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Sample records for adaptation growth arrest

  1. Escaping growth arrest in cancer

    NARCIS (Netherlands)

    Kortlever, R.M.

    2008-01-01

    We now have a general idea of which genes and cellular pathways are central in cancer development: uncontrolled growth governs establishment and spread of the disease. Nevertheless, to fully appreciate the consequences of the interplay of driver mutations in this genetic disease it is imperative we

  2. Growth arrest specific protein (GAS) 6

    DEFF Research Database (Denmark)

    Haase, T N; Rasmussen, Morten; Jaksch, C A M

    2013-01-01

    Aims/hypothesis Maternal low-protein (LP) diet during gestation results in a reduced beta cell mass in the offspring at birth and this may hamper the ability to adapt to high-energy food and sedentary lifestyle later in life. To investigate the biology behind the LP-offspring phenotype, this study...... that favours premature maturation of the beta cells....

  3. Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth.

    Science.gov (United States)

    Akkus, O; Rimnac, C M

    2001-06-01

    Knowledge of kinetics of fatigue crack growth of microcracks is important so as to understand the dynamics of bone adaptation, remodeling, and the etiology of fatigue-based failures of cortical bone tissue. In this respect, theoretical models (Taylor, J. Biomech., 31 (1998) 587-592; Taylor and Prendergast, Proc. Instn. Mech. Engrs. Part H 211 (1997) 369-375) of microcrack growth in cortical bone have predicted a decreasing microcrack growth rate with increasing microcrack length. However, these predictions have not been observed directly. This study investigated microcrack growth and arrest through observations of surface microcracks during cyclic loading (R=0.1, 50-80MPa) of human femoral cortical bone (male, n=4, age range: 37-40yr) utilizing a video microscopy system. The change in crack length and orientation of eight surface microcracks were measured with the number of fatigue cycles from four specimens. At the applied cyclic stresses, the microcracks propagated and arrested in generally less than 10,000 cycles. The fatigue crack growth rate of all microcracks decreased with increasing crack length following initial identification, consistent with theoretical predictions. The growth rate of the microcracks was observed to be in the range of 5x10(-5) to 5x10(-7)mmcycle(-1). In addition, many of the microcracks were observed not to grow beyond 150 microm and a cyclic stress intensity factor of 0.5MNm(-3/2). The results of this study suggest that cortical bone tissue may resist fracture at the microscale by deceleration of fatigue crack growth and arrest of microcracks.

  4. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

    Science.gov (United States)

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun

    2015-10-01

    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

  5. Coxa vara with proximal femoral growth arrest in patients who had neonatal extracorporeal membrane oxygenation.

    Science.gov (United States)

    DiFazio, Rachel L; Kocher, Minider S; Berven, Sigurd; Kasser, James

    2003-01-01

    This is a retrospective review of four patients in whom a pattern of coxa vara with proximal femoral growth arrest and metaphyseal irregularities developed. These patients were all treated with neonatal extracorporeal membrane oxygenation and presented with a progressive gait disturbance and pain, leg-length discrepancy, and limited abduction. Imaging revealed coxa vara with proximal femoral growth arrest. Two patients (three hips) underwent proximal femoral valgus osteotomy, one patient underwent fixation of a femoral neck fracture with subsequent greater trochanter transfer, and one patient is being observed. This case series suggests an association between neonatal extracorporeal membrane oxygenation and this unusual pattern of coxa vara with proximal femoral growth arrest.

  6. 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

    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...

  7. Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Martin, Katherine J.; Kenny, Paraic A.; Xhaja, Kris; Bosch, Irene; Yaswen, Paul; Bissell, Mina J.

    2006-02-08

    To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines. We show that genes that are significantly lower in the organized, growth arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.

  8. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

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    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  9. Physeal growth arrest after tibial lengthening in achondroplasia

    OpenAIRE

    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who und...

