

    Claudia Giovanna Leotta

    Full Text Available Different parts of the genome occupy specific compartments of the cell nucleus based on the gene content and the transcriptional activity. An example of this is the altered nuclear positioning of the HLXB9 gene in leukaemia cells observed in association with its over-expression. This phenomenon was attributed to the presence of a chromosomal translocation with breakpoint proximal to the HLXB9 gene. Before becoming an interesting gene in cancer biology, HLXB9 was studied as a developmental gene. This homeobox gene is also known as MNX1 (motor neuron and pancreas homeobox 1 and it is relevant for both motor neuronal and pancreatic beta cells development. A spectrum of mutations in this gene are causative of sacral agenesis and more broadly, of what is known as the Currarino Syndrome, a constitutional autosomal dominant disorder. Experimental work on animal models has shown that HLXB9 has an essential role in motor neuronal differentiation. Here we present data to show that, upon treatment with retinoic acid, the HLXB9 gene becomes over-expressed during the early stages of neuronal differentiation and that this corresponds to a reposition of the gene in the nucleus. More precisely, we used the SK-N-BE human neuroblastoma cell line as an in vitro model and we demonstrated a transient transcription of HLXB9 at the 4th and 5th days of differentiation that corresponded to the presence, predominantly in the cell nuclei, of the encoded protein HB9. The nuclear positioning of the HLXB9 gene was monitored at different stages: a peripheral location was noted in the proliferating cells whereas a more internal position was noted during differentiation, that is while HLXB9 was transcriptionally active. Our findings suggest that HLXB9 can be considered a marker of early neuronal differentiation, possibly involving chromatin remodeling pathways.

  9. Membrane receptor-mediated apoptosis and caspase activation in the differentiated EoL-1 eosinophilic cell line.

    Science.gov (United States)

    Al-Rabia, Mohammed W; Blaylock, Morgan G; Sexton, Darren W; Walsh, Garry M

    2004-06-01

    Caspases are key molecules in the control of apoptosis, but relatively little is known about their contribution to eosinophil apoptosis. We examined caspase-3, -8, and -9 activities in receptor ligation-dependent apoptosis induction in the differentiated human eosinophilic cell line EoL-1. Differentiated EoL-1 exhibited bi-lobed nuclei, eosinophil-associated membrane receptors, and basic granule proteins. Annexin-V fluorescein isothiocyanate binding to EoL-1 revealed significant (PEoL-1 but had no effect on constitutive (baseline) apoptosis at 16 and 20 h. Caspase activity was analyzed using the novel CaspaTag trade mark technique and flow cytometry. EoL-1 treated with pan-CD45, CD45RA, CD45RB, and CD95 mAb exhibited caspase-3 and -9 activation at 12 h post-treatment, which increased at 16 and 20 h. Activated caspase-8 was detected 12 and 16 h after ligation with CD45, CD45RA, CD45RB, and CD95 mAb followed by a trend toward basal levels at 20 h. CD69 ligation resulted in caspase-3 activation, a modest but significant activation of caspase-8, and a loss in mitochondrial transmembrane potential but had no significant effect on activation of caspase-9. Thus, the intrinsic and extrinsic caspase pathways are involved in controlling receptor ligation-mediated apoptosis induction in human eosinophils, findings that may aid the development of a more targeted, anti-inflammatory therapy for asthma.

  10. Discriminant cognitive factors in responder and non-responder patients with schizophrenia.

    Science.gov (United States)

    Stip, E; Lussier, I; Ngan, E; Mendrek, A; Liddle, P

    1999-12-01

    To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). Inpatient and outpatient units, Institute of Psychiatry. Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10). a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

  11. Differential response of two cell lines sequentially irradiated with low X-ray doses.

    Science.gov (United States)

    Güerci, A M; Dulout, F N; Grillo, C A; Seoane, A I

    2005-05-01

    An experiment was designed to compare the effect of repeated low doses of X-rays in two different cell lines: one transformed, epithelial like and aneuploid Chinese hamster ovary K-1 (CHO-K1); the other originated from a human primary culture, fibroblast, diploid and non-transformed, MRC-5. CHO and MRC-5 cells were cultured for 14 or eight passages, respectively. Irradiation was performed once per passage when cells were in the quiescent state (90 - 95% in G1/G0). Cells were exposed to 10.0 mSv X-ray doses. Ionizing radiation did not induce apoptosis or necrosis in the exposed CHO cell population. Significant increases of low-level damaged cells (degrees 1 and 2) were found for the 14 cycles of radiation when compared with controls, except for the first irradiation cycle. No significant increases in the frequency of cells with severe damage were observed. The frequency of MRC-5 cells with low-level damage increased significantly when compared with controls for radiation cycles seven and eight. Significant increases of apoptosis, necrosis and severe damage were found only for the highest dose. Transformed and non-transformed cell types responded differently to direct and indirect damage using low-dose repeat exposures to ionizing radiation. Though more investigation is needed to understand the mechanisms of radiation effects in chronic low-dose-exposed cell populations, cellular type should be taken into account in the design of in vitro experiments for understanding low-dose-irradiation effects.

  12. Accelerated differentiation of human induced pluripotent stem cells to blood-brain barrier endothelial cells.

    Science.gov (United States)

    Hollmann, Emma K; Bailey, Amanda K; Potharazu, Archit V; Neely, M Diana; Bowman, Aaron B; Lippmann, Ethan S

    2017-04-13

    Due to their ability to limitlessly proliferate and specialize into almost any cell type, human induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to generate human brain microvascular endothelial cells (BMECs), which compose the blood-brain barrier (BBB), for research purposes. Unfortunately, the time, expense, and expertise required to differentiate iPSCs to purified BMECs precludes their widespread use. Here, we report the use of a defined medium that accelerates the differentiation of iPSCs to BMECs while achieving comparable performance to BMECs produced by established methods. Induced pluripotent stem cells were seeded at defined densities and differentiated to BMECs using defined medium termed E6. Resultant purified BMEC phenotypes were assessed through trans-endothelial electrical resistance (TEER), fluorescein permeability, and P-glycoprotein and MRP family efflux transporter activity. Expression of endothelial markers and their signature tight junction proteins were confirmed using immunocytochemistry. The influence of co-culture with astrocytes and pericytes on purified BMECs was assessed via TEER measurements. The robustness of the differentiation method was confirmed across independent iPSC lines. The use of E6 medium, coupled with updated culture methods, reduced the differentiation time of iPSCs to BMECs from thirteen to 8 days. E6-derived BMECs expressed GLUT-1, claudin-5, occludin, PECAM-1, and VE-cadherin and consistently achieved TEER values exceeding 2500 Ω × cm 2 across multiple iPSC lines, with a maximum TEER value of 4678 ± 49 Ω × cm 2 and fluorescein permeability below 1.95 × 10 -7 cm/s. E6-derived BMECs maintained TEER above 1000 Ω × cm 2 for a minimum of 8 days and showed no statistical difference in efflux transporter activity compared to BMECs differentiated by conventional means. The method was also found to support long-term stability of BMECs harboring biallelic PARK2 mutations associated

  13. Metastatic Urothelial Carcinoma with Glandular Differentiation That Confirmed the Response by Autopsy Specimen to Second-Line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin plus Bevacizumab Chemotherapy

    Directory of Open Access Journals (Sweden)

    Taku Naiki

    2017-11-01

    Full Text Available The prognostic significance of glandular differentiation in urothelial carcinoma (UC is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin plus bevacizumab (mFOLFOX6+Bev. A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0 by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7 and negativity for cytokeratin 20 (CK20 and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation.

  14. Planar quadrature RF transceiver design using common-mode differential-mode (CMDM transmission line method for 7T MR imaging.

    Directory of Open Access Journals (Sweden)

    Ye Li

    Full Text Available The use of quadrature RF magnetic fields has been demonstrated to be an efficient method to reduce transmit power and to increase the signal-to-noise (SNR in magnetic resonance (MR imaging. The goal of this project was to develop a new method using the common-mode and differential-mode (CMDM technique for compact, planar, distributed-element quadrature transmit/receive resonators for MR signal excitation and detection and to investigate its performance for MR imaging, particularly, at ultrahigh magnetic fields. A prototype resonator based on CMDM method implemented by using microstrip transmission line was designed and fabricated for 7T imaging. Both the common mode (CM and the differential mode (DM of the resonator were tuned and matched at 298MHz independently. Numerical electromagnetic simulation was performed to verify the orthogonal B1 field direction of the two modes of the CMDM resonator. Both workbench tests and MR imaging experiments were carried out to evaluate the performance. The intrinsic decoupling between the two modes of the CMDM resonator was demonstrated by the bench test, showing a better than -36 dB transmission coefficient between the two modes at resonance frequency. The MR images acquired by using each mode and the images combined in quadrature showed that the CM and DM of the proposed resonator provided similar B1 coverage and achieved SNR improvement in the entire region of interest. The simulation and experimental results demonstrate that the proposed CMDM method with distributed-element transmission line technique is a feasible and efficient technique for planar quadrature RF coil design at ultrahigh fields, providing intrinsic decoupling between two quadrature channels and high frequency capability. Due to its simple and compact geometry and easy implementation of decoupling methods, the CMDM quadrature resonator can possibly be a good candidate for design blocks in multichannel RF coil arrays.

  15. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

    Science.gov (United States)

    Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

    2018-01-01

    Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  16. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line

    Directory of Open Access Journals (Sweden)

    Yuki Fujiwara

    2018-02-01

    Full Text Available Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA, which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF, an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP, and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  17. GARLIC — A general purpose atmospheric radiative transfer line-by-line infrared-microwave code: Implementation and evaluation

    International Nuclear Information System (INIS)

    Schreier, Franz; Gimeno García, Sebastián; Hedelt, Pascal; Hess, Michael; Mendrok, Jana; Vasquez, Mayte; Xu, Jian

    2014-01-01

    A suite of programs for high resolution infrared-microwave atmospheric radiative transfer modeling has been developed with emphasis on efficient and reliable numerical algorithms and a modular approach appropriate for simulation and/or retrieval in a variety of applications. The Generic Atmospheric Radiation Line-by-line Infrared Code — GARLIC — is suitable for arbitrary observation geometry, instrumental field-of-view, and line shape. The core of GARLIC's subroutines constitutes the basis of forward models used to implement inversion codes to retrieve atmospheric state parameters from limb and nadir sounding instruments. This paper briefly introduces the physical and mathematical basics of GARLIC and its descendants and continues with an in-depth presentation of various implementation aspects: An optimized Voigt function algorithm combined with a two-grid approach is used to accelerate the line-by-line modeling of molecular cross sections; various quadrature methods are implemented to evaluate the Schwarzschild and Beer integrals; and Jacobians, i.e. derivatives with respect to the unknowns of the atmospheric inverse problem, are implemented by means of automatic differentiation. For an assessment of GARLIC's performance, a comparison of the quadrature methods for solution of the path integral is provided. Verification and validation are demonstrated using intercomparisons with other line-by-line codes and comparisons of synthetic spectra with spectra observed on Earth and from Venus. - Highlights: • High resolution infrared-microwave radiative transfer model. • Discussion of algorithmic and computational aspects. • Jacobians by automatic/algorithmic differentiation. • Performance evaluation by intercomparisons, verification, validation

  18. Injection and Extraction Lines for the ILC Damping Rings

    International Nuclear Information System (INIS)

    Reichel, Ina

    2007-01-01

    The current design for the injection and extraction lines into and out of the ILC Damping Rings is presented as well as the design for the abort line. Due to changes of the geometric boundary conditions by other subsystems of the ILC, a modular approach has been used to be able to respond to recurring layout changes while reusing previously designed parts

  19. Genotype × Environment Interaction in Grass Pea (Lathyrus sativus L. Lines

    Directory of Open Access Journals (Sweden)

    G. B. Polignano

    2009-01-01

    performance of lines in each year. The analyses used arranged the lines into groups that were differentiable in terms of performances and stability. Our results provide useful information to aid the choice of grass pea lines in the Mediterranean marginal areas.

  20. Micro-Topographies Promote Late Chondrogenic Differentiation Markers in the ATDC5 Cell Line.

    Science.gov (United States)

    Le, Bach Q; Vasilevich, Aliaksei; Vermeulen, Steven; Hulshof, Frits; Stamatialis, Dimitrios F; van Blitterswijk, Clemens A; de Boer, Jan

    2017-05-01

    Chemical and mechanical cues are well-established influencers of in vitro chondrogenic differentiation of ATDC5 cells. Here, we investigate the role of topographical cues in this differentiation process, a study not been explored before. Previously, using a library of surface micro-topographies we found some distinct patterns that induced alkaline phosphatase (ALP) production in human mesenchymal stromal cells. ALP is also a marker for hypertrophy, the end stage of chondrogenic differentiation preceding bone formation. Thus, we hypothesized that these patterns could influence end-stage chondrogenic differentiation of ATDC5 cells. In this study, we randomly selected seven topographies among the ALP influencing hits. Cells grown on these surfaces displayed varying nuclear shape and actin filament structure. When stimulated with insulin-transferrin-selenium (ITS) medium, nodule formation occurred and in some cases showed alignment to the topographical patterns. Gene expression analysis of cells growing on topographical surfaces in the presence of ITS medium revealed a downregulation of early markers and upregulation of late markers of chondrogenic differentiation compared to cells grown on a flat surface. In conclusion, we demonstrated that surface topography in addition to other cues can promote hypertrophic differentiation suitable for bone tissue engineering.

  1. Relevance of brands and beef quality differentials for the consumer at the time of purchase

    Directory of Open Access Journals (Sweden)

    Carla Mecca Giacomazzi

    Full Text Available ABSTRACT The objective of this study was to identify the purchase habits and preferences of beef consumers, their level of knowledge on brands and products with quality differentials (certifications, packaging, premium lines, and the relevance of different attributes in the purchase decision, and to group consumers according to the profile of purchase decision. The methodology consisted of using an information-collecting instrument applied to 271 beef consumers. The data collected were analyzed using descriptive statistical analyses, chi-square analysis, and correspondence analysis, relating socio-demographic profile of the respondents with the other variables collected. Chi-square and correspondence analyses showed that younger consumers with lower levels of income and education are influenced by posters and advertisements at the point of sale, unaware of differentiated and branded products, and that they do not choose branded beef at the time of purchase. Consumers over 60 years showed a more conservative purchase profile, with no influence. The most valued attributes are appearance, price, and type of cut, being brand and certifications little relevant as tools to help decide the product purchase.

  2. Simultaneous influence of Stark effect and excessive line broadening on the Hα line

    Science.gov (United States)

    Cvetanović, Nikola; Ivković, Saša S.; Obradović, Bratislav M.; Kuraica, Milorad M.

    2017-12-01

    The aim of this paper is to study the combined influence of the Stark effect and the excessive Doppler broadening on the Balmer alpha line in hydrogen discharges. Since this line is a good candidate for measuring electric field in various types of discharges with different gas compositions, a simple method for field measurement based on polarization spectroscopy is developed, that includes all the excitation mechanisms. To simultaneously test the flexibility of the fitting procedure and investigate the excessive broadening, we applied the fitting procedure on line profiles obtained at a range of conditions from two different discharges. The range of pressures and voltages was examined in an abnormal glow and in dielectric barrier discharge operating with hydrogen gas. The model fitting function was able to respond and follow the change in the line profile caused by the change of conditions. This procedure can therefore be recommended for electric field measurement. Contribution to the "Topical Issue: Physics of Ionized Gases (SPIG 2016)", edited by Goran Poparic, Bratislav Obradovic, Dragana Maric and Aleksandar Milosavljevic.

  3. Prion protein expression regulates embryonic stem cell pluripotency and differentiation.

    Directory of Open Access Journals (Sweden)

    Alberto Miranda

    2011-04-01

    Full Text Available Cellular prion protein (PRNP is a glycoprotein involved in the pathogenesis of transmissible spongiform encephalopathies (TSEs. Although the physiological function of PRNP is largely unknown, its key role in prion infection has been extensively documented. This study examines the functionality of PRNP during the course of embryoid body (EB differentiation in mouse Prnp-null (KO and WT embryonic stem cell (ESC lines. The first feature observed was a new population of EBs that only appeared in the KO line after 5 days of differentiation. These EBs were characterized by their expression of several primordial germ cell (PGC markers until Day 13. In a comparative mRNA expression analysis of genes playing an important developmental role during ESC differentiation to EBs, Prnp was found to participate in the transcription of a key pluripotency marker such as Nanog. A clear switching off of this gene on Day 5 was observed in the KO line as opposed to the WT line, in which maximum Prnp and Nanog mRNA levels appeared at this time. Using a specific antibody against PRNP to block PRNP pathways, reduced Nanog expression was confirmed in the WT line. In addition, antibody-mediated inhibition of ITGB5 (integrin αvβ5 in the KO line rescued the low expression of Nanog on Day 5, suggesting the regulation of Nanog transcription by Prnp via this Itgb5. mRNA expression analysis of the PRNP-related proteins PRND (Doppel and SPRN (Shadoo, whose PRNP function is known to be redundant, revealed their incapacity to compensate for the absence of PRNP during early ESC differentiation. Our findings provide strong evidence for a relationship between Prnp and several key pluripotency genes and attribute Prnp a crucial role in regulating self-renewal/differentiation status of ESC, confirming the participation of PRNP during early embryogenesis.

  4. Differential screening and mass mapping of proteins from premalignant and cancer cell lines using nonporous reversed-phase HPLC coupled with mass spectrometric analysis.

    Science.gov (United States)

    Chong, B E; Hamler, R L; Lubman, D M; Ethier, S P; Rosenspire, A J; Miller, F R

    2001-03-15

    Nonporous (NPS) RP-HPLC has been used to rapidly separate proteins from whole cell lysates of human breast cell lines. The nonporous separation involves the use of hard-sphere silica beads of 1.5-microm diameter coated with C18, which can be used to separate proteins ranging from 5 to 90 kDa. Using only 30-40 microg of total protein, the protein molecular weights are detectable on-line using an ESI-oaTOF MS. Of hundreds of proteins detected in this mass range, approxinately 75-80 are more highly expressed. The molecular weight profiles can be displayed as a mass map analogous to a virtual "1-D gel" and differentially expressed proteins can be compared by image analysis. The separated proteins can also be detected by UV absorption and differentially expressed proteins quantified. The eluting proteins can be collected in the liquid phase and the molecular weight and peptide maps determined by MALDI-TOF MS for identification. It is demonstrated that the expressed protein profiles change during neoplastic progression and that many oncoproteins are readily detected. It is also shown that the response of premalignant cancer cells to estradiol can be rapidly screened by this method, demonstrating significant changes in response to an external agent. Ultimately, the proteins can be studied by peptide mapping to search for posttranslational modifications of the oncoproteins accompanying progression.

  5. Perceptual dimensions differentiate emotions.

    Science.gov (United States)

    Cavanaugh, Lisa A; MacInnis, Deborah J; Weiss, Allen M

    2015-08-26

    Individuals often describe objects in their world in terms of perceptual dimensions that span a variety of modalities; the visual (e.g., brightness: dark-bright), the auditory (e.g., loudness: quiet-loud), the gustatory (e.g., taste: sour-sweet), the tactile (e.g., hardness: soft vs. hard) and the kinaesthetic (e.g., speed: slow-fast). We ask whether individuals use perceptual dimensions to differentiate emotions from one another. Participants in two studies (one where respondents reported on abstract emotion concepts and a second where they reported on specific emotion episodes) rated the extent to which features anchoring 29 perceptual dimensions (e.g., temperature, texture and taste) are associated with 8 emotions (anger, fear, sadness, guilt, contentment, gratitude, pride and excitement). Results revealed that in both studies perceptual dimensions differentiate positive from negative emotions and high arousal from low arousal emotions. They also differentiate among emotions that are similar in arousal and valence (e.g., high arousal negative emotions such as anger and fear). Specific features that anchor particular perceptual dimensions (e.g., hot vs. cold) are also differentially associated with emotions.

  6. Errorless discrimination established by differential autoshaping1

    Science.gov (United States)

    Wilkie, Donald M.; Ramer, Donald G.

    1974-01-01

    In Experiment I, pigeons exposed to a differential autoshaping procedure pecked a key in the presence of the stimulus associated with reinforcement but did not peck, or pecked infrequently, in the presence of the stimulus associated with nonreinforcement. In Experiment II, pigeons were exposed to a differential autoshaping procedure in which one stimulus was associated with reinforcement and two stimuli were associated with nonreinforcement. The birds initially responded in the presence of one stimulus associated with nonreinforcement but never responded in the presence of the second stimulus associated with nonreinforcement. They were subsequently exposed to an autoshaping procedure in which reinforcement followed both these stimuli. The number of stimulus-reinforcement pairings required to establish pecking in the presence of the stimulus during which responses had not previously occurred suggested that such stimuli are inhibitory. These findings have implications for autoshaping, errorless discrimination, inhibition, and theories of discrimination byproducts. PMID:16811797

  7. Comparison of transcriptome profiles by Fusarium oxysporum inoculation between Fusarium yellows resistant and susceptible lines in Brassica rapa L.

    Science.gov (United States)

    Miyaji, Naomi; Shimizu, Motoki; Miyazaki, Junji; Osabe, Kenji; Sato, Maho; Ebe, Yusuke; Takada, Satoko; Kaji, Makoto; Dennis, Elizabeth S; Fujimoto, Ryo; Okazaki, Keiichi

    2017-12-01

    Resistant and susceptible lines in Brassica rapa have different immune responses against Fusarium oxysporum inoculation. Fusarium yellows caused by Fusarium oxysporum f. sp. conglutinans (Foc) is an important disease of Brassicaceae; however, the mechanism of how host plants respond to Foc is still unknown. By comparing with and without Foc inoculation in both resistant and susceptible lines of Chinese cabbage (Brassica rapa var. pekinensis), we identified differentially expressed genes (DEGs) between the bulked inoculated (6, 12, 24, and 72 h after inoculation (HAI)) and non-inoculated samples. Most of the DEGs were up-regulated by Foc inoculation. Quantitative real-time RT-PCR showed that most up-regulated genes increased their expression levels from 24 HAI. An independent transcriptome analysis at 24 and 72 HAI was performed in resistant and susceptible lines. GO analysis using up-regulated genes at 24 HAI indicated that Foc inoculation activated systemic acquired resistance (SAR) in resistant lines and tryptophan biosynthetic process and responses to chitin and ethylene in susceptible lines. By contrast, GO analysis using up-regulated genes at 72 HAI showed the overrepresentation of some categories for the defense response in susceptible lines but not in the resistant lines. We also compared DEGs between B. rapa and Arabidopsis thaliana after F. oxysporum inoculation at the same time point, and identified genes related to defense response that were up-regulated in the resistant lines of Chinese cabbage and A. thaliana. Particular genes that changed expression levels overlapped between the two species, suggesting that they are candidates for genes involved in the resistance mechanisms against F. oxysporum.

  8. Nuclear Mechanics and Stem Cell Differentiation.

    Science.gov (United States)

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

    Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

  9. 29-34 Yellow Rust Resistance in Advanced Lines and Commercial ...

    African Journals Online (AJOL)

    rust pathogen. The objective of this study was to characterize seedling yellow rust resistance in 21 advanced bread wheat lines and 20 cultivars from Ethiopia. Yellow rust infection types (ITs) produced on test wheat lines and cultivars from nine yellow rust races were compared with ITs produced on standard differential lines ...

  10. Privacy effects on self-reported drug use: interactions with survey mode and respondent characteristics.

    Science.gov (United States)

    Aquilino, W S

    1997-01-01

    This chapter examines the impact of interview privacy on self-reported illicit drug use. In 1991, interviews were completed with an urban-suburban sample of 2,417 adults aged 18 to 45. Results show that the presence of third parties during the interview significantly influences respondents' willingness to reveal illicit drug use. Among married respondents, presence of a spouse resulted in higher reporting of illicit drug use, while the presence of adults other than the spouse had a consistent negative effect on drug use reports. A parent's presence during the interview significantly reduced respondents' willingness to report illicit drug use. The pattern of findings suggests that the direction of effects due to third party presence is linked to two factors: the extent of the third party's knowledge of the information requested, and the degree of personal stake the third party may have in the respondent's answers. The differential impact of privacy by interview mode was also examined. Tests of interactions between privacy and interview mode failed to support the hypothesis that the use of self-administered answer sheets reduces privacy effects compared with interviewer-administered interviews.

  11. 19-nor vitamin-D analogs: a new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines.

    Science.gov (United States)

    Asou, H; Koike, M; Elstner, E; Cambell, M; Le, J; Uskokovic, M R; Kamada, N; Koeffler, H P

    1998-10-01

    We have studied the in vitro biological activities and mechanisms of action of 1,25-dihydroxyvitamin D3 (1,25D3) and nine potent 1,25D3 analogs on proliferation and differentiation of myeloid leukemia cell lines (HL-60, retinoic acid-resistant HL-60 [RA-res HL-60], NB4 and Kasumi-1). The common novel structural motiff for almost all the analogs included removal of C-19 (19-nor); each also had unsaturation of the side chain. All the compounds were potent; for example, the concentration of analogs producing a 50% clonal inhibition (ED50) ranged between 1 x 10(-9) to 4 x 10(-11) mol/L when using the HL-60 cell line. The most active compound [1, 25(OH)2-16,23E-diene-26-trifluoro-19-nor-cholecalciferol (Ro 25-9716)] had an ED50 of 4 x 10(-11) mol/L; in contrast, the 1,25D3 produced an ED50 of 10(-9) mol/L with the HL-60 target cells. Ro 25-9716 (10(-9) mol/L, 3 days) was a strong inducer of myeloid differentiation because it caused 92% of the HL-60 cells to express CD11b and 75% of these cells to reduce nitroblue tetrazolium (NBT). This compound (10(-8) mol/L, 4 days) also caused HL-60 cells to arrest in the G1 phase of the cell cycle (88% cells in G1 v 48% of the untreated control cells). The p27(kip-1), a cyclin-dependent kinase inhibitor which is important in blocking the cell cycle, was induced more quickly and potently by Ro 25-9716 (10(-7) mol/L, 0 to 5 days) than by 1,25D3, suggesting a possible mechanism by which these analogs inhibit proliferation of leukemic growth. The NB4 promyelocytic leukemia cells cultured with the Ro 25-9716 were also inhibited in their clonal proliferation (ED50, 5 x 10(-11) mol/L) and their expression of CD11b was enhanced (80% positive [10(-9) mol/L, 4 days] v 27% untreated NB4 cells). Moreover, the combination of Ro 25-9716 (10(-9) mol/L) and all-trans retinoic acid (ATRA, 10(-7) mol/L) induced 92% of the NB4 cells to reduce NBT, whereas only 26% of the cells became NBT positive after a similar exposure to the combination of 1,25D3

  12. Electrophysiological Characteristics of Embryonic Stem Cell-Derived Cardiomyocytes are Cell Line-Dependent

    Directory of Open Access Journals (Sweden)

    Tobias Hannes

    2015-01-01

    Full Text Available Background: Modelling of cardiac development, physiology and pharmacology by differentiation of embryonic stem cells (ESCs requires comparability of cardiac differentiation between different ESC lines. To investigate whether the outcome of cardiac differentiation is consistent between different ESC lines, we compared electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs of different murine ESC lines. Methods: Two wild-type (D3 and R1 and two transgenic ESC lines (D3/aPIG44 and CGR8/AMPIGX-7 were differentiated under identical culture conditions. The transgenic cell lines expressed enhanced green fluorescent protein (eGFP and puromycin-N-acetyltransferase under control of the cardiac specific α-myosin heavy chain (αMHC promoter. Action potentials (APs were recorded using sharp electrodes and multielectrode arrays in beating clusters of ESC-CMs. Results: Spontaneous AP frequency and AP duration (APD as well as maximal upstroke velocity differed markedly between unpurified CMs of the four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term recordings showed a high degree of variability within and between recordings in CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the αMHC+ population by puromycin treatment posed only minor changes to APD in D3/aPIG44, but significantly shortened APD in CGR8/AMPIGX-7. Conclusion: Electrophysiological properties of ESC-CMs are strongly cell line-dependent and can be influenced by purification of cardiomyocytes by antibiotic selection. Thus, conclusions on cardiac development, physiology and pharmacology derived from single stem cell lines have to be interpreted carefully.

  13. An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Julia TCW

    2017-08-01

    Full Text Available Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs, via a neural progenitor cell (NPC intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals. Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium, and rapid (<30 days method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.

  14. Effects of transforming growth factor-beta on growth and differentiation of the continuous rat thyroid follicular cell line, FRTL-5

    International Nuclear Information System (INIS)

    Morris, J.C. III; Ranganathan, G.; Hay, I.D.; Nelson, R.E.; Jiang, N.S.

    1988-01-01

    Transforming growth factor-beta (TGF beta) has been shown to influence the growth and differentiation of many widely varied cell types in vitro, including some that are endocrinologically active. We have investigated the previously unknown effects of this unique growth factor in the differentiated rat thyroid follicular cell line FRTL-5. The cells demonstrated specific, high affinity binding of TGF beta, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGF beta to the culture medium. TGF beta caused a significant reduction in TSH-sensitive adenylate cyclase activity in the cells. The addition of (Bu)2cAMP along with the growth factor to cultures partially reversed the characteristic morphological changes seen with TGF beta, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGF beta on the cells, we measured the influence of the growth factor on [125I]TSH binding. TGF beta did not compete for specific TSH-binding sites; however, exposure of the cells to TGF beta for 12 or more h resulted in a dose-dependent down-regulation of TSH receptors that was fully reversible. While cellular proliferation was potently inhibited by TGF beta, differentiated function, as manifest by iodine-trapping ability, was stimulated by the growth factor. This stimulation of iodine uptake was independent of, and additive to, the stimulatory effects of TSH. Finally, FRTL-5 cells in serum-free medium and in response to TSH were shown to secrete TGF beta-like activity that competed for [125I]TGF beta in a RRA. These studies suggest that TGF beta may represent an autocrine mechanism of controlling the growth response to TSH in thyroid follicular cells, while allowing the continuance of differentiated function

  15. Differential profiles of crack users in respondent-driven and institutional samples: a three-site comparison

    OpenAIRE

    Oteo Pérez, A.; Benschop, A.; Korf, D.J.

    2012-01-01

    Background/Aim: Respondent-driven sampling (RDS) is increasingly applied in social epidemiological surveys among ‘hidden populations’ of hard drug users. The objective of the present study was to assess whether the profile of frequent crack users recruited through RDS differed from those surveyed in two random institutional samples, i.e. low-threshold opiate substitution treatment (ST) and user rooms (URs). Methods: A total of 1,039 crack users (mean age 45.1 8 9.1 years; 81.5% males; 49.5% n...

  16. Correlatos valorativos das motivações para responder sem preconceito Value correlates of the motivations to respond without prejudice

    Directory of Open Access Journals (Sweden)

    Valdiney V. Gouveia

    2006-01-01

    Full Text Available O presente estudo teve como objetivo principal conhecer em que medida as motivações interna e externa para responder sem preconceito frente aos negros se correlacionam com os valores humanos. Para tanto, contou-se com a participação de 308 pessoas da cidade de João Pessoa (PB, distribuídas entre estudantes do ensino médio e universitário, bem como pessoas da população geral. Estes responderam, além de questões demográficas, o Questionário dos Valores Básicos, Escala de Desejabilidade Social e a Escala de Motivação Interna e Externa para Responder sem Preconceito. De acordo com os resultados, a motivação interna se correlacionou de modo positivo principalmente com os valores suprapessoais, como maturidade, beleza e conhecimento. No caso da motivação externa, esta o fez unicamente com os valores de realização, destacando-se entre eles prestígio e privacidade. Estes resultados são coerentes com aqueles apresentados na literatura, que indicam a oposição entre os valores de igualitarismo (suprapessoais vs. ética protestante (realização para explicar o preconceito e as motivações para não apresentar este tipo de atitude.The current study aimed at establishing to what extent both internal and external motivations to respond without prejudice towards Blacks would correlate with human values. As many as 308 subjects from João Pessoa - comprising high school and university students as well as individuals from the community as a whole - were considered. The Basic Values Questionnaire, the Impression Management Scale and the Scale of Internal and External Motivation to Respond without Prejudice, and also demographic questions were applied. Results showed that the internal motivation was positively correlated with the suprapersonal values, specifically maturity, beauty and knowledge. Moreover, the external motivation did correlate, predominantly, with the achievement values, specifically those of prestige and privacy. Such

  17. Identification of a unique hepatocellular carcinoma line, Li-7, with CD13(+) cancer stem cells hierarchy and population change upon its differentiation during culture and effects of sorafenib.

    Science.gov (United States)

    Yamada, Takeshi; Abei, Masato; Danjoh, Inaho; Shirota, Ryoko; Yamashita, Taro; Hyodo, Ichinosuke; Nakamura, Yukio

    2015-04-11

    Cancer stem cell (CSC) research has highlighted the necessity of developing drugs targeting CSCs. We investigated a hepatocellular carcinoma (HCC) cell line that not only has CSC hierarchy but also shows phenotypic changes (population changes) upon differentiation of CSC during culture and can be used for screening drugs targeting CSC. Based on a hypothesis that the CSC proportion should decrease upon its differentiation into progenitors (population change), we tested HCC cell lines (HuH-7, Li-7, PLC/PRF/5, HLF, HLE) before and after 2 months culture for several markers (CD13, EpCAM, CD133, CD44, CD90, CD24, CD166). Tumorigenicity was tested using nude mice. To evaluate the CSC hierarchy, we investigated reconstructivity, proliferation, ALDH activity, spheroid formation, chemosensitivity and microarray analysis of the cell populations sorted by FACS. Only Li-7 cells showed a population change during culture: the proportion of CD13 positive cells decreased, while that of CD166 positive cells increased. The high tumorigenicity of the Li-7 was lost after the population change. CD13(+)/CD166(-) cells showed slow growth and reconstructed the bulk Li-7 populations composed of CD13(+)/CD166(-), CD13(-)/CD166(-) and CD13(-)/CD166(+) fractions, whereas CD13(-)/CD166(+) cells showed rapid growth but could not reproduce any other population. CD13(+)/CD166(-) cells showed high ALDH activity, spheroid forming ability and resistance to 5-fluorouracil. Microarray analysis demonstrated higher expression of stemness-related genes in CD166(-) than CD166(+) fraction. These results indicated a hierarchy in Li-7 cells, in which CD13(+)/CD166(-) and CD13(-)/CD166(+) cells serve as slow growing CSCs and rapid growing progenitors, respectively. Sorafenib selectively targeted the CD166(-) fraction, including CD13(+) CSCs, which exhibited higher mRNA expression for FGF3 and FGF4, candidate biomarkers for sorafenib. 5-fluorouracil followed by sorafenib inhibited the growth of bulk Li-7

  18. Evaluation of Respondent-Driven Sampling

    Science.gov (United States)

    McCreesh, Nicky; Frost, Simon; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda Ndagire; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

    2012-01-01

    Background Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex-workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total-population data. Methods Total-population data on age, tribe, religion, socioeconomic status, sexual activity and HIV status were available on a population of 2402 male household-heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, employing current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). Results We recruited 927 household-heads. Full and small RDS samples were largely representative of the total population, but both samples under-represented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven-sampling statistical-inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven-sampling bootstrap 95% confidence intervals included the population proportion. Conclusions Respondent-driven sampling produced a generally representative sample of this well-connected non-hidden population. However, current respondent-driven-sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience

  19. Evaluation of respondent-driven sampling.

    Science.gov (United States)

    McCreesh, Nicky; Frost, Simon D W; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda N; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

    2012-01-01

    Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total population data. Total population data on age, tribe, religion, socioeconomic status, sexual activity, and HIV status were available on a population of 2402 male household heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, using current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). We recruited 927 household heads. Full and small RDS samples were largely representative of the total population, but both samples underrepresented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven sampling statistical inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven sampling bootstrap 95% confidence intervals included the population proportion. Respondent-driven sampling produced a generally representative sample of this well-connected nonhidden population. However, current respondent-driven sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience sampling method, and caution is required

  20. Development of an Inconsistent Responding Scale for the Triarchic Psychopathy Measure.

    Science.gov (United States)

    Mowle, Elyse N; Kelley, Shannon E; Edens, John F; Donnellan, M Brent; Smith, Shannon Toney; Wygant, Dustin B; Sellbom, Martin

    2017-08-01

    Inconsistent or careless responding to self-report measures is estimated to occur in approximately 10% of university research participants and may be even more common among offender populations. Inconsistent responding may be a result of a number of factors including inattentiveness, reading or comprehension difficulties, and cognitive impairment. Many stand-alone personality scales used in applied and research settings, however, do not include validity indicators to help identify inattentive response patterns. Using multiple archival samples, the current study describes the development of an inconsistent responding scale for the Triarchic Psychopathy Measure (TriPM; Patrick, 2010), a widely used self-report measure of psychopathy. We first identified pairs of correlated TriPM items in a derivation sample (N = 2,138) and then created a total score based on the sum of the absolute value of the differences for each item pair. The resulting scale, the Triarchic Assessment Procedure for Inconsistent Responding (TAPIR), strongly differentiated between genuine TriPM protocols and randomly generated TriPM data (N = 1,000), as well as between genuine protocols and those in which 50% of the original data were replaced with random item responses. TAPIR scores demonstrated fairly consistent patterns of association with some theoretically relevant correlates (e.g., inconsistency scales embedded in other personality inventories), although not others (e.g., measures of conscientiousness) across our cross-validation samples. Tentative TAPIR cut scores that may discriminate between attentively and carelessly completed protocols are presented. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Diagnosis and differential diagnosis of hydrocephalus in adults

    International Nuclear Information System (INIS)

    Langner, Soenke; Mensel, Birger; Kuehn, Jens Peter; Kirsch, Michael; Fleck, Steffen; Baldauf, Joerg

    2017-01-01

    Hydrocephalus is caused by an imbalance of production and absorption of cerebrospinal fluid (CSF) or obstruction of its pathways, resulting in ventricular dilatation and increased intracranial pressure. Imaging plays a crucial role in the diagnosis, differential diagnosis and planning of treatment. This review article presents the different types of hydrocephalus und their typical imaging appearance, describes imaging techniques, and discusses differential diagnoses of the different forms of hydrocephalus. Imaging plays a central role in the diagnosis of hydrocephalus. While magnetic resonance (MR) imaging is the first-line imaging modality, computed tomography (CT) is often the first-line imaging test in emergency patients.