  10. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    Science.gov (United States)

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

  11. Physeal growth arrest after tibial lengthening in achondroplasia

    Science.gov (United States)

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Results Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Interpretation Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence—especially when lengthening of more than 50% is attempted. PMID:22489887

  12. Growth-arrest-specific protein 2 inhibits cell division in Xenopus embryos.

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    Tong Zhang

    Full Text Available BACKGROUND: Growth-arrest-specific 2 gene was originally identified in murine fibroblasts under growth arrest conditions. Furthermore, serum stimulation of quiescent, non-dividing cells leads to the down-regulation of gas2 and results in re-entry into the cell cycle. Cytoskeleton rearrangements are critical for cell cycle progression and cell division and the Gas2 protein has been shown to co-localize with actin and microtubules in interphase mammalian cells. Despite these findings, direct evidence supporting a role for Gas2 in the mechanism of cell division has not been reported. METHODOLOGY AND PRINCIPAL FINDINGS: To determine whether the Gas2 protein plays a role in cell division, we over-expressed the full-length Gas2 protein and Gas2 truncations containing either the actin-binding CH domain or the tubulin-binding Gas2 domain in Xenopus laevis embryos. We found that both the full-length Gas2 protein and the Gas2 domain, but not the CH domain, inhibited cell division and resulted in multinucleated cells. The observation that Gas2 domain alone can arrest cell division suggests that Gas2 function is mediated by microtubule binding. Gas2 co-localized with microtubules at the cell cortex of Gas2-injected Xenopus embryos using cryo-confocal microscopy and co-sedimented with microtubules in cytoskeleton co-sedimentation assays. To investigate the mechanism of Gas2-induced cell division arrest, we showed, using a wound-induced contractile array assay, that Gas2 stabilized microtubules. Finally, electron microscopy studies demonstrated that Gas2 bundled microtubules into higher-order structures. CONCLUSION AND SIGNIFICANCE: Our experiments show that Gas2 inhibits cell division in Xenopus embryos. We propose that Gas2 function is mediated by binding and bundling microtubules, leading to cell division arrest.

  13. p53 oligomerization status modulates cell fate decisions between growth, arrest and apoptosis.

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    Fischer, Nicholas W; Prodeus, Aaron; Malkin, David; Gariépy, Jean

    2016-12-01

    Mutations in the oligomerization domain of p53 are genetically linked to cancer susceptibility in Li-Fraumeni Syndrome. These mutations typically alter the oligomeric state of p53 and impair its transcriptional activity. Activation of p53 through tetramerization is required for its tumor suppressive function by inducing transcriptional programs that lead to cell fate decisions such as cell cycle arrest or apoptosis. How p53 chooses between these cell fate outcomes remains unclear. Here, we use 5 oligomeric variants of p53, including 2 novel p53 constructs, that yield either monomeric, dimeric or tetrameric forms of p53 and demonstrate that they induce distinct cellular activities and gene expression profiles that lead to different cell fate outcomes. We report that dimeric p53 variants are cytostatic and can arrest cell growth, but lack the ability to trigger apoptosis in p53-null cells. In contrast, p53 tetramers induce rapid apoptosis and cell growth arrest, while a monomeric variant is functionally inactive, supporting cell growth. In particular, the expression of pro-arrest CDKN1A and pro-apoptotic P53AIP1 genes are important cell fate determinants that are differentially regulated by the oligomeric state of p53. This study suggests that the most abundant oligomeric species of p53 present in resting cells, namely p53 dimers, neither promote cell growth or cell death and that shifting the oligomeric state equilibrium of p53 in cells toward monomers or tetramers is a key parameter in p53-based cell fate decisions.

  14. Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review

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    Shoji Kaku

    2015-01-01

    Full Text Available Progressive fetal growth restriction (FGR is often an indication for delivery. In dichorionic diamniotic (DD twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR, the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for ≥2 weeks before 30 weeks of gestation. The interval from growth arrest to delivery was 21–24 days and the discordance was 33.7–49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus.

  15. MR imaging of pituitary hyperplasia in a child with growth arrest and primary hypothyroidism

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    Papakonstantinou, O.; Bakantaki, A.; Papadaki, E.; Gourtsoyiannis, N. [Dept. of Radiology, Medical School, University of Crete, Heraklion (Greece); Bitsori, M.; Mamoulakis, D. [Dept. of Pediatrics, Medical School, University of Crete, Heraklion (Greece)

    2000-03-01

    Magnetic resonance imaging of pituitary hyperplasia has been rarely described in children with primary hypothyroidism. We report a case of pituitary hyperplasia in a child presented with significant growth arrest and laboratory evidence of hypothyroidism. Magnetic resonance imaging revealed symmetrical pituitary enlargement simulating macroadenoma. After thyroid hormone replacement therapy, the child's height increased and pituitary enlargement regressed to normal. Awareness of MRI appearance of pituitary hyperplasia in children with laboratory evidence of hypothyroidism might avoid misdiagnosis for pituitary tumor, which may also manifest as growth disorder, obviating unnecessary surgery. (orig.)