  2. Differentiation of stem cells upon deprivation of exogenous FGF2

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  3. Micro-Topographies Promote Late Chondrogenic Differentiation Markers in the ATDC5 Cell Line

    NARCIS (Netherlands)

    Le, Bach Q.; Vasilevich, Aliaksei; Vermeulen, Steven; Hulshof, Frits; Stamatialis, Dimitrios F.; Van Blitterswijk, Clemens A.; De Boer, Jan

    2017-01-01

    Chemical and mechanical cues are well-established influencers of in vitro chondrogenic differentiation of ATDC5 cells. Here, we investigate the role of topographical cues in this differentiation process, a study not been explored before. Previously, using a library of surface micro-topographies we

  4. On-line Shopping on B2C Markets in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Pilík Michal

    2012-12-01

    Full Text Available The paper deals with the e-commerce theory and is aimed primarily at its usage in business-toconsumer markets. On-line purchasing management is increasing not only in the Czech Republic but also in Europe and all over the world. The customers who think rationally use on-line shopping because of money saving, speed delivery and the possibility of product comparison. This paper presents the results of a project financed by the Czech Science Foundation P403/11/ P175: The factors influencing customers’ on-line behaviour in e-commerce environment on B2C and B2B markets in the Czech Republic. 89 % of respondents use e-shops for buying products in the Czech Republic. 32 % of them use the Internet for regular purchases and 57 % of them irregularly. 11 % of respondents have not used e-shops yet.

  5. MediSim: A Prototype VR System for Training Medical First Responders

    Energy Technology Data Exchange (ETDEWEB)

    Stansfield, S.; Shawver, D.; Sobel, A.

    1997-12-31

    This paper presents a prototype virtual reality (VR) system for training medical first responders. The initial application is to battlefield medicine and focuses on the training of medical corpsmen and other front-line personnel who might be called upon to provide emergency triage on the battlefield. The system is built upon Sandia`s multi-user, distributed VR platform and provides an interactive, immersive simulation capability. The user is represented by an Avatar and is able to manipulate his virtual instruments and carry out medical procedures. A dynamic casualty simulation provides realistic cues to the patient`s condition (e.g. changing blood pressure and pulse) and responds to the actions of the trainee (e.g. a change in the color of a patient`s skin may result from a check of the capillary refill rate). The current casualty simulation is of an injury resulting in a tension pneumothorax. This casualty model was developed by the University of Pennsylvania and integrated into the Sandia MediSim system.

  6. Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene

    DEFF Research Database (Denmark)

    Efrat, S; Linde, S; Kofod, Hans

    1988-01-01

    Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The ...... both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype....

  7. 29 CFR 98.1000 - Respondent.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Respondent. 98.1000 Section 98.1000 Labor Office of the Secretary of Labor GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 98.1000 Respondent. Respondent means a person against whom an agency has initiated a debarment or suspension action. ...

  8. Lie symmetries in differential equations

    International Nuclear Information System (INIS)

    Pleitez, V.

    1979-01-01

    A study of ordinary and Partial Differential equations using the symmetries of Lie groups is made. Following such a study, an application to the Helmholtz, Line-Gordon, Korleweg-de Vries, Burguer, Benjamin-Bona-Mahony and wave equations is carried out [pt

  9. Amitriptyline converts non-responders into responders to low-frequency electroacupuncture-induced analgesia in rats.

    Science.gov (United States)

    Fais, Rafael S; Reis, G M; Rossaneis, A C; Silveira, J W S; Dias, Q M; Prado, W A

    2012-07-26

    The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 μg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. Rats selected as non-responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. A Simple Evacuation Modeling and Simulation Tool for First Responders

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Daniel B [ORNL; Payne, Patricia W [ORNL

    2015-01-01

    Although modeling and simulation of mass evacuations during a natural or man-made disaster is an on-going and vigorous area of study, tool adoption by front-line first responders is uneven. Some of the factors that account for this situation include cost and complexity of the software. For several years, Oak Ridge National Laboratory has been actively developing the free Incident Management Preparedness and Coordination Toolkit (IMPACT) to address these issues. One of the components of IMPACT is a multi-agent simulation module for area-based and path-based evacuations. The user interface is designed so that anyone familiar with typical computer drawing tools can quickly author a geospatially-correct evacuation visualization suitable for table-top exercises. Since IMPACT is designed for use in the field where network communications may not be available, quick on-site evacuation alternatives can be evaluated to keep pace with a fluid threat situation. Realism is enhanced by incorporating collision avoidance into the simulation. Statistics are gathered as the simulation unfolds, including most importantly time-to-evacuate, to help first responders choose the best course of action.

  11. DNA microarrays of baculovirus genomes: differential expression of viral genes in two susceptible insect cell lines.

    Science.gov (United States)

    Yamagishi, J; Isobe, R; Takebuchi, T; Bando, H

    2003-03-01

    We describe, for the first time, the generation of a viral DNA chip for simultaneous expression measurements of nearly all known open reading frames (ORFs) in the best-studied members of the family Baculoviridae, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV). In this study, a viral DNA chip (Ac-BmNPV chip) was fabricated and used to characterize the viral gene expression profile for AcMNPV in different cell types. The viral chip is composed of microarrays of viral DNA prepared by robotic deposition of PCR-amplified viral DNA fragments on glass for ORFs in the NPV genome. Viral gene expression was monitored by hybridization to the DNA fragment microarrays with fluorescently labeled cDNAs prepared from infected Spodoptera frugiperda, Sf9 cells and Trichoplusia ni, TnHigh-Five cells, the latter a major producer of baculovirus and recombinant proteins. A comparison of expression profiles of known ORFs in AcMNPV elucidated six genes (ORF150, p10, pk2, and three late gene expression factor genes lef-3, p35 and lef- 6) the expression of each of which was regulated differently in the two cell lines. Most of these genes are known to be closely involved in the viral life cycle such as in DNA replication, late gene expression and the release of polyhedra from infected cells. These results imply that the differential expression of these viral genes accounts for the differences in viral replication between these two cell lines. Thus, these fabricated microarrays of NPV DNA which allow a rapid analysis of gene expression at the viral genome level should greatly speed the functional analysis of large genomes of NPV.

  12. Effects of collisions on linear and non-linear spectroscopic line shapes

    International Nuclear Information System (INIS)

    Berman, P.R.

    1978-01-01

    A fundamental physical problem is the determination of atom-atom, atom-molecule and molecule-molecule differential and total scattering cross sections. In this work, a technique for studying atomic and molecular collisions using spectroscopic line shape analysis is discussed. Collisions occurring within an atomic or molecular sample influence the sample's absorptive or emissive properties. Consequently the line shapes associated with the linear or non-linear absorption of external fields by an atomic system reflect the collisional processes occurring in the gas. Explicit line shape expressions are derived characterizing linear or saturated absorption by two-or three-level 'active' atoms which are undergoing collisions with perturber atoms. The line shapes may be broadened, shifted, narrowed, or distorted as a result of collisions which may be 'phase-interrupting' or 'velocity-changing' in nature. Systematic line shape studies can be used to obtain information on both the differential and total active atom-perturber scattering cross sections. (Auth.)

  13. Squamous-lined cyst of the pancreas: Radiological–pathological correlation

    International Nuclear Information System (INIS)

    Kubo, T.; Takeshita, T.; Shimono, T.; Hashimoto, S.; Miki, Y.

    2014-01-01

    Pancreatic cystic lesions are increasingly being detected incidentally because of the increased use of cross-sectional imaging. Squamous-lined cysts of the pancreas (lymphoepithelial cyst, epidermoid cyst, and dermoid cyst) are rare cystic lesions lined with squamous epithelium. Distinguishing squamous-lined cysts from other cystic lesions of the pancreas is important to avoid unnecessary surgery, because squamous-lined cysts of the pancreas have no malignant potential. The purpose of this review is to describe findings on computed tomography and magnetic resonance imaging and the histopathological characteristics of squamous-lined cysts, and to summarize the key points of differential diagnosis for pancreatic cystic lesions

  14. Neurotrophic effects of growth/differentiation factor 5 in a neuronal cell line

    OpenAIRE

    Toulouse, André; Collins, Grace C.; Sullivan, Aideen M.

    2012-01-01

    The neurotrophin growth/differentiation factor 5 (GDF5) is studied as a potential therapeutic agent for Parkinson's disease as it is believed to play a role in the development and maintenance of the nigrostriatal system. Progress in understanding the effects of GDF5 on dopaminergic neurones has been hindered by the use of mixed cell populations derived from primary cultures or in vivo experiments, making it difficult to differentiate between direct and indirect effects of GDF5 treatment on ne...

  15. Anatomicopathological basis and clinical diagnostic significance of Kerley's A line

    International Nuclear Information System (INIS)

    Wang Zhenguang; Ma Daqing; Chen Budong; He Wen; Wang Xinlian; Guan Yansheng; Zhang Yansong

    2007-01-01

    Objective: To study anatomic and pathological basis of Kerley's A line, and to evaluate the role of Kerley's A line in differential diagnosis of diffuse lung diseases (DLD). Methods: HRCT scans, gross specimen section(50-100 μm thickness) and histologic section(5-8 μm thickness) were performed and analyzed comparatively on 28 dry lung specimens from the patients with coal worker's pneumoconiosis and occupational exposure history to coal dusts. At the same time, HRCT images of 176 patients with DLD were retrospectively reviewed for the detection of Kerley's A line. Results: Kerley's A lines were seen in 17 of 28 lung specimens on coronal HRCT images. The anatomic basis of Kerley's A line represented the continuity of two or more thickened interlobular septa (14 eases) and incomplete fibrotic septa between segments or subsegments (3 cases). Histologically, the linear opacities represented the deposits of coal dust, fibrosis, edema, inflammation, thickened vessel wall within interlobular septa. Kerley's A lines were present in 11 of 176 patients (6.3%) including interstitial pulmonary edema (5 cases), viral pneumonia (2 cases), lymphangitic carcinomatosis (2 cases), sarcoidosis (1 cases) and pulmonary alveolar proteinosis (1 cases). Conclusion: Kerley's A line has a limited usefulness in the differential diagnosis of DLD because it is seen infrequently and not discermable. (authors)

  16. Heterogeneity of osteosarcoma cell lines led to variable responses in reprogramming.

    Science.gov (United States)

    Choong, Pei Feng; Teh, Hui Xin; Teoh, Hoon Koon; Ong, Han Kiat; Choo, Kong Bung; Sugii, Shigeki; Cheong, Soon Keng; Kamarul, Tunku

    2014-01-01

    Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.

  17. Heterogeneity of Osteosarcoma Cell Lines Led to Variable Responses in Reprogramming

    Science.gov (United States)

    Choong, Pei Feng; Teh, Hui Xin; Teoh, Hoon Koon; Ong, Han Kiat; Choo, Kong Bung; Sugii, Shigeki; Cheong, Soon Keng; Kamarul, Tunku

    2014-01-01

    Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture. PMID:25170299

  18. The role of risk perception in willingness to respond to the 2014-2016 West African Ebola outbreak

    DEFF Research Database (Denmark)

    Gee, Stephanie; Skovdal, Morten

    2017-01-01

    using NVivo 10. Results: We found that numerous individual and social-level factors played a role in modifying risk perception in health workers. Institutional trust emerged as a key risk attenuator, as did past experience, self-efficacy, duty of care, humanitarian ethos, and cognitive heuristics...... workers is essential for an effective epidemic response, health workforce capacity in times of crisis may be significantly impacted by how risks are perceived by health staff. This study aimed to explore how risk perceptions influenced healthcare workers’ willingness to respond during this outbreak....... Methods: Through in-depth interviews with 11 front-line international health care workers who chose to respond to the West Africa outbreak, this qualitative study explores how perceptions of risk developed and subsequently mediated the decision to respond to the outbreak. Data was thematically organized...

  19. An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Tcw, Julia; Wang, Minghui; Pimenova, Anna A; Bowles, Kathryn R; Hartley, Brigham J; Lacin, Emre; Machlovi, Saima I; Abdelaal, Rawan; Karch, Celeste M; Phatnani, Hemali; Slesinger, Paul A; Zhang, Bin; Goate, Alison M; Brennand, Kristen J

    2017-08-08

    Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Samsuddin Khan

    2014-07-01

    Full Text Available Background: There are limited data on the failure of second-line antiretroviral therapy (ART and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62% responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0. No serious treatment-related adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL

  1. Sustainable production of azadirachtin from differentiated in vitro cell lines of neem (Azadirachta indica)

    Science.gov (United States)

    Singh, Mithilesh; Chaturvedi, Rakhi

    2013-01-01

    Azadirachtin has high industrial demand due to its immediate application as an ecofriendly, biodegradable biopesticide and also due to its various other significant bioactivities. To date, the only commercially feasible way to produce azadirachtin is extraction from seeds, but their availability is very limited as the tree flowers only once a year and only one-third of the fruits are collected due to operational problems. Further, due to the strict out-breeding nature of the plant, the seeds are highly heterozygous, resulting in inconsistent metabolite production. Therefore, in the present study, to achieve sustainable production of azadirachtin, dedifferentiated and redifferentiated calli derived from various explants of neem—zygotic embryo, leaf and ovary—were investigated for their potential to biosynthesize azadirachtin. High-performance liquid chromatography analysis of the in vitro cell lines showed the presence of azadirachtin in all the samples tested, the content of which in cultured cells varied with explant source and cell differentiation response. The presence of azadirachtin in samples was further confirmed by positive electrospray ionization mass spectroscopy. The zygotic embryo cultures of neem accumulated much higher amounts of azadirachtin than leaf and ovary cultures. Furthermore, organized in vitro callus cultures (redifferentiated) supported higher azadirachtin biosynthesis, while unorganized callus cultures (dedifferentiated) supported the least. The maximum azadirachtin content of 2.33 mg g−1 dry weight was obtained from redifferentiated immature zygotic embryo cultures.

  2. NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

    Science.gov (United States)

    Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

    2012-02-01

    Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

  3. Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2009-03-01

    Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

  4. Nucleotide excision repair in differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Wees, Caroline van der [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Jansen, Jacob [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Laarse, Arnoud van der [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert van [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands)]. E-mail: l.mullenders@lumc.nl

    2007-01-03

    Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions and operates via two NER subpathways, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Although detailed information is available on expression and efficiency of NER in established mammalian cell lines, little is known about the expression of NER pathways in (terminally) differentiated cells. The majority of studies in differentiated cells have focused on repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4PP) because of the high frequency of photolesions at low level of toxicity and availability of sensitive technologies to determine photolesions in defined regions of the genome. The picture that emerges from these studies is blurred and rather complex. Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression. This repair phenotype is clearly different from human terminal differentiated neurons. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. In contrast, in intact rat spermatogenic cells repair was very inefficient at the genome overall level and in transcriptionally active genes indicating that GGR and TCR are non-functional. Also, non-differentiated mouse embryonic stem (ES) cells exhibit low levels of NER after UV irradiation. However, the mechanisms that lead to low NER activity are clearly different: in differentiated spermatogenic cells differences in chromatin compaction and sequestering of NER proteins may underlie the lack of NER activity in pre-meiotic cells, whereas in non-differentiated ES cells NER is impaired by a strong apoptotic response.

  5. Investigating on-line pornography at the University of Johannesburg

    Directory of Open Access Journals (Sweden)

    P. Laughton

    2008-01-01

    Full Text Available The on-line user of today has access to a vast collection of information resources. In addition, the developments in Internet and Web technologies have made it even easier for surfers to anonymously get access to on-line pornography. The purpose of this research was to investigate the extent to which access to on-line pornography at the University of Johannesburg can be managed. For the empirical part of this research 1037 questionnaires were proportionally distributed to and completed by students on all five campuses of the university. The questionnaire consisted of four sections: biographical information; university computer facility usage; university acceptable use policy; and personal experience with university computer facilities. The gender distribution for the sample was almost even, with a total of 49,4% male participants and 50,6% female, with the largest grouping of respondents (61,6% aged between 19 years and 21 years. Of the respondents, 36,7% indicated that exposure to unsolicited pornography did not bother them. When asked to what extent students should have access to pornography, 60,5% stated 'None' while 32,6% believed that 'Restricted' access should be granted for research purposes and 6,9% believed that students should be granted 'Total' access to pornography. Results from the research will be used to manage access to on-line resources at the University of Johannesburg better.

  6. Evaluation of the neurotoxic/neuroprotective role of organoselenides using differentiated human neuroblastoma SH-SY5Y cell line challenged with 6-hydroxydopamine.

    Science.gov (United States)

    Lopes, Fernanda Martins; Londero, Giovana Ferreira; de Medeiros, Liana Marengo; da Motta, Leonardo Lisbôa; Behr, Guilherme Antônio; de Oliveira, Valeska Aguiar; Ibrahim, Mohammad; Moreira, José Cláudio Fonseca; Porciúncula, Lisiane de Oliveira; da Rocha, João Batista Teixeira; Klamt, Fábio

    2012-08-01

    It is well established that oxidative stress plays a major role in several neurodegenerative conditions, like Parkinson disease (PD). Hence, there is an enormous effort for the development of new antioxidants compounds with therapeutic potential for the management of PD, such as synthetic organoselenides molecules. In this study, we selected between nine different synthetic organoselenides the most eligible ones for further neuroprotection assays, using the differentiated human neuroblastoma SH-SY5Y cell line as in vitro model. Neuronal differentiation of exponentially growing human neuroblastoma SH-SY5Y cells was triggered by cultivating cells with DMEM/F12 medium with 1% of fetal bovine serum (FBS) with the combination of 10 μM retinoic acid for 7 days. Differentiated cells were further incubated with different concentrations of nine organoselenides (0.1, 0.3, 3, 10, and 30 μM) for 24 h and cell viability, neurites densities and the immunocontent of neuronal markers were evaluated. Peroxyl radical scavenging potential of each compound was determined with TRAP assay. Three organoselenides tested presented low cytotoxicity and high antioxidant properties. Pre-treatment of cells with those compounds for 24 h lead to a significantly neuroprotection against 6-hydroxydopamine (6-OHDA) toxicity, which were directly related to their antioxidant properties. Neuroprotective activity of all three organoselenides was compared to diphenyl diselenide (PhSe)₂, the simplest of the diaryl diselenides tested. Our results demonstrate that differentiated human SH-SY5Y cells are suitable cellular model to evaluate neuroprotective/neurotoxic role of compounds, and support further evaluation of selected organoselenium molecules as potential pharmacological and therapeutic drugs in the treatment of PD.

  7. Differentiation as symbiosis.

    Science.gov (United States)

    Chigira, M; Watanabe, H

    1994-07-01

    Preservation of the identity of DNA is the ultimate goal of multicellular organisms. An abnormal DNA sequence in cells within an individual means its parasitic nature in cell society as shown in tumors. Somatic gene arrangement and gene mutation in development may be considered as de novo formation of parasites. It is likely that the developmental process with genetic alterations means symbiosis between altered cells and germ line cells preserving genetic information without alterations, when somatic alteration of DNA sequence is a major mechanism of differentiation. According to the selfish gene theory of Dawkins, germ line cells permit symbiosis when somatic cell society derives clear profit for the replication of original DNA copies.

  8. Pulmonary edema: radiographic differential diagnosis

    International Nuclear Information System (INIS)

    Yoo, Dong Soo; Choi, Young Hi; Kim, Seung Cheol; An, Ji Hyun; Lee, Jee Young; Park, Hee Hong

    1997-01-01

    To evaluate the feasibility of using chest radiography to differentiate between three different etiologies of pulmonary edema. Plain chest radiographs of 77 patients, who were clinically confirmed as having pulmonary edema, were retrospectively reviewed. The patients were classified into three groups : group 1 (cardiogenic edema : n = 35), group 2 (renal pulmonary edema : n = 16) and group 3 (permeability edema : n = 26). We analyzed the radiologic findings of air bronchogram, heart size, peribronchial cuffing, septal line, pleural effusion, vascular pedicle width, pulmonary blood flow distribution and distribution of pulmonary edema. In a search for radiologic findings which would help in the differentiation of these three etiologies, each finding was assessed. Cardiogenic and renal pulmonary edema showed overlapping radiologic findings, except for pulmonary blood flow distribution. In cardiogenic pulmonary edema (n=35), cardiomegaly (n=29), peribronchial cuffing (n=29), inverted pulmonary blood flow distribution (n=21) and basal distribution of edema (n=20) were common. In renal pulmonary edema (n=16), cardiomegaly (n=15), balanced blood flow distribution (n=12), and central (n=9) or basal distribution of edema (n=7) were common. Permeability edema (n=26) showed different findings. Air bronchogram (n=25), normal blood flow distribution (n=14) and peripheral distribution of edema (n=21) were frequent findings, while cardiomegaly (n=7), peribronchial cuffing (n=7) and septal line (n=5) were observed in only a few cases. On plain chest radiograph, permeability edema can be differentiated from cardiogenic or renal pulmonary edema. The radiographic findings which most reliably differentiated these two etiologies were air bronchogram, distribution of pulmonary edema, peribronchial cuffing and heart size. Only blood flow distribution was useful for radiographic differentiation of cardiogenic and renal edema

  9. How Consumers Respond to Corporate Social Responsibility Initiative: Cause Related Marketing vs Philantrophy

    Directory of Open Access Journals (Sweden)

    Lisia Astari Pertiwi

    2016-12-01

    Full Text Available Increasing in demand of CSR from various stakeholders has caused company’s CSR motives to be more complex. CSR activities are not only founded on the benevolence of corporate agents but also as part of a corporate strategy formulated in pursuit of stakeholder interest. This study investigate whether CSR motives could enhance customer trust and satisfaction. Focus on two CSR initiatives conducted by GrabTaxi (transportation industry and Alfamart (retail industry, the purposes is to demonstrate how two type CSR initiative could delivered perceived motives and create loyalty. Cross-sectional offline and on- line survey was conducted on 175 respondents of GrabTaxi and 192 respondents of Alfamart. Structural Equation Interestingly, even though respondent perceived firm-serving motives (as strategic objectives and reactive motives (as expected by stakeholder, CSR initiative could create trust and satisfaction.Struc- tural Equation Modelling as data analysis to test 5 hypotheses. The results show slightly different in the context of cause-related marketing (GrabTaxi, and philanthropy (Alfamart. Even though all respondents perceived that CSR is motivated by mix motives (benevolent and strategic, how these motives influence trust, satisfaction, and further loyalty are different. Two-type of CSR initiative ie Cause Related Market- ing (CrM and philanthropy can provide firm-serving motive, public serving motive and reactive motive. These motives could encourage trust and satisfaction through path motive-trust-satisfaction (directly or indirectly through trust-customer loyalty. Interestingly, even though respondent perceived firm-serving motives (as strategic objectives and reactive motives (as expected by stakeholder, CSR initiative could create trust and satisfaction.

  10. Characterization of stem-like cells in a new astroblastoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Coban, Esra Aydemir; Kasikci, Ezgi [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul (Turkey); Karatas, Omer Faruk [Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum (Turkey); Suakar, Oznur; Kuskucu, Aysegul [Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul (Turkey); Altunbek, Mine [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul (Turkey); Türe, Uğur [Department of Neurosurgery, Yeditepe University School of Medicine, Istanbul (Turkey); Sahin, Fikrettin [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul (Turkey); Bayrak, Omer Faruk, E-mail: ofbayrak@yeditepe.edu.tr [Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul (Turkey)

    2017-03-15

    Cell lines established from tumors are the most commonly used models in cancer research, and their use in recent years has enabled a greater understanding of the biology of cancer and the means to develop effective treatment strategies. Astroblastomas are uncommon neuroepithelial tumors of glial origin, predominantly affecting young people, mainly teenagers and children, predominantly females. To date, only a single study has reported that astroblastomas contain a large number of neural stem-like cells, which had only a partial proliferation capacity and differentiation. Our objective was to establish an astroblastoma cell line to investigate the presence of astroblastic cells and cancer stem-like cells. The migratory and invasion abilities of the cells were quantified with invasion and migration assays and compared to a glioblastoma cell line. The presence of stem cells was detected with surface-marker analysis by using flow cytometry, and measuring the differentiation ability with a differentiation assay and the self-renewal capacity with a sphere-forming assay. These characteristics may determine whether this novel cell line is a model for astroblastomas that may have stem-cell characteristics. With this novel cell line, scientists can investigate the molecular pathways underlying astroblastomas and develop new therapeutic strategies for patients with these tumors. - Highlights: • An establishment of a novel astroblastoma cell line was proposed. • The presence of astroblastic cells and cancer stem-like cells was investigated. • The molecular pathways underlying astroblastomas may be investigated. • New therapeutic strategies for patients with astroblastoma may be developed.

  11. Sonicated Protein Fractions of Mycoplasma hyopneumoniae Induce Inflammatory Responses and Differential Gene Expression in a Murine Alveolar Macrophage Cell Line.

    Science.gov (United States)

    Damte, Dereje; Lee, Seung-Jin; Birhanu, Biruk Tesfaye; Suh, Joo-Won; Park, Seung-Chun

    2015-12-28

    Mycoplasma hyopneumoniae is known to cause porcine enzootic pneumonia (EP), an important disease in swine production. The objective of this study was to examine the effects of sonicated protein fractions of M. hyopneumoniae on inflammatory response and gene expression in the murine alveolar macrophage MH-S cell line. The effects of sonicated protein fractions and intact M. hyopneumoniae on the gene expression of cytokines and iNOS were assessed using RT-PCR. The Annealing Control Primer (ACP)-based PCR method was used to screen differentially expressed genes. Increased transcription of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, COX-2, and iNOS mRNA was observed after exposure to the supernatant (SPT), precipitant (PPT), and intact M. hyopneumoniae protein. A time-dependent analysis of the mRNA expression revealed an upregulation after 4 h for IL-6 and iNOS and after 12 h for IL-1β and TNF-α, for both SPT and PPT; the fold change in COX-2 expression was less. A dose- and time-dependent correlation was observed in nitrite (NO) production for both protein fractions; however, there was no significant difference between the effects of the two protein fractions. In a differential gene analysis, PCR revealed differential expression for nine gene bands after 3 h of stimulation - only one gene was downregulated, while the remaining eight were upregulated. The results of this study provide insights that help improve our understanding of the mechanisms underlying the pathogenesis of and macrophage defenses against M. hyopneumoniae assault, and suggest targets for future studies on therapeutic interventions for M. hyopneumoniae infections.

  12. Numerical modelling of multimode fibre-optic communication lines

    Energy Technology Data Exchange (ETDEWEB)

    Sidelnikov, O S; Fedoruk, M P [Novosibirsk State University, Novosibirsk (Russian Federation); Sygletos, S; Ferreira, F [Aston University, England, Birmingham, B4 7ET (United Kingdom)

    2016-01-31

    The results of numerical modelling of nonlinear propagation of an optical signal in multimode fibres with a small differential group delay are presented. It is found that the dependence of the error vector magnitude (EVM) on the differential group delay can be reduced by increasing the number of ADC samples per symbol in the numerical implementation of the differential group delay compensation algorithm in the receiver. The possibility of using multimode fibres with a small differential group delay for data transmission in modern digital communication systems is demonstrated. It is shown that with increasing number of modes the strong coupling regime provides a lower EVM level than the weak coupling one. (fibre-optic communication lines)

  13. Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Fredriksson, Maritha; Li, Yan; Stålman, Anders; Haldosén, Lars-Arne; Felländer-Tsai, Li

    2013-09-02

    Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiation of mesenchymal stem cells. The murine fibroblast C3H10T1/2 cell line was induced to tenocytic differentiation by growth differentiation factor-7. Cell proliferation and differentiation with the exposure of different concentrations of triamcinolone acetonide and diclofenac were measured by WST-1 assay and real-time polymerase chain reaction analysis, respectively. Cell proliferation was decreased in a concentration-dependent manner when exposed to triamcinolone acetonide and diclofenac. In addition to tenocytic differentiation, adipocyte formation was observed, both at gene expression and microscopic level, when the cells were exposed to triamcinolone acetonide or high concentrations of diclofenac. Our results indicate that triamcinolone acetonide and diclofenac might alter mesenchymal stem cell differentiation in a nonfavorable way regarding tendon regeneration; therefore, these medications should be used with more caution clinically.

  14. Differential Radiosensitizing Potential of Temozolomide in MGMT Promoter Methylated Glioblastoma Multiforme Cell Lines

    International Nuclear Information System (INIS)

    Nifterik, Krista A. van; Berg, Jaap van den; Stalpers, Lukas J.A.; Lafleur, M. Vincent M.; Leenstra, Sieger; Slotman, Ben J.; Hulsebos, Theo J.M.; Sminia, Peter

    2007-01-01

    Purpose: To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated γ-irradiation. Methods and Materials: Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of γ-irradiation. Repeated TMZ doses were given before and concurrent with irradiation treatment. Immediately plated clonogenic cell-survival curves were determined for both the single-dose and the fractionated irradiation experiments. To establish the net effect of clonogenic cell survival and cell proliferation, growth curves were determined, expressed as the number of surviving cells. Results: All three cell lines showed MGMT promoter methylation, lacked MGMT protein expression, and were sensitive to TMZ. The isotoxic TMZ concentrations used were in a clinically feasible range of 10 μmol/L (AMC-3046), 3 μmol/L (VU-109), and 2.5 μmol/L (VU-122). Temozolomide was able to radiosensitize two cell lines (AMC 3046 and VU-122) using single-dose irradiation. A reduction in the number of surviving cells after treatment with the combination of TMZ and fractionated irradiation was seen in all three cell lines, but only AMC 3046 showed a radiosensitizing effect. Conclusions: This study on TMZ-sensitive GBM cell lines shows that TMZ can act as a radiosensitizer and is at least additive to γ-irradiation. Enhancement of the radiation response by TMZ seems to be independent of the epigenetically silenced MGMT gene

  15. Efficacy, safety and cost per responder of biologics in the treatment of non-radiographic axial spondyloarthritis.

    Science.gov (United States)

    Olivieri, Ignazio; Fanizza, Caterina; Gilio, Michele; Ravasio, Roberto

    2016-01-01

    Anti-tumour necrosis factor (TNF) agents are recommended as second-line therapy for patients with axial spondyloarthropathies. This analysis reviewed data on studies investigating the efficacy and tolerability of anti-TNF agents in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who had failed first-line non-steroidal anti-inflammatory (NSAID) treatment. Efficacy data from RCTs were used to calculate the number needed to treat (NNT) for individual anti-TNFs and then the cost per responder was determined to provide an indication of the value of each therapy. A systematic literature review and analysis of search results over the period January 2008 to September 2014 identified four randomised placebo-controlled trials that were included in the analysis. Adalimumab, etanercept and certolizumab pegol were all effective and well tolerated in patients with nr-axSpA. A patient was more likely to reach ASAS20 or ASAS40 when treated with etanercept or adalimumab, the NNT was lowest for adalimumab, and the risk of adverse events was higher with certolizumab pegol 200 mg every 2 weeks. The cost per responder (NNT) was lowest for adalimumab, followed closely by certolizumab 400 mg every 4 weeks, intermediate for certolizumab 200 mg every 2 weeks and highest for etanercept. Although all anti-TNF agents were associated with clinical improvement in patients with nr-axSpA, adalimumab presented a better cost per responder than etanercept and certolizumab pegol.

  16. 76 FR 62343 - Certain Lined Paper Products From India: Notice of Preliminary Results of Antidumping Duty...

    Science.gov (United States)

    2011-10-07

    ... Lined Paper Products from India: Selection of Respondents for Individual Review'' (Respondent Selection... purposes of determining appropriate product comparisons to U.S. sales. Because Riddhi did not have home market sales of subject merchandise during the POR, all products produced by Riddhi covered by the...

  17. Fractional Order Differentiation by Integration and Error Analysis in Noisy Environment

    KAUST Repository

    Liu, Dayan

    2015-03-31

    The integer order differentiation by integration method based on the Jacobi orthogonal polynomials for noisy signals was originally introduced by Mboup, Join and Fliess. We propose to extend this method from the integer order to the fractional order to estimate the fractional order derivatives of noisy signals. Firstly, two fractional order differentiators are deduced from the Jacobi orthogonal polynomial filter, using the Riemann-Liouville and the Caputo fractional order derivative definitions respectively. Exact and simple formulae for these differentiators are given by integral expressions. Hence, they can be used for both continuous-time and discrete-time models in on-line or off-line applications. Secondly, some error bounds are provided for the corresponding estimation errors. These bounds allow to study the design parameters\\' influence. The noise error contribution due to a large class of stochastic processes is studied in discrete case. The latter shows that the differentiator based on the Caputo fractional order derivative can cope with a class of noises, whose mean value and variance functions are polynomial time-varying. Thanks to the design parameters analysis, the proposed fractional order differentiators are significantly improved by admitting a time-delay. Thirdly, in order to reduce the calculation time for on-line applications, a recursive algorithm is proposed. Finally, the proposed differentiator based on the Riemann-Liouville fractional order derivative is used to estimate the state of a fractional order system and numerical simulations illustrate the accuracy and the robustness with respect to corrupting noises.

  18. Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein.

    Science.gov (United States)

    Eaton, A D; Zimmermann, C; Delaney, B; Hurley, B P

    2017-08-01

    An experimental platform employing human derived intestinal epithelial cell (IEC) line monolayers grown on permeable Transwell ® filters was previously investigated to differentiate between hazardous and innocuous proteins. This approach was effective at distinguishing these types of proteins and perturbation of monolayer integrity, particularly transepithelial electrical resistance (TEER), was the most sensitive indicator. In the current report, in vitro indicators of monolayer integrity, cytotoxicity, and inflammation were evaluated using primary (non-transformed) human polarized small intestinal epithelial barriers cultured on Transwell ® filters to compare effects of a hazardous protein (Clostridium difficile Toxin A [ToxA]) and an innocuous protein (bovine serum albumin [BSA]). ToxA exerted a reproducible decrease on barrier integrity at doses comparable to those producing effects observed from cell line-derived IEC monolayers, with TEER being the most sensitive indicator. In contrast, BSA, tested at concentrations substantially higher than ToxA, did not cause changes in any of the tested variables. These results demonstrate a similarity in response to certain proteins between cell line-derived polarized IEC models and a primary human polarized small intestinal epithelial barrier model, thereby reinforcing the potential usefulness of cell line-derived polarized IECs as a valid experimental platform to differentiate between hazardous and non-hazardous proteins. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Spectral line polarimetry with a channeled polarimeter.

    Science.gov (United States)

    van Harten, Gerard; Snik, Frans; Rietjens, Jeroen H H; Martijn Smit, J; Keller, Christoph U

    2014-07-01

    Channeled spectropolarimetry or spectral polarization modulation is an accurate technique for measuring the continuum polarization in one shot with no moving parts. We show how a dual-beam implementation also enables spectral line polarimetry at the intrinsic resolution, as in a classic beam-splitting polarimeter. Recording redundant polarization information in the two spectrally modulated beams of a polarizing beam-splitter even provides the possibility to perform a postfacto differential transmission correction that improves the accuracy of the spectral line polarimetry. We perform an error analysis to compare the accuracy of spectral line polarimetry to continuum polarimetry, degraded by a residual dark signal and differential transmission, as well as to quantify the impact of the transmission correction. We demonstrate the new techniques with a blue sky polarization measurement around the oxygen A absorption band using the groundSPEX instrument, yielding a polarization in the deepest part of the band of 0.160±0.010, significantly different from the polarization in the continuum of 0.2284±0.0004. The presented methods are applicable to any dual-beam channeled polarimeter, including implementations for snapshot imaging polarimetry.

  20. Gene ontology of differentially expressed genes in the Necrotic enteritis induced chicken lines

    Science.gov (United States)

    Necrotic enteritis caused by Clostridium perfringens has become prevalent in the broiler industry due to the withdrawal of antibiotics in poultry feed. The expression level of intestinal mRNA from two chicken lines (line 6.3: MD-resistant and 7.2: MD-susceptible) was significantly different followi...

  1. Differential heat shock response of primary human cell cultures and established cell lines

    DEFF Research Database (Denmark)

    Richter, W W; Issinger, O G

    1986-01-01

    degrees C treatment, whereas in immortalized cell lines usually 90% of the cells were found in suspension. Enhanced expression of the major heat shock protein (hsp 70) was found in all heat-treated cells. In contrast to the primary cell cultures, established and transformed cell lines synthesized...

  2. Identification of differentially expressed proteins during human urinary bladder cancer progression.

    Science.gov (United States)

    Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

    2005-01-01

    Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

  3. Comprehensive transcriptome analyses correlated with untargeted metabolome reveal differentially expressed pathways in response to cell wall alterations.

    Science.gov (United States)

    Reem, Nathan T; Chen, Han-Yi; Hur, Manhoi; Zhao, Xuefeng; Wurtele, Eve Syrkin; Li, Xu; Li, Ling; Zabotina, Olga

    2018-03-01

    This research provides new insights into plant response to cell wall perturbations through correlation of transcriptome and metabolome datasets obtained from transgenic plants expressing cell wall-modifying enzymes. Plants respond to changes in their cell walls in order to protect themselves from pathogens and other stresses. Cell wall modifications in Arabidopsis thaliana have profound effects on gene expression and defense response, but the cell signaling mechanisms underlying these responses are not well understood. Three transgenic Arabidopsis lines, two with reduced cell wall acetylation (AnAXE and AnRAE) and one with reduced feruloylation (AnFAE), were used in this study to investigate the plant responses to cell wall modifications. RNA-Seq in combination with untargeted metabolome was employed to assess differential gene expression and metabolite abundance. RNA-Seq results were correlated with metabolite abundances to determine the pathways involved in response to cell wall modifications introduced in each line. The resulting pathway enrichments revealed the deacetylation events in AnAXE and AnRAE plants induced similar responses, notably, upregulation of aromatic amino acid biosynthesis and changes in regulation of primary metabolic pathways that supply substrates to specialized metabolism, particularly those related to defense responses. In contrast, genes and metabolites of lipid biosynthetic pathways and peroxidases involved in lignin polymerization were downregulated in AnFAE plants. These results elucidate how primary metabolism responds to extracellular stimuli. Combining the transcriptomics and metabolomics datasets increased the power of pathway prediction, and demonstrated the complexity of pathways involved in cell wall-mediated signaling.

  4. Is Social Categorization Spatially Organized in a "Mental Line"? Empirical Evidences for Spatial Bias in Intergroup Differentiation.

    Science.gov (United States)

    Presaghi, Fabio; Rullo, Marika

    2018-01-01

    Social categorization is the differentiation between the self and others and between one's own group and other groups and it is such a natural and spontaneous process that often we are not aware of it. The way in which the brain organizes social categorization remains an unresolved issue. We present three experiments investigating the hypothesis that social categories are mentally ordered from left to right on an ingroup-outgroup continuum when membership is salient. To substantiate our hypothesis, we consider empirical evidence from two areas of psychology: research on differences in processing of ingroups and outgroups and research on the effects of spatial biases on processing of quantitative information (e.g., time; numbers) which appears to be arranged from left to right on a small-large continuum, an effect known as the spatial-numerical association of response codes (SNARC). In Experiments 1 and 2 we tested the hypothesis that when membership of a social category is activated, people implicitly locate ingroup categories to the left of a mental line whereas outgroup categories are located on the far right of the same mental line. This spatial organization persists even when stimuli are presented on one of the two sides of the screen and their (explicit) position is spatially incompatible with the implicit mental spatial organization of social categories (Experiment 3). Overall the results indicate that ingroups and outgroups are processed differently. The results are discussed with respect to social categorization theory, spatial agency bias, i.e., the effect observed in Western cultures whereby the agent of an action is mentally represented on the left and the recipient on the right, and the SNARC effect.

  5. Comparison of different methods for erythroid differentiation in the K562 cell line.

    Science.gov (United States)

    Shariati, Laleh; Modaress, Mehran; Khanahmad, Hossein; Hejazi, Zahra; Tabatabaiefar, Mohammad Amin; Salehi, Mansoor; Modarressi, Mohammad Hossein

    2016-08-01

    To compare methods for erythroid differentiation of K562 cells that will be promising in the treatment of beta-thalassemia by inducing γ-globin synthesis. Cells were treated separately with: RPMI 1640 medium without glutamine, RPMI 1640 medium without glutamine supplemented with 1 mM sodium butyrate, RPMI 1640 medium supplemented with 1 mM sodium butyrate, 25 µg cisplatin/ml, 0.1 µg cytosine arabinoside/ml. The highest differentiation (84 %) with minimum toxicity was obtained with cisplatin at 15 µg /ml. Real-time RT-PCR showed that expression of the γ-globin gene was significantly higher in the cells differentiated with cisplatin compared to undifferentiated cells (P < 0.001). Cisplatin is useful in the experimental therapy of ß-globin gene defects and can be considered for examining the basic mechanism of γ-reactivation.

  6. 78 FR 62614 - Guttman Energy, Inc., PBF Holding Company LLC v. Buckeye Pipe Line Company, L.P., Laurel Pipe...

    Science.gov (United States)

    2013-10-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. OR14-4-000] Guttman Energy, Inc., PBF Holding Company LLC v. Buckeye Pipe Line Company, L.P., Laurel Pipe Line Company, L.P... complaint against Buckeye Pipe Line Company L.P. and Laurel Pipe Line Company L.P. (Respondents) challenging...

  7. Synchronization with propagation - The functional differential equations

    Science.gov (United States)

    Rǎsvan, Vladimir

    2016-06-01

    The structure represented by one or several oscillators couple to a one-dimensional transmission environment (e.g. a vibrating string in the mechanical case or a lossless transmission line in the electrical case) turned to be attractive for the research in the field of complex structures and/or complex behavior. This is due to the fact that such a structure represents some generalization of various interconnection modes with lumped parameters for the oscillators. On the other hand the lossless and distortionless propagation along transmission lines has generated several research in electrical, thermal, hydro and control engineering leading to the association of some functional differential equations to the basic initial boundary value problems. The present research is performed at the crossroad of the aforementioned directions. We shall associate to the starting models some functional differential equations - in most cases of neutral type - and make use of the general theorems for existence and stability of forced oscillations for functional differential equations. The challenges introduced by the analyzed problems for the general theory are emphasized, together with the implication of the results for various applications.

  8. Differential biological effects of iodoacetate in mammalian cell lines; radio sensitization and radio protection

    International Nuclear Information System (INIS)

    Yadav, Usha; Anjaria, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Shirsath, K.B.; Bhat, Nagesh N.; Balakrishnan, Sreedevi; Sapra, B.K.; Nairy, Rajesha

    2014-01-01

    There are several studies where it has been shown that Iodoacetate (IA) possesses in vivo anti-tumor activity. The fact that it is a model glycolytic inhibitor makes it more interesting. As seen in recent trends, glycolytic inhibitors are emerging as new strategy for cancer therapeutic research taking advantage of glycolytic phenotype of cancerous tissues. IA has been reported to have radioprotective effects in yeast cells and human lymphocytes. Biological effects of IA in response to radiation in mammalian cell lines are not well documented. We screened IA for cytotoxicity using clonogenic assay at different concentrations ranging from 0.1 to 2.5 μg/ml using three different mammalian cell lines; A-549 (human lung carcinoma cell line), MCF-7 (human mammary cancer cell line) and a noncancerous CHO (Chinese hamster ovary cell line). For studying radioprotective/radio sensitizing efficacy, cells were exposed to 4 Gy of 60 Co-γ radiation using a teletherapy source at a dose rate of 1 Gy/min, following which IA post-treatment was carried out. Clonogenic and micronucleus assay were performed to assess radioprotection/sensitization. The results indicated that IA was highly cytotoxic in cancerous cell lines A-549 (IC 50 =1.25 μg/ml) and MCF-7 (IC 50 = 1.9 μg/ml). In contrast, it was totally non-toxic in non-cancerous cell line, viz. CHO, in the same concentration range. In addition, IA exhibited radio protective effect in CHO cell line, whereas in other two cancer cell lines, viz. A-549 and MCF-7, radio sensitizing effect was seen as judged by induction of cell killing and micronuclei. In conclusion, lA, a model glycolytic inhibitor, was found to be selectively cytotoxic in cancer cells as compared to normal cells. Further, it reduced radiation induced damage (micronuclei and cell killing) in normal cells but increased it in cancer cells indicating its potential use in cancer therapy. (author)

  9. Empathic Concern and the Desire to Help as Separable Components of Compassionate Responding.

    Science.gov (United States)

    Ministero, Lauren M; Poulin, Michael J; Buffone, Anneke E K; DeLury, Shane

    2018-04-01

    When do people experience versus regulate responses to compassion-evoking stimuli? We hypothesized that compassionate responding is composed of two factors-empathic concern and the desire to help-and that these would be differentially affected by perspective taking and self-affirmation. Exploratory (Study 1) and confirmatory (Study 2) factor analyses indicated that a compassion measure consisted of two factors corresponding to empathic concern and the desire to help. In Study 1 ( N = 237), participants with high emotion regulation ability reported less empathic concern for multiple children than for one, but perspective taking prevented this effect. In Study 2 ( N = 155), participants reported less desire to help multiple children, but only in the presence of self-affirmation. In both the studies, empathic concern predicted greater distress while the desire to help predicted greater chances of donating. Compassionate responding may consist of two separable facets that collapse under distinct conditions and that predict distinct outcomes.

  10. Insulin redirects differentiation from cardiogenic mesoderm and endoderm to neuroectoderm in differentiating human embryonic stem cells.

    NARCIS (Netherlands)

    Freund, C.M.A.H.; Ward-van Oostwaard, D.; Monshouwer-Kloots, J.; van den Brink, S.; van Rooijen, M.A.; Xu, X.; Zweigerdt, R.; Mummery, C.L.; Passier, R.

    2008-01-01

    Human embryonic stem cells (hESC) can proliferate indefinitely while retaining the capacity to form derivatives of all three germ layers. We have reported previously that hESC differentiate into cardiomyocytes when cocultured with a visceral endoderm-like cell line (END-2). Insulin/insulin-like

  11. Treating Chronic Tension-type Headache Not Responding to Amitriptyline Hydrochloride With Paroxetine Hydrochloride: A Pilot Evaluation

    Science.gov (United States)

    Holroyd, Kenneth A.; Labus, Jennifer S.; O'Donnell, Francis J.; Cordingley, Gary E.

    2007-01-01

    Context In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. Objective To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. Design and Setting Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. Participants and Intervention Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. Outcome Measures Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. Results In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. Conclusions We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo. PMID:14511278

  12. Derivation and characterization of the NIH registry human stem cell line NYSCF100 line under defined feeder-free conditions

    Directory of Open Access Journals (Sweden)

    Ana Sevilla

    2018-05-01

    Full Text Available The human embryonic stem cell line NYSCFe001-A was derived from a day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe001-A line, registered as NYSCF100 on the NIH registry, presents normal karyotype, is mycoplasma free, expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro.

  13. Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward.

    Science.gov (United States)

    Sanders, Amy Cecilia; Hussain, Ali J; Hen, René; Zhuang, Xiaoxi

    2007-11-01

    The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment.

  14. Fractional Order Differentiation by Integration and Error Analysis in Noisy Environment

    KAUST Repository

    Liu, Dayan; Gibaru, Olivier; Perruquetti, Wilfrid; Laleg-Kirati, Taous-Meriem

    2015-01-01

    respectively. Exact and simple formulae for these differentiators are given by integral expressions. Hence, they can be used for both continuous-time and discrete-time models in on-line or off-line applications. Secondly, some error bounds are provided

  15. Occluded object reconstruction for first responders with augmented reality glasses using conditional generative adversarial networks

    OpenAIRE

    Yun, Kyongsik; Lu, Thomas; Chow, Edward

    2018-01-01

    Firefighters suffer a variety of life-threatening risks, including line-of-duty deaths, injuries, and exposures to hazardous substances. Support for reducing these risks is important. We built a partially occluded object reconstruction method on augmented reality glasses for first responders. We used a deep learning based on conditional generative adversarial networks to train associations between the various images of flammable and hazardous objects and their partially occluded counterparts....

  16. Influences on call outcomes among Veteran callers to the National Veterans Crisis Line

    Science.gov (United States)

    Britton, Peter C.; Bossarte, Robert M.; Thompson, Caitlin; Kemp, Janet; Conner, Kenneth R.

    2016-01-01

    This evaluation examined the association of caller and call characteristics with proximal outcomes of Veterans Crisis Line calls. From October 1-7, 2010, 665 Veterans with recent suicidal ideation or a history of attempted suicide called the Veterans Crisis Line, 646 had complete data and were included in the analyses. A multivariable multinomial logistic regression was conducted to identify correlates of a favorable outcome, either a resolution or a referral, when compared to an unfavorable outcome, no resolution or referral. A multivariable logistic regression was used to identify correlates of responder-rated caller risk in a subset of calls. Approximately 84% of calls ended with a favorable outcome, 25% with a resolution and 59% with a referral to a local health care provider. Calls from high-risk callers had greater odds of ending with a referral than without a resolution or referral, as did weekday calls (6:00 am to 5:59 pm EST, Monday through Friday). Responders used caller intent to die and the absence of future plans to determine caller risk. Findings suggest that the Veterans Crisis Line is a useful mechanism for generating referrals for high-risk Veteran callers. Responders appeared to use known risk and protective factors to determine caller risk. PMID:23611446

  17. Rapamycin and CHIR99021 Coordinate Robust Cardiomyocyte Differentiation From Human Pluripotent Stem Cells Via Reducing p53-Dependent Apoptosis.

    Science.gov (United States)

    Qiu, Xiao-Xu; Liu, Yang; Zhang, Yi-Fan; Guan, Ya-Na; Jia, Qian-Qian; Wang, Chen; Liang, He; Li, Yong-Qin; Yang, Huang-Tian; Qin, Yong-Wen; Huang, Shuang; Zhao, Xian-Xian; Jing, Qing

    2017-10-02

    Cardiomyocytes differentiated from human pluripotent stem cells can serve as an unexhausted source for a cellular cardiac disease model. Although small molecule-mediated cardiomyocyte differentiation methods have been established, the differentiation efficiency is relatively unsatisfactory in multiple lines due to line-to-line variation. Additionally, hurdles including line-specific low expression of endogenous growth factors and the high apoptotic tendency of human pluripotent stem cells also need to be overcome to establish robust and efficient cardiomyocyte differentiation. We used the H9-human cardiac troponin T-eGFP reporter cell line to screen for small molecules that promote cardiac differentiation in a monolayer-based and growth factor-free differentiation model. We found that collaterally treating human pluripotent stem cells with rapamycin and CHIR99021 during the initial stage was essential for efficient and reliable cardiomyocyte differentiation. Moreover, this method maintained consistency in efficiency across different human embryonic stem cell and human induced pluripotent stem cell lines without specifically optimizing multiple parameters (the efficiency in H7, H9, and UQ1 human induced pluripotent stem cells is 98.3%, 93.3%, and 90.6%, respectively). This combination also increased the yield of cardiomyocytes (1:24) and at the same time reduced medium consumption by about 50% when compared with the previous protocols. Further analysis indicated that inhibition of the mammalian target of rapamycin allows efficient cardiomyocyte differentiation through overcoming p53-dependent apoptosis of human pluripotent stem cells during high-density monolayer culture via blunting p53 translation and mitochondrial reactive oxygen species production. We have demonstrated that mammalian target of rapamycin exerts a stage-specific and multifaceted regulation over cardiac differentiation and provides an optimized approach for generating large numbers of functional

  18. Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines.

    Science.gov (United States)

    Challier, C; Uphoff, C C; Janssen, J W; Drexler, H G

    1996-05-01

    The ufo protein (also termed axl) is a member of a new family of receptor tyrosine kinases and is encoded by a transforming gene that was initially isolated from primary human myeloid leukemia cells by DNA-mediated transformation of NIH/3T3 cells. The ligand, Gas6, a protein S-related molecule lacking any known function yet, has recently been identified. We report the expression pattern of ufo mRNA in a panel of 76 human continuous leukemia-lymphoma cell lines. The gene was not expressed in cell lines derived from lymphoid malignancies (n=28), but transcription was seen in 3/11 myeloid, 0/6 monocytic, 9/13 erythroid and 11/18 megakaryocytic cell lines. Several cell lines were treated with phorbol ester leading to significant upregulation of the ufo message in constitutively positive cells. An apparent ufo mRNA overexpression was not found in any of the positive leukemia cell lines, but was identified in the drug-resistant subclones of the cervix carcinoma cell line HeLa. Southern blot analysis of restriction enzyme-digested genomic DNA did not provide evidence for gene amplification, but the HeLa subclones showed banding patterns suggestive of gene rearrangement. Two main ufo mRNA bands of 3.2 and 5.0 kb were identified; no differences in the half-lives (t1/2 = 2.5 h) of these two mRNA species could be identified. In summary, ufo, representing a novel type of receptor tyrosine kinase, is expressed solely in myeloid and erythro-megakaryocytic leukemias but not in lymphoid malignancies. These and previous data suggest an involvement of the ufo receptor tyrosine kinase in normal and malignant myelopoiesis; however, its exact role, if any, and mode of operation in leukemogenesis remains to be determined.

  19. 76 FR 16609 - Proposed Information Collection; Comment Request; Identification of Human Cell Lines Project

    Science.gov (United States)

    2011-03-24

    ... differentiate among cell lines, as described in Designation: ASN-0002 Authentication of Human Cell Lines... NIST (contact information above). III. Data OMB Control Number: None. Form Number: None. Type of Review...

  20. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    Science.gov (United States)

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  1. Stochastic differentiation into an osteoclast lineage from cloned macrophage-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Shin-Ichi, E-mail: shayashi@med.tottori-u.ac.jp [Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503 (Japan); Murata, Akihiko; Okuyama, Kazuki; Shimoda, Yuhki; Hikosaka, Mari [Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503 (Japan); Yasuda, Hisataka [Planning and Development, Bioindustry Division, Oriental Yeast Co., Ltd, Itabashi-Ku, Tokyo 174-8505 (Japan); Yoshino, Miya [Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-Cho, Yonago, Tottori 683-8503 (Japan)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer The frequency of C7 differentiation into osteoclast was low and constant. Black-Right-Pointing-Pointer Only extended C7 cell cultures exponentially increased osteoclast+ cultures. Black-Right-Pointing-Pointer C7 cell differentiation into committed osteoclast precursors is on 'autopilot'. Black-Right-Pointing-Pointer The system may maintain the stem cell self-renewal and differentiation. -- Abstract: Differentiation into osteoclasts is induced by a macrophage colony-stimulating factor and receptor activator of nuclear-factor {kappa}B ligand. The macrophage-like cell line, C7 has the potential to differentiate into osteoclasts when it is cultured with both factors for 6 days. Although C7 is an established cell line, the frequency of differentiation into this lineage was less than 10%, and the ratio was maintained at a constant level, even after repeated cloning. In this study, to increase the differentiation of C7 cells to osteoclasts, C7 derivative treatments with several activators and/or inhibitors were performed for 3 days prior to setting osteoclast induction analysis; however, a reagent to significantly up-regulate the frequency of differentiation was not found. Only extended cultures for osteoclastogenesis exponentially increased the frequency of osteoclast precursors. It is likely that C7 cell differentiation into committed osteoclast precursors is on 'autopilot' rather than requiring specific signals to drive this process.

  2. Stochastic differentiation into an osteoclast lineage from cloned macrophage-like cells

    International Nuclear Information System (INIS)

    Hayashi, Shin-Ichi; Murata, Akihiko; Okuyama, Kazuki; Shimoda, Yuhki; Hikosaka, Mari; Yasuda, Hisataka; Yoshino, Miya

    2012-01-01

    Highlights: ► The frequency of C7 differentiation into osteoclast was low and constant. ► Only extended C7 cell cultures exponentially increased osteoclast+ cultures. ► C7 cell differentiation into committed osteoclast precursors is on ‘autopilot’. ► The system may maintain the stem cell self-renewal and differentiation. -- Abstract: Differentiation into osteoclasts is induced by a macrophage colony-stimulating factor and receptor activator of nuclear-factor κB ligand. The macrophage-like cell line, C7 has the potential to differentiate into osteoclasts when it is cultured with both factors for 6 days. Although C7 is an established cell line, the frequency of differentiation into this lineage was less than 10%, and the ratio was maintained at a constant level, even after repeated cloning. In this study, to increase the differentiation of C7 cells to osteoclasts, C7 derivative treatments with several activators and/or inhibitors were performed for 3 days prior to setting osteoclast induction analysis; however, a reagent to significantly up-regulate the frequency of differentiation was not found. Only extended cultures for osteoclastogenesis exponentially increased the frequency of osteoclast precursors. It is likely that C7 cell differentiation into committed osteoclast precursors is on ‘autopilot’ rather than requiring specific signals to drive this process.

  3. On organizing principles of discrete differential geometry. Geometry of spheres

    International Nuclear Information System (INIS)

    Bobenko, Alexander I; Suris, Yury B

    2007-01-01

    Discrete differential geometry aims to develop discrete equivalents of the geometric notions and methods of classical differential geometry. This survey contains a discussion of the following two fundamental discretization principles: the transformation group principle (smooth geometric objects and their discretizations are invariant with respect to the same transformation group) and the consistency principle (discretizations of smooth parametrized geometries can be extended to multidimensional consistent nets). The main concrete geometric problem treated here is discretization of curvature-line parametrized surfaces in Lie geometry. Systematic use of the discretization principles leads to a discretization of curvature-line parametrization which unifies circular and conical nets.

  4. Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

    OpenAIRE

    Khwanraj, Kawinthra; Phruksaniyom, Chareerut; Madlah, Suriyat; Dharmasaroja, Permphan

    2015-01-01

    The human neuroblastoma SH-SY5Y cell line has been used as a dopaminergic cell model for Parkinson's disease research. Whether undifferentiated or differentiated SH-SY5Y cells are more suitable remains controversial. This study aims to evaluate the expression of apoptosis-related mRNAs activated by MPP+ and evaluate the differential expression of tyrosine hydroxylase (TH) in undifferentiated and retinoic acid- (RA-) induced differentiated cells. The western blot results showed a gradual decre...

  5. Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory.

    Science.gov (United States)

    Chao, Thomas; Radoncic, Vanya; Hien, Denise; Bedi, Gillinder; Haney, Margaret

    2018-04-01

    Stress responding is linked to drug use, but little is known about stress responses in cannabis smokers. We investigated acute stress responding in cannabis smokers as a function of trauma exposure and sex, and relationships between stress responses and cannabis relapse. 125 healthy, non-treatment-seeking daily cannabis smokers (23F, 102 M) completed the Trier Social Stress Task (TSST), a standardized laboratory stressor; subsets also completed a trauma questionnaire (n = 106) and a laboratory cannabis relapse measure (n = 54). Stress responding was assessed with heart rate (HR), salivary cortisol (CORT), and self-rated mood. Cannabis smokers reporting at least one trauma exposure had higher CORT and anxiety overall compared to those reporting no trauma. Stress responding did not differ as a function of binary trauma exposure, although total number of exposures correlated positively with CORT and anxiety during stress. Females reported increased nervousness after stress relative to males matched to the females for cannabis and cigarette use. An interactive effect of sex and trauma on HR suggested that females with trauma exposure have increased cardiovascular stress responding relative to those without such exposure, with no differential effect in males. Stress responding did not predict laboratory cannabis relapse. We report differences in acute stress responding as a function of trauma, sex, and their interaction in a large sample of relatively homogenous cannabis smokers. Further investigation of how trauma impacts stress responding in male and female cannabis smokers, and how this relates to different aspects of cannabis use, is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    Background: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response...... and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

  7. Augmentation of the Differentiation Response to Antitumor Antimalarials

    National Research Council Canada - National Science Library

    Rahim, Rayhana

    2003-01-01

    .... We have shown that the quinoline antimalarials chloroquine (CO) and hydroxychioroquine (HCQ) inhibit proliferation and induce differentiation in breast cancer cell lines without toxicity to normal MCF-10A cells...

  8. Financial reserve. Hospitals leery of credit lines, factoring receivables.

    Science.gov (United States)

    Edwards, D E; Hamilton, W C; Hauser, R

    1991-10-01

    Opening lines of credit and factoring (selling) accounts receivable are two ways to generate operating cash that non-healthcare industries have long used successfully. A recent survey of hospital officials across the nation, however, showed these techniques are used infrequently in health care. Among the 281 hospitals responding: Only 45 percent use lines of credit; Less than 5 percent pursue accounts receivable factoring; and Only 12 percent plan to begin factoring receivables in the future. As hospitals look for ways to offset depleted cash reserves, these percentages may increase.

  9. Identification of differentially expressed proteins during human urinary bladder cancer progression

    DEFF Research Database (Denmark)

    Memon, Ashfaque Ahmed; chang, Jong. w; Oh, Bong R.

    2005-01-01

    and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder...... cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may...

  10. Exceptional Responders Initial Feasibility Results

    Science.gov (United States)

    A pilot study evaluating identification of cancer patients who respond to treatment that is ineffective in at least 90 percent of patients found that it was indeed able to confirm a majority of proposed patients as exceptional responders based on clinical

  11. 7 CFR 3017.1000 - Respondent.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Respondent. 3017.1000 Section 3017.1000 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 3017.1000 Respondent...

  12. Hypoxia induces adipogenic differentitation of myoblastic cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Itoigawa, Yoshiaki [Tohoku University School of Medicine, Sendai (Japan); Juntendo University School of Medicine, Tokyo (Japan); Kishimoto, Koshi N., E-mail: kishimoto@med.tohoku.ac.jp [Tohoku University School of Medicine, Sendai (Japan); Okuno, Hiroshi; Sano, Hirotaka [Tohoku University School of Medicine, Sendai (Japan); Kaneko, Kazuo [Juntendo University School of Medicine, Tokyo (Japan); Itoi, Eiji [Tohoku University School of Medicine, Sendai (Japan)

    2010-09-03

    Research highlights: {yields} C2C12 and G8 myogenic cell lines treated by hypoxia differentiate into adipocytes. {yields} The expression of C/EBP{beta}, {alpha} and PPAR{gamma} were increased under hypoxia. {yields} Myogenic differentiation of C2C12 was inhibited under hypoxia. -- Abstract: Muscle atrophy usually accompanies fat accumulation in the muscle. In such atrophic conditions as back muscles of kyphotic spine and the rotator cuff muscles with torn tendons, blood flow might be diminished. It is known that hypoxia causes trans-differentiation of mesenchymal stem cells derived from bone marrow into adipocytes. However, it has not been elucidated yet if hypoxia turned myoblasts into adipocytes. We investigated adipogenesis in C2C12 and G8 murine myogenic cell line treated by hypoxia. Cells were also treated with the cocktail of insulin, dexamethasone and IBMX (MDI), which has been known to inhibit Wnt signaling and promote adipogenesis. Adipogenic differentiation was seen in both hypoxia and MDI. Adipogenic marker gene expression was assessed in C2C12. CCAAT/enhancer-binding protein (C/EBP) {beta}, {alpha} and peroxisome proliferator activating receptor (PPAR) {gamma} were increased by both hypoxia and MDI. The expression profile of Wnt10b was different between hypoxia and MDI. The mechanism for adipogenesis of myoblasts in hypoxia might be regulated by different mechanism than the modification of Wnt signaling.

  13. Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

    Science.gov (United States)

    Patton, N M; Brown, R V; Middleton, C C

    1975-01-01

    Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

  14. Involvement of CRF2 signaling in enterocyte differentiation.

    Science.gov (United States)

    Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Powell, Rebecca; Buisson, Alain; Bonaz, Bruno; Jacquier-Sarlin, Muriel

    2017-07-28

    To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation. For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CRF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CRF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TRITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mRNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor krüppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by RT-PCR and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric method. CRF2 protein is preferentially expressed in undifferentiated epithelial cells from

  15. Derivation of the human embryonic stem cell line RCM1

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-03-01

    Full Text Available The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

  16. Principles of Economics Textbooks: Innovation and Product Differentiation--A Response.

    Science.gov (United States)

    Sichel, Werner

    1988-01-01

    Focusing on areas of contention, the author responds to "Principles of Economics Textbooks: Innovation and Product Differentiation" by Stiglitz. Contends that Stiglitz's description of principles textbooks is insufficient, states that the textbook market is more oligopolistic than monopolistic, and cautions writers against deleting parts…

  17. Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, L. H.; Madsen, B; Teisner, Børge

    1998-01-01

    GH exerts adipogenic activity in several preadipocyte cell lines, whereas in primary rat preadipocytes, GH has an antiadipogenic activity. To better understand the molecular mechanism involved in adipocyte differentiation, the expression of adipocyte-specific genes was analyzed in differentiating...

  18. PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.

    Science.gov (United States)

    Di Loreto, S; D'Angelo, B; D'Amico, M A; Benedetti, E; Cristiano, L; Cinque, B; Cifone, M G; Cerù, M P; Festuccia, C; Cimini, A

    2007-06-01

    Neuroblastomas are pediatric tumors originating from immature neuroblasts in the developing peripheral nervous system. Differentiation therapies could help lowering the high mortality due to rapid tumor progression to advanced stages. Oleic acid has been demonstrated to promote neuronal differentiation in neuronal cultures. Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells. The results obtained demonstrate that many, but not all, oleic acid effects are mediated by PPARbeta and support a role for PPARbeta in neuronal differentiation strongly pointing towards PPAR ligands as new therapeutic strategies against progression and recurrences of neuroblastoma.

  19. Signal differentiation in position tracking control of dc motors

    International Nuclear Information System (INIS)

    Beltran-Carbajal, F; Valderrabano-Gonzalez, A; Rosas-Caro, J C

    2015-01-01

    An asymptotic differentiation approach with respect to time is used for on-line estimation of velocity and acceleration signals in controlled dc motors. The attractive feature of this differentiator of signals is that it does not require any system mathematical model, which allows its use in engineering systems that require the signal differentiation for its control, identification, fault detection, among other applications. Moreover, it is shown that the differentiation approach can be applied for output signals showing a chaotic behavior. In addition a differential flatness control scheme with additional integral compensation of the output error is proposed for tracking tasks of position reference trajectories for direct current electric motors using angular position measurements only

  20. Mobile-Only Web Survey Respondents

    NARCIS (Netherlands)

    Lugtig, P.J.|info:eu-repo/dai/nl/304824658; Toepoel, V.|info:eu-repo/dai/nl/304576034; amin, alerk

    2016-01-01

    Web surveys are no longer completed on just a desktop or laptop computer. Respondents increasingly use mobile devices, such as tablets and smartphones to complete web surveys. In this article, we study how respondents in the American Life Panel complete surveys using varying devices. We show that

  1. Correlation between membrane fluidity cellular development and stem cell differentiation

    KAUST Repository

    Noutsi, Pakiza

    2016-12-01

    Cell membranes are made up of a complex structure of lipids and proteins that diffuse laterally giving rise to what we call membrane fluidity. During cellular development, such as neuronal differentiation, cell membranes undergo dramatic structural changes induced by proteins such as ARC and Cofilin among others in the case of synaptic modification. In this study we used the generalized polarization (GP) property of fluorescent probe Laurdan using two-photon microscopy to determine membrane fluidity as a function of time and for various cell lines. A low GP value corresponds to a higher fluidity and a higher GP value is associated with a more rigid membrane. Four different cell lines were monitored such as hN2, NIH3T3, HEK293 and L6 cells. As expected, NIH3T3 cells have more rigid membrane at earlier stages of their development. On the other hand neurons tend to have the highest membrane fluidity early in their development emphasizing its correlation with plasticity and the need for this malleability during differentiation. This study sheds light on the involvement of membrane fluidity during neuronal differentiation and development of other cell lines.

  2. The effect of bright lines in environmental risk communication

    International Nuclear Information System (INIS)

    Wilson, K.N.; Desvousges, W.H.; Smith, K.V.; Payne, J.

    1993-01-01

    Bright lines in environmental risk communication refer to the specific levels at which an environmental risk becomes a serious health threat and action should be taken to mitigate its effects. This study examined the effect of ''bright lines'' in risk communication by emphasizing the radon exposure threshold level of 4 picocuries per liter. Specifically, the authors developed a computer-assisted interview containing bright-line versions of risk information. The bright-line version contained a range of possible radon levels, the corresponding number of estimated lung cancer cases, the relative health risk from radon compared to other health risks, and the EPA guidelines for mitigating levels above 4 picocuries in the home. The non-bright line version was identical to the bright-line version, except it did not include the EPA's mitigation recommendations. Effect measures included respondents' change in perceived risk after reading their materials, intended testing behavior, and advice to their neighbor for a specified radon level either above or below the 4 picocury threshold level. This paper discusses broader policy implications for designing effective risk communication programs

  3. Derivation, characterization and retinal differentiation of induced ...

    Indian Academy of Sciences (India)

    2013-01-11

    Jan 11, 2013 ... ing the differentiating medium with a RPE-cell-line-condi- tioned medium. 2. ... medium and plated into four 100 mm dishes and the cultures ... mitotically inactivated by applying 5000 rad of radiation in a .... Temperature °C.

  4. Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines

    Directory of Open Access Journals (Sweden)

    M. Crescimanno

    2009-01-01

    Full Text Available The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance. Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At IC50 dose level (17 ug/ml and 32 ug/ml respectively for sensitive and resistant cell lines, the crude extract induced differentiation associated with the expression of CD14 monocytic cell lines but not that of CD11 granulocityc cell surface antigen. Further investigations are in progress to better clarify the mechanism by which olive oil phenols induce diffentiation on this cell line.

  5. GARLIC - A general purpose atmospheric radiative transfer line-by-line infrared-microwave code: Implementation and evaluation

    Science.gov (United States)

    Schreier, Franz; Gimeno García, Sebastián; Hedelt, Pascal; Hess, Michael; Mendrok, Jana; Vasquez, Mayte; Xu, Jian

    2014-04-01

    A suite of programs for high resolution infrared-microwave atmospheric radiative transfer modeling has been developed with emphasis on efficient and reliable numerical algorithms and a modular approach appropriate for simulation and/or retrieval in a variety of applications. The Generic Atmospheric Radiation Line-by-line Infrared Code - GARLIC - is suitable for arbitrary observation geometry, instrumental field-of-view, and line shape. The core of GARLIC's subroutines constitutes the basis of forward models used to implement inversion codes to retrieve atmospheric state parameters from limb and nadir sounding instruments. This paper briefly introduces the physical and mathematical basics of GARLIC and its descendants and continues with an in-depth presentation of various implementation aspects: An optimized Voigt function algorithm combined with a two-grid approach is used to accelerate the line-by-line modeling of molecular cross sections; various quadrature methods are implemented to evaluate the Schwarzschild and Beer integrals; and Jacobians, i.e. derivatives with respect to the unknowns of the atmospheric inverse problem, are implemented by means of automatic differentiation. For an assessment of GARLIC's performance, a comparison of the quadrature methods for solution of the path integral is provided. Verification and validation are demonstrated using intercomparisons with other line-by-line codes and comparisons of synthetic spectra with spectra observed on Earth and from Venus.

  6. Experimental Model to Study the Role of Retinoblastoma Gene Product (pRb) for Determination of Adipocyte Differentiation.

    Science.gov (United States)

    Popov, B V; Shilo, P S; Zhidkova, O V; Zaichik, A M; Petrov, N S

    2015-06-01

    Using stable constitutive expression of retinoblastoma gene product (pRb) in polypotent mesenchymal 10T1/2 cells we obtained stable cell lines hyperexpressing functionally active or inactive mutant pRb. The cells producing active exogenous pRb demonstrated high sensitivity to adipocyte differentiation inductors, whereas production of inactive form of the exogenous protein suppressed adipocyte differentiation. The obtained lines can serve as the experimental model for studying the role of pRb in determination of adipocyte differentiation.

  7. Responder Technology Alert (February 2015)

    Energy Technology Data Exchange (ETDEWEB)

    Upton, Jaki F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stein, Steven L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-04-10

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in the areas wearable technology.

  8. Establishment and culture optimization of a new type of pituitary immortalized cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kokubu, Yuko [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Asashima, Makoto [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577 (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan)

    2015-08-07

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  9. Presenilin expression during induced differentiation of the human neuroblastoma SH-SY5Y cell line.

    Science.gov (United States)

    Flood, Fiona; Sundström, Erik; Samuelsson, Eva-Britt; Wiehager, Birgitta; Seiger, Ake; Johnston, Janet A; Cowburn, Richard F

    2004-06-01

    Human neuroblastoma SH-SY5Y cells stably transfected with both wild-type and exon-9 deleted (deltaE9) presenilin constructs were used to study the role of the presenilin proteins during differentiation. Cells transfected with either wild-type or deltaE9 PS1, of which the latter abolishes normal endoproteolytic cleavage of the protein, showed no obvious differences in their ability to differentiate to a neuronal-like phenotype upon treatment with retinoic acid (RA). A defined pattern of PS1 expression was observed during differentiation with both RA and the phorbol ester TPA. Full-length PS1 was shown to increase dramatically within 5-24 h of RA treatment. TPA gave an earlier and longer lasting increase in full-length PS1 levels. The intracellular distribution pattern of PS1 was markedly altered following RA treatment. Within 24h PS1 was highly up-regulated throughout the cell body around the nucleus. Between 2 and 4 weeks PS1 staining appeared punctate and also localised to the nucleus. Increases in PS1 expression upon treatment with RA and TPA were blocked by treatment with cycloheximide, indicating a role of de-novo protein synthesis in this effect. PS2 expression remained unchanged during differentiation. Levels of full-length PS1 were also seen to increase during neurogenesis and neuronal differentiation in the forebrain of first trimester human foetuses between 6.5 and 11 weeks. These combined observations support the idea that PS1 is involved in neuronal differentiation by a mechanism likely independent of endoproteolysis of the protein.

  10. Minimization over randomly selected lines

    Directory of Open Access Journals (Sweden)

    Ismet Sahin

    2013-07-01

    Full Text Available This paper presents a population-based evolutionary optimization method for minimizing a given cost function. The mutation operator of this method selects randomly oriented lines in the cost function domain, constructs quadratic functions interpolating the cost function at three different points over each line, and uses extrema of the quadratics as mutated points. The crossover operator modifies each mutated point based on components of two points in population, instead of one point as is usually performed in other evolutionary algorithms. The stopping criterion of this method depends on the number of almost degenerate quadratics. We demonstrate that the proposed method with these mutation and crossover operations achieves faster and more robust convergence than the well-known Differential Evolution and Particle Swarm algorithms.

  11. First Responders and Criticality Accidents

    Energy Technology Data Exchange (ETDEWEB)

    Valerie L. Putman; Douglas M. Minnema

    2005-11-01

    Nuclear criticality accident descriptions typically include, but do not focus on, information useful to first responders. We studied these accidents, noting characteristics to help (1) first responders prepare for such an event and (2) emergency drill planners develop appropriate simulations for training. We also provide recommendations to help people prepare for such events in the future.

  12. A/T test system for production line; Seisan line yo A/T test system

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-10

    This paper introduces an A/T test system for production line made by Meidensha, Inc. Rates and technology of mounting auto-transmissions (A/T) in recent automobiles are improving year after year. A/T production line testers were fabricated and supplied, including those for European countries. This system has the following features: the system employs low inertia AC motor, and is capable of performing tests in close conditions to actual cars; an insulated gate bipolar transistor (IGBT) inverter was employed to achieve control accuracy improvement and noise reduction; high-velocity transient measurement is possible by using a computer system based on the WindowsNT; a solenoid current slant control was employed to respond to electronically controlled A/T; and noise and vibration shift feeling instrumentation can also be used on option. Number of supply is four sets of front engine/front wheel drive (FF) car A/T testers for overseas countries, and two sets of FF A/T tests for use in Japan. (NEDO)

  13. Line width of Josephson flux flow oscillators

    DEFF Research Database (Denmark)

    Koshelets, V.P.; Dmitriev, P.N.; Sobolev, A.S.

    2002-01-01

    to be proven before one initiates real FFO applications. To achieve this goal a comprehensive set of line width measurements of the FFO operating in different regimes has been performed. FFOs with tapered shape have been successfully implemented in order to avoid the superfine resonant structure with voltage...... spacing of about 20 nV and extremely low differential resistance, recently observed in the IVC of the standard rectangular geometry. The obtained results have been compared with existing theories and FFO models in order to understand and possibly eliminate excess noise in the FFO. The intrinsic line width...