  16. Growth Arrest Specific 2 Is Up-Regulated in Chronic Myeloid Leukemia Cells and Required for Their Growth

    OpenAIRE

    Haixia Zhou; Yue Ge; Lili Sun; Wenjuan Ma; Jie Wu; Xiuyan Zhang; Xiaohui Hu; Eaves, Connie J; Depei Wu; Yun Zhao

    2014-01-01

    Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML), the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2) regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form o...

  17. Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.

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    Suo, Guangli; Sadarangani, Anil; Tang, Wingchung; Cowan, Bryan D; Wang, Jean Y J

    2014-09-01

    Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.

  18. Modulation of medium pH by Caulobacter crescentus facilitates recovery from uranium-induced growth arrest.

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    Park, Dan M; Jiao, Yongqin

    2014-09-01

    The oxidized form of uranium [U(VI)] predominates in oxic environments and poses a major threat to ecosystems. Due to its ability to mineralize U(VI), the oligotroph Caulobacter crescentus is an attractive candidate for U(VI) bioremediation. However, the physiological basis for U(VI) tolerance is unclear. Here we demonstrated that U(VI) caused a temporary growth arrest in C. crescentus and three other bacterial species, although the duration of growth arrest was significantly shorter for C. crescentus. During the majority of the growth arrest period, cell morphology was unaltered and DNA replication initiation was inhibited. However, during the transition from growth arrest to exponential phase, cells with shorter stalks were observed, suggesting a decoupling between stalk development and the cell cycle. Upon recovery from growth arrest, C. crescentus proliferated with a growth rate comparable to that of a control without U(VI), although a fraction of these cells appeared filamentous with multiple replication start sites. Normal cell morphology was restored by the end of exponential phase. Cells did not accumulate U(VI) resistance mutations during the prolonged growth arrest, but rather, a reduction in U(VI) toxicity occurred concomitantly with an increase in medium pH. Together, these data suggest that C. crescentus recovers from U(VI)-induced growth arrest by reducing U(VI) toxicity through pH modulation. Our finding represents a unique U(VI) detoxification strategy and provides insight into how microbes cope with U(VI) under nongrowing conditions, a metabolic state that is prevalent in natural environments.

  19. Protandry, sexual size dimorphism, and adaptive growth.

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    Morbey, Yolanda E

    2013-12-21

    Adaptive growth refers to the strategic adjustment of growth rate by individuals to maximize some component of fitness. The concept of adaptive growth proliferated in the 1990s, in part due to an influential theoretical paper by Peter Abrams and colleagues. In their 1996 paper, Abrams et al. explored the effects of time stress on optimal growth rate, development time, and adult size in seasonal organisms. In this review, I explore how the concept of adaptive growth informs our understanding of protandry (the earlier arrival of males to sites of reproduction than females) and sexual size dimorphism in seasonal organisms. I conclude that growth rate variation is an important mechanism that helps to conserve optimal levels of protandry and sexual size dimorphism in changing environments.

  20. Necdin, a p53-target gene, is an inhibitor of p53-mediated growth arrest.

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    Julie Lafontaine

    Full Text Available In vitro, cellular immortalization and transformation define a model for multistep carcinogenesis and current ongoing challenges include the identification of specific molecular events associated with steps along this oncogenic pathway. Here, using NIH3T3 cells, we identified transcriptionally related events associated with the expression of Polyomavirus Large-T antigen (PyLT, a potent viral oncogene. We propose that a subset of these alterations in gene expression may be related to the early events that contribute to carcinogenesis. The proposed tumor suppressor Necdin, known to be regulated by p53, was within a group of genes that was consistently upregulated in the presence of PyLT. While Necdin is induced following p53 activation with different genotoxic stresses, Necdin induction by PyLT did not involve p53 activation or the Rb-binding site of PyLT. Necdin depletion by shRNA conferred a proliferative advantage to NIH3T3 and PyLT-expressing NIH3T3 (NIHLT cells. In contrast, our results demonstrate that although overexpression of Necdin induced a growth arrest in NIH3T3 and NIHLT cells, a growing population rapidly emerged from these arrested cells. This population no longer showed significant proliferation defects despite high Necdin expression. Moreover, we established that Necdin is a negative regulator of p53-mediated growth arrest induced by nutlin-3, suggesting that Necdin upregulation could contribute to the bypass of a p53-response in p53 wild type tumors. To support this, we characterized Necdin expression in low malignant potential ovarian cancer (LMP where p53 mutations rarely occur. Elevated levels of Necdin expression were observed in LMP when compared to aggressive serous ovarian cancers. We propose that in some contexts, the constitutive expression of Necdin could contribute to cancer promotion by delaying appropriate p53 responses and potentially promote genomic instability.