  14. Response of Turkey Muscle Satellite Cells to Thermal Challenge. II. Transcriptome Effects in Differentiating Cells

    Directory of Open Access Journals (Sweden)

    Kent M. Reed

    2017-11-01

    Full Text Available Background: Exposure of poultry to extreme temperatures during the critical period of post-hatch growth can seriously affect muscle development and thus compromise subsequent meat quality. This study was designed to characterize transcriptional changes induced in turkey muscle satellite cells by thermal challenge during differentiation. Our goal is to better define how thermal stress alters breast muscle ultrastructure and subsequent development.Results: Skeletal muscle satellite cells previously isolated from the Pectoralis major muscle of 7-wk-old male turkeys (Meleagris gallopavo from two breeding lines: the F-line (16 wk body weight-selected and RBC2 (randombred control line were used in this study. Cultured cells were induced to differentiate at 38°C (control or thermal challenge temperatures of 33 or 43°C. After 48 h of differentiation, cells were harvested and total RNA was isolated for RNAseq analysis. Analysis of 39.9 Gb of sequence found 89% mapped to the turkey genome (UMD5.0, annotation 101 with average expression of 18,917 genes per library. In the cultured satellite cells, slow/cardiac muscle isoforms are generally present in greater abundance than fast skeletal isoforms. Statistically significant differences in gene expression were observed among treatments and between turkey lines, with a greater number of genes affected in the F-line cells following cold treatment whereas more differentially expressed (DE genes were observed in the RBC2 cells following heat treatment. Many of the most significant pathways involved signaling, consistent with ongoing cellular differentiation. Regulation of Ca2+ homeostasis appears to be significantly affected by temperature treatment, particularly cold treatment.Conclusions: Satellite cell differentiation is directly influenced by temperature at the level of gene transcription with greater effects attributed to selection for fast growth. At lower temperature, muscle-associated genes in the

  15. Criticality Safety Basics for INL Emergency Responders

    Energy Technology Data Exchange (ETDEWEB)

    Valerie L. Putman

    2012-08-01

    This document is a modular self-study guide about criticality safety principles for Idaho National Laboratory emergency responders. This guide provides basic criticality safety information for people who, in response to an emergency, might enter an area that contains much fissionable (or fissile) material. The information should help responders understand unique factors that might be important in responding to a criticality accident or in preventing a criticality accident while responding to a different emergency.

    This study guide specifically supplements web-based training for firefighters (0INL1226) and includes information for other Idaho National Laboratory first responders. However, the guide audience also includes other first responders such as radiological control personnel.

    For interested readers, this guide includes clearly marked additional information that will not be included on tests. The additional information includes historical examples (Been there. Done that.), as well as facts and more in-depth information (Did you know …).

    INL criticality safety personnel revise this guide as needed to reflect program changes, user requests, and better information. Revision 0, issued May 2007, established the basic text. Revision 1 incorporates operation, program, and training changes implemented since 2007. Revision 1 increases focus on first responders because later responders are more likely to have more assistance and guidance from facility personnel and subject matter experts. Revision 1 also completely reorganized the training to better emphasize physical concepts behind the criticality controls that help keep emergency responders safe. The changes are based on and consistent with changes made to course 0INL1226.

  16. The probability of reinforcement per trial affects posttrial responding and subsequent extinction but not within-trial responding.

    Science.gov (United States)

    Harris, Justin A; Kwok, Dorothy W S

    2018-01-01

    During magazine approach conditioning, rats do not discriminate between a conditional stimulus (CS) that is consistently reinforced with food and a CS that is occasionally (partially) reinforced, as long as the CSs have the same overall reinforcement rate per second. This implies that rats are indifferent to the probability of reinforcement per trial. However, in the same rats, the per-trial reinforcement rate will affect subsequent extinction-responding extinguishes more rapidly for a CS that was consistently reinforced than for a partially reinforced CS. Here, we trained rats with consistently and partially reinforced CSs that were matched for overall reinforcement rate per second. We measured conditioned responding both during and immediately after the CSs. Differences in the per-trial probability of reinforcement did not affect the acquisition of responding during the CS but did affect subsequent extinction of that responding, and also affected the post-CS response rates during conditioning. Indeed, CSs with the same probability of reinforcement per trial evoked the same amount of post-CS responding even when they differed in overall reinforcement rate and thus evoked different amounts of responding during the CS. We conclude that reinforcement rate per second controls rats' acquisition of responding during the CS, but at the same time, rats also learn specifically about the probability of reinforcement per trial. The latter learning affects the rats' expectation of reinforcement as an outcome of the trial, which influences their ability to detect retrospectively that an opportunity for reinforcement was missed, and, in turn, drives extinction. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  17. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    Eguchi, Goro

    1980-01-01

    To develop the method to induce the appearance of differentiation in amelanotic melanoma, experimental control of differentiation in B-16 melanoma cells of mice was discussed. Human melanoma cells and yellow melanin pigment cells useful for a fundamental study of radiotherapy for cancer were cultured and were differentiated into some lines. Melanotic B-16 cells and amelanotic B-16 cells were irradiated with thermal neutron (neutron: 2.7 x 10 12 , γ-dose: 32.3 rad) after they were cultured in culture solution containing 10 γ/ml of 10 B-dopa for 13 hours. A fine structure 5 hours after the irradiation in one of 5 experimental cases showed aggregated disintegration of melanin pigment particles, markedly deformed and fragmentized nucleus, and structural changes in cell membrane. (Tsunoda, M.)

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

    Science.gov (United States)

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

    2010-05-11

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

  19. L-059: EPR-First responders: Radiological emergency manual for first responders

    International Nuclear Information System (INIS)

    2011-01-01

    This conference is an emergency manual review about the first responders knowledge. The IAEA safety standard manuals, the medical gestion, the security forces and the fast communications are very important in a radiological emergency

  20. Qualitative tissue differentiation by analysing the intensity ratios of atomic emission lines using laser induced breakdown spectroscopy (LIBS): prospects for a feedback mechanism for surgical laser systems.

    Science.gov (United States)

    Kanawade, Rajesh; Mahari, Fanuel; Klämpfl, Florian; Rohde, Maximilian; Knipfer, Christian; Tangermann-Gerk, Katja; Adler, Werner; Schmidt, Michael; Stelzle, Florian

    2015-01-01

    The research work presented in this paper focuses on qualitative tissue differentiation by monitoring the intensity ratios of atomic emissions using 'Laser Induced Breakdown Spectroscopy' (LIBS) on the plasma plume created during laser tissue ablation. The background of this study is to establish a real time feedback control mechanism for clinical laser surgery systems during the laser ablation process. Ex-vivo domestic pig tissue samples (muscle, fat, nerve and skin) were used in this experiment. Atomic emission intensity ratios were analyzed to find a characteristic spectral line for each tissue. The results showed characteristic elemental emission intensity ratios for the respective tissues. The spectral lines and intensity ratios of these specific elements varied among the different tissue types. The main goal of this study is to qualitatively and precisely identify different tissue types for tissue specific laser surgery. © 2015 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag.

  1. The characteristics of non-respondents and respondents of a mental health survey among evacuees in a disaster: The Fukushima Health Management Survey.

    Science.gov (United States)

    Horikoshi, Naoko; Iwasa, Hajime; Yasumura, Seiji; Maeda, Masaharu

    2017-12-19

    The Fukushima Medical University conducted a mental health care program for evacuees after the Fukushima Daiichi nuclear power plant accident. However, the mental health status of non-respondents has not been considered for surveys using questionnaires. Therefore, the aim of this study was to clarify the characteristics of non-respondents and respondents. The target population of the survey (FY2011-2013) is people living in the nationally designated evacuation zone of Fukushima prefecture. Among these, the participants were 967 people (20 years or older). We examined factors that affected the difference between the groups of participants (i.e., non-respondents and respondents) using multivariate logistic regression analysis. Employment was higher in non-respondents (p=0.022) and they were also more socially isolated (p=0.047) when compared to respondents; non-respondents had a higher proportional risk of psychological distress compared to respondents (pemployment status (OR=1.99, 95% confidence interval [CI]:1.12-3.51) and psychological distress (OR=2.17, 95% CI:1.01-4.66). We found that non-respondents had a significantly higher proportion of psychological distress compared to the respondents. Although the non-respondents were the high-risk group, it is not possible to grasp the complexity of the situation by simply using questionnaire surveys. Therefore, in the future it is necessary to direct our efforts towards the mental health of non-respondents and respondents alike.

  2. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Jensen, Charlotte H; Gutierrez, Gloria

    2004-01-01

    Dlk-1/Pref-1 was identified as a novel regulator of human skeletal stem cell differentiation. Dlk1/Pref-1 is expressed in bone and cultured osteoblasts, and its constitutive overexpression led to inhibition of osteoblast and adipocyte differentiation of human marrow stromal cells. INTRODUCTION......: Molecular control of human mesenchymal stem cell (hMSC) differentiation into osteoblasts and adipocytes is not known. In this study, we examined the role of delta-like 1/preadipocyte factor-1 (Dlk1/Pref-1) in regulating the differentiation of hMSCs. MATERIALS AND METHODS: As a model for hMSCs, we have...... was used to confirm the in vitro effect of Dlk/Pref-1 on bone formation. RESULTS: Dlk1/Pref-1 was found to be expressed in fetal and adult bone, hMSCs, and some osteoblastic cell lines. A retroviral vector containing the human Dlk1/Pref-1 cDNA was used to create a cell line (hMSC-dlk1) expressing high...

  3. Mecamylamine, dihydro-β-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine

    Science.gov (United States)

    Struthers, Amanda M.; Wilkinson, Jamie L.; Dwoskin, Linda P.; Crooks, Peter A.; Bevins, Rick A.

    2009-01-01

    Current smokers express the desire to quit. However, the majority find it difficult to remain abstinent. As such, research efforts continually seek to develop more effective treatment. One such area of research involves the interoceptive stimulus effects of nicotine as either a discriminative stimulus in an operant drug discrimination task, or more recently as a conditional stimulus (CS) in a discriminated goal-tracking task. The present work investigated the potential role nicotinic acetylcholine receptors in the CS effects of nicotine (0.4 mg/kg) using antagonists with differential selectivity for β2*, α7*, α6β2*, and α3β4* receptors. Methyllycaconitine (MLA) had no effect on nicotine-evoked conditioned responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose dependently blocked responding evoked by the nicotine CS. In a time-course assessment of mecamylamine and DHβE, each blocked conditioned responding when given 5 min before testing and still blocked conditioned responding when administered 200 min before testing. Two novel bis-picolinium analogs (N, N’-(3, 3′-(dodecan-1,12-diyl)-bis-picolinium dibromide [bPiDDB], and N, N’-(decan-1,10-diyl)-bis-picolinium diiodide [bPiDI]) did not block nicotine-evoked conditioned responding. Finally, pretreatment with low dose combinations of mecamylamine, dextromethorphan, and/or bupropion were used to target α3β4* receptors. No combination blocked conditioned responding evoked by the training dose of nicotine. However, a combination of mecamylamine and dextromethorphan partially blocked nicotine-evoked conditioned responding to a lower dose of nicotine (0.1 mg/kg). These results indicate that β2* and potentially α3β4* nicotinic acetylcholine receptors play a role in the CS effects of nicotine and are potential targets for the development of nicotine cessation aids. PMID:19778551

  4. Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

    International Nuclear Information System (INIS)

    Medina, D.; Oborn, C.J.; Li, M.L.; Bissell, M.J.

    1987-01-01

    The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appeared to represent myoepithelial cells. The cell lines were examined for expression of β-casein mRNA in the presence or absence of prolactin. The inducibility of β-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types

  5. Intercellular signaling pathways active during and after growth and differentiation of the lumbar vertebral growth plate.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2011-06-15

    Vertebral growth plates at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the major signaling pathways active in the postnatal mouse lumbar vertebral growth plate. The growth of all long bones is known to occur by cartilaginous growth plates. The growth plate is composed of layers of chondrocyets that actively proliferate, differentiate, die and, are replaced by bone. The role of major cell signaling pathways has been suggested for regulation of the fetal long bones. But not much is known about the molecular or cellular signals that control the postnatal vertebral growth plate and hence postnatal vertebral bone growth. Understanding such molecular mechanisms will help design therapeutic treatments for vertebral growth disorders such as scoliosis. Antibodies against activated downstream intermediates were used to identify cells in the growth plate responding to BMP, TGFβ, and FGF in cryosections of lumbar vertebrae from different postnatal age mice to identify the zones that were responding to these signals. Reporter mice were used to identify the chondrocytes responding to hedgehog (Ihh), and Wnt signaling. We present a spatial/temporal map of these signaling pathways during growth, and differentiation of the mouse lumbar vertebral growth plate. During growth and differentiation of the vertebral growth plate, its different components respond at different times to different intercellular signaling ligands. Response to most of these signals is dramatically downregulated at the end of vertebral growth.

  6. Characterization of type and genetic diversity among soybean cyst nematode differentiators

    Directory of Open Access Journals (Sweden)

    Éder Matsuo

    2012-04-01

    Full Text Available The development of soybean cyst nematode, Heterodera glycines Ichinohe, resistant genotypes with high yields has been one of the objectives of soybean (Glycine max (L. Merrill breeding programs. The objective of this study was to characterize the pathotype of soybean cyst nematodes and analyze the genetic diversity of ten differentiator lines ('Lee 74', Peking, Pickett, PI 88788, PI 90763, PI 437654, PI 209332, PI 89772, PI 548316 and 'Hartwig'. Inoculum was obtained from plants cultivated in field soil in Viçosa, state of Minas Gerais, Brazil. Thirty-four days after inoculating each plant with 4,000 eggs, the number of females, female index, total number of eggs, number of eggs per female, reproduction factor, plant height, number of nodes, fresh and dry matter weights were assessed. The differential lines were first grouped with Scott-Knott test. Subsequently, the genetic diversity was evaluated using dendrograms, graphic analysis and the Tocher grouping method. The inoculum of H. glycines obtained from NBSGBP-UFV was characterized as HG Type 0. The differentiating lines were divergent, and PI 89772, PI 437654, 'Hartwig' and 'Peking' had the greatest potential for use in breeding programs.

  7. Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human b lymphoma cell line bl36

    Directory of Open Access Journals (Sweden)

    Joubert-Caron Raymonde

    2001-12-01

    Full Text Available Abstract Background 5-AzaCytidine (AzaC is a DNA demethylating drugs that has been shown to inhibit cell growth and to induce apoptosis in certain cancer cells. Induced expression of the galectin1 (Gal1 protein, a galactoside-binding protein distributed widely in immune cells, has been described in cultured hepatoma-derived cells treated with AzaC and this event may have a role in the effect of the drug. According to this hypothesis, we investigated the effect of AzaC and Gal1 on human lymphoid B cells phenotype. Methods The effect of AzaC and Gal1 on cell growth and phenotype was determined on the Burkitt lymphoma cell line BL36. An immunocytochemical analysis for detection of Gal1 protein expression was performed in AzaC-treated cells. To investigate the direct effects of Gal1, recombinant Gal1 was added to cells. Results Treatment of lymphoid B cells with AzaC results in: i a decrease in cell growth with an arrest of the cell cycle at G0/G1 phase, ii phenotypic changes consistent with a differentiated phenotype, and iii the expression of p16, a tumor-suppressor gene whose expression was dependent of its promoter demethylation, and of Gal1. A targeting of Gal 1 to the plasma membrane follows its cytosolic expression. To determine which of the effects of AzaC might be secondary to the induction of Gal1, recombinant Gal1 was added to BL36 cells. Treated cells displayed growth inhibition and phenotypic changes consistent with a commitment toward differentiation. Conclusions Altered cell growth and expression of the cell surface plasma cell antigen, CD138 are detectable in BL36 cells treated by AzaC as well as by Gal1. It seems that AzaC-induced Gal1 expression and consequent binding of Gal1 on its cell membrane receptor may be, in part, involved in AzaC-induced plasmacytic differentiation.

  8. Differential gene expression of wheat progeny with contrasting levels of transpiration efficiency.

    Science.gov (United States)

    Xue, Gang-Ping; McIntyre, C Lynne; Chapman, Scott; Bower, Neil I; Way, Heather; Reverter, Antonio; Clarke, Bryan; Shorter, Ray

    2006-08-01

    High water use efficiency or transpiration efficiency (TE) in wheat is a desirable physiological trait for increasing grain yield under water-limited environments. The identification of genes associated with this trait would facilitate the selection for genotypes with higher TE using molecular markers. We performed an expression profiling (microarray) analysis of approximately 16,000 unique wheat ESTs to identify genes that were differentially expressed between wheat progeny lines with contrasting TE levels from a cross between Quarrion (high TE) and Genaro 81 (low TE). We also conducted a second microarray analysis to identify genes responsive to drought stress in wheat leaves. Ninety-three genes that were differentially expressed between high and low TE progeny lines were identified. One fifth of these genes were markedly responsive to drought stress. Several potential growth-related regulatory genes, which were down-regulated by drought, were expressed at a higher level in the high TE lines than the low TE lines and are potentially associated with a biomass production component of the Quarrion-derived high TE trait. Eighteen of the TE differentially expressed genes were further analysed using quantitative RT-PCR on a separate set of plant samples from those used for microarray analysis. The expression levels of 11 of the 18 genes were positively correlated with the high TE trait, measured as carbon isotope discrimination (Delta(13)C). These data indicate that some of these TE differentially expressed genes are candidates for investigating processes that underlie the high TE trait or for use as expression quantitative trait loci (eQTLs) for TE.

  9. NKX6.1 induced pluripotent stem cell reporter lines for isolation and analysis of functionally relevant neuronal and pancreas populations

    Directory of Open Access Journals (Sweden)

    Shailesh Kumar Gupta

    2018-05-01

    Full Text Available Recent studies have reported significant advances in the differentiation of human pluripotent stem cells to clinically relevant cell types such as the insulin producing beta-like cells and motor neurons. However, many of the current differentiation protocols lead to heterogeneous cell cultures containing cell types other than the targeted cell fate. Genetically modified human pluripotent stem cells reporting the expression of specific genes are of great value for differentiation protocol optimization and for the purification of relevant cell populations from heterogeneous cell cultures. Here we present the generation of human induced pluripotent stem cell (iPSC lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterization of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. Cell sorting and gene expression profiling by RNA sequencing revealed that NKX6.1-positive cells from pancreatic differentiations closely resemble human beta cells. Furthermore, functional characterization of the isolated cells demonstrated that glucose-stimulated insulin secretion is mainly confined to the NKX6.1-positive cells. We expect that the NKX6.1-GFP iPSC lines and the results presented here will contribute to the further refinement of differentiation protocols and characterization of hPSC-derived beta cells and motor neurons for disease modelling and cell replacement therapies. Keywords: Human induced pluripotent stem cells, NKX6.1, Reporter cell line, Directed differentiation, hiPSC-derived beta cells

  10. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease.

    Science.gov (United States)

    Xie, Hong-rong; Hu, Lin-sen; Li, Guo-yi

    2010-04-20

    To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic (DAergic) neurons for Parkinson's disease (PD) research and to determine the effect of differentiation on this cell model. The data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals (Pubmed 1973 to 2009). After searching the literature, 60 articles were selected to address this review. The SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-beta-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium (MPP(+)) uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons. Differentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxicity and neuroprotection and are thus more relevant to experimental PD research.

  11. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression

    DEFF Research Database (Denmark)

    Davidsen, Peter K; Gallagher, Iain J; Hartman, Joseph W

    2011-01-01

    MicroRNAs (miRNA), small noncoding RNA molecules, may regulate protein synthesis, while resistance exercise training (RT) is an efficient strategy for stimulating muscle protein synthesis in vivo. However, RT increases muscle mass, with a very wide range of effectiveness in humans. We therefore...... determined the expression level of 21 abundant miRNAs to determine whether variation in these miRNAs was able to explain the variation in RT-induced gains in muscle mass. Vastus lateralis biopsies were obtained from the top and bottom ~20% of responders from 56 young men who undertook a 5 day/wk RT program...... for 12 wk. Training-induced muscle mass gain was determined by dual-energy X-ray absorptiometry, and fiber size was evaluated by histochemistry. The expression level of each miRNA was quantified using TaqMan-based quantitative PCR, with the analysis carried out in a blinded manner. Gene ontology...

  12. Development of free running differential. Development of differential with an actuator and a clutch which disconnects the traction; Free running defu no kaihatsu. Kirippanashi kiko oyobi actuator wo naizoshita differential sochi no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, N; Teraoka, M; Ishikawa, O; Nagaoka, T; Ugajin, K [Tochigi Fuji Sangyo Co. Ltd., Tochigi (Japan)

    1997-10-01

    Free Running Differential has an effect on fuel economy and noise reduction from drive line for four wheel drive vehicle. It has an actuator and a clutch which disconnects the traction from no driving side tire when two wheel drive is selected. this unit can be installed in conventional differential carrier with no design change. It is compact in design and low in cost. We evaluate it as having a dominant position among any other Free running system. 7 figs.

  13. Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers.

    Science.gov (United States)

    Roggenbuck, Dirk; Borghi, Maria Orietta; Somma, Valentina; Büttner, Thomas; Schierack, Peter; Hanack, Katja; Grossi, Claudia; Bodio, Caterina; Macor, Paolo; von Landenberg, Philipp; Boccellato, Francesco; Mahler, Michael; Meroni, Pier Luigi

    2016-05-21

    Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)). Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (β2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-β2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human β2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human β2GPI or after CL-micelle absorption. Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM aß2GPI and aCL. Anti-CL and anti-ß2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and ß2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL) + samples than in patients with APS. HumoAb against domain 1 recognized β2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-β2GPI humoAbs. The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.

  14. Asymptotic behavior of solutions of linear multi-order fractional differential equation systems

    OpenAIRE

    Diethelm, Kai; Siegmund, Stefan; Tuan, H. T.

    2017-01-01

    In this paper, we investigate some aspects of the qualitative theory for multi-order fractional differential equation systems. First, we obtain a fundamental result on the existence and uniqueness for multi-order fractional differential equation systems. Next, a representation of solutions of homogeneous linear multi-order fractional differential equation systems in series form is provided. Finally, we give characteristics regarding the asymptotic behavior of solutions to some classes of line...

  15. A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis

    Directory of Open Access Journals (Sweden)

    Rachita Dhurat

    2018-01-01

    Full Text Available The Conidiobolus coronatus-related rhinoentomophthoromycosis in immunocompetent and immunocompromised (HIV negative individuals has been treated successfully with antifungal drugs. However, C. coronatus infections in first-line antiretroviral therapy (ART-resistant (HIV infected individuals particularly with rhinoentomophthoromycosis have not been reported previously. Here, we describe a case of itraconazole non-responding rhinoentomophthoromycosis in an HIV-infected patient with first-line antiretroviral (ART drug resistance which was successfully managed through systematic diagnostic and therapeutic approaches in dermatologic setting. A 32-year-old HIV-1-infected man presented with painless swelling, nasal redness and respiratory difficulty. The patient was receiving first-line ART and had a history of traumatic injury before the onset of nasopharyngeal manifestations. The patient's previous history included oral candidiasis and pulmonary tuberculosis.

  16. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    Science.gov (United States)

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

    2017-01-01

    ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

  17. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    Directory of Open Access Journals (Sweden)

    Ludovic Arandel

    2017-04-01

    Full Text Available Myotonic dystrophy type 1 (DM1 and type 2 (DM2 are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations.

  18. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

    Science.gov (United States)

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

    2017-04-01

    Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

  19. Effects of sodium phenylbutyrate on differentiation and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cell lines.

    Science.gov (United States)

    Meng, Mei; Jiang, Jun Mei; Liu, Hui; In, Cheng Yong; Zhu, Ju Ren

    2005-01-01

    To explore the effects of sodium phenylbutyrate on the proliferation, differentiation, cell cycle arrest and induction of the P(21WAF1/CIP1) anti-oncogene in human liver carcinoma cell lines Bel-7402 and HepG2. Bel-7402 and HepG2 human liver carcinoma cells were treated with sodium phenylbutyrate at different concentrations. Light microscopy was used to observe morphological changes in the carcinoma cells. Effects on the cell cycle were detected by using flow cytometry. P(21WAF1/CIP1) expression was determined by both reverse transcription-polymerase chain reaction and western blotting. Statistical analysis was performed by using one-way anova and Student's t-test. Sodium phenylbutyrate treatment caused time- and dose-dependent growth inhibition of Bel-7402 and HepG2 cells. This treatment also caused a decline in the proportion of S-phase cells and an increase in the proportion of G(0)/G(1) cells. Sodium phenylbutyrate increased the expression of P(21WAF1/CIP1). Sodium phenylbutyrate inhibits the proliferation of human liver carcinoma cells Bel-7402 and HepG2, induces partial differentiation, and increases the expression of P(21WAF1/CIP1).

  20. Two-Year-Old Children Differentiate Test Questions from Genuine Questions

    Science.gov (United States)

    Grosse, Gerlind; Tomasello, Michael

    2012-01-01

    Children are frequently confronted with so-called "test questions". While genuine questions are requests for missing information, test questions ask for information obviously already known to the questioner. In this study we explored whether two-year-old children respond differentially to one and the same question used as either a genuine question…

  1. ANALYSIS AND SIMULATION OF MAIN MAGNET TRANSMISSION LINE EFFECT

    Energy Technology Data Exchange (ETDEWEB)

    ZHANG,W.; MARNERIS, I.; SANDBERG, J.

    2007-06-25

    A main magnet chain forms a pair of transmission lines. Pulse-reflection-caused voltage and current differentiation throughout the magnet chain can have adverse effect on main magnet field quality. This effect is associated with magnet system configuration, coupling efficiency, and parasitic parameters. A better understanding of this phenomenon will help us in new design and existing system upgrade. In this paper, we exam the transmission line effect due to different input functions as well as configuration, coupling, and other parameters.

  2. Dependent Interviewing and Sub-Optimal Responding

    Directory of Open Access Journals (Sweden)

    Johannes Eggs

    2015-02-01

    Full Text Available With proactive dependent interviewing (PDI respondents are reminded of the answer they gave in the previous interview, before being asked about their current status. PDI is used in panel surveys to assist respondent recall and reduce spurious changes in responses over time. PDI may however provide scope for new errors if respondents falsely accept the previous information as still being an accurate description of their current situation. In this paper we use data from the German Labour Market and Social Security panel study, in which an error was made with the preload data for a PDI question about receipt of welfare benefit. The survey data were linked to individual administrative records on receipt of welfare benefit. A large proportion of respondents accepted the false preload. This behaviour seems mainly driven by the difficulty of the response task: respondents with a more complex history of receipt according to the records were more likely to confirm the false preload. Personality also seemed related to the probability of confirming. Predictors of satisficing, indicators of satisficing on other items in the survey, and characteristics of the survey and interviewer were not predictive of confirming the false preload.

  3. The Influence of Physical Fatigue on Work on a Production Line

    Directory of Open Access Journals (Sweden)

    Kołodziej Sabina

    2017-09-01

    Full Text Available The purpose of this study is to determine the factors having impacts on the physical fatigue of employees and to analyse its influence on work on a production line. In order to carry out these objectives, a comprehensive research was conducted in a medium enterprise producing processed fruit and vegetable products. Air temperature and humidity tests, employee survey, production line productivity measurements, and other observations were performed. Large variations in temperature and humidity were observed during the analysed period. Analysing the survey results, attention was paid to the declared length of sleeping of employees after each shift, the time when they feel fatigue and the factors that, according to respondents, have the greatest impact on the work performed. Attempts were made to determine the wellbeing of employees and to indicate the disturbing symptoms. Special attention was paid to the negative phenomena felt by respondents. The main factors affecting the physical fatigue of employees were identified and described. We sought to explain the impacts of physical fatigue on work on the production line. Improvements, which should help to reduce fatigue and improve working conditions, have been proposed. The analysis provided interesting information that could be used in various food manufacturing companies.

  4. Amyloid protein-mediated differential DNA methylation status regulates gene expression in Alzheimer’s disease model cell line

    International Nuclear Information System (INIS)

    Sung, Hye Youn; Choi, Eun Nam; Ahn Jo, Sangmee; Oh, Seikwan; Ahn, Jung-Hyuck

    2011-01-01

    Highlights: ► Genome-wide DNA methylation pattern in Alzheimer’s disease model cell line. ► Integrated analysis of CpG methylation and mRNA expression profiles. ► Identify three Swedish mutant target genes; CTIF, NXT2 and DDR2 gene. ► The effect of Swedish mutation on alteration of DNA methylation and gene expression. -- Abstract: The Swedish mutation of amyloid precursor protein (APP-sw) has been reported to dramatically increase beta amyloid production through aberrant cleavage at the beta secretase site, causing early-onset Alzheimer’s disease (AD). DNA methylation has been reported to be associated with AD pathogenesis, but the underlying molecular mechanism of APP-sw-mediated epigenetic alterations in AD pathogenesis remains largely unknown. We analyzed genome-wide interplay between promoter CpG DNA methylation and gene expression in an APP-sw-expressing AD model cell line. To identify genes whose expression was regulated by DNA methylation status, we performed integrated analysis of CpG methylation and mRNA expression profiles, and identified three target genes of the APP-sw mutant; hypomethylated CTIF (CBP80/CBP20-dependent translation initiation factor) and NXT2 (nuclear exporting factor 2), and hypermethylated DDR2 (discoidin domain receptor 2). Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored mRNA expression of these three genes, implying methylation-dependent transcriptional regulation. The profound alteration in the methylation status was detected at the −435, −295, and −271 CpG sites of CTIF, and at the −505 to −341 region in the promoter of DDR2. In the promoter region of NXT2, only one CpG site located at −432 was differentially unmethylated in APP-sw cells. Thus, we demonstrated the effect of the APP-sw mutation on alteration of DNA methylation and subsequent gene expression. This epigenetic regulatory mechanism may contribute to the pathogenesis of AD.

  5. Multimedia applications in differential services

    International Nuclear Information System (INIS)

    Mahfooz, S.; Merabti, M.; Pereira, R.

    2003-01-01

    In this paper we present a mechanism to provide Quality of Service (QoS) guarantees to different multimedia applications that share link bandwidth in IP-based differential services domain. In this mechanism weights are associated with each and to individual users according to their priorities. In order to evaluate the performance of our scheme we conducted simulations. The test data used portray different multimedia applications i.e. MPEG-2, IP telephony. The simulation results obtained show the effectiveness of our scheme for multimedia applications by allocating link share to each multimedia application and minimising end-to-end transmission delay 9Y bringing them in line with the recommended standard acceptable transmission delay for multimedia applications. This paper also presents extension to our proposed Relative Bandwidth Sharing (RES) scheme for differential services. We have identified and highlighted the role of border routers and core routers in differential services domain. Exploring features of Internet Protocol IPv6 in our architecture. (author)

  6. Comparison of the effect of interferon on two human hepatoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, M; Schoub, B D; Lyons, S F; Chiu, M N [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Virology

    1985-06-01

    Two human hepatoma cell lines, the PLC/PRF/5 and the Mahlavu cells, which differ in their production of the hepatitis B surface antigen (HBsAg), responded differently to interferon (IFN). After IFN treatment both cell lines were able to inhibit Sindbis virus replication. Oligo A synthetase (E enzyme) could be activated in the PLC/PRF/5 cells although they were not sensitive to exogenous 2 - 5 oligoadenylic acid (2 - 5 A). In contrast, the Mahlavu cells were sensitive to exogenous 2 - 5 A, but unable to activate the E enzyme. Both cell lines were unable to stimulate phosphorylation of the exogenous initiator factor eIF-2.

  7. Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin.

    Science.gov (United States)

    Parsanezhad, M E; Alborzi, S; Zarei, A; Dehbashi, S; Omrani, G

    2001-10-01

    To evaluate the clinical features, endocrine and metabolic profiles in clomiphene (CC) responders and non-responders with polycystic ovarian disease (PCOD), and to examine the effects of metformin (MTF) on the above parameters of CC resistance. A prospective clinical trial was undertaken at the infertility division of a university teaching hospital. Forty-one CC responders were selected and their hormonal and clinical features were determined. Forty-one CC-resistant PCOD women were also selected and clinical features; metabolic and hormonal profiles before and after treatment with MTF 1500 mg/day for 6-8 weeks were evaluated. Women who failed to conceive were treated by CC while continuing to take MTF. CC responders had higher insulin levels while non-responders were hyperinsulinemic. Menstrual irregularities improved in 30%. Mean+/-S.D. area under curve of insulin decreased from 297.58+/-191.33 to 206+/-0.1 mIU/ml per min (P=0.005). Only 39.39% ovulated and 24.24% conceived. PCOD is associated with insulin resistance (IR) particularly in CC-resistant women. Insulin resistance and androgen levels are significantly higher in obese patients. MTF therapy improved hyperandrogenemia, IR, and pregnancy rate.

  8. DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Lenz Heinz-Josef

    2009-11-01

    Full Text Available Abstract Background Despite the significant progress made in colon cancer chemotherapy, advanced disease remains largely incurable and novel efficacious chemotherapies are urgently needed. Histone deacetylase inhibitors (HDACi represent a novel class of agents which have demonstrated promising preclinical activity and are undergoing clinical evaluation in colon cancer. The goal of this study was to identify genes in colon cancer cells that are differentially regulated by two clinically advanced hydroxamic acid HDACi, vorinostat and LBH589 to provide rationale for novel drug combination partners and identify a core set of HDACi-regulated genes. Methods HCT116 and HT29 colon cancer cells were treated with LBH589 or vorinostat and growth inhibition, acetylation status and apoptosis were analyzed in response to treatment using MTS, Western blotting and flow cytometric analyses. In addition, gene expression was analyzed using the Illumina Human-6 V2 BeadChip array and Ingenuity® Pathway Analysis. Results Treatment with either vorinostat or LBH589 rapidly induced histone acetylation, cell cycle arrest and inhibited the growth of both HCT116 and HT29 cells. Bioinformatic analysis of the microarray profiling revealed significant similarity in the genes altered in expression following treatment with the two HDACi tested within each cell line. However, analysis of genes that were altered in expression in the HCT116 and HT29 cells revealed cell-line-specific responses to HDACi treatment. In addition a core cassette of 11 genes modulated by both vorinostat and LBH589 were identified in both colon cancer cell lines analyzed. Conclusion This study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets

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

    Directory of Open Access Journals (Sweden)

    Hermanova Marketa

    2010-05-01

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

  10. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  11. Rat embryonic palatal shelves respond to TCDD in organ culture

    International Nuclear Information System (INIS)

    Abbott, B.D.; Birnbaum, L.S.

    1990-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a highly toxic environmental contaminant, is teratogenic in mice, inducing cleft palate (CP) and hydronephrosis at doses which are not overtly maternally or embryo toxic. Palatal shelves of embryonic mice respond to TCDD, both in vivo and in organ culture, with altered differentiation of medial epithelial cells. By contrast, in the rat TCDD produces substantial maternal, embryonic, and fetal toxicity, including fetal lethality, with few malformations. In this study the possible effects of maternal toxicity on induction of cleft palate were eliminated by exposure of embryonic rat palatal shelves in organ culture. The shelves were examined for specific TCDD-induced alterations in differentiation of the medial cells. On Gestation Day (GD) 14 or 15 palatal shelves from embryonic F344 rats were placed in organ culture for 2 to 3 days (IMEM:F12 medium, 5% FBS, 0.1% DMSO) containing 0, 1 x 10(-8), 1 x 10(-9), 1 x 10(-10), or 5 x 10(-11) M TCDD. The medial epithelial peridermal cells degenerated on shelves exposed to control media or 5 x 10(-11) M TCDD. Exposure to 10(-10), 10(-9), and 10(-8) M TCDD inhibited this degeneration in 20, 36, and 60% of the shelves, respectively, and was statistically significant at the two highest doses. A normally occurring decrease in [3H]TdR incorporation was inhibited in some GD 15 shelves cultured with 10(-10) and 10(-9) M TCDD. The medial cells of TCDD-exposed shelves continued to express high levels of immunohistochemically detected EGF receptors. The altered differentiation of rat medial epithelium is similar to that reported for TCDD-exposed mouse medial cells in vivo and in vitro. However, in order to obtain these responses, the cultured rat shelves require much higher concentrations of TCDD than the mouse shelves

  12. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  13. The soleal line: a cause of tibial pseudoperiostitis.

    Science.gov (United States)

    Levine, A H; Pais, M J; Berinson, H; Amenta, P S

    1976-04-01

    An unusually prominent soleal line (a normal anatomic variant) may mimic periosteal reaction along the posterior margin of the proximal tibial shaft. This area of pseudoperiostitis is differentiated from hyperostoses arising from the anterior tibial tubercle and the interosseous membrane. It is always associated with normal, undisturbed architecture of the underlying bone.

  14. Method and cell lines for the production of monoclonal antibodies to human glycophorin A

    Science.gov (United States)

    Bigbee, W.L.; Fong, S.S.N.; Jensen, R.H.; Vanderlaan, M.

    Cloned mouse hybridoma cell lines have been established which continuously produce antibodies that differentiate between the M and N forms of human glycophorin A. These antibodies have potential application as human blood group reagents, as markers for terminally differentiated erythroid cells and as immunofluorescent labels of somatically variant human erythrocytes.

  15. Sonic hedgehog expressing and responding cells generate neuronal diversity in the medial amygdala

    Directory of Open Access Journals (Sweden)

    Machold Robert P

    2010-05-01

    Full Text Available Abstract Background The mammalian amygdala is composed of two primary functional subdivisions, classified according to whether the major output projection of each nucleus is excitatory or inhibitory. The posterior dorsal and ventral subdivisions of the medial amygdala, which primarily contain inhibitory output neurons, modulate specific aspects of innate socio-sexual and aggressive behaviors. However, the development of the neuronal diversity of this complex and important structure remains to be fully elucidated. Results Using a combination of genetic fate-mapping and loss-of-function analyses, we examined the contribution and function of Sonic hedgehog (Shh-expressing and Shh-responsive (Nkx2-1+ and Gli1+ neurons in the medial amygdala. Specifically, we found that Shh- and Nkx2-1-lineage cells contribute differentially to the dorsal and ventral subdivisions of the postnatal medial amygdala. These Shh- and Nkx2-1-lineage neurons express overlapping and non-overlapping inhibitory neuronal markers, such as Calbindin, FoxP2, nNOS and Somatostatin, revealing diverse fate contributions in discrete medial amygdala nuclear subdivisions. Electrophysiological analysis of the Shh-derived neurons additionally reveals an important functional diversity within this lineage in the medial amygdala. Moreover, inducible Gli1CreER(T2 temporal fate mapping shows that early-generated progenitors that respond to Shh signaling also contribute to medial amygdala neuronal diversity. Lastly, analysis of Nkx2-1 mutant mice demonstrates a genetic requirement for Nkx2-1 in inhibitory neuronal specification in the medial amygdala distinct from the requirement for Nkx2-1 in cerebral cortical development. Conclusions Taken together, these data reveal a differential contribution of Shh-expressing and Shh-responding cells to medial amygdala neuronal diversity as well as the function of Nkx2-1 in the development of this important limbic system structure.