  1. Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest

    Institute of Scientific and Technical Information of China (English)

    Long-Zhu Li; Hong-Xia Deng; Wen-Zhu Lou; Xue-Yan Sun; Meng-Wan Song; Jing Tao; Bing-Xiu Xiao; Jun-Ming Guo

    2012-01-01

    AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

  2. Adapting RRT growth for heterogeneous environments

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    Denny, Jory

    2013-11-01

    Rapidly-exploring Random Trees (RRTs) are effective for a wide range of applications ranging from kinodynamic planning to motion planning under uncertainty. However, RRTs are not as efficient when exploring heterogeneous environments and do not adapt to the space. For example, in difficult areas an expensive RRT growth method might be appropriate, while in open areas inexpensive growth methods should be chosen. In this paper, we present a novel algorithm, Adaptive RRT, that adapts RRT growth to the current exploration area using a two level growth selection mechanism. At the first level, we select groups of expansion methods according to the visibility of the node being expanded. Second, we use a cost-sensitive learning approach to select a sampler from the group of expansion methods chosen. Also, we propose a novel definition of visibility for RRT nodes which can be computed in an online manner and used by Adaptive RRT to select an appropriate expansion method. We present the algorithm and experimental analysis on a broad range of problems showing not only its adaptability, but efficiency gains achieved by adapting exploration methods appropriately. © 2013 IEEE.

  3. p15(INK4b) in HDAC inhibitor-induced growth arrest.

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    Hitomi, Toshiaki; Matsuzaki, Youichirou; Yokota, Tomoya; Takaoka, Yuuki; Sakai, Toshiyuki

    2003-11-20

    Histone deacetylase (HDAC) inhibitors arrest human tumor cells at the G1 phase of the cell cycle and activate the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1). However, several studies have suggested the existence of a p21(WAF1/Cip1)-independent molecular pathway. We report here that HDAC inhibitors, trichostatin A (TSA) and sodium butyrate, activate the p15(INK4b) gene, a member of the INK4 gene family, through its promoter in HaCaT cells. Furthermore, we show that up-regulation of p15(INK4b) by TSA is associated with cell growth inhibition of HCT116 p21 (-/-) cells. Our findings suggest that p15(INK4b) is one of the important molecular targets of HDAC inhibitors.

  4. Glycogen synthesis correlates with androgen-dependent growth arrest in prostate cancer

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    Gorin Frederic A

    2005-03-01

    Full Text Available Abstract Background Androgen withdrawal in normal prostate or androgen-dependent prostate cancer is associated with the downregulation of several glycolytic enzymes and with reduced glucose uptake. Although glycogen metabolism is known to regulate the intracellular glucose level its involvement in androgen response has not been studied. Methods We investigated the effects of androgen on glycogen phosphorylase (GP, glycogen synthase (GS and on glycogen accumulation in the androgen-receptor (AR reconstituted PC3 cell line containing either an empty vector (PC3-AR-V or vector with HPV-E7 (PC3-AR-E7 and the LNCaP cell line. Results Androgen addition in PC3 cells expressing the AR mimics androgen ablation in androgen-dependent prostate cells. Incubation of PC3-AR-V or PC3-AR-E7 cells with the androgen R1881 induced G1 cell cycle arrest within 24 hours and resulted in a gradual cell number reduction over 5 days thereafter, which was accompanied by a 2 to 5 fold increase in glycogen content. 24 hours after androgen-treatment the level of Glucose-6-P (G-6-P had increased threefold and after 48 hours the GS and GP activities increased twofold. Under this condition inhibition of glycogenolysis with the selective GP inhibitor CP-91149 enhanced the increase in glycogen content and further reduced the cell number. The androgen-dependent LNCaP cells that endogenously express AR responded to androgen withdrawal with growth arrest and increased glycogen content. CP-91149 further increased glycogen content and caused a reduction of cell number. Conclusion Increased glycogenesis is part of the androgen receptor-mediated cellular response and blockage of glycogenolysis by the GP inhibitor CP-91149 further increased glycogenesis. The combined use of a GP inhibitor with hormone therapy may increase the efficacy of hormone treatment by decreasing the survival of prostate cancer cells and thereby reducing the chance of cancer recurrence.

  5. Overexpressed active Notch1 induces cell growth arrest of HeLa cervical carcinoma cells.

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    Wang, L; Qin, H; Chen, B; Xin, X; Li, J; Han, H

    2007-01-01

    Human cervical carcinoma is one of the most common malignant tumors, but the mechanisms that orchestrate the multiple oncogenic insults required for initiation and progression are not clear. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis, but perturbed Notch signaling may contribute to tumorigenesis. We now show that Notch1 is detected in all cervical cancer, including advanced diseases. We also constitutively overexpressed active Notch1 in human cervical carcinoma to explore the effects of Notch1 signaling on human cervical carcinoma cell growth and to investigate the underlying molecular mechanisms. The signaling may participate in the development of human cervical carcinoma cells, but overexpressed active Notch1 inhibits their growth through induction of cell cycle arrest. Increased Notch1 signaling induced a downmodulation of human papillomavirus transcription through suppression of activator protein (AP)-1 activity by upregulation of c-Jun and the decreased expression of c-Fos. Thus, Notch1 signaling plays a key role and exerts dual effects, functioning in context-specific manner.

  6. The lag-phase during diauxic growth is a trade-off between fast adaptation and high growth rate

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    Chu, Dominique; Barnes, David J.

    2016-04-01

    Bi-phasic or diauxic growth is often observed when microbes are grown in a chemically defined medium containing two sugars (for example glucose and lactose). Typically, the two growth stages are separated by an often lengthy phase of arrested growth, the so-called lag-phase. Diauxic growth is usually interpreted as an adaptation to maximise population growth in multi-nutrient environments. However, the lag-phase implies a substantial loss of growth during the switch-over. It therefore remains unexplained why the lag-phase is adaptive. Here we show by means of a stochastic simulation model based on the bacterial PTS system that it is not possible to shorten the lag-phase without incurring a permanent growth-penalty. Mechanistically, this is due to the inherent and well established limitations of biological sensors to operate efficiently at a given resource cost. Hence, there is a trade-off between lost growth during the diauxic switch and the long-term growth potential of the cell. Using simulated evolution we predict that the lag-phase will evolve depending on the distribution of conditions experienced during adaptation. In environments where switching is less frequently required, the lag-phase will evolve to be longer whereas, in frequently changing environments, the lag-phase will evolve to be shorter.

  7. Interaction of influenza virus NS1 protein with growth arrest-specific protein 8

    Directory of Open Access Journals (Sweden)

    Yu Mengbin

    2009-12-01

    Full Text Available Abstract NS1 protein is the only non-structural protein encoded by the influenza A virus, and it contributes significantly to disease pathogenesis by modulating many virus and host cell processes. A two-hybrid screen for proteins that interact with NS1 from influenza A yielded growth arrest-specific protein 8. Gas8 associated with NS1 in vitro and in vivo. Deletion analysis revealed that the N-terminal 260 amino acids of Gas8 were able to interact with NS1, and neither the RNA-binding domain nor the effector domain of NS1 was sufficient for the NS1 interaction. We also found that actin, myosin, and drebrin interact with Gas8. NS1 and β-actin proteins could be co-immunoprecipitated from extracts of transfected cells. Furthermore, actin and Gas8 co-localized at the plasma membrane. These results are discussed in relation to the possible functions of Gas8 protein and their relevance in influenza virus release.

  8. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    Full Text Available Nasopharyngeal carcinoma is a common malignant tumor in the head and neck. Because of frequent recurrence and distant metastasis which are the main causes of death, better treatment is needed. Indole-3-carbinol (I3C, a natural phytochemical found in the vegetables of the cruciferous family, shows anticancer effect through various signal pathways. I3C induces G1 arrest in NPC cell line with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1 and pRb. In vivo, nude mice receiving I3C protectively or therapeutically exhibited smaller tumors than control group after they were inoculated with nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb in preventive treatment group and drug treatment group both decreased compared with the control group. We conclude that I3C can inhibit the growth of NPC in vitro and in vivo by suppressing the expression of CDK and cyclin families. The drug was safe and had no toxic effects on normal tissues and organs.