  16. Empathy, ToM, and self-other differentiation: an fMRI study of internal states.

    Science.gov (United States)

    Reniers, Renate L E P; Völlm, Birgit A; Elliott, Rebecca; Corcoran, Rhiannon

    2014-02-01

    This study used functional magnetic resonance imaging to examine the neural substrates of empathy, Theory of Mind (ToM), and self-other differentiation involved in the adaptive understanding of people's internal states. Three conditions were distinguished in both sad and neutral (no obvious emotion) contexts. The empathy condition involved imagining what another person is feeling while the more cognitively loaded ToM condition involved imagining what would make another person feel better. The self-reference condition required participants to imagine how they would feel in someone else's situation. Areas previously implicated in empathy, ToM, and self-other differentiation were identified within the different conditions, regardless of emotional context. Specifically, the frontal and temporal poles responded more strongly for ToM than for empathy. The self-reference condition was associated with stronger dorsolateral prefrontal response than the empathy condition, while the reverse comparison revealed a stronger role for right frontal pole. Activations in frontal pole and orbitofrontal cortex were shared between the three conditions. Contrasts of parameter estimates demonstrated modulation by emotional context. The findings of common and differential patterns of responding observed in prefrontal and temporal regions suggest that within the social cognition network empathy, ToM and self-other differentiation have distinct roles that are responsive to context.

  17. Responders and non-responders to drug treatment in social phobia : Differences at baseline and prediction of response

    NARCIS (Netherlands)

    Slaap, BR; Westenberg, HGM; DenBoer, JA

    1996-01-01

    Differences between responders and non-responders to drug therapy were investigated in social phobia. Two previously published studies were pooled to obtain data of 30 patients who were treated for 12 weeks with brofaromine or fluvoxamine. Four criterion variables were used to divide patients in

  18. A stromal myoid cell line provokes thymic erythropoiesis between ...

    African Journals Online (AJOL)

    Background: The thymus provides an optimal cellular and humoral microenvironment for cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide called thymotaxine by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular ...

  19. High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

    Science.gov (United States)

    Haralambieva, Iana H; Oberg, Ann L; Dhiman, Neelam; Ovsyannikova, Inna G; Kennedy, Richard B; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

    2012-11-15

    The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

  20. Adaptive method of lines

    CERN Document Server

    Saucez, Ph

    2001-01-01

    The general Method of Lines (MOL) procedure provides a flexible format for the solution of all the major classes of partial differential equations (PDEs) and is particularly well suited to evolutionary, nonlinear wave PDEs. Despite its utility, however, there are relatively few texts that explore it at a more advanced level and reflect the method''s current state of development.Written by distinguished researchers in the field, Adaptive Method of Lines reflects the diversity of techniques and applications related to the MOL. Most of its chapters focus on a particular application but also provide a discussion of underlying philosophy and technique. Particular attention is paid to the concept of both temporal and spatial adaptivity in solving time-dependent PDEs. Many important ideas and methods are introduced, including moving grids and grid refinement, static and dynamic gridding, the equidistribution principle and the concept of a monitor function, the minimization of a functional, and the moving finite elem...

  1. Absence of Rapid Propagation through the Purkinje Network as a Potential Cause of Line Block in the Human Heart with Left Bundle Branch Block.

    Science.gov (United States)

    Okada, Jun-Ichi; Washio, Takumi; Nakagawa, Machiko; Watanabe, Masahiro; Kadooka, Yoshimasa; Kariya, Taro; Yamashita, Hiroshi; Yamada, Yoko; Momomura, Shin-Ichi; Nagai, Ryozo; Hisada, Toshiaki; Sugiura, Seiryo

    2018-01-01

    Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear. Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system. Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings. Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line

  2. Modeling and Control of a Manufacturing Flow Line using Partial Differential Equations

    NARCIS (Netherlands)

    Berg, van den R.A.; Lefeber, A.A.J.; Rooda, J.E.

    2008-01-01

    This brief deals with a control framework for manufacturing flow lines. For this framework, a continuous approximation model of the manufacturing system is required, which is computationally feasible and able to accurately describe the dynamics of the system (both throughput and flow time). Often

  3. Remote mechanical C line

    International Nuclear Information System (INIS)

    Nuttall, K.R.; Gardner, P.R.

    1991-01-01

    Westinghouse Hanford Company is developing a desk-top simulation based training program on the operation of the Remote Mechanical C (RMC) Line process in the Plutonium Finishing Plant on the Hanford site, Richland, Washington. Simulations display aod contioually update current values of system parameters on computer graphics of RMC line equipment. Students are able to operate a variety of controllers to maintain proper system status. Programmed faults, selectable by the course instructor, can be used to test student responses to off-normal events. Prior to operation of the simulation, students are given computer-based tutorials on the function, processes, operation, and error conditions associated with individual components. By including the capability of operating each individual component - valves, heaters, agitators, etc. - the computer-based training (CBT) lessons become an interactive training manual. From one perspective RMC represents one step in the diffusion of the well-known and well-documented simulator training activities for nuclear reactor operators to other training programs, equally critical, perhaps, but less well scrutinized in the past. Because of the slowly responding nature of the actual process, RMC can retain many of the capabilities of practice and testing in a simulated work environment while avoiding the cost of a full scale simulator and the exposure and waste developed by practice runs of the RMC line. From another perspective RMC suggests training advances even beyond the most faithful simulators. For example, by integrating CBT lessons with the simulation, RMC permits students to focus in on specific processes occurring inside chosen components. In effect, the interactive training manual is available on-line with the simulation itself. Cost are also discussed

  4. Derivation and characterization of the NYSCFe003-A human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Ana Sevilla

    2017-12-01

    Full Text Available The human embryonic stem cell line NYSCFe003-A was derived from a day 5 to day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe003-A line expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro. The line presents normal karyotype and is mycoplasma free.

  5. Responder Technology Alert Monthly (January 2015)

    Energy Technology Data Exchange (ETDEWEB)

    Upton, Jaki F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stein, Steven L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-02-01

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in the areas wearable technology.

  6. Responder Technology Alert Monthly (December 2014)

    Energy Technology Data Exchange (ETDEWEB)

    Upton, Jaki F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stein, Steven L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-02-13

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in the areas wearable technology.

  7. Improved Reading Gate For Vertical-Bloch-Line Memory

    Science.gov (United States)

    Wu, Jiin-Chuan; Stadler, Henry L.; Katti, Romney R.

    1994-01-01

    Improved design for reading gate of vertical-Bloch-line magnetic-bubble memory increases reliability of discrimination between binary ones and zeros. Magnetic bubbles that signify binary "1" and "0" produced by applying sufficiently large chopping currents to memory stripes. Bubbles then propagated differentially in bubble sorter. Method of discriminating between ones and zeros more reliable.

  8. Modeling Group Differences in OLS and Orthogonal Regression: Implications for Differential Validity Studies

    Science.gov (United States)

    Kane, Michael T.; Mroch, Andrew A.

    2010-01-01

    In evaluating the relationship between two measures across different groups (i.e., in evaluating "differential validity") it is necessary to examine differences in correlation coefficients and in regression lines. Ordinary least squares (OLS) regression is the standard method for fitting lines to data, but its criterion for optimal fit…

  9. Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.

    Science.gov (United States)

    Mailer, Reiner K W; Gisterå, Anton; Polyzos, Konstantinos A; Ketelhuth, Daniel F J; Hansson, Göran K

    2017-05-26

    The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T-cell differentiation remains unknown. To investigate hepatic T-cell subsets upon hypercholesterolemia. We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor-β1 in the liver. Adoptive transfer experiments revealed that intrahepatically differentiated Treg cells relocated to the inflamed aorta in atherosclerosis-prone low-density lipoprotein receptor deficient ( Ldlr -/- ) mice. Moreover, hypercholesterolemia induced the differentiation of intrahepatic, but not intrasplenic, Th17 cells in wild-type mice, whereas the disrupted liver homeostasis in hypercholesterolemic Ldlr -/- mice led to intrahepatic Th1 cell differentiation and CD11b + CD11c + leukocyte accumulation. Our results elucidate a new mechanism that controls intrahepatic T-cell differentiation during atherosclerosis development and indicates that intrahepatically differentiated T cells contribute to the CD4 + T-cell pool in the atherosclerotic aorta. © 2017 American Heart Association, Inc.

  10. Application of Green's differential equation to the analysis of ion-matrix sheaths around wedge-shaped cathodes

    International Nuclear Information System (INIS)

    Donolato, C

    2005-01-01

    A relation between the gradient of the electric field and mean curvature of equipotential surfaces (Green's differential equation) is applied to a two-dimensional free-boundary problem arising in the study of ion sheaths around wedge-shaped cathodes. With the assumption that the equipotential lines are hyperbolae, this relation leads to a nonlinear ordinary differential equation for the potential along the bisector line of the wedge. An approximate solution is found, which yields, in particular, the sheath width along this line as a function of the wedge angle. The resulting values are in good agreement with published results obtained by numerically solving Poisson's equation

  11. Derivation of keratinocytes from chicken embryonic stem cells: Establishment and characterization of differentiated proliferative cell populations

    Directory of Open Access Journals (Sweden)

    Mathilde Couteaudier

    2015-03-01

    Full Text Available A common challenge in avian cell biology is the generation of differentiated cell-lines, especially in the keratinocyte lineage. Only a few avian cell-lines are available and very few of them show an interesting differentiation profile. During the last decade, mammalian embryonic stem cell-lines were shown to differentiate into almost all lineages, including keratinocytes. Although chicken embryonic stem cells had been obtained in the 1990s, few differentiation studies toward the ectodermal lineage were reported. Consequently, we explored the differentiation of chicken embryonic stem cells toward the keratinocyte lineage by using a combination of stromal induction, ascorbic acid, BMP4 and chicken serum. During the induction period, we observed a downregulation of pluripotency markers and an upregulation of epidermal markers. Three homogenous cell populations were derived, which were morphologically similar to chicken primary keratinocytes, displaying intracellular lipid droplets in almost every pavimentous cell. These cells could be serially passaged without alteration of their morphology and showed gene and protein expression profiles of epidermal markers similar to chicken primary keratinocytes. These cells represent an alternative to the isolation of chicken primary keratinocytes, being less cumbersome to handle and reducing the number of experimental animals used for the preparation of primary cells.

  12. Relationship of calcitonin mRNA expression to the differentiation state of HL 60 cells.

    Science.gov (United States)

    Kiefer, P; Bacher, M; Pflüger, K H

    1994-05-01

    Raised plasma levels of immunoreactive human calcitonin (ihCT) can be found in patients with myeloid leukemia and seem to indicate a poor prognosis. High levels were found in acute undifferentiated and acute myeloblastic leukemia. To test whether CT expression could be a marker of myeloid differentiation, we used the promyelocytic leukemia cell line HL 60 which also expresses ihCT as a model system for myeloid differentiation. Exponentially growing HL 60 cells as well as differentiation induced HL 60 cells expressed a single 1.0 Kb CT transcript. The induction of HL 60 cell differentiation along the granulocytic lineage by DMSO or HMBA had no effect on the level of CT transcripts. Induction of monocytic/macrophagic differentiation by TPA resulted in a transient, about 10-fold elevated expression of CT steady state mRNA after 24 h. In contrast to TPA, induction of HL 60 cell differentiation along the monocytic pathway by Vit D3 had no detectable effect on the level of the CT in RNA expression at corresponding time points. These findings suggest that the transient induction of CT steady state mRNA expression by TPA is rather a direct effect of the phorbol ester than commitment along the monocytic line of differentiation.

  13. Chemo-mechanical control of neural stem cell differentiation

    Science.gov (United States)

    Geishecker, Emily R.

    Cellular processes such as adhesion, proliferation, and differentiation are controlled in part by cell interactions with the microenvironment. Cells can sense and respond to a variety of stimuli, including soluble and insoluble factors (such as proteins and small molecules) and externally applied mechanical stresses. Mechanical properties of the environment, such as substrate stiffness, have also been suggested to play an important role in cell processes. The roles of both biochemical and mechanical signaling in fate modification of stem cells have been explored independently. However, very few studies have been performed to study well-controlled chemo-mechanotransduction. The objective of this work is to design, synthesize, and characterize a chemo-mechanical substrate to encourage neuronal differentiation of C17.2 neural stem cells. In Chapter 2, Polyacrylamide (PA) gels of varying stiffnesses are functionalized with differing amounts of whole collagen to investigate the role of protein concentration in combination with substrate stiffness. As expected, neurons on the softest substrate were more in number and neuronal morphology than those on stiffer substrates. Neurons appeared locally aligned with an expansive network of neurites. Additional experiments would allow for statistical analysis to determine if and how collagen density impacts C17.2 differentiation in combination with substrate stiffness. Due to difficulties associated with whole protein approaches, a similar platform was developed using mixed adhesive peptides, derived from fibronectin and laminin, and is presented in Chapter 3. The matrix elasticity and peptide concentration can be individually modulated to systematically probe the effects of chemo-mechanical signaling on differentiation of C17.2 cells. Polyacrylamide gel stiffness was confirmed using rheological techniques and found to support values published by Yeung et al. [1]. Cellular growth and differentiation were assessed by cell counts

  14. Alternative Splicing of G9a Regulates Neuronal Differentiation

    Directory of Open Access Journals (Sweden)

    Ana Fiszbein

    2016-03-01

    Full Text Available Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10 through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10+ isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation.

  15. What is the role of health systems in responding to domestic violence? An evidence review.

    Science.gov (United States)

    Spangaro, Jo

    2017-12-01

    Objective The aim of the present study was to review and analyse academic literature and program evaluations to identify promising evidence for health system responses to domestic violence in Australia and internationally. Methods English-language literature published between January 2005 and March 2016 was retrieved from search results using the terms 'domestic violence' or 'intimate partner violence' in different combinations with other relevant terms, resulting in 1671 documents, of which 59 were systematic reviews. Electronic databases (Medline (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psycinfo, Social work Abstracts, Informit, Violence and Abuse Abstracts, Family Studies Abstracts, Cochrane Library of Systematic Reviews and EMBASE) were searched and narrative analysis undertaken. Results This review details the evidence base for the following interventions by health services responding to domestic violence: first-line responses, routine screening, risk assessment and safety planning, counselling with women, mother-child interventions, responses to perpetrators, child protection notifications, training and system-level responses. Conclusions There is growing evidence for the effectiveness of health service interventions to reduce the extent of harm caused by domestic violence. What is known about the topic? Domestic violence is a significant problem globally with enormous human, social and economic costs. Although women who have experienced abuse make extensive use of healthcare services, health services have lagged behind the policing, criminal justice and other human service domains in responding to domestic violence. What does this paper add? The present comprehensive review identifies best-practice health system responses to domestic violence. What are the implications for practitioners? Health systems can play a key role in identifying and responding to domestic violence for women who often do not access other services

  16. Diagnosis and Differential Diagnosis of Hydrocephalus in Adults.

    Science.gov (United States)

    Langner, Sönke; Fleck, Steffen; Baldauf, Jörg; Mensel, Birger; Kühn, Jens Peter; Kirsch, Michael

    2017-08-01

    Purpose  Hydrocephalus is caused by an imbalance of production and absorption of cerebrospinal fluid (CSF) or obstruction of its pathways, resulting in ventricular dilatation and increased intracranial pressure. Imaging plays a crucial role in the diagnosis, differential diagnosis and planning of treatment. Methods  This review article presents the different types of hydrocephalus und their typical imaging appearance, describes imaging techniques, and discusses differential diagnoses of the different forms of hydrocephalus. Results and Conclusion  Imaging plays a central role in the diagnosis of hydrocephalus. While magnetic resonance (MR) imaging is the first-line imaging modality, computed tomography (CT) is often the first-line imaging test in emergency patients. Key points   · Occlusive hydrocephalus is caused by obstruction of CSF pathways.. · Malabsorptive hydrocephalus is caused by impaired CSF absorption.. · The MR imaging protocol should always include sagittal high-resolution T2-weighted images.. · When an inflammatory etiology is suspected, imaging with contrast agent administration is necessary.. Citation Format · Langner S, Fleck S, Baldauf J et al. Diagnosis and Differential Diagnosis of Hydrocephalus in Adults. Fortschr Röntgenstr 2017; 189: 728 - 739. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Ectopic expression and knocking-down of LINE-1 mRNA in human mesenchymal stem cells: impact on in vitro osteogenic and adipogenic differentiation

    KAUST Repository

    Atinbayeva, Nazerke

    2018-05-01

    There are two classes of transposable elements: DNA transposons and retrotransposons. DNA transposons spread in the genome by “cut and paste” mechanism. In contrast, retrotransposons use copy and paste strategy involving RNA and retrotranscriptase mediated mechanism; these include long interspersed nuclear elements-1 (LINE-1, L1) and short interspersed nuclear elements (SINE). In mammals, in order to maintain genome integrity both types of transposons are tightly repressed. However, some copies of retrotransposons are still active in germ cells contributing to natural variation. Surprisingly, recent reports indicate that also somatic cells support L1 reactivation in early development, in particular in the brain leading to mosaicism. However, whether L1 retrotransposition is a part of other cell lineage developmental programs and its functional significance in the context of cell differentiation remain to be elucidated. To address this question, I investigated whether L1 retrotransposition was occurring during in vitro osteogenic and adipogenic differentiation of bone marrow derived human mesenchymal stem cells (hMSCs). Interestingly, clinical observations have revealed loss of bone density in HIV-infected individuals treated with nucleoside analogs that inhibit HIV retrotranscriptase, as well as the endogenous one encoded by L1s. This observation made us to hypothesize that transposable elements played a positive role in post-natal bone homeostasis. I found that while adipogenesis is “retrotransposition free”, osteogenic differentiation is a “retrotransposition-prone” process and its inhibition blocks its genetic program. Indeed, L1 DNA content does not change during adipogenic differentiation and that of retrotranscriptase does not have any effect on the acquisition of a terminally differentiated phenotype. In contrast, soon after MSCs commitment into pre-osteoblasts, L1 retrotransposable elements increase their expression and actively transpose

  18. Identification of differentially expressed genes in brown planthopper Nilaparvata lugens (Hemiptera: Delphacidae) responding to host plant resistance.

    Science.gov (United States)

    Yang, Zhifan; Zhang, Futie; Zhu, Lili; He, Guangcun

    2006-02-01

    The brown planthopper Nilaparvata lugens Stål is one of the major insect pests of rice Oryza sativa L. The host resistance exhibits profound effects on growth, development and propagation of N. lugens. To investigate the molecular response of N. lugens to host resistance, a cDNA-amplified fragment length polymorphism (cDNA-AFLP) technique was employed to identify the differentially expressed genes in the nymphs feeding on three rice varieties. Of the 2,800 cDNA bands analysed, 54 were up-regulated and seven down-regulated qualitatively in N. lugens when the ingestion sources were changed from susceptible rice plants to resistant ones. Sequence analysis of the differential transcript-derived fragments showed that the genes involved in signalling, stress response, gene expression regulation, detoxification and metabolism were regulated by host resistance. Four of the transcript-derived fragments corresponding to genes encoding for a putative B subunit of phosphatase PP2A, a nemo kinase, a cytochrome P450 monooxygenase and a prolyl endopeptidase were further characterized in detail. Northern blot analysis confirmed that the expression of the four genes was enhanced in N. lugens feeding on resistant rice plants. The roles of these genes in the defensive response of N. lugens to host plant resistance were discussed.

  19. Characteristics of bovine inner cell mass-derived cell lines and their fate in chimeric conceptuses.

    Science.gov (United States)

    Furusawa, Tadashi; Ohkoshi, Katsuhiro; Kimura, Koji; Matsuyama, Shuichi; Akagi, Satoshi; Kaneda, Masahiro; Ikeda, Mitsumi; Hosoe, Misa; Kizaki, Keiichiro; Tokunaga, Tomoyuki

    2013-08-01

    Bovine embryonic stem (ES) cells have the potential to provide significant benefits in a range of agricultural and biomedical applications. Here, we employed a combination of conventional methods using glycogen synthase kinase 3 and mitogen-activated protein kinase inhibitors to establish ES cell lines from in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) bovine embryos. Five male cell lines were established from IVF embryos, and two female and three male cell lines from SCNT blastocysts; we named these lines bovine ES cell-like cells (bESLCs). The lines exhibited dome-shaped colonies, stained positively for alkaline phosphatase, and expressed pluripotent stem cell markers such as POU5F1, SOX2, and SSEA-1. The expression levels of these markers, especially for NANOG, varied among the cell lines. A DNA methylation assay showed the POU5F1 promoter region was hypomethylated compared to fibroblast cells. An in vitro differentiation assay showed that endoderm and ectoderm marker genes, but not mesoderm markers, were upregulated in differentiating bESLCs. To examine bESLCs in later embryonic stages, we created 22 chimeric blastocysts with a male bESLC line carrying a GFP marker gene and transferred these to a recipient cow. Four chimeric embryos were subsequently retrieved on Day 13 and retransferred to two recipient cows. One living fetus was obtained at Day 62. GFP signals were not identified in fetal cells by fluorescence microscopy; however, genomic PCR analysis detected the GFP gene in major organs. Clusters of GFP-positive cells were observed in amniotic membranes, suggesting that bESLCs can be categorized as a novel type of ICM-derived cells that can potentially differentiate into epiblast and hypoblast lineages.

  20. Conic Sections and the Discovery of a Novel Curve Using Differential Equations

    Science.gov (United States)

    de Alwis, Amal

    2013-01-01

    We began by observing a variety of properties related to the tangent and normal lines of three conic sections: a parabola, an ellipse, and a hyperbola. Some of these properties include specific relationships between the x- and y-intercepts of the tangent and normal lines. Using these properties, we were able to form several differential equations.…

  1. Responding to Misbehavior

    OpenAIRE

    Telep, Valya Goodwin, 1955-

    2009-01-01

    This series of lessons was prepared for parents like you - parents who want to do a better job of disciplining their children. The lessons were especially written for parents of preschool children, ages two to six, but some of the discipline methods are appropriate for older children, too. This lesson focuses on responding to misbehavior.

  2. Bioreactor cultivation enhances NTEB formation and differentiation of NTES cells into cardiomyocytes.

    Science.gov (United States)

    Lü, Shuanghong; Liu, Sheng; He, Wenjun; Duan, Cuimi; Li, Yanmin; Liu, Zhiqiang; Zhang, Ye; Hao, Tong; Wang, Yanmeng; Li, Dexue; Wang, Changyong; Gao, Shaorong

    2008-09-01

    Autogenic embryonic stem cells established from somatic cell nuclear transfer (SCNT) embryos have been proposed as unlimited cell sources for cell transplantation-based treatment of many genetic and degenerative diseases, which can eliminate the immune rejection that occurs after transplantation. In the present study, pluripotent nuclear transfer ES (NTES) cell lines were successfully established from different strains of mice. One NTES cell line, NT1, with capacity of germline transmission, was used to investigate in vitro differentiation into cardiomyocytes. To optimize differentiation conditions for mass production of embryoid bodies (NTEBs) from NTES cells, a slow-turning lateral vessel (STLV) rotating bioreactor was used for culturing the NTES cells to produce NTEBs compared with a conventional static cultivation method. Our results demonstrated that the NTEBs formed in STLV bioreactor were more uniform in size, and no large necrotic centers with most of the cells in NTEBs were viable. Differentiation of the NTEBs formed in both the STLV bioreactor and static culture into cardiomyocytes was induced by ascorbic acid, and the results demonstrated that STLV-produced NTEBs differentiated into cardiomyocytes more efficiently. Taken together, our results suggested that STLV bioreactor provided a more ideal culture condition, which can facilitate the formation of better quality NTEBs and differentiation into cardiomyocytes more efficiently in vitro.

  3. Differentiating case-based learning from problem-based learning after a twoday introductory workshop on case-based learning

    Directory of Open Access Journals (Sweden)

    Aqil Mohammad Daher

    2017-12-01

    Full Text Available Background Considerable overlap exists between case-based learning (CBL and problem-based learning (PBL and differentiating between the two can be difficult for a lot of the academicians. Aims This study gauged the ability of members of medical school, familiar with a problem-based learning (PBL curriculum, to differentiate between case-based learning (CBL and PBL after a two-day workshop on CBL. Methods A questionnaire was distributed to all participants, attending the introductory course on CBL. It was designed to document the basic characteristics of the respondents, their preference for either CBL or PBL, their ability to recognize differences between CBL and PBL, and their overall perception of the course. Results Of the total workshop participants, 80.5 per cent returned the completed questionnaire. The mean age of the respondents was 44.12±12.31 years and women made up a slight majority. Majority favoured CBL over PBL and felt it was more clinical, emphasizes on self-directed learning, provides more opportunities for learning, permits in-depth exploration of cases, has structured environment and encourages the use of all learning resources. On the respondents’ ability to discriminate CBL from PBL, a weighted score of 39.9 per cent indicated a failure on the part of the respondents to correctly identify differences between CBL and PBL. Less than half opined that CBL was a worthwhile progression from PBL and about third would recommend CBL over PBL. Conclusion It seems that majority of the respondents failed to adequately differentiate between CBL and PBL and didn’t favour CBL over PBL.

  4. The management of differentiated thyroid cancer in Europe in 1988

    International Nuclear Information System (INIS)

    Baldet, L.; Jaffiol, C.; Percheron, C.; Manderscheid, J.-C.; Coste-Seignovert, B.; Glinoer, D.

    1989-01-01

    In order to know how thyroid nodules and differentiated thyroid cancers are investigated and treated in 1988, an international inquiry was performed by mean of a questionnaire based on a well-defined case report of a 35-year-old female with a solitary small thyroid nodule. Clinicians were asked to indicate their diagnostic and therapeutic approaches to the reported case and to some variations. Analysis of the 157 responses from thyroid experts showed that three in vitro tests (sensitive-TSH, free T 4 and total T 4 ) and three in vivo tests ( 99m Tc or radioiodide scintiscan, fine needle aspiration and ultrasonography) were performed most frequently. In the case of a solid and cold nodule and in the absence of fine needle aspiration results, 19% of respondents advocated suppressive therapy and 81% surgery. In the same clinical case, but whom fine needle aspiration had been performed and cytology was benign, surgery was advocated by 24%, suppressive therapy by 48% and a regular follow-up without treatment by 28% of respondents. When surgery was performed and the diagnosis was a differentiated thyroid cancer, (near) total thyroidectomy was more frequently chosen than partial thyroidectomy in both papillary (60 and 40%, respectively, of respondents) and follicular (74 and 26%, respectively, of respondents) cancers; 80% of clinicians did not change their surgical technique in relation to histological type of the tumour. Total thyroidectomy was more often recommended in most of the clinical or anatomical variations compared with the basic case repot. Pre- og postoperative hormonal therapy was initiated with L-T 4 and TSH suppression was controlled by sensitive-TSH and thyroblobulin determinations. After total thyroidectomy, 131 I was used with similar modalities for papillary and follicular cancers to ablate a thyroid remnant. (author)

  5. Degree of Suppression of Mouse Myoblast Cell Line C₂C12 Differentiation Varies According to Chondroitin Sulfate Subtype.

    Science.gov (United States)

    Warita, Katsuhiko; Oshima, Nana; Takeda-Okuda, Naoko; Tamura, Jun-Ichi; Hosaka, Yoshinao Z

    2016-10-21

    Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C₂C 12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time. After immunostaining of the formed myotubes with an anti-MHC antibody, we counted the number of nuclei in the myotubes and then calculated the fusion index (FI) as a measure of myotube differentiation. The FI values of all the CS-treated groups were lower than the FI value of the control group, especially the group treated with CS-E, which displayed notable suppression of myotube formation. To confirm that the sugar chain in CS-E is important in the suppression of differentiation, chondroitinase ABC (ChABC), which catabolizes CS, was added to the media. The addition of ChABC led to the degradation of CS-E, and neutralized the suppression of myotube formation by CS-E. Collectively, it can be concluded that the degree of suppression of differentiation depends on the subtype of CS and that CS-E strongly suppresses myogenic differentiation. We conclude that the CS sugar chain has inhibitory action against myoblast cell fusion.

  6. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged...

  7. Responding to Tragedy

    Science.gov (United States)

    Coopman, J. T.

    2009-01-01

    In this article, the author, a superintendent of Clark-Pleasant School Corporation in Whiteland, Indiana, relates how she and the school community responded to a car accident that killed two students. The author stresses the need to develop a comprehensive crisis plan. It is also important to be sensitive to the needs of family members who are…

  8. Standardized Index of Shape (SIS): a quantitative DCE-MRI parameter to discriminate responders by non-responders after neoadjuvant therapy in LARC

    Energy Technology Data Exchange (ETDEWEB)

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Radiology; Sansone, Mario [Naples Univ. ' ' Federico II' ' (Italy). Dept. of Biomedical, Electronics and Telecommunications Engineering; Avallone, Antonio [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Gastrointestinal Medical Oncology; Delrio, Paolo [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Gastrointestinal surgical Oncology; Pecori, Biagio [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Radiotherapy; Tatangelo, Fabiana [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Diagnostic Pathology; Ciliberto, Gennaro [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy)

    2015-07-15

    To investigate the potential of DCE-MRI to discriminate responders from non-responders after neoadjuvant chemo-radiotherapy (CRT) for locally advanced rectal cancer (LARC). We investigated several shape parameters for the time-intensity curve (TIC) in order to identify the best combination of parameters between two linear parameter classifiers. Seventy-four consecutive patients with LARC were enrolled in a prospective study approved by our ethics committee. Each patient gave written informed consent. After surgery, pathological TNM and tumour regression grade (TRG) were estimated. DCE-MRI semi-quantitative analysis (sqMRI) was performed to identify the best parameter or parameter combination to discriminate responders from non-responders in response monitoring to CRT. Percentage changes of TIC shape descriptors from the baseline to the presurgical scan were assessed and correlated with TRG. Receiver operating characteristic analysis and linear classifier were applied. Forty-six patients (62.2 %) were classified as responders, while 28 subjects (37.8 %) were considered as non-responders. sqMRI reached a sensitivity of 93.5 % and a specificity of 82.1 % combining the percentage change in Maximum Signal Difference (ΔMSD) and Wash-out Slope (ΔWOS), the Standardized Index of Shape (SIS). SIS obtains the best result in discriminating responders from non-responders after CRT in LARC, with a cut-off value of -3.0 %. (orig.)

  9. Derivation and characterization of human embryonic stem cell lines from the Chinese population

    Institute of Scientific and Technical Information of China (English)

    Zhao Wu; Huimin Dai; Lei Qian; Qing Tian; Lei Xiao; Xiaojun Tan; Hui Li; Lingjun Rao; Lixiazi He; Lei Bao; Jing Liao; Chun Cui; Zhenyu Zuo; Qiao Li

    2011-01-01

    Human embryonic stem cells (hESCs) can self-renew indefinitely and differentiate into all cell types in the human body. Therefore, they are valuable in regenerative medicine, human developmental biology and drug discovery. A number of hESC lines have been derived from the Chinese population,but limited of them are available for research purposes. Here we report the derivation and characterization of two hESC lines derived from human blastocysts of Chinese origin. These hESCs express alkaline phosphatase and hESC-specific markers, including Oct4, Nanog, SSEA-3, SSEA-4,TRA-1-60 and TRA-1-81. They also have high levels of telomerase activity and normal karyotypes. These cells can form embryoid body in vitro and can be differentiated into all three germ layers in vivo by teratoma formation. The newly established hESCs will be distributed for research purposes.The availability of hESC lines from the Chinese population will facilitate studies on the differences in hESCs from different ethnic groups.

  10. SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress

    OpenAIRE

    Gao, Jing; Feng, Zhihui; Wang, Xueqiang; Zeng, Mengqi; Liu, Jing; Han, Shujun; Xu, Jie; Chen, Lei; Cao, Ke; Long, Jiangang; Li, Zongfang; Shen, Weili; Liu, Jiankang

    2017-01-01

    Recent studies have revealed robust metabolic changes during cell differentiation. Mitochondria, the organelles where many vital metabolic reactions occur, may play an important role. Here, we report the involvement of SIRT3-regulated mitochondrial stress in osteoblast differentiation and bone formation. In both the osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts, robust mitochondrial biogenesis and supercomplex formation were observed during differentiation, accompanied by in...

  11. Existence of solutions to boundary value problem of fractional differential equations with impulsive

    Directory of Open Access Journals (Sweden)

    Weihua JIANG

    2016-12-01

    Full Text Available In order to solve the boundary value problem of fractional impulsive differential equations with countable impulses and integral boundary conditions on the half line, the existence of solutions to the boundary problem is specifically studied. By defining suitable Banach spaces, norms and operators, using the properties of fractional calculus and applying the contraction mapping principle and Krasnoselskii's fixed point theorem, the existence of solutions for the boundary value problem of fractional impulsive differential equations with countable impulses and integral boundary conditions on the half line is proved, and examples are given to illustrate the existence of solutions to this kind of equation boundary value problems.

  12. Modern quantum kinetic theory and spectral line shapes

    International Nuclear Information System (INIS)

    Monchick, L.

    1991-01-01

    The modern quantum kinetic theory of spectral line shapes is outlined and a typical calculation of a Raman scattered line shape described. The distinguishing feature of this calculation is that it was completely ab initio and therefore constituted a test of modern quantum kinetic theory, the state of the art in computing molecular-scattering cross sections, and novel methods of solving kinetic equations. The computation employed a large assortment of tools: group theory, finite-element methods, classic methods of solving coupled sets of ordinary differential equations, graph methods of combining angular momenta, and matrix methods of solving integral equations. Agreement with experimental results was excellent. 13 refs

  13. The method of diagnosis and classification of the gingival line defects of the teeth hard tissues

    Directory of Open Access Journals (Sweden)

    Olena Bulbuk

    2017-06-01

    Full Text Available For solving the problem of diagnosis and treatment of hard tissue defects the significant role belongs to the choice of tactics for dental treatment of hard tissue defects located in the gingival line of any tooth. This work aims to study the problems of diagnosis and classification of gingival line defects of the teeth hard tissues. That will contribute to the objectification of differentiated diagnostic and therapeutic approaches in the dental treatment of various clinical variants of these defects localization. The objective of the study – is to develop the anatomical-functional classification for differentiated estimation of hard tissue defects in the gingival part, as the basis for the application of differential diagnostic-therapeutic approaches to the dental treatment of hard tissue defects disposed in the gingival part of any tooth. Materials and methods of investigation: There was conducted the examination of 48 patients with hard tissue defects located in the gingival part of any tooth. To assess the magnitude of gingival line destruction the periodontal probe and X-ray examination were used. Results. The result of the performed research the classification of the gingival line defects of the hard tissues was offered using exponent power. The value of this indicator is equal to an integer number expressed in millimeters of distance from the epithelial attachment to the cavity’s bottom of defect. Conclusions. The proposed classification fills an obvious gap in academic representations about hard tissue defects located in the gingival part of any tooth. Also it offers the prospects of consensus on differentiated diagnostic-therapeutic approaches in different clinical variants of location.  This classification builds methodological “bridge of continuity” between therapeutic and prosthetic dentistry in the field of treatment of the gingival line defects of dental hard tissues.

  14. Noggin and Wnt3a enable BMP4-dependent differentiation of telencephalic stem cells into GluR-agonist responsive neurons

    DEFF Research Database (Denmark)

    Andersson, Therese; Duckworth, Joshua K; Fritz, Nicolas

    2011-01-01

    levels, that in turn exerted a concentration-dependent inhibition of BMP4-mediated mesenchymal differentiation of NSCs. Instead, BMP4 exposure of NSCs induced neuronal differentiation in mesenchyme-preventing conditions, whereas treatment with recombinant noggin alone did not. Wnt signaling is known...... to be essential for the development of neurons derived from the dorsal telencephalon, and co-stimulation of NSCs with BMP4+Wnt3a resulted in a synergistic effect yielding significantly increased number of mature neurons compared to stimulation with each factor alone. Thus whereas only a subset of BMP4-induced...... neurons derived from telencephalic NSCs, responded to glutamate receptor (GluR) agonists, over 80% of BMP4+Wnt3a-induced neurons responded appropriately to GluR-agonists. Our results increase the understanding of the role for BMP4 in differentiation of telencephalic multipotent progenitors, and reveal...

  15. EXAMINATION OF THE VISUAL ACUITY ON THE LCD OPTOTYPE WITH WHOLE-LINE AND INTERPOLATION METHOD

    OpenAIRE

    Zajíček Tomáš; Veselý Petr; Veselý Petr; Synek Svatopluk; Synek Svatopluk

    2012-01-01

    The goal of this work is to show the possibility of us using the LCD optotype in common optometrist practice. Furthermore two commonly used methods for measuring visual acuity will be compared. 69 respondents were used for the measurements. The respondents were divided into two groups according to the measured LCD optotype. The visual acuity was measured using the whole-line method on modified Snellen charts as well as the interpolation method on ETDRS charts. Measurements were taken on the S...

  16. Galaxy emission line classification using three-dimensional line ratio diagrams

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, Frédéric P. A.; Dopita, Michael A.; Kewley, Lisa J.; Sutherland, Ralph S. [Research School of Astronomy and Astrophysics, Australian National University, Canberra, ACT 2611 (Australia); Scharwächter, Julia [Observatoire de Paris, LERMA (CNRS: UMR8112), 61 Av. de l' Observatoire, F-75014 Paris (France); Basurah, Hassan M.; Ali, Alaa; Amer, Morsi A., E-mail: frederic.vogt@anu.edu.au [Astronomy Department, King Abdulaziz University, P.O. Box 80203, Jeddah (Saudi Arabia)

    2014-10-01

    Two-dimensional (2D) line ratio diagnostic diagrams have become a key tool in understanding the excitation mechanisms of galaxies. The curves used to separate the different regions—H II-like or excited by an active galactic nucleus (AGN)—have been refined over time but the core technique has not evolved significantly. However, the classification of galaxies based on their emission line ratios really is a multi-dimensional problem. Here we exploit recent software developments to explore the potential of three-dimensional (3D) line ratio diagnostic diagrams. We introduce the ZQE diagrams, which are a specific set of 3D diagrams that separate the oxygen abundance and the ionization parameter of H II region-like spectra and also enable us to probe the excitation mechanism of the gas. By examining these new 3D spaces interactively, we define the ZE diagnostics, a new set of 2D diagnostics that can provide the metallicity of objects excited by hot young stars and that cleanly separate H II region-like objects from the different classes of AGNs. We show that these ZE diagnostics are consistent with the key log [N II]/Hα versus log [O III]/Hβ diagnostic currently used by the community. They also have the advantage of attaching a probability that a given object belongs to one class or the other. Finally, we discuss briefly why ZQE diagrams can provide a new way to differentiate and study the different classes of AGNs in anticipation of a dedicated follow-up study.

  17. Comparison of MicroRNAs Mediated in Reactivation of the γ-Globin in β-Thalassemia Patients, Responders and Non-Responders to Hydroxyurea.

    Science.gov (United States)

    Hojjati, Mohammad T; Azarkeivan, Azita; Pourfathollah, Ali A; Amirizadeh, Naser

    2017-03-01

    Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin (Hb) disorders, and many efforts have been made to reveal the mechanism behind it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are thought to be involved in this process. Among β-thalassemia (β-thal) patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and five healthy individuals, five responders and five non-responders, were also included in the study. Erythroid progenitors were isolated by magnetic activated cell sorting (MACS) and miRNA expression analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We showed that γ-globin, miR-210 and miR-486-3p had higher levels in the responders than the non-responders group. Moreover, miR-150 and miR-320 had higher levels in the healthy group than both non-responders and responders groups, but the expression of miR-96 did not show any significant difference between the study groups. To the best of our knowledge, this is the first study proposing that 'induction of cellular hypoxic condition by Hb F inducing agents' could be the milestone of possible mechanisms that explain why responders are able to reactivate γ-globin genes and subsequently, more production of Hb F, in response to these agents in comparison to non-responders. However, further investigations need to be performed to verify this hypothesis.

  18. Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Damián Hernández

    2016-01-01

    Full Text Available Background. Human induced pluripotent stem cells (iPSCs are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

  19. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Observations of far-infrared line profiles in the Orion-KL region

    International Nuclear Information System (INIS)

    Crawford, M.K.; Lugten, J.B.; Fitelson, W.; Genzel, R.; Melnick, G.; Harvard-Smithsonian Center for Astrophysics, Cambridge, MA)

    1986-01-01

    Measurements of several far-infrared emission line profiles in the Orion-KL region are reported. The emission from the CO, OH, and forbidden O I emission lines toward the BN-KL and H2 peak 1 positions probably comes from dense, hot molecular gas in the Orion-KL shock. The CO and forbidden O I lines have similar profiles, suggesting that the high-velocity forbidden O I emission also arises in magnetohydrodynamic cloud shocks. The velocity centroids of the lines are somewhat blueshifted. The far-infrared data thus support the interpretation that the blue asymmetry of the H2 2 micron lines is not mainly due to differential dust extinction, but rather to the kinematics and geometry of the shocked gas in the Orion-KL outflow. The forbidden O I and CO lines, however, have significantly less extreme blueshifted emission than the H2 lines. Both the forbidden O I 63 micron and forbidden C II 158 micron lines have features strongly supporting a common origin near the surface of the Orion molecular cloud. 28 references

  1. Coaxial tube array space transmission line characterization

    International Nuclear Information System (INIS)

    Switzer, C.A.; Bents, D.J.

    1987-01-01

    The coaxial tube array tether/transmission line used to connect an SP-100 nuclear power system to the space station was characterized over the range of reactor-to-platform separation distances of 1 to 10 km. Characterization was done with respect to array performance, physical dimensions and masses. Using a fixed design procedure, a family of designs was generated for the same power level (300 kWe), power loss (1.5 percent), and meteoroid survival probability (99.5 percent over 10 yr). To differentiate between vacuum insulated and gas insulated lines, two different maximum values of the E field were considered: 20 kV/cm (appropriate to vacuum insulation) and 50 kV/cm (compressed SF6). Core conductor, tube, bumper, standoff, spacer and bumper support dimensions, and masses were also calculated. The results of the characterization show mainly how transmission line size and mass scale with reactor-to-platform separation distance

  2. Induction of DNA-strand breaks after X- irradiation in murine bone cells of various differentiation capacities

    Science.gov (United States)

    Lau, P.; Hellweg, C. E.; Kirchner, S.; Arenz, A.; Baumstark-Khan, C.; Horneck, G.

    Bone loss resulting from long-duration space flight is a well known medical risk for space travellers, as a weakened skeleton is more susceptible to bone fractures. In addition to weightlessness the astronaut is also exposed to cosmic ionizing radiation. In order to elucidate changes in bone cell metabolism by ionizing radiation, a ground-based bone cell model has been developed. This model consists of a bunch of immortalized murine osteocyte, osteoblast and pre-osteoblast cell lines representing discrete stages of differentiation: The osteocyte cell line MLO-Y4 (obtained from L. Bonewald, Kansas City, USA), the osteoblast cell line OCT-1 (obtained from D. Chen, San Antonio, USA), and the subclones 4 and 24 of the osteoblast cell line MC3T3-E1 (obtained from ATCC, Manassas, Virginia, USA). Regarding their growth properties, MLO-Y4 cells show the highest growth velocity with a doubling time of 15.8 h. The osteoblast cell line OCT-1 has a doubling time of 27.3 h. The respective values for MC3T3-E1 subclone 24 and S4 are 90.5 h and 51.6 h. To investigate the stage of differentiation, the expression of alkaline phosphatase, of osteocalcin and of E11 was examined. Survival after X-ray exposure was determined using the colony forming ability test. The resulting dose-effect relationships revealed significant differences. The parameter D0 of the survival curves ranges between 1.8 Gy for OCT-1, 1.9 Gy for MLO-Y4, 2.0 Gy for subclone 24 and 2,3 Gy for subclone 4. The quantitative acquisition of DNA-strand breaks was performed by Fluorescent Analysis of DNA-Unwinding (FADU). The results can be correlated with the corresponding survival curve. In conclusion, the cell lines with higher differentiation levels are less sensitive to radiation when compared to the lower differentiated osteoblast cell lines.

  3. Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

    Directory of Open Access Journals (Sweden)

    Ryo Kurita

    Full Text Available Transfusion of red blood cells (RBCs is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.

  4. Differential cytotoxic effects of mono-(2-ethylhexyl) phthalate on blastomere-derived embryonic stem cells and differentiating neurons

    International Nuclear Information System (INIS)

    Lim, Chun Kyu; Kim, Suel-Kee; Ko, Duck Sung; Cho, Jea Won; Jun, Jin Hyun; An, Su-Yeon; Han, Jung Ho

    2009-01-01

    Potential applications of embryonic stem (ES) cells are not limited to regenerative medicine but can also include in vitro screening of various toxicants. In this study, we established mouse ES cell lines from isolated blastomeres of two-cell stage embryos and examined their potential use as an in vitro system for the study of developmental toxicity. Two ES cell lines were established from 69 blastomere-derived blastocysts (2.9%). The blastomere-derived ES (bm-ES) cells were treated with mono-(2-ethylhexyl) phthalate (MEHP) in an undifferentiated state or after directed differentiation into early neural cell types. We observed significantly decreased cell viability when undifferentiated bm-ES cells were exposed to a high dose of MEHP (1000 μM). The cytotoxic effects of MEHP were accompanied by increased DNA fragmentation, nuclear condensation, and activation of Caspase-3, which are biochemical and morphological features of apoptosis. Compared to undifferentiated bm-ES cells, considerably lower doses of MEHP (50 and 100 μM) were sufficient to induce cell death in early neurons differentiated from bm-ES cells. At the lower doses, the number of neural cells positive for the active form of Caspase-3 was greater than that for undifferentiated bm-ES cells. Thus, our data indicate that differentiating neurons are more sensitive to MEHP than undifferentiated ES cells, and that undifferentiated ES cells may have more efficient defense systems against cytotoxic stresses. These findings might contribute to the development of a new predictive screening method for assessment of hazards for developmental toxicity.

  5. Regional differentiation of retinoic acid-induced human pluripotent embryonic carcinoma stem cell neurons.

    Directory of Open Access Journals (Sweden)

    Dennis E Coyle

    Full Text Available The NTERA2 cl D1 (NT2 cell line, derived from human teratocarcinoma, exhibits similar properties as embryonic stem (ES cells or very early neuroepithelial progenitors. NT2 cells can be induced to become postmitotic central nervous system neurons (NT2N with retinoic acid. Although neurons derived from pluripotent cells, such as NT2N, have been characterized for their neurotransmitter phenotypes, their potential suitability as a donor source for neural transplantation also depends on their ability to respond to localized environmental cues from a specific region of the CNS. Therefore, our study aimed to characterize the regional transcription factors that define the rostocaudal and dorsoventral identity of NT2N derived from a monolayer differentiation paradigm using quantitative PCR (qPCR. Purified NT2N mainly expressed both GABAergic and glutamatergic phenotypes and were electrically active but did not form functional synapses. The presence of immature astrocytes and possible radial glial cells was noted. The NT2N expressed a regional transcription factor code consistent with forebrain, hindbrain and spinal cord neural progenitors but showed minimal expression of midbrain phenotypes. In the dorsoventral plane NT2N expressed both dorsal and ventral neural progenitors. Of major interest was that even under the influence of retinoic acid, a known caudalization factor, the NT2N population maintained a rostral phenotype subpopulation which expressed cortical regional transcription factors. It is proposed that understanding the regional differentiation bias of neurons derived from pluripotent stem cells will facilitate their successful integration into existing neuronal networks within the CNS.

  6. Cell adhesion molecules expression pattern indicates that somatic cells arbitrate gonadal sex of differentiating bipotential fetal mouse gonad.

    Science.gov (United States)

    Piprek, Rafal P; Kolasa, Michal; Podkowa, Dagmara; Kloc, Malgorzata; Kubiak, Jacek Z

    2017-10-01

    Unlike other organ anlagens, the primordial gonad is sexually bipotential in all animals. In mouse, the bipotential gonad differentiates into testis or ovary depending on the genetic sex (XY or XX) of the fetus. During gonad development cells segregate, depending on genetic sex, into distinct compartments: testis cords and interstitium form in XY gonad, and germ cell cysts and stroma in XX gonad. However, our knowledge of mechanisms governing gonadal sex differentiation remains very vague. Because it is known that adhesion molecules (CAMs) play a key role in organogenesis, we suspected that diversified expression of CAMs should also play a crucial role in gonad development. Using microarray analysis we identified 129 CAMs and factors regulating cell adhesion during sexual differentiation of mouse gonad. To identify genes expressed differentially in three cell lines in XY and XX gonads: i) supporting (Sertoli or follicular cells), ii) interstitial or stromal cells, and iii) germ cells, we used transgenic mice expressing EGFP reporter gene and FACS cell sorting. Although a large number of CAMs expressed ubiquitously, expression of certain genes was cell line- and genetic sex-specific. The sets of CAMs differentially expressed in supporting versus interstitial/stromal cells may be responsible for segregation of these two cell lines during gonadal development. There was also a significant difference in CAMs expression pattern between XY supporting (Sertoli) and XX supporting (follicular) cells but not between XY and XX germ cells. This indicates that differential CAMs expression pattern in the somatic cells but not in the germ line arbitrates structural organization of gonadal anlagen into testis or ovary. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Transcriptome-based identification and characterization of genes commonly responding to five different insecticides in the diamondback moth, Plutella xylostella.

    Science.gov (United States)

    Gao, Yue; Kim, Kyungmun; Kwon, Deok Ho; Jeong, In Hong; Clark, J Marshall; Lee, Si Hyeock

    2018-01-01

    When the 3rd instar larvae of the diamondback moth (DBM), Plutella xylostella, were pretreated with sublethal doses (LC 10 ) and then subsequently exposed to lethal doses (LC 50 ) of chlorantraniliprole, cypermethrin, dinotefuran, indoxacarb and spinosad via leaf dipping, their tolerance to insecticides was significantly enhanced. To identify genes that commonly respond to the treatment of different insecticides and are responsible for the tolerance enhancement, transcriptomic profiles of larvae treated with sublethal doses of the five insecticides were compared with that of untreated control. A total of 117,181 transcripts with a mean length of 662bp were generated by de novo assembly, of which 35,329 transcripts were annotated. Among them, 125, 143, 182, 215 and 149 transcripts were determined to be up-regulated whereas 67, 45, 60, 60 and 38 genes were down-regulated following treatments with chlorantraniliprole, cypermethrin, dinotefuran, indoxacarb and spinosad, respectively. Gene ontology (GO) analysis of differentially expressed genes (DEGs) revealed little differences in their GO profiles between treatments with different insecticides except for spinosad. Finally, the DEGs commonly responding to all insecticides were selected for further characterization, and some of their over-transcription levels were confirmed by quantitative PCR. The most notable examples of commonly responding over-transcribed genes were two cytochrome P450 genes (Cyp301a1 and Cyp9e2) and nine cuticular protein genes. In contrast, several genes composing the mitochondrial energy generation system were significantly down-regulated in all treated larvae. Considering the distinct structure and mode of action of the five insecticides tested, the differentially expressed genes identified in this study appear to be involved in general chemical defense at the initial stage of intoxication. Their possible roles in the tolerance/resistance development were discussed. Copyright © 2017 Elsevier

  8. Recruiting an Internet Panel Using Respondent-Driven Sampling

    Directory of Open Access Journals (Sweden)

    Schonlau Matthias

    2014-06-01

    Full Text Available Respondent-driven sampling (RDS is a network sampling technique typically employed for hard-to-reach populations when traditional sampling approaches are not feasible (e.g., homeless or do not work well (e.g., people with HIV. In RDS, seed respondents recruit additional respondents from their network of friends. The recruiting process repeats iteratively, thereby forming long referral chains.

  9. Fear conditioning following a unilateral anterior temporal lobectomy: reduced autonomic responding and stimulus contingency knowledge.

    Science.gov (United States)

    Coppens, Evelien; van Paesschen, Wim; Vandenbulcke, Mathieu; Vansteenwegen, Debora

    2010-03-01

    Animal research demonstrated that during fear conditioning the amygdala plays a central role in forming an association between the conditioned stimulus (CS) and the unconditioned stimulus (US). Lesion studies conducted in patients who underwent a unilateral anterior temporal lobe resection, however; yielded contradictory findings. To date, it remains unclear whether amygdala damage only affects fear-conditioned startle responding or impairs both the latter and fear-conditioned skin conductance responding (SCR). Moreover inconsistency exists regarding the preservation of contingency knowledge in amygdala-damaged patients. In the current study, a differential fear conditioning task was presented to a unilaterally amygdala-damaged patient group and a healthy control group, recording fear-potentiated startle responses along with SCRs. Retrospectively, the valence of the CSs and contingency awareness was assessed. Unlike the control group, unilaterally amygdala-damaged patients showed neither in their SCRs nor in their valence ratings an effect of fear conditioning. The startle data, however, yielded in none of the two test groups fear-conditioned responding. Finally, considerably fewer patients (37.5%) than controls (95%) acquired correct memory of the presented contingency. Based on these findings we concluded that the fear conditioning impairment in amygdala-damaged patients was not restricted to SCRs, but also affected valence ratings and memory of the presented contingency. A broader theory of the amygdala as relevance detector is proposed in order to account for the diverse neurological findings obtained so far.

  10. Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

    Science.gov (United States)

    Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David

    2017-02-01

    More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Extended passaging increases the efficiency of neural differentiation from induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Koehler Karl R

    2011-08-01

    Full Text Available Abstract Background The use of induced pluripotent stem cells (iPSCs for the functional replacement of damaged neurons and in vitro disease modeling is of great clinical relevance. Unfortunately, the capacity of iPSC lines to differentiate into neurons is highly variable, prompting the need for a reliable means of assessing the differentiation capacity of newly derived iPSC cell lines. Extended passaging is emerging as a method of ensuring faithful reprogramming. We adapted an established and efficient embryonic stem cell (ESC neural induction protocol to test whether iPSCs (1 have the competence to give rise to functional neurons with similar efficiency as ESCs and (2 whether the extent of neural differentiation could be altered or enhanced by increased passaging. Results Our gene expression and morphological analyses revealed that neural conversion was temporally delayed in iPSC lines and some iPSC lines did not properly form embryoid bodies during the first stage of differentiation. Notably, these deficits were corrected by continual passaging in an iPSC clone. iPSCs with greater than 20 passages (late-passage iPSCs expressed higher expression levels of pluripotency markers and formed larger embryoid bodies than iPSCs with fewer than 10 passages (early-passage iPSCs. Moreover, late-passage iPSCs started to express neural marker genes sooner than early-passage iPSCs after the initiation of neural induction. Furthermore, late-passage iPSC-derived neurons exhibited notably greater excitability and larger voltage-gated currents than early-passage iPSC-derived neurons, although these cells were morphologically indistinguishable. Conclusions These findings strongly suggest that the efficiency neuronal conversion depends on the complete reprogramming of iPSCs via extensive passaging.

  12. Functional requirements of cellular differentiation: lessons from Bacillus subtilis.

    Science.gov (United States)

    Narula, Jatin; Fujita, Masaya; Igoshin, Oleg A

    2016-12-01

    Successful execution of differentiation programs requires cells to assess multitudes of internal and external cues and respond with appropriate gene expression programs. Here, we review how Bacillus subtilis sporulation network deals with these tasks focusing on the lessons generalizable to other systems. With feedforward loops controlling both production and activation of downstream transcriptional regulators, cells achieve ultrasensitive threshold-like responses. The arrangement of sporulation network genes on the chromosome and transcriptional feedback loops allow coordination of sporulation decision with DNA-replication. Furthermore, to assess the starvation conditions without sensing specific metabolites, cells respond to changes in their growth rates with increased activity of sporulation master regulator. These design features of the sporulation network enable cells to robustly decide between vegetative growth and sporulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Effect of Chromatin Structure on the Extent and Distribution of DNA Double Strand Breaks Produced by Ionizing Radiation; Comparative Study of hESC and Differentiated Cells Lines.

    Science.gov (United States)

    Venkatesh, Priyanka; Panyutin, Irina V; Remeeva, Evgenia; Neumann, Ronald D; Panyutin, Igor G

    2016-01-02

    Chromatin structure affects the extent of DNA damage and repair. Thus, it has been shown that heterochromatin is more protective against DNA double strand breaks (DSB) formation by ionizing radiation (IR); and that DNA DSB repair may proceed differently in hetero- and euchromatin regions. Human embryonic stem cells (hESC) have a more open chromatin structure than differentiated cells. Here, we study the effect of chromatin structure in hESC on initial DSB formation and subsequent DSB repair. DSB were scored by comet assay; and DSB repair was assessed by repair foci formation via 53BP1 antibody staining. We found that in hESC, heterochromatin is confined to distinct regions, while in differentiated cells it is distributed more evenly within the nuclei. The same dose of ionizing radiation produced considerably more DSB in hESC than in differentiated derivatives, normal human fibroblasts; and one cancer cell line. At the same time, the number of DNA repair foci were not statistically different among these cells. We showed that in hESC, DNA repair foci localized almost exclusively outside the heterochromatin regions. We also noticed that exposure to ionizing radiation resulted in an increase in heterochromatin marker H3K9me3 in cancer HT1080 cells, and to a lesser extent in IMR90 normal fibroblasts, but not in hESCs. These results demonstrate the importance of chromatin conformation for DNA protection and DNA damage repair; and indicate the difference of these processes in hESC.

  14. WS-020: EPR-First Responders: Cards of response measures for first responders

    International Nuclear Information System (INIS)

    2011-01-01

    The purpose of this working session is that the participants know how to use the cards of response measures for first responders. In a radiological emergency is useful to have cards which contains a list of the steps to be followed as well as the protection instructions and risk evaluation

  15. Effects of atmospheric hydrogen fluoride upon Drosophila melanogaster. I. Differential genotyptic response

    Energy Technology Data Exchange (ETDEWEB)

    Gerdes, R A; Smith, J D; Applegate, H G

    1971-01-01

    Four inbred lines of Drosophila melanogaster were exposed to various concentrations of gaseous hydrogen fluoride for a period of six weeks. The effects upon the viability of these populations were predominantly linear with respect to fluoride concentration over the range tested. Differential responses of the inbred lines were interpreted to mean that tolerance to fluoride contamination is influenced by genotype. 4 references, 1 figure, 1 table.

  16. Comparative Genomic Analysis of Transgenic Poplar Dwarf Mutant Reveals Numerous Differentially Expressed Genes Involved in Energy Flow

    Directory of Open Access Journals (Sweden)

    Su Chen

    2014-09-01

    Full Text Available In our previous research, the Tamarix androssowii LEA gene (Tamarix androssowii late embryogenesis abundant protein Mrna, GenBank ID: DQ663481 was transferred into Populus simonii × Populus nigra. Among the eleven transgenic lines, one exhibited a dwarf phenotype compared to the wild type and other transgenic lines, named dwf1. To uncover the mechanisms underlying this phenotype, digital gene expression libraries were produced from dwf1, wild-type, and other normal transgenic lines, XL-5 and XL-6. Gene expression profile analysis indicated that dwf1 had a unique gene expression pattern in comparison to the other two transgenic lines. Finally, a total of 1246 dwf1-unique differentially expressed genes were identified. These genes were further subjected to gene ontology and pathway analysis. Results indicated that photosynthesis and carbohydrate metabolism related genes were significantly affected. In addition, many transcription factors genes were also differentially expressed in dwf1. These various differentially expressed genes may be critical for dwarf mutant formation; thus, the findings presented here might provide insight for our understanding of the mechanisms of tree growth and development.

  17. Diagnosis and differential diagnosis of hydrocephalus in adults; Diagnostik und Differenzialdiagnostik des Hydrozephalus beim Erwachsenen

    Energy Technology Data Exchange (ETDEWEB)

    Langner, Soenke; Mensel, Birger; Kuehn, Jens Peter; Kirsch, Michael [Univ. Medicine Greifswald (Germany). Inst. for Diagnostic Radiology and Neuroradiology; Fleck, Steffen; Baldauf, Joerg [Univ. Medicine Greifswald (Germany). Dept. of Neurosurgery

    2017-08-15

    Hydrocephalus is caused by an imbalance of production and absorption of cerebrospinal fluid (CSF) or obstruction of its pathways, resulting in ventricular dilatation and increased intracranial pressure. Imaging plays a crucial role in the diagnosis, differential diagnosis and planning of treatment. This review article presents the different types of hydrocephalus und their typical imaging appearance, describes imaging techniques, and discusses differential diagnoses of the different forms of hydrocephalus. Imaging plays a central role in the diagnosis of hydrocephalus. While magnetic resonance (MR) imaging is the first-line imaging modality, computed tomography (CT) is often the first-line imaging test in emergency patients.

  18. Careless responding in internet-based quality of life assessments.

    Science.gov (United States)

    Schneider, Stefan; May, Marcella; Stone, Arthur A

    2018-04-01

    Quality of life (QoL) measurement relies upon participants providing meaningful responses, but not all respondents may pay sufficient attention when completing self-reported QoL measures. This study examined the impact of careless responding on the reliability and validity of Internet-based QoL assessments. Internet panelists (n = 2000) completed Patient-Reported Outcomes Measurement Information System (PROMIS®) short-forms (depression, fatigue, pain impact, applied cognitive abilities) and single-item QoL measures (global health, pain intensity) as part of a larger survey that included multiple checks of whether participants paid attention to the items. Latent class analysis was used to identify groups of non-careless and careless responders from the attentiveness checks. Analyses compared psychometric properties of the QoL measures (reliability of PROMIS short-forms, correlations among QoL scores, "known-groups" validity) between non-careless and careless responder groups. Whether person-fit statistics derived from PROMIS measures accurately discriminated careless and non-careless responders was also examined. About 7.4% of participants were classified as careless responders. No substantial differences in the reliability of PROMIS measures between non-careless and careless responder groups were observed. However, careless responding meaningfully and significantly affected the correlations among QoL domains, as well as the magnitude of differences in QoL between medical and disability groups (presence or absence of disability, depression diagnosis, chronic pain diagnosis). Person-fit statistics significantly and moderately distinguished between non-careless and careless responders. The results support the importance of identifying and screening out careless responders to ensure high-quality self-report data in Internet-based QoL research.

  19. Analysis of mitochondrial function and localisation during human embryonic stem cell differentiation in vitro.

    Directory of Open Access Journals (Sweden)

    Andrew B J Prowse

    Full Text Available Human embryonic stem cell (hESC derivatives show promise as viable cell therapy options for multiple disorders in different tissues. Recent advances in stem cell biology have lead to the reliable production and detailed molecular characterisation of a range of cell-types. However, the role of mitochondria during differentiation has yet to be fully elucidated. Mitochondria mediate a cells response to altered energy requirements (e.g. cardiomyocyte contraction and, as such, the mitochondrial phenotype is likely to change during the dynamic process of hESC differentiation. We demonstrate that manipulating mitochondrial biogenesis alters mesendoderm commitment. To investigate mitochondrial localisation during early lineage specification of hESCs we developed a mitochondrial reporter line, KMEL2, in which sequences encoding the green fluorescent protein (GFP are targeted to the mitochondria. Differentiation of KMEL2 lines into the three germ layers showed that the mitochondria in these differentiated progeny are GFP positive. Therefore, KMEL2 hESCs facilitate the study of mitochondria in a range of cell types and, importantly, permit real-time analysis of mitochondria via the GFP tag.

  20. determination of stresses caused by infinitely long line loads on ...

    African Journals Online (AJOL)

    user

    2016-10-04

    Oct 4, 2016 ... long line loads on semi-infinite homogeneous elastic soils. Airy's stress functions of the Cartesian coordinates system were used to express the governing equations of plane strain elasticity for a semi-infinite homogeneous soil as a biharmonic problem. The fourth order partial differential equation was then ...

  1. On the Market for Principles of Economics Textbooks: Innovation and Product Differentiation--A Response.

    Science.gov (United States)

    Schiller, Bradley

    1988-01-01

    Responding to Stiglitz's article "On the Market for Principles of Economics Textbooks: Innovation and Product Differentiation," Schiller disputes the claim that there is growing dissatisfaction with textbooks, stating that the central issue in the debate is "how best to teach economic principles." Discusses the importance of…

  2. Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines.

    Science.gov (United States)

    Binder, Zev A; Wilson, Kelli M; Salmasi, Vafi; Orr, Brent A; Eberhart, Charles G; Siu, I-Mei; Lim, Michael; Weingart, Jon D; Quinones-Hinojosa, Alfredo; Bettegowda, Chetan; Kassam, Amin B; Olivi, Alessandro; Brem, Henry; Riggins, Gregory J; Gallia, Gary L

    2016-01-01

    Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants. Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling. Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors. We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

  3. A Novel Guidance Law with Line-of-Sight Acceleration Feedback for Missiles against Maneuvering Targets

    Directory of Open Access Journals (Sweden)

    Kemao Ma

    2014-01-01

    Full Text Available Terminal guidance law design and its implementation are considered for homing missiles against maneuvering targets. The lateral acceleration dynamics are taken into account in the design. In the guidance law design, the line-of-sight acceleration signals are incorporated into the acceleration reference signals to compensate for the targets’ maneuvers. Then the commanded accelerations are designed and the convergent tracking of the lateral accelerations to these signals is proven theoretically. In the guidance implementation, a linear high-gain differentiator is used to estimate the line-of-sight rates and the line-of-sight acceleration signals. To avoid the magnifying effects of higher order differentiation, a practical design of commanded accelerations is given to realize approximate tracking of the lateral accelerations to the given reference signals. Simulation is conducted for both cases with and without measurement noises. The simulation results justify the feasibility of the design and the implementation.

  4. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise...

  5. Line emissions from sonoluminescence in aqueous solutions of halide salts without noble gases

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Jinfu, E-mail: liang.shi2007@163.com [The Key Laboratory of Modern Acoustics, Ministry of Education, Institution of Acoustics, Nanjing University, Nanjing 210093 (China); School of Physics and Electronic Science, Guizhou Normal University, Guiyang 550001 (China); Chen, Weizhong, E-mail: wzchen@nju.edu.cn [The Key Laboratory of Modern Acoustics, Ministry of Education, Institution of Acoustics, Nanjing University, Nanjing 210093 (China); Zhou, Chao; Cui, Weicheng; Chen, Zhan [The Key Laboratory of Modern Acoustics, Ministry of Education, Institution of Acoustics, Nanjing University, Nanjing 210093 (China)

    2015-02-20

    Line emissions of trivalent terbium (Tb{sup 3+}) ion were observed from single-bubble sonoluminescence (SL) in an aqueous solution of terbium chloride (TbCl{sub 3}) that contained no noble gas. In addition, sodium (Na) lines were observed in multi-bubble SL in aqueous solutions of various halide salts that contained no noble gas. These observations show that the halide ions, such as Cl{sup −}, Br{sup −}, and I{sup −}, help for line emissions as the noble gases. The intensity of a line emission depends on both the chemical species produced by cavitation bubbles and the temperature of SL bubble that responds to the driving ultrasound pressure. With the increase of driving pressure, some line emissions attached to the continuous spectrum may become increasingly clear, while other line emissions gradually become indistinct. - Highlights: • Line emissions of Tb(III) ions were observed without the presence of noble gases. • The halide ions help to generate a line emission during sonoluminescence. • The intensity of a line emission mainly depends on the bubble's temperature. • The definition of a line emission is related to the temperature of caviation bubble and the kind of host liquid.

  6. Purinergic receptors and calcium signalling in human pancreatic duct cell lines

    DEFF Research Database (Denmark)

    Hansen, Mette R; Krabbe, Simon; Novak, Ivana

    2008-01-01

    pancreatic duct cell lines PANC-1 and CFPAC-1. Expression of P2 receptors was examined using RT-PCR and immunocytochemistry. Both cell lines, and also Capan-1 cells, express RNA transcripts for the following receptors: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11-14 and P2X1, P2X2, P2X4, P2X5, P2X6 and P2X7. Using Fura-2...... and single-cell imaging we tested effects of various nucleotide analogues on intracellular Ca(2+) signals in PANC-1 and CFPAC-1 cells. The cell lines responded to all nucleotides with the following efficiency: UTP >or= ATP = ATPgammaS > BzATP. ATP, UTP and ATPgammaS elicited oscillatory responses. Bz...

  7. Robust fractional order differentiators using generalized modulating functions method

    KAUST Repository

    Liu, Dayan

    2015-02-01

    This paper aims at designing a fractional order differentiator for a class of signals satisfying a linear differential equation with unknown parameters. A generalized modulating functions method is proposed first to estimate the unknown parameters, then to derive accurate integral formulae for the left-sided Riemann-Liouville fractional derivatives of the studied signal. Unlike the improper integral in the definition of the left-sided Riemann-Liouville fractional derivative, the integrals in the proposed formulae can be proper and be considered as a low-pass filter by choosing appropriate modulating functions. Hence, digital fractional order differentiators applicable for on-line applications are deduced using a numerical integration method in discrete noisy case. Moreover, some error analysis are given for noise error contributions due to a class of stochastic processes. Finally, numerical examples are given to show the accuracy and robustness of the proposed fractional order differentiators.

  8. Robust fractional order differentiators using generalized modulating functions method

    KAUST Repository

    Liu, Dayan; Laleg-Kirati, Taous-Meriem

    2015-01-01

    This paper aims at designing a fractional order differentiator for a class of signals satisfying a linear differential equation with unknown parameters. A generalized modulating functions method is proposed first to estimate the unknown parameters, then to derive accurate integral formulae for the left-sided Riemann-Liouville fractional derivatives of the studied signal. Unlike the improper integral in the definition of the left-sided Riemann-Liouville fractional derivative, the integrals in the proposed formulae can be proper and be considered as a low-pass filter by choosing appropriate modulating functions. Hence, digital fractional order differentiators applicable for on-line applications are deduced using a numerical integration method in discrete noisy case. Moreover, some error analysis are given for noise error contributions due to a class of stochastic processes. Finally, numerical examples are given to show the accuracy and robustness of the proposed fractional order differentiators.

  9. Differential Item Functioning Analysis of the Mental, Emotional, and Bodily Toughness Inventory

    Science.gov (United States)

    Gao, Yong; Mack, Mick G.; Ragan, Moira A.; Ragan, Brian

    2012-01-01

    In this study the authors used differential item functioning analysis to examine if there were items in the Mental, Emotional, and Bodily Toughness Inventory functioning differently across gender and athletic membership. A total of 444 male (56.3%) and female (43.7%) participants (30.9% athletes and 69.1% non-athletes) responded to the Mental,…

  10. Analytical study for the ability of nonlinear transmission lines to generate solitons

    International Nuclear Information System (INIS)

    Mostafa, S.I.

    2009-01-01

    The ability of the nonlinear transmission lines (NLTL) has been studied analytically, in this paper to generate solitons and to cause waveform spreading. This can be achieved by balancing nonlinearity and dispersion. A new technique of improved tanh method (ITM) and improved sech methods (ISM) is applied to the nonlinear partial differential equation that describes the NLTL. It is found that the parameters of the transmission line play an important role in controlling the shape of the soliton.

  11. Differentiation of human B lymphocyte subpopulations induced by an alloreactive helper T-cell clone

    International Nuclear Information System (INIS)

    Anderson, S.J.; Hummell, D.S.; Lawton, A.R.

    1988-01-01

    We have used cloned alloreactive helper T cells to determine if direct T cell-B cell interaction can induce differentiation of human peripheral blood B cells which do not respond to pokeweed mitogen (PWM). T-cell clone 2F8 was derived from a one-way mixed lymphocyte reaction. 2F8 cells are T3+T4+T8-IL-2R+ and proliferate in response to irradiated stimulator cells, but not autologous cells, in the absence of exogenous interleukin-2. 2F8 cells provide allospecific help for polyclonal proliferation and differentiation of B cells in the absence of any other stimulus. The magnitude of this response is comparable to that of the response of the same B cells to PWM and fresh autologous T cells. 2F8 cells could also provide nonspecific help for unrelated donor B cells in the presence of PWM, with no requirement for costimulation by irradiated stimulator cells. Allospecific stimulation of B cells was completely inhibited by antibodies to class II major histocompatibility complex (MHC) framework determinants and was abrogated by 1000-rad irradiation. Cloned 2F8 T cells stimulated differentiation of both small, high-density B cells and larger B cells, generating up to 30% plasma cells with either fraction. B cells forming rosettes with mouse erythrocytes were also induced to differentiate by the helper T cell clone. As found previously, neither small, high-density B cells nor mouse rosette+ B cells responded well to PWM. Direct interaction with allospecific T cells induces differentiation of a broader spectrum of B cells than soluble growth and differentiation factors in conjunction with polyclonal activators such as PWM and protein A containing staphylococci

  12. Thermography for detection of scaling in slurry lines and process vessels

    International Nuclear Information System (INIS)

    Capolingua, Adam; Petrik, Andrew

    2006-01-01

    A major problem in many of today's refineries and mineral processing plants is internal scale build-up within slurry lines and process vessels. Consequences of such an internal scale build-up within lines and vessels include machinery damage, flow restrictions, blockages and localised pipe wear. These problems lead to a loss of production, increased maintenance costs, impinge on worker safety, increase environmental hazards and inevitably reduces profit for the organisation of concern. Hence, the application of an efficient and accurate non-intrusive detection method for locating internal scale within kilometres of lines and numerous process vessels is imperative to reduce maintenance costs and limit production losses. Thermography has been found to be a very useful NDT technique for applications where there is a differential between the ambient and internal product temperatures. The 'insulating' effect of the internal scaling results in a reduced external temperature over the associated area. These temperature differentials can be efficiently detected via a thermographic scan. While this technique is relatively straightforward, the interpretation of the thermographic images usually requires reasonable skill and experience to assess the true extent of each problem detected. In some cases, the true location and extent of scaling within the slurry lines may not be thermally obvious due to the nature of the internal scaling. In such cases, the use of other complementary methods to effectively 'listen'in to the lines has proved to be a valuable procedure. In particular a technology that is typically used in vibration monitoring to assess bearing and gear degradation has been successfully applied in conjunction with thermography to assess lines with localised or dislodged scale. This paper presents a number of case studies where thermography was either applied independently or in conjunction with other measurement techniques, to detect and assess different internal

  13. Isolation and characterization of conditionally immortalized mouse glomerular endothelial cell lines.

    Science.gov (United States)

    Rops, Angelique L; van der Vlag, Johan; Jacobs, Cor W; Dijkman, Henry B; Lensen, Joost F; Wijnhoven, Tessa J; van den Heuvel, Lambert P; van Kuppevelt, Toin H; Berden, Jo H

    2004-12-01

    The culture and establishment of glomerular cell lines has proven to be an important tool for the understanding of glomerular cell functions in glomerular physiology and pathology. Especially, the recent establishment of a conditionally immortalized visceral epithelial cell line has greatly boosted the research on podocyte biology. Glomeruli were isolated from H-2Kb-tsA58 transgenic mice that contain a gene encoding a temperature-sensitive variant of the SV40 large tumor antigen, facilitating proliferative growth at 33 degrees C and differentiation at 37 degrees C. Glomerular endothelial cells were isolated from glomerular outgrowth by magnetic beads loaded with CD31, CD105, GSL I-B4, and ULEX. Clonal cell lines were characterized by immunofluorescence staining with antibodies/lectins specific for markers of endothelial cells, podocytes, and mesangial cells. Putative glomerular endothelial cell lines were analyzed for (1) cytokine-induced expression of adhesion molecules; (2) tube formation on Matrigel coating; and (3) the presence of fenestrae. As judged by immunostaining for Wilms tumor-1, smooth muscle actin (SMA), podocalyxin, and von Willebrand factor (vWF), we obtained putative endothelial, podocyte and mesangial cell lines. The mouse glomerular endothelial cell clone #1 (mGEnC-1) was positive for vWF, podocalyxin, CD31, CD105, VE-cadherin, GSL I-B4, and ULEX, internalized acetylated-low-density lipoprotein (LDL), and showed increased expression of adhesion molecules after activation with proinflammatory cytokines. Furthermore, mGEnC-1 formed tubes and contained nondiaphragmed fenestrae. The mGEnC-1 represents a conditionally immortalized cell line with various characteristics of differentiated glomerular endothelial cells when cultured at 37 degrees C. Most important, mGEnC-1 contains nondiaphragmed fenestrae, which is a unique feature of glomerular endothelial cells.