  9. Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle.

    Science.gov (United States)

    Zore, Gajanan B; Thakre, Archana D; Jadhav, Sitaram; Karuppayil, S Mohan

    2011-10-15

    Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole.

  10. Fibroblasts from long-lived Snell dwarf mice are resistant to oxygen-induced in vitro growth arrest

    DEFF Research Database (Denmark)

    Maynard, Scott P; Miller, Richard A

    2006-01-01

    Snell dwarf mice live longer than controls, and show lower age-adjusted rates of lethal neoplastic diseases. Fibroblast cells from adult dwarf mice are resistant to the lethal effects of oxidative and nonoxidative stresses, including the carcinogen methyl methanesulfonate. We now report that dwarf...... in skin fibroblasts by the hormonal milieu of the Snell dwarf lead to resistance to multiple forms of injury, including the oxidative damage that contributes to growth arrest in vitro and neoplasia in intact mice....

  11. SUMO modification of Stra13 is required for repression of cyclin D1 expression and cellular growth arrest.

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    Yaju Wang

    Full Text Available Stra13, a basic helix-loop-helix (bHLH transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1 cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1, attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.

  12. Growth arrest specific 2 is up-regulated in chronic myeloid leukemia cells and required for their growth.

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    Haixia Zhou

    Full Text Available Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML, the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2 regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form of GAS2 (GAS2DN to target GAS2, which resulted in calpain activity enhancement and growth inhibition of both K562 and MEG-01 cells. Targeting GAS2 also sensitized K562 cells to Imatinib mesylate (IM. GAS2DN suppressed the tumorigenic ability of MEG-01 cells and impaired the tumour growth as well. Moreover, the CD34+ cells from CML patients and healthy donors were transduced with control and GAS2DN lentiviral vectors, and the CD34+ transduced (YFP+ progeny cells (CD34+YFP+ were plated for colony-forming cell (CFC assay. The results showed that GAS2DN inhibited the CFC production of CML cells by 57±3% (n = 3, while affected those of normal hematopoietic cells by 31±1% (n = 2. Next, we found the inhibition of CML cells by GAS2DN was dependent on calpain activity but not the degradation of beta-catenin. Lastly, we generated microarray data to identify the differentially expressed genes upon GAS2DN and validated that the expression of HNRPDL, PTK7 and UCHL5 was suppressed by GAS2DN. These 3 genes were up-regulated in CML cells compared to normal control cells and the growth of K562 cells was inhibited upon HNRPDL silence. Taken together, we have demonstrated that GAS2 is up-regulated in CML cells and the inhibition of GAS2 impairs the growth of CML cells, which indicates GAS2 is a novel regulator of CML cells and a potential therapeutic target of this disease.

  13. Overexpression of a novel gene, Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    MCM10 protein is an essential replication factor involved in the initiation of DNA replication. A mcm10 mutant (mcm10-1) of budding yeast shows a growth arrest at 37℃. In the present work, we have isolated a mcm10-1 suppressor strain, which grows at 37℃. Interestingly, this mcm10-1 suppressor undergoes cell cycle arrest at 14℃. A novel gene, YLR003c, is identified by high-copy complementation of this suppressor. We called it as Cmsl (Complementation of Mcm 10 Suppressor). Furthermore, the experiments of transformation show that cells of mcm10-1 suppressor with high-copy plasmid but not low-copy plasmid grow at 14℃, indicating that overexpression of Cmsl can rescue the growth arrest of this mcm10 suppressor at non-permissive temperature. These results suggest that CMS1 protein may functionally interact with MCM10 protein and play a role in the regulation of DNA replication and cell cycle control.

  14. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Gloria A. Santa-Gonzalez

    2016-10-01

    Full Text Available Many environmental and physiological stresses are chronic. Thus, cells are constantly exposed to diverse types of genotoxic insults that challenge genome stability, including those that induce oxidative DNA damage. However, most in vitro studies that model cellular response to oxidative stressors employ short exposures and/or acute stress models. In this study, we tested the hypothesis that chronic and repeated exposure to a micromolar concentration of hydrogen peroxide (H2O2 could activate DNA damage responses, resulting in cellular adaptations. For this purpose, we developed an in vitro model in which we incubated mouse myoblast cells with a steady concentration of ~50 μM H2O2 for one hour daily for seven days, followed by a final challenge of a 10 or 20X higher dose of H2O2 (0.5 or 1 mM. We report that intermittent long-term exposure to this oxidative stimulus nearly eliminated cell toxicity and significantly decreased genotoxicity (in particular, a >5-fold decreased in double-strand breaks resulting from subsequent acute exposure to oxidative stress. This protection was associated with cell cycle arrest in G2/M and induction of expression of nine DNA repair genes. Together, this evidence supports an adaptive response to chronic, low-level oxidative stress that results in genomic protection and up-regulated maintenance of cellular homeostasis.

  15. Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest.

    Science.gov (United States)

    Lan, Qiusheng; Li, Shoufeng; Lai, Wei; Xu, Heyang; Zhang, Yang; Zeng, Yujie; Lan, Wenjian; Chu, Zhonghua

    2015-08-17

    The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.

  16. Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest

    Directory of Open Access Journals (Sweden)

    Qiusheng Lan

    2015-08-01

    Full Text Available The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2 apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.

  17. Sequential signaling cascade of IL-6 and PGC-1α is involved in high glucose-induced podocyte loss and growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Il; Park, Soo Hyun, E-mail: parksh@chonnam.ac.kr

    2013-06-14

    Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.

  18. HipA-triggered growth arrest and β-lactam tolerance in Escherichia coli are mediated by RelA-dependent ppGpp synthesis.

    Science.gov (United States)

    Bokinsky, Gregory; Baidoo, Edward E K; Akella, Swetha; Burd, Helcio; Weaver, Daniel; Alonso-Gutierrez, Jorge; García-Martín, Héctor; Lee, Taek Soon; Keasling, Jay D

    2013-07-01

    Persistence is a phenomenon whereby a subpopulation of bacterial cells enters a transient growth-arrested state that confers antibiotic tolerance. While entrance into persistence has been linked to the activities of toxin proteins, the molecular mechanisms by which toxins induce growth arrest and the persistent state remain unclear. Here, we show that overexpression of the protein kinase HipA in Escherichia coli triggers growth arrest by activating synthesis of the alarmone guanosine tetraphosphate (ppGpp) by the enzyme RelA, a signal typically associated with amino acid starvation. We further demonstrate that chemically suppressing ppGpp synthesis with chloramphenicol relieves inhibition of DNA replication initiation and RNA synthesis in HipA-arrested cells and restores vulnerability to β-lactam antibiotics. HipA-arrested cells maintain glucose uptake and oxygen consumption and accumulate amino acids as a consequence of translational inhibition. We harness the active metabolism of HipA-arrested cells to provide a bacteriophage-resistant platform for the production of biotechnologically relevant compounds, which may represent an innovative solution to the costly problem of phage contamination in industrial fermentations.

  19. Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Fata, Jimmie E.; Martin, Katherine J.; Yaswen, Paul; Bissell, Mina J.

    2009-06-03

    PTEN is a dual function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two non-malignant human mammary epithelial cell lines (HMECs) that form polarized, growth-arrested structures (acini) when cultured in 3-dimensional laminin-rich extracellular matrix gels (3D lrECM). As acini begin to form, PTEN accumulates in both the cytoplasm, and at cell-cell contacts where it colocalizes with E-cadherin/{beta}-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function-blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in SKBR3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in 3D lrECM indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus appears to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells.

  20. Berberine inhibits growth and induces G1 arrest and apoptosis in human cholangiocarcinoma QBC939 cells.

    Science.gov (United States)

    He, Wei; Wang, Bin; Zhuang, Yun; Shao, Dong; Sun, Kewen; Chen, Jianping

    2012-01-01

    The chemotherapeutic approach using non-toxic natural products may be one of the strategies for the management of the cholangiocarcinoma. Here we report that in vitro treatment of human cholangiocarcinoma QBC939 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability and induced cell death in a dose-dependent manner, which was associated with an increase in G1 arrest. Our western blot analysis showed that berberine-induced G1 cell cycle arrest was mediated through the increased expression of cyclin-dependent kinase inhibitors (Cdki) proteins (Cip1/p21 and Kip1/p27); a simultaneous decrease in Cdk2 and Cdk4 and cyclins D1, and reduced activity of the Cyclins-Cdk complex. In additional studies, treatment of QBC939 cells with different concentrations (10, 40, 80 μM) of berberine for 48 h resulted in a significant dose-dependent increase in apoptosis compared to the non-berberine-treated control, which was associated with an increased expression of pro-apoptotic protein Bax and decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Together, this study for the first time identified berberine as a chemotherapeutic agent against human cholangiocarcinoma cells QBC939 cells in vitro. Further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of cholangiocarcinoma.