  14. Severe Recurrent Achalasia Cardia Responding to Treatment of Severe Autoimmune Acquired Haemophilia

    Directory of Open Access Journals (Sweden)

    H. Al-Jafar

    2012-09-01

    Full Text Available Acquired haemophilia A and severe acquired achalasia are both very rare conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease induced by deficiency or malfunction of coagulation factor VIII. Congenital haemophilia is an inherited disease transmitted by the mother through X-linked inheritance and primarily affects males. However, acquired haemophilia A is a serious, sudden-onset, autoimmune disease that affects either sex. In addition, achalasia is a disease of the oesophagus caused by abnormal function of the nerves and muscles. It causes swallowing difficulties due to the inability of the lower oesophageal sphincter to relax during swallowing, leading to dysphagia, regurgitation and chest pain. In this report, we describe the case of a patient with severe, newly diagnosed, acquired haemophilia A with long-standing, recurrent achalasia; the achalasia had recurred 3 times despite complete and proper surgical fixation. Acquired haemophilia A is treated with immunosuppressive therapy. High-dose steroid therapy was administered for 7 months, during which the patient responded well; moreover, the achalasia did not recur for more than 2 years. The response of the achalasia to immunosuppressive therapy suggests that achalasia may be an autoimmune disorder and that there may be an association between both diseases. The findings of the present case suggest that achalasia may favourably respond to steroid therapy as a first-line treatment prior to surgery.

  15. Responder Technology Alert Monthly (Oct-Nov 2014)

    Energy Technology Data Exchange (ETDEWEB)

    Upton, Jaki F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stein, Steven L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-01-21

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in the areas wearable technology.

  16. Induction of expression of two phenotypic markers of pulmonary type II cells in a cultured cell line

    International Nuclear Information System (INIS)

    Henderson, R.F.; Waide, J.J.; Scott, G.G.

    1994-01-01

    The functions of pulmonary type II cells, such as synthesis of pulmonary surfactant and metabolism of inhaled xenobiotics, can be studied in primary isolates of lung cells. However, isolated type II cells, when cultured, quickly lose the phenotypic expressions characteristics of type II cells, including surfactant lipid and protein synthesis and alkaline phosphatase (AP) activity. A cultured cell line that maintained expression of type II cell markers of differentiation would be advantageous for the study of such functions as surfactant synthesis and secretion. Such a cell line would allow generation of a large number of homogeneous cells for study. The purpose of the current study was to induce markers of differentiated type II cells in a cultured cell line to facilitate studies of factors that control surfactant synthesis and secretion

  17. Knowledge of severe acute respiratory syndrome among community physicians, nurses, and emergency medical responders.

    Science.gov (United States)

    Tice, Alan Douglas; Kishimoto, Mitsumasa; Dinh, Chuong Hoang; Lam, Geoffrey Tak-Kin; Marineau, Michelle

    2006-01-01

    The preparedness levels of front-line clinicians including physicians, nurses, emergency medical responders (EMRs), and other medical staff working in clinics, offices and ambulatory care centers must be assessed, so these personnel are able to deal with communicable and potentially lethal diseases, such as severe acute respiratory syndrome (SARS). In order to determine the knowledge of these clinicians, a survey of their understanding of SARS and their use of educational resources was administered. A questionnaire was distributed to physicians, nurses, and EMRs attending conferences on SARS in the summer of 2003. Questions related to information sources, knowledge of SARS, and plans implemented in their workplace to deal with it. Statistical analysis was performed using the Statistical Package for the Social Sciences (10.1 Program, SPSS Inc., Chicago, Illinois). A total of 201 community healthcare providers (HCPs) participated in the study. A total of 51% of the participants correctly identified the incubation period of SARS; 48% correctly identified the symptoms of SARS; and 60% knew the recommended infection control precautions to take for families. There was little difference in knowledge among the physicians, nurses, and EMRs evaluated. Media outlets such as newspapers, journals, television, and radio were reported as the main sources of information on SARS. However, there appears to be a growing use of the Internet, which correlated best with the correct answers on symptoms of SARS. Fewer than one-third of respondents were aware of a protocol for SARS in their workplace. A total of 60% reported that N-95 masks were available in their workplace. These findings suggest the need for more effective means of education and training for front-line clinicians, as well as the institution of policies and procedures in medical offices, clinics, and emergency services in the community.

  18. Resources and Constraints of Line Manager Agency in Municipal Reforms

    Directory of Open Access Journals (Sweden)

    Tuula Heiskanen

    2015-10-01

    Full Text Available The context of this study is the nation-wide reform of local government in Finland, focusing on line managers and their scope of agency. Our data comprise two large-scale surveys of 40 municipalities in 2009 and 38 in 2011. The respondents were line managers from different levels of the hierarchy and, for comparative purposes, staff from the same units. Resources and constraints of agency were studied both in relation to the immediate work of the respondents and to the broader issues of municipality reform. Broad-scale reforms proceed in stages that require different forms of agency. Predominantly, a higher position in the hierarchy seemed to give better conditions for agency, but this was not always the case. Notable were the high values for intrinsic rewards of work given by all groups, indicating the existence of conditions that enable new cognitive and learning challenges to be met. It seems that this potential was not actualized satisfactorily in the accomplishment of development activities. The supervisor’s influence on the social climate of the units was evident in the longitudinal setting. From the perspective of distributed agency, this result is highly significant when one considers that the social environment is the immediate context of agency.

  19. Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma.

    Science.gov (United States)

    Mohanta, Simple; Siddappa, Gangotri; Valiyaveedan, Sindhu Govindan; Dodda Thimmasandra Ramanjanappa, Ravindra; Das, Debashish; Pandian, Ramanan; Khora, Samanta Sekhar; Kuriakose, Moni Abraham; Suresh, Amritha

    2017-06-01

    Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p squamous cell carcinoma origin (93.49 ± 0.47%, p squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.

  20. Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

    Directory of Open Access Journals (Sweden)

    Kawinthra Khwanraj

    2015-01-01

    Full Text Available The human neuroblastoma SH-SY5Y cell line has been used as a dopaminergic cell model for Parkinson’s disease research. Whether undifferentiated or differentiated SH-SY5Y cells are more suitable remains controversial. This study aims to evaluate the expression of apoptosis-related mRNAs activated by MPP+ and evaluate the differential expression of tyrosine hydroxylase (TH in undifferentiated and retinoic acid- (RA- induced differentiated cells. The western blot results showed a gradual decrease in TH in undifferentiated cells and a gradual increase in TH in differentiated cells from days 4 to 10 after cell plating. Immunostaining revealed a gradual increase in TH along with neuritic outgrowth in differentiated cells on days 4 and 7 of RA treatment. For the study on cell susceptibility to MPP+ and the expression of apoptosis-related genes, MTT assay showed a decrease in cell viability to approximately 50% requiring 500 and 1000 μM of MPP+ for undifferentiated and RA-differentiated cells, respectively. Using real-time RT-PCR, treatment with 500 μM MPP+ led to significant increases in the Bax/Bcl-2 ratio, p53, and caspase-3 in undifferentiated cells but was without significance in differentiated cells. In conclusion, differentiated cells may be more suitable, and the shorter duration of RA differentiation may make the SH-SY5Y cell model more accessible.

  1. Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Yoshitaka Sunami

    Full Text Available Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia-retinoic acid receptor α (PML-RAR-α stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.

  2. Measurement of the differential pressure of liquid metals

    International Nuclear Information System (INIS)

    Metz, H.J.

    1975-01-01

    This patent relates to an improved means for measuring the differential pressure between any two points in a process liquid metal coolant loop, wherein the flow of liquid metal in a pipe is opposed by a permanent magnet liquid metal pump until there is almost zero flow shown by a magnetic type flowmeter. The pressure producing the liquid metal flow is inferred from the rate of rotation of the permanent magnet pump. In an alternate embodiment, a differential pressure transducer is coupled to a process pipeline by means of high-temperature bellows or diaphragm seals, and a permanent magnet liquid metal pump in the high-pressure transmission line to the pressure transducer can be utilized either for calibration of the transducer or for determining the process differential pressure as a function of the magnet pump speed

  3. Measurement of the differential pressure of liquid metals

    Science.gov (United States)

    Metz, H.J.

    1975-09-01

    This patent relates to an improved means for measuring the differential pressure between any two points in a process liquid metal coolant loop, wherein the flow of liquid metal in a pipe is opposed by a permanent magnet liquid metal pump until there is almost zero flow shown by a magnetic type flowmeter. The pressure producing the liquid metal flow is inferred from the rate of rotation of the permanent magnet pump. In an alternate embodiment, a differential pressure transducer is coupled to a process pipeline by means of high-temperature bellows or diaphragm seals, and a permanent magnet liquid metal pump in the high-pressure transmission line to the pressure transducer can be utilized either for calibration of the transducer or for determining the process differential pressure as a function of the magnet pump speed. (auth)

  4. Development of buffalo (Bubalus bubalis embryonic stem cell lines from somatic cell nuclear transferred blastocysts

    Directory of Open Access Journals (Sweden)

    Syed Mohmad Shah

    2015-11-01

    Full Text Available We developed buffalo embryonic stem cell lines from somatic cell nuclear transfer derived blastocysts, produced by hand-guided cloning technique. The inner cell mass of the blastocyst was cut mechanically using a Microblade and cultured onto feeder cells in buffalo embryonic stem (ES cell culture medium at 38 °C in a 5% CO2 incubator. The stem cell colonies were characterized for alkaline phosphatase activity, karyotype, pluripotency and self-renewal markers like OCT4, NANOG, SOX2, c-Myc, FOXD3, SSEA-1, SSEA-4, TRA-1-60, TRA-1-81 and CD90. The cell lines also possessed the capability to differentiate across all the three germ layers under spontaneous differentiation conditions.

  5. The role of valence focus and appraisal overlap in emotion differentiation.

    Science.gov (United States)

    Erbas, Yasemin; Ceulemans, Eva; Koval, Peter; Kuppens, Peter

    2015-06-01

    Emotion differentiation refers to the level of specificity with which people distinguish between their emotional states and is considered to play an important role for psychological well-being. Yet, not much is known about what characterizes people high or low in emotion differentiation and what underlies these differences. In 2 studies involving experience sampling (Studies 1-2) and lab based (Study 2) methods, we investigated how emotion differentiation is related to individual differences in valence focus and the overlap in appraisal patterns between emotions. In line with expectations, results showed that high levels of both positive and negative emotion differentiation are related to lower levels of valence focus and lower levels of appraisal overlap between emotions. These findings suggest that individuals who are low in emotion differentiation mainly emphasize the valence aspect of emotions while individuals who are high in emotion differentiation make stronger distinctions between emotions in terms of their underlying appraisal profiles. (c) 2015 APA, all rights reserved).

  6. Acute Chemical Incidents With Injured First Responders, 2002-2012.

    Science.gov (United States)

    Melnikova, Natalia; Wu, Jennifer; Yang, Alice; Orr, Maureen

    2018-04-01

    IntroductionFirst responders, including firefighters, police officers, emergency medical services, and company emergency response team members, have dangerous jobs that can bring them in contact with hazardous chemicals among other dangers. Limited information is available on responder injuries that occur during hazardous chemical incidents. We analyzed 2002-2012 data on acute chemical incidents with injured responders from 2 Agency for Toxic Substances and Disease Registry chemical incident surveillance programs. To learn more about such injuries, we performed descriptive analysis and looked for trends. The percentage of responders among all injured people in chemical incidents has not changed over the years. Firefighters were the most frequently injured group of responders, followed by police officers. Respiratory system problems were the most often reported injury, and the respiratory irritants, ammonia, methamphetamine-related chemicals, and carbon monoxide were the chemicals more often associated with injuries. Most of the incidents with responder injuries were caused by human error or equipment failure. Firefighters wore personal protective equipment (PPE) most frequently and police officers did so rarely. Police officers' injuries were mostly associated with exposure to ammonia and methamphetamine-related chemicals. Most responders did not receive basic awareness-level hazardous material training. All responders should have at least basic awareness-level hazardous material training to recognize and avoid exposure. Research on improving firefighter PPE should continue. (Disaster Med Public Health Preparedness. 2018;12:211-221).

  7. Effect of Different Structure Type Traffic On Railway Line Capacity

    Directory of Open Access Journals (Sweden)

    Gleba Radosław

    2017-04-01

    Full Text Available The article points to methods of analyzing railway traffic conditions based on two parameters: capacity and delay of trains. The impact of the differentiated railway type structure on the capacity of the railway line was presented. Particular attention has been paid to the assessment of commonly used simplifications in analyzes.

  8. HYC-24L Demonstrates Greater Effectiveness With Less Pain Than CPM-22.5 for Treatment of Perioral Lines in a Randomized Controlled Trial.

    Science.gov (United States)

    Butterwick, Kimberly; Marmur, Ellen; Narurkar, Vic; Cox, Sue Ellen; Joseph, John H; Sadick, Neil S; Tedaldi, Ruth; Wheeler, Sarah; Kolodziejczyk, Julia K; Gallagher, Conor J

    2015-12-01

    This trial compares the effectiveness and safety of HYC-24L (Juvéderm Ultra XC; Allergan plc, Dublin, Ireland) (24 mg/mL of hyaluronic acid, 0.3% lidocaine) and CPM-22.5 (Belotero Balance; Merz Aesthetics, Raleigh, NC) (22.5 mg/mL of hyaluronic acid) for the treatment of perioral lines. Men and women aged 35 years or older with moderate-to-severe perioral lines were recruited for this randomized controlled, rater-blinded, 2-arm trial. The primary endpoint was a comparison of rater-assessed responder rates by the validated 4-point Perioral Lines Severity Scale at Month 6; responders were those who showed a ≥1 point improvement. A secondary endpoint was subject-assessed change in perioral lines measured by the Global Assessment of Change Scale. A total of 136 subjects received treatment and 132 completed the trial (mean age: 58 ± 8 years). Total volume injected was 1.18 mL (HYC-24L) and 1.32 mL (CPM-22.5). At Month 6, a significantly greater proportion of HYC-24L subjects responded to treatment (87%) than CPM-22.5 subjects (72%) (p CPM-22.5 subjects, with the greatest difference at Month 6. No unexpected adverse events occurred. HYC-24L subjects showed a higher response rate and a greater improvement in their perioral lines than CPM-22.5 subjects for up to 6 months.

  9. First Responders Guide to Computer Forensics: Advanced Topics

    National Research Council Canada - National Science Library

    Nolan, Richard; Baker, Marie; Branson, Jake; Hammerstein, Josh; Rush, Kris; Waits, Cal; Schweinsberg, Elizabeth

    2005-01-01

    First Responders Guide to Computer Forensics: Advanced Topics expands on the technical material presented in SEI handbook CMU/SEI-2005-HB-001, First Responders Guide to Computer Forensics [Nolan 05...

  10. Use of differential item functioning analysis to assess the equivalence of translations of a questionnaire

    NARCIS (Netherlands)

    Petersen, Morten Aa; Groenvold, Mogens; Bjorner, Jakob B.; Aaronson, Neil; Conroy, Thierry; Cull, Ann; Fayers, Peter; Hjermstad, Marianne; Sprangers, Mirjam; Sullivan, Marianne

    2003-01-01

    In cross-national comparisons based on questionnaires, accurate translations are necessary to obtain valid results. Differential item functioning (DIF) analysis can be used to test whether translations of items in multi-item scales are equivalent to the original. In data from 10,815 respondents

  11. Effect of resveratrol on proliferation and differentiation of embryonic cardiomyoblasts

    International Nuclear Information System (INIS)

    Leong, C.-W.; Wong, C.H.; Lao, S.-C.; Leong, Emilia Conceicao; Lao, Iok Fong; Law, Patrick Tik Wan; Fung, Kwok Pui; Tsang, Kam Sze; Waye, Mary Miu-Yee; Tsui, Stephen Kwok-Wing; Wang Yitao; Lee, Simon Ming-Yuen

    2007-01-01

    Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found largely in the skins of red grapes, has been used as a nutritional supplement or an investigational new drug for prevention of cardiovascular diseases. Previous reports showed that resveratrol had a protective effect against oxidative agent-induced cell injury. Our studies indicate that resveratrol plays a role in the differentiation of cardiomyoblasts. The cardiomyoblast cell line, H9c2, was exposed to 30-120 μM resveratrol for up to 5 days. Resveratrol inhibits cardiomyoblast proliferation without causing cells injury. Moreover, resveratrol treatment modulated the differentiation of morphological characteristics including elongation and cell fusion in cardiomyoblasts. Proliferation and differentiation of H9c2 cells were further revealed by measurement of the mRNA expression of a cell cycle marker (CDK2), a differentiation marker (myogenin), and a contractile apparatus protein (MLC-2). Gene expression analysis revealed that resveratrol promoted entry into cell cycle arrest but extended the myogenic differentiation progress. These results have implications for the role of resveratrol in modulating cell cycle control and differentiation in cardiomyoblasts

  12. Genomic data reveal Toxoplasma gondii differentiation mutants are also impaired with respect to switching into a novel extracellular tachyzoite state.

    Directory of Open Access Journals (Sweden)

    Pamela J Lescault

    2010-12-01

    Full Text Available Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites. Microarray quantification of the variation in genome-wide RNA levels for each parasite line and times after induction allowed us to describe states in the normal differentiation process, to analyze mutant lines in the context of these states, and to identify genes that may have roles in initiating the transition from tachyzoite to bradyzoite. Gene expression patterns in wild-type parasites undergoing differentiation suggest a novel extracellular state within the tachyzoite stage. All mutant lines exhibit aberrant regulation of bradyzoite gene expression and notably some of the mutant lines appear to exhibit high proportions of the intracellular tachyzoite state regardless of whether they are intracellular or extracellular. In addition to the genes identified by the insertional mutagenesis screen, mixture model analysis allowed us to identify a small number of genes, in mutants, for which expression patterns could not be accounted for using the three parasite states--genes that may play a mechanistic role in switching from the tachyzoite to bradyzoite stage.

  13. Cell lines radiosensitization of thyroid cancer by histone deacetylase inhibitors

    International Nuclear Information System (INIS)

    Perona, M; Dagrosa, M A; Rossich, L; Casal, M; Pisarev, M A; Thomasz, L; Juvenal G J

    2012-01-01

    Introduction: Thyroid cancer is the most common endocrine neoplasia. Surgical resection and radioactive iodine is an effective treatment for well-differentiated tumors. Histone deacetylase inhibitors (HDAC-I) are agents that cause hyperacetylation of histone proteins and as a consequence remodeling of chromatin structure. They can induce growth arrest, differentiation and apoptotic cell death in different tumor cells. The use of HDAC-I agents could be of utility to enhance the response to external radiation therapy of those thyroid cancers that are refractory to most conventional therapeutic treatments. Objective: To study the effect of HDAC-I as radiosensitizers for the treatment of thyroid cancer and their ability to induce differentiation of thyroid cancer cells. Materials and methods: The human thyroid follicular (WRO) and papillary (TPC-1) carcinoma cell lines were seeded and incubated with increasing doses (0, 0.3, 0.5, 1 and 1.5 mM) of the HDAC-I sodium butirate (NaB) and valproic acid (VA) to evaluate cell proliferation and iodide uptake. Cells were irradiated with a 60 Co γ-ray source (1 ± 5% Gy/min) and postirradiation survival was quantified with the colony formation assay. Survival fraction at 2 Gy (SF2) was calculated for each cell line. Cell cycle and cell death were evaluated at a dose of 3 Gy. Iodide uptake, PCR analysis and transient transfection studies were performed. Results: Cell proliferation was not significantly suppressed after 24 hours of incubation with both drugs at all assayed doses. Iodide uptake was not modified after incubation with HDAC-I of both cell lines. SF2 was reduced from 68 ± 1.6 % in the control WRO cells to 42 ± 3.8 % (P<0.001) in NaB-treated cells. In TPC-1 SF2 was reduced from 32 ± 1.1 % in the control cells to 24 ± 0.8 % (P<0.01). In VA-treated cells SF2 was reduced from 69 ± 0.02 % in control WRO cells to 56 ± 0.01 % (P<0.01) and from 31 ± 2 % in control TPC-1 cells to 11 ± 1 % (P<0.01). There was an arrest

  14. Derivation and characterisation of the human embryonic stem cell lines, NOTT1 and NOTT2.

    Science.gov (United States)

    Priddle, Helen; Allegrucci, Cinzia; Burridge, Paul; Munoz, Maria; Smith, Nigel M; Devlin, Lyndsey; Sjoblom, Cecilia; Chamberlain, Sarah; Watson, Sue; Young, Lorraine E; Denning, Chris

    2010-04-01

    The ability to maintain human embryonic stem cells (hESCs) during long-term culture and yet induce differentiation to multiple lineages potentially provides a novel approach to address various biomedical problems. Here, we describe derivation of hESC lines, NOTT1 and NOTT2, from human blastocysts graded as 3BC and 3CB, respectively. Both lines were successfully maintained as colonies by mechanical passaging on mouse embryonic feeder cells or as monolayers by trypsin-passaging in feeder-free conditions on Matrigel. Undifferentiated cells retained expression of pluripotency markers (OCT4, NANOG, SSEA-4, TRA-1-60 and TRA-1-81), a stable karyotype during long-term culture and could be transfected efficiently with plasmid DNA and short interfering RNA. Differentiation via formation of embryoid bodies resulted in expression of genes associated with early germ layers and terminal lineage specification. The electrophysiology of spontaneously beating NOTT1-derived cardiomyocytes was recorded and these cells were shown to be pharmacologically responsive. Histological examination of teratomas formed by in vivo differentiation of both lines in severe immunocompromised mice showed complex structures including cartilage or smooth muscle (mesoderm), luminal epithelium (endoderm) and neuroectoderm (ectoderm). These observations show that NOTT1 and NOTT2 display the accepted characteristics of hESC pluripotency.

  15. Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

    Science.gov (United States)

    Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

    2017-01-01

    An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

  16. Differentiation of car rental services in the Croatian market

    Directory of Open Access Journals (Sweden)

    Karolina Karlo Marijanović

    2010-06-01

    Full Text Available A number of service companies focus on service differentiation nowadays. The companies that manage to deliver superior service are winners and may serve as an example of how the growth of services has changed business. The first part of the paper presents an analysis of the Croatian car rental services market. The theoretical part of the paper provides an insight into the characteristics of services in general, followed by an overview of the characteristics and features of the companies operating in the local market. The second part of the paper deals with the work of Porter and his three generic strategies, and with his differentiation strategy in particular. Subsequently, all possibilities of differentiation strategies that are appropriate to the car rental services are analyzed. Beside global recession, the Croatian market is currently also struggling with huge competition and companies cannot generate profit without continuous differentiation of all elements of service. In the third chapter the following hypothesis is set: By a continuous differentiation of all elements of the services marketing mix small businesses can compete with large international companies. Acceptance or rejection of the hypothesis is shown by the research conducted among users of the specific service. Its results fully confirm the set hypothesis. The fact that, despite global recession, the majority of respondents believes the survival of small- and medium-sized companies which continuously differentiate their business activities to be unquestionable is indeed encouraging.

  17. TET2 deficiency inhibits mesoderm and hematopoietic differentiation in human embryonic stem cells

    DEFF Research Database (Denmark)

    Langlois, Thierry; da Costa Reis Monte Mor, Barbara; Lenglet, Gaëlle

    2014-01-01

    . Here, we show that TET2 expression is low in human embryonic stem (ES) cell lines and increases during hematopoietic differentiation. ShRNA-mediated TET2 knockdown had no effect on the pluripotency of various ES cells. However, it skewed their differentiation into neuroectoderm at the expense...... profile, including abnormal expression of neuronal genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased hematopoietic development. In conclusion, our work suggests that TET2 is involved in different stages of human embryonic development, including induction of the mesoderm...... and hematopoietic differentiation. Stem Cells 2014....

  18. LET effects on normal and radiosensitive cell lines

    International Nuclear Information System (INIS)

    Geard, C.R.; Travisano, M.

    1986-01-01

    Charged particles in the track segment mode were produced by the RARAF Van de Graaff accelerator and used to irradiate two CHO cell lines, a radiosensitive hypermutable line EM9 and its normal parent AA8. Asynchronous cells were irradiated attached to 6 micrometer thick Mylar with protons, deuterons and helium-3 particles at LETs ranging from 10 to 150 keV per micrometer. A 50 kVp x-ray tube integrated into the track segment facility provided a low LET comparison. Following irradiation cells were monitored for clonogenicity, and in a separate series of experiments frequencies of sister chromatid exchanges. Up to 9 experiments were carried out at each LET, with a total of 8 radiations of different LETs being compared. The optimally effective LET for cell survival was between 80 and 120 keV per micrometer, with the 150 keV per micrometer particles indicating energy wastage. The differential between the normal and radiosensitive cell lines was maintained at all LETs

  19. Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A.

    Science.gov (United States)

    Liu, Fuzhou; Shen, Weiwei; Qiu, Hao; Hu, Xu; Zhang, Chao; Chu, Tongwei

    2015-03-01

    Prostate cancer metastasis to bone is the second most commonly diagnosed malignant disease among men worldwide. Such metastatic disease is characterized by the presence of osteoblastic bone lesions, and is associated with high rates of mortality. However, the various mechanisms involved in prostate cancer-induced osteoblastic differentiation have not been fully explored. Semaphorin 3A (Sema 3A) is a newly identified regulator of bone metabolism which stimulates differentiation of pre-osteoblastic cells under physiological conditions. We investigated in this study whether prostate cancer cells can mediate osteoblastic activity through Sema 3A. We cultured osteoprogenitor MC3T3-E1 cells in prostate cancer-conditioned medium, and analyzed levels of Sema 3A protein in diverse prostate cancer cell lines to identify cell lines in which Sema 3A production showed a positive correlation with osteo-stimulation. C4-2 cells were stably transfected with Sema 3A short hairpin RNA to further determine whether Sema 3A contributes to the ability of C4-2 cells to induce osteoblastic differentiation. Down-regulation of Sema 3A expression decreased indicators of C4-2 CM-induced osteoblastic differentiation, including alkaline phosphatase production and mineralization. Additionally, silencing or neutralizing Sema 3A in C4-2 cells resulted in diminished β-catenin expression in osteogenitor MC3T3-E1 cells. Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the β-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions. © 2014 Wiley Periodicals, Inc.

  20. Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

    Science.gov (United States)

    Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

    2013-05-05

    Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

  1. MODULAR RESEARCH EQUIPMENT FOR ON-LINE INSPECTION IN ADVANCED MANUFACTURING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Davrajh, S.

    2012-11-01

    Full Text Available The significance of inspection processes increases when producing parts with high levels of customer input. These processes must adapt to variations in significant product characteristics. Mass customisation and reconfigurable manufacturing are currently being researched as ways to respond to high levels of customer input. This paper presents the research and development of modular inspection equipment that was designed to meet the on-line quality requirements of mass customisation and reconfigurable manufacturing environments. Simulated results were analysed for application in an industrial environment. The implementation of the equipment in South Africa is briefly discussed. The research indicates that manufacturers need only invest in the required equipment configurations when they are needed for on-line inspection.

  2. Development and characterization of a bovine monocyte-derived macrophage cell line

    Science.gov (United States)

    Monocytes circulate in the blood, and later differentiate into macrophages in the tissues. They are components of the innate arm of the immune response and are one of the first lines of defense again invading pathogens. However, they also serve as host cells for intracellular pathogens such as Mycob...

  3. An exploratory study of work-family conflicts and enrichment of front-line hotel employees in the Philippines

    OpenAIRE

    Nabong, Tristan Kirby Mansueto

    2012-01-01

    Master's thesis in International hotel and tourism management The study aims to explore and identify the front-line hotel employees’ issues and perceptions of work-life balance in the Philippine context. The respondents were front-line hotel personnel assigned to various departments of selected top luxury hotels in the Philippines. Self-administered questionnaires were used to collect the data. Factor analysis discovered five factors: (1) time-based conflict; (2) strain-based conflict; (3...

  4. Achievement motivation and memory: achievement goals differentially influence immediate and delayed remember-know recognition memory.

    Science.gov (United States)

    Murayama, Kou; Elliot, Andrew J

    2011-10-01

    Little research has been conducted on achievement motivation and memory and, more specifically, on achievement goals and memory. In the present research, the authors conducted two experiments designed to examine the influence of mastery-approach and performance-approach goals on immediate and delayed remember-know recognition memory. The experiments revealed differential effects for achievement goals over time: Performance-approach goals showed higher correct remember responding on an immediate recognition test, whereas mastery-approach goals showed higher correct remember responding on a delayed recognition test. Achievement goals had no influence on overall recognition memory and no consistent influence on know responding across experiments. These findings indicate that it is important to consider quality, not just quantity, in both motivation and memory, when studying relations between these constructs.

  5. Inter-Industry and Inter-Firm Wage and Hours Differentials in Switzerland

    OpenAIRE

    José V. Ramirez

    2000-01-01

    In the present paper, we analyse the role of demand factors on wages and hours in Switzerland. To accomplish this task, we used the 1996 Swiss Wage Structure Survey, a large employee-employer survey. Results indicate that capital intensity appears to have a certain impact on the relation between wages and hours: the "inter-industry wage-hours differentials line" we inferred is clearly positive. Further, an analysis of the determinants of inter-firm wage differentials shows that the internal o...

  6. Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children.

    Science.gov (United States)

    Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi

    2016-10-01

    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.

  7. Precise ion optical description of strip-line pulsed magnetic lenses

    International Nuclear Information System (INIS)

    Varentsov, D.; Spiller, P.; Eickhoff, H.; Hoffmann, D.H.H.

    2002-01-01

    A specific computer code has been developed to investigate ion optical properties of a new generation of pulsed strip-line high current magnets. The code is based on a modern 'Differential Algebra' computational technique and it is able to calculate transfer matrices of pulsed strip-line magnets up to arbitrary order. The realistic three-dimensional distribution of the magnetic field in pulsed lenses as well as all the fringing field effects are taken into account in the simulations. We have demonstrated, that for precise description of such magnets one cannot use the existing ion optical codes where ideal multipole field distributions and fringing fields, typical for conventional iron-dominated magnets are assumed. The transfer matrix elements of pulsed strip-line lenses differ significantly from those of conventional magnets, especially in higher orders

  8. A Value-Based Business Approach to Product Line Software Engineering

    Directory of Open Access Journals (Sweden)

    Raman K. Agrawalla

    2009-08-01

    Full Text Available The present conceptual paper is an attempt to provide a Value-Based Business Approach (VBBA to product line software engineering. It argues that Product line software engineering should be seen as a system and considered as a means towards the end of appropriating more and more value for the business firm; contingent upon the fact that it provides value to customer and customer's customers operating its value creating system with agility, speed, economy and innovation; getting governed by the positive sum value creation outlook and guided by value- based management. With our value-based business triad, the product line engineering process can hope to achieve simultaneously value, variety and volume, product differentiation and cost leadership enabling the business firm to land on the virtuous value spiral.

  9. Atmospheric pressure and temperature profiling using near IR differential absorption lidar

    Science.gov (United States)

    Korb, C. L.; Schwemmer, G. K.; Dombrowski, M.; Weng, C. Y.

    1983-01-01

    The present investigation is concerned with differential absorption lidar techniques for remotely measuring the atmospheric temperature and pressure profile, surface pressure, and cloud top pressure-height. The procedure used in determining the pressure is based on the conduction of high-resolution measurements of absorption in the wings of lines in the oxygen A band. Absorption with respect to these areas is highly pressure sensitive in connection with the mechanism of collisional line broadening. The method of temperature measurement utilizes a determination of the absorption at the center of a selected line in the oxygen A band which originates from a quantum state with high ground state energy.

  10. Pharmacophore-based screening of differentially-expressed PGF, DDIT4, COMP and CHI3L1 from hMSC cell lines reveals five novel therapeutic compounds for primary osteoporosis

    Directory of Open Access Journals (Sweden)

    Catherine Jessica Lai

    2016-06-01

    Full Text Available As many societies age, primary osteoporosis (PO is increasingly a major health problem. Current drug treatments such as alendronate and risedronate have known side effects. We took an agnostic empirical approach to find PO therapeutic compounds. We examined 13,548,960 probe data-points from mesenchymal stromal cell (hMSC lines and found that PGF, DDIT4, and COMP to be up-regulated, and CHI3L1, down-regulated. We then identified their druggable domains. For the up-regulated differentially-expressed genes, we used protein–protein interactions to find residue clusters as binding surfaces. We then employed pharmacophore models to screen 15,407,096 conformations of 22,723,923 compounds, which identified (6R,9R-6-(2-furyl-9-(1H-indol-3-yl-2-(trifluoromethyl-5,6,7, 9-tetrahydro-4H[1,2,4]triazolo[5,1],(2S-N1-[2-[2-(methylamino-2-oxo-ethyl]phenyl]-N2-phenylpyrrolidine-1,2-dicarboxamide, and 2-furyl-(1H-indol-3-yl-methyl-BLAHone as candidate compounds. For the down-regulated CH13L1, we relied on genome-wide disease signatures to identify (11alpha-9-fluoro-11,17,21-trihydroxypregn-4-ene-3,20-dione and Genistein as candidate compounds. Our approach differs from previous research as we did not confine our drug targets to hypothesized compounds in the existing literature. Instead, we allowed the full expression profile of PO cell lines to reveal the most desirable targets. Second, our differential gene analysis revealed both up- and down-regulated genes, in contrast to the literature, which has focused on inhibiting only up-regulated genes. Third, our virtual screening universe of 22,723,923 compounds was more than 100 times larger than those in the known literature.

  11. Reduction in DNA repair capacity following differentiation of murine proadipocytes

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Meyn, R.E.

    1988-01-01

    It has been suggested that terminally differentiated mammalian cells have a decreased DNA repair capacity, compared with proliferating stem cells. To investigate this hypothesis, we have examined γ-ray-induced DNA strand breaks and their repair in the murine proadipocyte stem cell line 3T3-T. By exposure to human plasma, 3T3-T cells can be induced to undergo nonterminal and then terminal differentiation. DNA strand breaks were evaluated using the technique of alkaline elution. No difference was detected among stem, nonterminally differentiated, and terminally differentiated cells in the initial levels of radiation-induced DNA strand breaks. Each of the strand break dose responses increased as a linear function of γ-ray dose. The strand breaks induced by 4 Gy rejoined following biphasic kinetics for each cell type. At each time point examined after irradiation, however, the percentage of strand breaks that had not rejoined in terminally differentiated cells was three to six times greater than in stem cells. The rate of strand break rejoining in nonterminally differentiated cells was of an intermediate value between that of the stem and of the terminally differentiated cells. These results indicate that, at least for 3T3-T cells, differentiated cells have a reduced capacity for DNA repair

  12. Methodology for Assessing Radiation Detectors Used by Emergency Responders

    International Nuclear Information System (INIS)

    Piotr Wasiolek; April Simpson

    2008-01-01

    The threat of weapons of mass destruction terrorism resulted in the U.S. Department of Homeland Security deploying large quantities of radiation detectors throughout the emergency responder community. However, emergency responders specific needs were not always met by standard health physics instrumentation used in radiation facilities. Several American National Standards Institute standards were developed and approved to evaluate the technical capabilities of detection equipment. Establishing technical capability is a critical step, but it is equally important to emergency responders that the instruments are easy to operate and can withstand the rugged situations they encounter. The System Assessment and Validation for Emergency Responders (SAVER) Program (managed by the U.S. Department of Homeland Security, Office of Grants and Training, Systems Support Division) focuses predominantly on the usability, ergonomics, readability, and other features of the detectors, rather than performance controlled by industry standards and the manufacturers. National Security Technologies, LLC, as a SAVER Technical Agent, conducts equipment evaluations using active emergency responders who are familiar with the detection equipment and knowledgeable of situations encountered in the field, which provides more relevant data to emergency responders

  13. Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

    Science.gov (United States)

    Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

    2005-10-01

    Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

  14. A Generalized Logistic Regression Procedure to Detect Differential Item Functioning among Multiple Groups

    Science.gov (United States)

    Magis, David; Raiche, Gilles; Beland, Sebastien; Gerard, Paul

    2011-01-01

    We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence…

  15. Occupational therapists’ conceptions on mental health care line

    Directory of Open Access Journals (Sweden)

    Michelle Helena Pereira de Paiva

    2012-12-01

    Full Text Available The care line recommended by the Brazilian Health System - SUS must be attained by every professionalof the area, milieu and subject. This study aimed to know the occupational therapists’ conceptions about the lineof care in mental health. The data of this study were obtained from a questionnaire sent via virtual network ofcontacts and snowball technique. Data were subjected to qualitative and quantitative analysis. Most participantswere professionals from the southeast region of the country with over five years of training. They exercise theprofessional activity mainly in Psychiatric Hospitals, Psychosocial Assistance Centers – CAPS II and MentalHealth Clinics. There was no registry of professional performance in Residential Therapeutic Services – SRTand Outpatient Clinics - UBS. Regarding care line, six participants did not respond and five were unaware of theterm, followed by the psychosocial rehabilitation principles and therapeutic project; only one answer identified care line as a practice based on care management with reception principles and articulation of social networksand services. Results showed that the professionals’ practices are little guided in care line logic; however, thereis the need systematization of the assistance according this logic in order to apply the Psychiatric Reform,searching the quality of life improvement and reestablishment of the citizenship of people with psychologicaldistress insofar as, in addition to optimizing the care network, which promotes comprehensive humane careand social contractualism.

  16. Generation of human induced pluripotent stem cell lines from human dermal fibroblasts using a non-integration system

    Directory of Open Access Journals (Sweden)

    Kyung-Ok Uhm

    2017-05-01

    Full Text Available We generated human induced pluripotent stem cells (hiPSCs from dermal fibroblasts using a Sendai virus (SeV-based gene delivery method. The generated hiPSC line, KSCBi002-A, has a normal karyotype (46,XY. The pluripotency and differentiation capacity were characterized by comparison with those of a human embryonic stem cell line. This cell line is registered and available from the National Stem Cell Bank, Korea National Institute of Health.

  17. Exotic behavior of elastic scattering differential cross-sections of weakly bound nucleus 17F at small angles

    International Nuclear Information System (INIS)

    Han Jianlong; Hu Zhengguo; Zhang Xueyin; Yuan Xiaohua; Xu Huagen; Qi Huirong; Wang Yue; Jia Fei; Wu Lijie; Ding Xianli; Gao Qi; Gao Hui; Bai Zhen

    2006-01-01

    The differential cross-sections for elastic scattering of 17 F and 17 O on 208 Pb have been measured at Radioactive Ion Beam Line at Lanzhou (RIBLL). The variation of the logarithms of differential cross-sections with the square of scattering angles shows clearly that there exists a turning point in the range of small scattering angles (6 degree-20 degree) for 17 F having exotic structure, while no turning point was observed in the 17 O elastic scattering. The experimental results have been compared with previous data. Systematical analysis on the available data seems to conclude that there is an exotic behavior of elastic scattering differential cross-sections of weakly bound nuclei with halo or skin structure as compared with that of the ordinary nuclei near stable line. Therefore the fact that the turning point of the logarithms of differential cross-sections appears at small angle for weakly bound nuclei could be used as a new probe to investigate the halo and skin phenomenon. (authors)

  18. Do differentials in the support and advice available at UK schools and colleges influence candidate performance in the medical school admissions interview? A survey of direct school leaver applicants to a UK medical school.

    Science.gov (United States)

    Lambe, Paul; Waters, Catherine; Bristow, David

    2013-09-01

    To our knowledge, nothing is known about whether differentials in support and advice during preparation for the interview influence candidate performance and thereby contribute to bias in selection for medical school. To assess if differences in advice and support with preparation for the medical school admissions interview given type of school last attended influence interview score achieved by direct school leaver applicants to study on an undergraduate UK medical degree course. Confidential self-completed on-line questionnaire survey. Interview performance was positively related to whether a teacher, tutor or career advisors at the School or College last attended had advised a respondent to prepare for the interview, had advised about the various styles of medical interview used and the types of questions asked, and what resources were available to help in preparation. Respondents from Private/Independent schools were more likely than those from State schools to have received such advice and support. Differentials in access to advice on and support with preparation for the medical school interview may advantage some candidates over others. This inequity would likely be ameliorated by the provision of an authoritative and comprehensive guide to applying to medical school outlining admission requirements and the preparation strategy applicants should use in order to best meet those requirements. The guide could be disseminated to the Principals of all UK schools and colleges and freely available electronic versions signposted in medical school prospectuses and the course descriptor on the Universities and Colleges Admissions Service.

  19. MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their differentiation and tumorigenicity

    International Nuclear Information System (INIS)

    Samaraweera, Leleesha; Grandinetti, Kathryn B; Huang, Ruojun; Spengler, Barbara A; Ross, Robert A

    2014-01-01

    Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties. A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation. Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD. Thus, miRNAs define distinct NB cell phenotypes

  20. Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656

    Science.gov (United States)

    Lannutti, Brian J.; Blake, Noel; Gandhi, Manish J.; Reems, Jo Anna; Drachman, Jonathan G.

    2005-01-01

    Megakaryocytes (MKs) undergo successive rounds of endomitosis during differentiation, resulting in polyploidy (typically, 16-64N). Previous studies have demonstrated that this occurs through an interruption of normal cell cycle progression during anaphase. However, the molecular mechanism(s) controlling this unique process is undefined. In the present report, we examine the effect of an Src kinase inhibitor, SU6656, on thrombopoietin (TPO)-induced growth and differentiation. Remarkably, when SU6656 (2.5 μM) was added to a megakaryocytic cell line, UT-7/TPO, the cells ceased cell division but continued to accumulate DNA by endomitosis. During this interval, CD41 and CD61 expression on the cell surface increased. Similar effects on polyploidization and MK differentiation were seen with expanded primary MKs, bone marrow from 2 patients with myelodysplastic syndrome, and other cell lines with MK potential. Our data suggest that SU6656 might be useful as a differentiation-inducing agent for MKs and is an important tool for understanding the molecular basis of MK endomitosis. PMID:15677565

  1. Radiosensitivity related to neuroendocrine and endodermal differentation in lung carcinoma lines

    International Nuclear Information System (INIS)

    Duchesne, G.; Casoni, A.; Pera, M.

    1988-01-01

    A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentation. An index of the degree of neuroendocrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurofilaments and an embryonic endodermal cell marker, which allowed identification of three groups showing high, intermediate or low neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endodermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. 30 refs.; 3 figs.; 3 tabs

  2. Development and Validation of an On-Line Water Toxicity Sensor with Immobilized Luminescent Bacteria for On-Line Surface Water Monitoring.

    Science.gov (United States)

    Woutersen, Marjolijn; van der Gaag, Bram; Abrafi Boakye, Afua; Mink, Jan; Marks, Robert S; Wagenvoort, Arco J; Ketelaars, Henk A M; Brouwer, Bram; Heringa, Minne B

    2017-11-22

    Surface water used for drinking water production is frequently monitored in The Netherlands using whole organism biomonitors, with for example Daphnia magna or Dreissena mussels, which respond to changes in the water quality. However, not all human-relevant toxic compounds can be detected by these biomonitors. Therefore, a new on-line biosensor has been developed, containing immobilized genetically modified bacteria, which respond to genotoxicity in the water by emitting luminescence. The performance of this sensor was tested under laboratory conditions, as well as under field conditions at a monitoring station along the river Meuse in The Netherlands. The sensor was robust and easy to clean, with inert materials, temperature control and nutrient feed for the reporter organisms. The bacteria were immobilized in sol-gel on either an optical fiber or a glass slide and then continuously exposed to water. Since the glass slide was more sensitive and robust, only this setup was used in the field. The sensor responded to spikes of genotoxic compounds in the water with a minimal detectable concentration of 0.01 mg/L mitomycin C in the laboratory and 0.1 mg/L mitomycin C in the field. With further optimization, which should include a reduction in daily maintenance, the sensor has the potential to become a useful addition to the currently available biomonitors.

  3. Development and Validation of an On-Line Water Toxicity Sensor with Immobilized Luminescent Bacteria for On-Line Surface Water Monitoring

    Directory of Open Access Journals (Sweden)

    Marjolijn Woutersen

    2017-11-01

    Full Text Available Surface water used for drinking water production is frequently monitored in The Netherlands using whole organism biomonitors, with for example Daphnia magna or Dreissena mussels, which respond to changes in the water quality. However, not all human-relevant toxic compounds can be detected by these biomonitors. Therefore, a new on-line biosensor has been developed, containing immobilized genetically modified bacteria, which respond to genotoxicity in the water by emitting luminescence. The performance of this sensor was tested under laboratory conditions, as well as under field conditions at a monitoring station along the river Meuse in The Netherlands. The sensor was robust and easy to clean, with inert materials, temperature control and nutrient feed for the reporter organisms. The bacteria were immobilized in sol-gel on either an optical fiber or a glass slide and then continuously exposed to water. Since the glass slide was more sensitive and robust, only this setup was used in the field. The sensor responded to spikes of genotoxic compounds in the water with a minimal detectable concentration of 0.01 mg/L mitomycin C in the laboratory and 0.1 mg/L mitomycin C in the field. With further optimization, which should include a reduction in daily maintenance, the sensor has the potential to become a useful addition to the currently available biomonitors.

  4. Conversational assessment in memory clinic encounters: interactional profiling for differentiating dementia from functional memory disorders.

    Science.gov (United States)

    Jones, Danielle; Drew, Paul; Elsey, Christopher; Blackburn, Daniel; Wakefield, Sarah; Harkness, Kirsty; Reuber, Markus

    2016-01-01

    In the UK dementia is under-diagnosed, there is limited access to specialist memory clinics, and many of the patients referred to such clinics are ultimately found to have functional (non-progressive) memory disorders (FMD), rather than a neurodegenerative disorder. Government initiatives on 'timely diagnosis' aim to improve the rate and quality of diagnosis for those with dementia. This study seeks to improve the screening and diagnostic process by analysing communication between clinicians and patients during initial specialist clinic visits. Establishing differential conversational profiles could help the timely differential diagnosis of memory complaints. This study is based on video- and audio recordings of 25 initial consultations between neurologists and patients referred to a UK memory clinic. Conversation analysis was used to explore recurrent communicative practices associated with each diagnostic group. Two discrete conversational profiles began to emerge, to help differentiate between patients with dementia and functional memory complaints, based on (1) whether the patient is able to answer questions about personal information; (2) whether they can display working memory in interaction; (3) whether they are able to respond to compound questions; (4) the time taken to respond to questions; and (5) the level of detail they offer when providing an account of their memory failure experiences. The distinctive conversational profiles observed in patients with functional memory complaints on the one hand and neurodegenerative memory conditions on the other suggest that conversational profiling can support the differential diagnosis of functional and neurodegenerative memory disorders.

  5. Investigating on-line pornography at the University of Johannesburg

    Directory of Open Access Journals (Sweden)

    P. Laughton

    2007-12-01

    (61,6% aged between 19 years and 21 years. Of the respondents, 36,7% indicated that exposure to unsolicited pornography did not bother them. When asked to what extent students should have access to pornography, 60,5% stated 'None' while 32,6% believed that 'Restricted' access should be granted for research purposes and 6,9% believed that students should be granted 'Total' access to pornography. Results from the research will be used to manage access to on-line resources at the University of Johannesburg better.

  6. Isolation of a primate embryonic stem cell line.

    OpenAIRE

    Thomson, J A; Kalishman, J; Golos, T G; Durning, M; Harris, C P; Becker, R A; Hearn, J P

    1995-01-01

    Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. Here we report the derivation of a cloned cell line (R278.5) from a rhesus monkey blastocyst that remains undifferentiated in continuous passage for > 1 year, maintains a normal XY karyotype, and expresses the cell surface markers (alkaline phosphatase, stage-specific embryonic antigen 3, st...

  7. Differential features of sister-chromatid exchange responses to ultraviolet radiation and caffeine in xeroderma pigmentosum lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Tohda, H.; Oikawa, A.

    1983-01-01

    Sister-chromatic exchange (SCE) induced by ultraviolet (UV) irradiation and viability after UV irradiation were studied in lymphoblastoid cell lines derived from 7 patients with xeroderma pigmentosum (XP) and 6 normal donors. UV irradiation caused significant increases of SCEs in both XP and normal cells. In 3 XP cell lines, which were deficient in unscheduled DNA synthesis (UDS) and sensitive to the killing effect of UV, very high SCE frequencies were observed after UV irradiation. Cells from a patient with the De Sanctis-Cacchione syndrome were the most sensitive to UV in terms of both SCE induction and cell killing. In 2 of 4 UDS-proficient XP cell lines tested, the incidences of UV-induced SCEs were similar to those in normal cell lines, but in 2 other UDS-proficient lines from 2 XP patients with skin cancer, the frequencies of UV-induced SCEs were significantly higher than in normal cells. (orig./AJ)

  8. Children's cognitive representation of the mathematical number line.

    Science.gov (United States)

    Rouder, Jeffrey N; Geary, David C

    2014-07-01

    Learning of the mathematical number line has been hypothesized to be dependent on an inherent sense of approximate quantity. Children's number line placements are predicted to conform to the underlying properties of this system; specifically, placements are exaggerated for small numerals and compressed for larger ones. Alternative hypotheses are based on proportional reasoning; specifically, numerals are placed relative to set anchors such as end points on the line. Traditional testing of these alternatives involves fitting group medians to corresponding regression models which assumes homogenous residuals and thus does not capture useful information from between- and within-child variation in placements across the number line. To more fully assess differential predictions, we developed a novel set of hierarchical statistical models that enable the simultaneous estimation of mean levels of and variation in performance, as well as developmental transitions. Using these techniques we fitted the number line placements of 224 children longitudinally assessed from first to fifth grade, inclusive. The compression pattern was evident in mean performance in first grade, but was the best fit for only 20% of first graders when the full range of variation in the data are modeled. Most first graders' placements suggested use of end points, consistent with proportional reasoning. Developmental transition involved incorporation of a mid-point anchor, consistent with a modified proportional reasoning strategy. The methodology introduced here enables a more nuanced assessment of children's number line representation and learning than any previous approaches and indicates that developmental improvement largely results from midpoint segmentation of the line. © 2014 John Wiley & Sons Ltd.

  9. Life-history traits in an evergreen Mediterranean oak respond differentially to previous experimental environments

    Directory of Open Access Journals (Sweden)

    J. M. Rey Benayas

    2008-06-01

    Full Text Available Living organisms respond both to current and previous environments, which can have important consequences on population dynamics. However, there is little experimental evidence based on long-term field studies of the effects of previous environments on the performance of individuals. We tested the hypothesis that trees that establish under different environmental conditions perform differently under similar post-establishment conditions. We used the slow-growing, evergreen Mediterranean oak Quercus ilex subsp. rotundifolia as target species. We analyzed the effects of previous environments, competition effects and tradeoffs among life-history traits (survival, growth, and reproduction. We enhanced seedling establishment for three years by reducing abiotic environmental harshness by means of summer irrigation and artificial shading in 12 experimental plots, while four plots remained as controls. Then these treatments were interrupted for ten years. Seedlings under ameliorated environmental conditions survived and grew faster during early establishment. During the post-management period, previous treatments 1 did not have any effect on survival, 2 experienced a slower above-ground growth, 3 decreased root biomass as indicated from reflectivity of Ground Penetration Radar, 4 increased acorn production mostly through a greater canopy volume and 5 increased acorn production effort. The trees exhibited a combination of effects related to acclimation for coping with abiotic stress and effects of intra-specific competition. In accordance with our hypothesis, tree performance overall depended on previous environmental conditions, and the response was different for different life-history traits. We recommend early management because it increased plot cover, shortened the time to attain sexual maturity and increased the amount of acorn production. Plots such as those assessed in this study may act as sources of propagules in deforested

  10. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because...

  11. Differential sensitivity of long-sleep and short-sleep mice to high doses of cocaine.

    Science.gov (United States)

    de Fiebre, C M; Ruth, J A; Collins, A C

    1989-12-01

    The cocaine sensitivity of male and female long-sleep (LS) and short-sleep (SS) mice, which have been selectively bred for differential ethanol-induced "sleep-time," was examined in a battery of behavioral and physiological tests. Differences between these two mouse lines were subtle and were seen primarily at high doses. At high doses, SS mice were more sensitive than LS mice, particularly to cocaine-induced hypothermia; however, significant hypothermia was not seen except at doses which were very near to the seizure threshold. During a 60-min test of locomotor activity, LS mice showed greater stimulation of Y-maze activity by 20 mg/kg cocaine than SS mice. Consistent with the finding of subtle differences in sensitivity to low doses of cocaine. LS and SS mice did not differ in sensitivity to cocaine inhibition of synaptosomal uptake of [3H]-dopamine, [3H]-norepinephrine or [3H]-5-hydroxytryptamine. However, consistent with the finding of differential sensitivity to high doses of cocaine, SS mice were more sensitive to the seizure-producing effects of the cocaine and lidocaine, a local anesthetic. It is hypothesized that the differential sensitivity of these mouse lines to high doses of cocaine is due to differential sensitivity to cocaine's actions on systems that regulate local anesthetic effects. Selective breeding for differential duration of alcohol-induced "sleep-time" may have resulted in differential ion channel structure or function in these mice.

  12. Ion channels in a skeletal muscle cell line from a Duchenne muscular dystrophy patient.

    Science.gov (United States)

    Caviedes, R; Caviedes, P; Liberona, J L; Jaimovich, E

    1994-09-01

    A cell line (RCDMD), derived from a muscle biopsy taken from a 7-year-old patient with Duchenne muscular dystrophy (DMD), was established in vitro using conditioned media from the UCHT1 thyroid cell line as described elsewhere (Biochim Biophys Acta 1992; 1134:247-255). Unlike other cell lines established by the same procedure, RCDMD cells were highly refractory to transformation and the resulting cell line grew slowly with a doubling time of approximately 72 h. Further, cells continue to grow after more than 20 doublings and 15 passages. Some of the characteristics of the cell line include lack of reaction with antidystrophin antibodies and the presence of receptors for the dihydropyridine PN200-110 (Kd) = 0.3 +/- 0.05 nmol/L and Bmax = 1.06 +/- 0.03 pmol/mg protein) and for alpha-bungarotoxin (Kd = 1.02 +/- 0.17 nmol/L and Bmax = 4.2 +/- 0.37 pmol/mg protein). Patch clamped cells in the voltage clamp configuration lack ion currents when growing in complete medium with high serum, but they can be induced to differentiate by serum deprivation and addition of hormones and trace elements. After 5 days in differentiating medium, noninactivating, delayed rectifier potassium currents are seen. At day 12, A-type, inactivating potassium currents as well as transient inward currents are seen. In conditions in which sodium and potassium currents are absent, a very fast activating and fast inactivating calcium current was evident. The cell line offers the possibility of studying cellular mechanisms in the pathophysiology of DMD.

  13. Numerical solution of three-dimensional magnetic differential equations

    International Nuclear Information System (INIS)

    Reiman, A.H.; Greenside, H.S.

    1987-02-01

    A computer code is described that solves differential equations of the form B . del f = h for a single-valued solution f, given a toroidal three-dimensional divergence-free field B and a single-valued function h. The code uses a new algorithm that Fourier decomposes a given function in a set of flux coordinates in which the field lines are straight. The algorithm automatically adjusts the required integration lengths to compensate for proximity to low order rational surfaces. Applying this algorithm to the Cartesian coordinates defines a transformation to magnetic coordinates, in which the magnetic differential equation can be accurately solved. Our method is illustrated by calculating the Pfirsch-Schlueter currents for a stellarator

  14. Responding to Children's Drawings

    Science.gov (United States)

    Watts, Robert

    2010-01-01

    This article aims to explore the issues that face primary school teachers when responding to children's drawings. Assessment in art and design is an ongoing concern for teachers with limited experience and confidence in the area and, although children's drawings continue to be a focus of much research, the question of what it is that teachers say…

  15. Clozapine modifies the differentiation program of human adipocytes inducing browning.

    Science.gov (United States)

    Kristóf, E; Doan-Xuan, Q-M; Sárvári, A K; Klusóczki, Á; Fischer-Posovszky, P; Wabitsch, M; Bacso, Z; Bai, P; Balajthy, Z; Fésüs, L

    2016-11-29

    Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly upregulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested whether browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors, it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the upregulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine-induced beige cells displayed increased basal and oligomycin-inhibited (proton leak) oxygen consumption, but these cells showed a lower response to cAMP stimulus as compared with control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for the treatment of SGA-induced weight gain.

  16. The effect of sudden server breakdown on the performance of a disassembly line

    Science.gov (United States)

    Udomsawat, Gun; Gupta, Surendra M.

    2005-11-01

    Product and material recovery relies on the disassembly process to separate target components or materials from the end-of-life (EOL) products. Disassembly line is especially effective when products in large quantity are disassembled. Unlike an assembly line, a disassembly line is more complex and is subjected to numerous uncertainties including stochastic and multi-level arrivals of component demands, stochastic arrival times for EOL products, and process interruption due to equipment failure. These factors seriously impair the control mechanism in the disassembly line. A common production control mechanism is the traditional push system (TPS). TPS responds to the aforementioned complications by carrying substantial amounts of inventories. An alternative control mechanism is a newly developed multi-kanban pull system (MKS) that relies on dynamic routing of kanbans, which tends to minimize the system's inventories while maintaining demand serviceability. In this paper we explore the impact of sudden breakdown of server on the performance of a disassembly line. We compare the overall performances of the TPS and MKS by considering two scenarios. We present the solution procedure and results for these cases.

  17. Ultrastructural cytochemical prospective study of adult acute lymphoblastic leukemia: detection of peroxidase activity in patients failing to respond to treatment.

    Science.gov (United States)

    Reiffers, J; Darmendrail, V; Larrue, J; Villenave, I; Bernard, P; Boisseau, M; Broustet, A

    1981-08-15

    Ultrastructural cytochemical studies revealed peroxidase activity in five of 25 adult patients with apparent null lymphoblastic leukemia (ALL) in whom the peroxidase reaction studied with light microscopy was negative. None of these 5 patients responded to a chemotherapy regimen used for adult ALL. The importance of ultrastructural cytochemistry which allows the recognition of myeloblastic differentiation in undifferentiated blast cells is also demonstrated. The correct classification of such cases may be important for prognosis because they appear to be resistant to the chemotherapy used in treating ALL.

  18. Comparative analysis of gene expression in normal and cancer human prostate cell lines

    Directory of Open Access Journals (Sweden)

    E. E. Rosenberg

    2014-04-01

    Full Text Available Prostate cancer is one of the main causes of mortality in men with malignant tumors. The urgent problem was a search for biomarkers of prostate cancer, which would allow distinguishing between aggressive metastatic and latent tumors. The aim of this work was to search for differentially expressed genes in normal epithelial cells PNT2 and prostate cancer cell lines LNCaP, DU145 and PC3, produced from tumors with different aggressiveness and metas­tatic ability. Such genes might be used to create a panel of prognostic markers for aggressiveness and metastasis. Relative gene expression of 65 cancer-related genes was determined by the quantitative polymerase chain reaction (Q-PCR. Expression of 29 genes was changed in LNCaP cells, 20 genes in DU145 and 16 genes in PC3 cell lines, compared with normal line PNT2. The obtained data make it possible to conclude that the epithelial-mesenchymal cell transition took place, which involved the loss of epithelial markers, reduced cell adhesion and increased migration. We have also found few differentially expressed genes among 3 prostate cancer cell lines. We have found that genes, involved in cell adhesion (CDH1, invasiveness and metastasis (IL8, CXCL2 and cell cycle control (P16, CCNE1 underwent most changes. These genes might be used for diagnosis and prognosis of invasive metastatic prostate tumors.

  19. Accelerating the numerical simulation of magnetic field lines in tokamaks using the GPU

    International Nuclear Information System (INIS)

    Kalling, R.C.; Evans, T.E.; Orlov, D.M.; Schissel, D.P.; Maingi, R.; Menard, J.E.; Sabbagh, S.A.

    2011-01-01

    Highlights: → Tokamak magnetic field lines are simulated on a GPU. → Numerical integration of a set of nonlinear differential equations is required. → Using the GPU yields a significant reduction in processing time compared to the CPU. → Computational runs that took days now take hours. → These gains have been accomplished without significant hardware expense. - Abstract: TRIP3D is a field line simulation code that numerically integrates a set of nonlinear magnetic field line differential equations. The code is used to study properties of magnetic islands and stochastic or chaotic field line topologies that are important for designing non-axisymmetric magnetic perturbation coils for controlling plasma instabilities in future machines. The code is very computationally intensive and for large runs can take on the order of days to complete on a traditional single CPU. This work describes how the code was converted from Fortran to C and then restructured to take advantage of GPU computing using NVIDIA's CUDA. The reduction in computing time has been dramatic where runs that previously took days now take hours allowing a scale of problem to be examined that would previously not have been attempted. These gains have been accomplished without significant hardware expense. Performance, correctness, code flexibility, and implementation time have been analyzed to gauge the success and applicability of these methods when compared to the traditional multi-CPU approach.

  20. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

    International Nuclear Information System (INIS)

    Lin, Yi-Ting; Ding, Jing-Ya; Li, Ming-Yang; Yeh, Tien-Shun; Wang, Tsu-Wei; Yu, Jenn-Yah

    2012-01-01

    Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: ► YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. ► YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. ► Knockdown of Gli2 rescues the Yap-overexpression phenotype in P19 cells. ► Knockdown of Gli2 rescues the Yap

  1. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yi-Ting; Ding, Jing-Ya [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Li, Ming-Yang [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yeh, Tien-Shun [Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Wang, Tsu-Wei [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yu, Jenn-Yah [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan (China)

    2012-09-10

    Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap

  2. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation

    DEFF Research Database (Denmark)

    Pérez-Galán, Patricia; Mora-Jensen, Helena; Weniger, Marc A

    2011-01-01

    bortezomib-resistant MCL cell lines and primary tumor cells from MCL patients with inferior clinical response to bortezomib also expressed plasmacytic features. Knockdown of IRF4 was toxic for the subset of MCL cells with plasmacytic differentiation, but only slightly sensitized cells to bortezomib. We...

  3. Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine.

    Science.gov (United States)

    O'Sullivan, Finbarr; Keenan, Joanne; Aherne, Sinead; O'Neill, Fiona; Clarke, Colin; Henry, Michael; Meleady, Paula; Breen, Laura; Barron, Niall; Clynes, Martin; Horgan, Karina; Doolan, Padraig; Murphy, Richard

    2017-11-07

    To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array. Quantitative Label-free LC-MS/MS proteomic analysis was performed using a Dionex Ultimate 3000 RSLCnano system coupled to a hybrid linear ion trap/Orbitrap mass spectrometer. Peptide identities were validated in Proteome Discoverer 2.1 and were subsequently imported into Progenesis QI software for further analysis. Hierarchical cluster analysis for all three parallel datasets (miRNA, proteomics, mRNA) was conducted in the R software environment using the Euclidean distance measure and Ward's clustering algorithm. The prediction of miRNA and oppositely correlated protein/mRNA interactions was performed using TargetScan 6.1. GO biological process, molecular function and cellular component enrichment analysis was carried out for the DE miRNA, protein and mRNA lists via the Pathway Studio 11.3 Web interface using their Mammalian database. Differential expression (DE) profiling comparing the intestinal cell lines HT-29 and Caco-2 identified 1795 Genes, 168 Proteins and 160 miRNAs as DE between the two cell lines. At the gene level, 1084 genes were upregulated and 711 were downregulated in the Caco-2 cell line relative to the HT-29 cell line. At the protein level, 57 proteins were found to be upregulated and 111 downregulated in the Caco-2 cell line relative to the HT-29 cell line. Finally, at the miRNAs level, 104 were upregulated and 56 downregulated in the Caco-2 cell line relative to the HT-29 cell line. Gene ontology (GO) analysis of the DE mRNA identified cell adhesion, migration and ECM organization, cellular lipid

  4. Simulation of the beam guiding of the SAPHIR experiment by means of a differential-equation model

    International Nuclear Information System (INIS)

    Greve, T.

    1991-08-01

    This paper shows the numerical simulation of a beam line by means of a model of differential equations simulating the beam line from the Bonn Electron Stretcher Accelerator ELSA to the SAPHIR spectrometer. Furthermore a method for calculating the initial values based on measurements of beam profiles is being discussed. (orig.) [de

  5. Effects of ultrasound on the proliferation and differentiation of cementoblast lineage cells

    NARCIS (Netherlands)

    Inubushi, T.; Tanaka, E.; Rego, E.B.; Kitagawa, M.; Kawazoe, A.; Ohta, A.; Okada, H.; Koolstra, J.H.; Miyauchi, M.; Takata, T.; Tanne, K.

    2008-01-01

    Background: The purpose of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) stimulation on the proliferation and differentiation of cementoblast lineage cells. Methods: An immortalized human periodontal ligament cell line (HPL) showing immature cementoblastic

  6. CAMAC-compatible differential pulse discriminator-counter

    International Nuclear Information System (INIS)

    Tselikov, I.V.

    1988-01-01

    A differential pulse discriminator-counter for a Moessbauer spectrometer is described. Input pulses are collected according to the following algorithm; a pulse is admitted into the channel depending on whether or not the preceding pulse fell into the discrimination window. The circuit does not contain delay lines to allow for the delay lines to allow for the delay of the signal from the upper-level discriminator with respect to the signal from the lower-level discriminator due to the finite rise time of the input pulses, which makes it possible to reduce the dead time of the discriminator to the actuation time of the threshold circuits. The pulse count rate is 150 MHz, the input amplitude is +/-3 V, the dead time is 6 nsec, and the delay from input to output is 14 nsec. The unit is CAMAC-compatible

  7. Power in health care organizations: contemplations from the first-line management perspective.

    Science.gov (United States)

    Isosaari, Ulla

    2011-01-01

    The aim of this paper is to examine health care organizations' power structures from the first-line management perspective. What liable power structures derive from the theoretical bases of bureaucratic, professional and result based organizations, and what power type do health care organizations represent, according to the empirical data? The paper seeks to perform an analysis using Mintzberg's power configurations of instrument, closed system, meritocracy and political arena. The empirical study was executed at the end of 2005 through a survey in ten Finnish hospital districts in both specialized and primary care. Respondents were all first-line managers in the area and a sample of staff members from internal disease, surgical and psychiatric units, as well as out-patient and primary care units. The number of respondents was 1,197 and the response percentage was 38. The data were analyzed statistically. As a result, it can be seen that a certain kind of organization structure supports the generation of a certain power type. A bureaucratic organization generates an instrument or closed system organization, a professional organization generates meritocracy and also political arena, and a result-based organization has a connection to political arena and meritocracy. First line managers regarded health care organizations as instruments when staff regarded them mainly as meritocracies having features of political arena. Managers felt their position to be limited by rules, whereas staff members regarded their position as having lots of space and influence potential. If the organizations seek innovative and active managers at the unit level, they should change the organizational structure and redistribute the work so that there could be more space for meaningful management. This research adds to the literature and gives helpful suggestions that will be of interest to those in the position of first-line management in health care.

  8. The Differential Roles of Parents in the Family, as Reported by a Group of Iranian Adolescents.

    Science.gov (United States)

    Tashakkori, Abbas; Mehryar, Amir H.

    1982-01-01

    Investigated the relative roles of Iranian mothers and fathers in responding to various socialization needs of their offspring. Findings indicated a considerable degree of parental role differentiation, with mothers being dominant in the supportive-emotional areas and fathers taking responsibility for the authoritative-punitive aspects. (Author)

  9. 4E-BP1 regulates the differentiation of white adipose tissue.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

    2013-07-01

    4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  10. The phase transition lines in pair approximation for the basic reinfection model SIRI

    International Nuclear Information System (INIS)

    Stollenwerk, Nico; Martins, Jose; Pinto, Alberto

    2007-01-01

    For a spatial stochastic epidemic model we investigate in the pair approximation scheme the differential equations for the moments. The basic reinfection model of susceptible-infected-recovered-reinfected or SIRI type is analysed, its phase transition lines calculated analytically in this pair approximation

  11. Interviewer-Respondent Interactions in Conversational and Standardized Interviewing

    Science.gov (United States)

    Mittereder, Felicitas; Durow, Jen; West, Brady T.; Kreuter, Frauke; Conrad, Frederick G.

    2018-01-01

    Standardized interviewing (SI) and conversational interviewing are two approaches to collect survey data that differ in how interviewers address respondent confusion. This article examines interviewer-respondent interactions that occur during these two techniques, focusing on requests for and provisions of clarification. The data derive from an…

  12. Cubic systems with invariant affine straight lines of total parallel multiplicity seven

    Directory of Open Access Journals (Sweden)

    Alexandru Suba

    2013-12-01

    Full Text Available In this article, we study the planar cubic differential systems with invariant affine straight lines of total parallel multiplicity seven. We classify these system according to their geometric properties encoded in the configurations of invariant straight lines. We show that there are only 17 different topological phase portraits in the Poincar\\'e disc associated to this family of cubic systems up to a reversal of the sense of their orbits, and we provide representatives of every class modulo an affine change of variables and rescaling of the time variable.

  13. Applications of the energy differentiation type radiation line sensor to such as inspection for the plumbing corrosion

    International Nuclear Information System (INIS)

    Tomita, Yasuhiro; Shirayanagi, Yuji; Matsui, Shinjiro; Kamiya, Yosuke; Kobayashi, Akira

    2015-01-01

    The authors have engaged in development of the next-generation radiation detectors that can give information on energy such as X-rays and γ-rays, and commercialized an energy discrimination type radiation line sensor capable of discriminating the energy of photons using a CdTe radiation detector element. This paper introduces the structure and principles of this energy discrimination type radiation line sensor. As the basic application, it also introduces the material identification, energy discrimination type X-ray CT imaging, and the quantitative determination of iron plate thickness using X-ray. In addition, it introduces the radiation line sensor we have developed for inspecting the reduced amount of wall thickness of piping with insulation materials. This radiation line sensor for pipe thinning inspection combined with radiation sources (X-rays, γ-rays) and a transport system is capable of accurately and efficiently inspecting reduced wall thickness, while moving the censor on the covered pipe with heat insulating materials through remote control, without removing piping insulation materials and without stopping the use of piping. (A.O.)

  14. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  15. Effective collision strengths of quasar ultraviolet emission lines

    International Nuclear Information System (INIS)

    Osterbrock, D.E.; Wallace, R.K.

    1977-01-01

    The best available published collision strengths for excitation of permitted and semiforbidden emission lines of abundant ions observed or expected in quasars have been collected and averaged over Maxwellian velocity distributions. For a few ions for which calculations are not available, extrapolation along isoelectronic sequences or in principal quantum number n was used to estimate values. These collision strengths were used to correct differentially published photoionization models of quasars, and the corrected models compared with published observational data

  16. The Method of Lines for Ternary Diffusion Problems

    Directory of Open Access Journals (Sweden)

    Henryk Leszczyński

    2014-01-01

    Full Text Available The method of lines (MOL for diffusion equations with Neumann boundary conditions is considered. These equations are transformed by a discretization in space variables into systems of ordinary differential equations. The proposed ODEs satisfy the mass conservation law. The stability of solutions of these ODEs with respect to discrete L2 norms and discrete W1,∞ norms is investigated. Numerical examples confirm the parabolic behaviour of this model and very regular dynamics.

  17. Genome-wide comparative transcriptome analysis of CMS-D2 and its maintainer and restorer lines in upland cotton.

    Science.gov (United States)

    Wu, Jianyong; Zhang, Meng; Zhang, Bingbing; Zhang, Xuexian; Guo, Liping; Qi, Tingxiang; Wang, Hailin; Zhang, Jinfa; Xing, Chaozhu

    2017-06-08

    Cytoplasmic male sterility (CMS) conferred by the cytoplasm from Gossypium harknessii (D2) is an important system for hybrid seed production in Upland cotton (G. hirsutum). The male sterility of CMS-D2 (i.e., A line) can be restored to fertility by a restorer (i.e., R line) carrying the restorer gene Rf1 transferred from the D2 nuclear genome. However, the molecular mechanisms of CMS-D2 and its restoration are poorly understood. In this study, a genome-wide comparative transcriptome analysis was performed to identify differentially expressed genes (DEGs) in flower buds among the isogenic fertile R line and sterile A line derived from a backcross population (BC 8 F 1 ) and the recurrent parent, i.e., the maintainer (B line). A total of 1464 DEGs were identified among the three isogenic lines, and the Rf1-carrying Chr_D05 and its homeologous Chr_A05 had more DEGs than other chromosomes. The results of GO and KEGG enrichment analysis showed differences in circadian rhythm between the fertile and sterile lines. Eleven DEGs were selected for validation using qRT-PCR, confirming the accuracy of the RNA-seq results. Through genome-wide comparative transcriptome analysis, the differential expression profiles of CMS-D2 and its maintainer and restorer lines in Upland cotton were identified. Our results provide an important foundation for further studies into the molecular mechanisms of the interactions between the restorer gene Rf1 and the CMS-D2 cytoplasm.

  18. Resistance Evaluation of Radish (Raphanus sativus L. Inbred Lines against Turnip mosaic virus

    Directory of Open Access Journals (Sweden)

    Ju-Yeon Yoon

    2017-03-01

    Full Text Available Leaves of twenties radish (Raphanus sativus L. inbred lines were mechanically inoculated with Turnip mosaic virus (TuMV strain HY to evaluate TuMV resistance of the radish inbred lines. The inoculated radish plants were incubated at 22°C±3°C and resistance assessment was examined using symptom development for 4 weeks. Based on the reactions of differential radish inbred lines, 16 radish lines were produced mild mosaic, mottling, mosaic and severe mosaic symptoms by TuMV infection. These results were confirmed by RT-PCR analysis of TuMV coat protein gene, suggesting that TuMV is responsible for the disease symptoms. Four resistant radish lines did not induce systemic mosaic symptoms on upper leaves and chlorosis in stem tissues for 4 weeks, showing they were symptomless by 8 weeks. Further examination of TuMV infection in the 4 radish lines showed no TuMV infection in all systemic leaves. These results suggest that the 4 radish lines are highly resistant to TuMV.

  19. International Scavenging for First Responder Guidance and Tools: IAEA Products

    Energy Technology Data Exchange (ETDEWEB)

    Stern, W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Berthelot, L. [Brookhaven National Lab. (BNL), Upton, NY (United States); Bachner, K. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2017-05-05

    In fiscal years (FY) 2016 and 2017, with support from the U.S. Department of Homeland Security (DHS), Brookhaven National Laboratory (BNL) examined the International Atomic Energy Agency (IAEA) radiological emergency response and preparedness products (guidance and tools) to determine which of these products could be useful to U.S. first responders. The IAEA Incident and Emergency Centre (IEC), which is responsible for emergency preparedness and response, offers a range of tools and guidance documents for responders in recognizing, responding to, and recovering from radiation emergencies and incidents. In order to implement this project, BNL obtained all potentially relevant tools and products produced by the IAEA IEC and analyzed these materials to determine their relevance to first responders in the U.S. Subsequently, BNL organized and hosted a workshop at DHS National Urban Security Technology Laboratory (NUSTL) for U.S. first responders to examine and evaluate IAEA products to consider their applicability to the United States. This report documents and describes the First Responder Product Evaluation Workshop, and provides recommendations on potential steps the U.S. federal government could take to make IAEA guidance and tools useful to U.S. responders.

  20. Transcripts and MicroRNAs Responding to Salt Stress in Musa acuminata Colla (AAA Group cv. Berangan Roots.

    Directory of Open Access Journals (Sweden)

    Wan Sin Lee

    Full Text Available Physiological responses to stress are controlled by expression of a large number of genes, many of which are regulated by microRNAs. Since most banana cultivars are salt-sensitive, improved understanding of genetic regulation of salt induced stress responses in banana can support future crop management and improvement in the face of increasing soil salinity related to irrigation and climate change. In this study we focused on determining miRNA and their targets that respond to NaCl exposure and used transcriptome sequencing of RNA and small RNA from control and NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome and identify orthologous and Musa-specific miRNA responding to salinity. We observed that, banana roots responded to salinity stress with changes in expression for a large number of genes (9.5% of 31,390 expressed unigenes and reduction in levels of many miRNA, including several novel miRNA and banana-specific miRNA-target pairs. Banana roots expressed a unique set of orthologous and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent manner. Gene expression patterns of miRNA compared with those of their predicted mRNA targets indicated that a majority of the differentially expressed miRNAs were down-regulated in response to increased salinity, allowing increased expression of targets involved in diverse biological processes including stress signaling, stress defence, transport, cellular homeostasis, metabolism and other stress-related functions. This study may contribute to the understanding of gene regulation and abiotic stress response of roots and the high-throughput sequencing data sets generated may serve as important resources related to salt tolerance traits for functional genomic studies and genetic improvement in banana.