  1. The mitogen-activated protein kinase pathway mediates growth arrest or E1A-dependent apoptosis in SKBR3 human breast cancer cells.

    Science.gov (United States)

    Blagosklonny, M V

    1998-11-09

    Previously, we have shown that phorbol ester (PMA) induces p21(WAF1/CIP1)-dependent growth arrest in SKBr3 breast cancer and LNCaP prostate cancer cells. Here, I demonstrate that inhibition of Raf-1 kinase by dominant-negative Raf-1 or pharmacological depletion of Raf-1 prevented PMA-mediated induction of p21(WAF1/CIP1). Similarly, PD98059, a specific inhibitor of MEK, abolished p21(WAF1/CIP1) induction and PMA-induced growth arrest. Like PMA, the H-ras oncogene, another activator of the Raf-1/MEK/MAPK pathway, transactivated p21(WAF1/CIP1) in SKBr3 cells. I further investigated PMA-induced growth arrest following infection of SKBr3 cells with 12S E1A-expressing adenovirus. Although high levels of E1A oncoprotein prevented both PMA-induced p21(WAF1/CIP1) and growth arrest, smaller amounts of E1A abrogated growth arrest without down-regulation of p21(WAF1/CIP1). Therefore, E1A can stimulate proliferation downstream of p21(WAF1/CIP1). Albeit less effective than full activity, either Rb- or p300-binding activity of E1A was sufficient for the abrogation of PMA-mediated growth arrest. E1A-driven proliferation of PMA-treated SKBr3 cells was accompanied by apoptosis. New therapeutic approaches can be envisioned that would utilize stimulation of the Raf-1/MEK/MAPK pathway to inhibit growth of PMA-sensitive cancer cells.

  2. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  3. Ethyl acetate extract of Squilla oratoria suppresses growth of HepG2 cells by inducing S phase arrest

    Directory of Open Access Journals (Sweden)

    Xiangwei Qi

    2013-08-01

    Full Text Available Objective: The oceans and seas are a rich source of organisms from which anti-cancer drugs can be isolated and developed. Marine organisms have been screened in our laboratory, and organic solvent extracts of Squilla oratoria (ESO have been shown to possess cytostatic effects on cancer cell lines of diverse origins. To explore the underlying mechanisms, the growth inhibition by ESO was investigated in the present study. Methods: Human hepatocellular carcinoma (HCC derived cells (HepG2 were used. The cells were challenged with ESO, cell cycle profile was assayed, and level of proliferating cell nuclear antigen (PCNA expression and that of cyclin D1 and cyclin A were evaluated with flow cytomtery. The in vivo antitumor effect of ESO was tested in nude mouse xenografts. PCNA expression was evaluated immunohistochemically in nude mouse xenograft tissues. Results: With the increase in dose of injected ESO, expression of PCNA by human HCC xenografts increased. ESO inhibited the growth of human HCC HepG2 cells both in vitro and in vivo. The effect was correlated with arrest of the cell cycle in S phase. Expression of PCNA, which is a cell-cycle regulator that promotes S phase entry, was elevated in both cell lines and xenografts whereas that of cyclins that promote M phase entry was down-regulated by exposure to ESO. Conclusion: Growth inhibition was explained by arrest of the cell cycle in S phase and down-regulation of molecules that promote cells to enter S phase. [J Exp Integr Med 2013; 3(4.000: 313-322

  4. An optimization protocol for Swiss 3T3 feeder cell growth-arrest by Mitomycin C dose-to-volume derivation strategy.

    Science.gov (United States)

    Chugh, Rishi Man; Chaturvedi, Madhusudan; Yerneni, Lakshmana Kumar

    2017-04-01

    Feeder cell functionality following growth-arrest with the cost-effective Mitomycin C vis-à-vis irradiation is controversial due to several methodological variables reported. Earlier, we demonstrated variability in growth arrested Swiss 3T3 feeder cell life-span following titration of feeder cell densities with Mitomycin C concentrations which led to the derivation of doses per cell. Alternatively, to counter the unexpected feeder regrowth at high exposure cell density, we proposed titration of a fixed density with arithmetically derived volumes of Mitomycin C solution that corresponded to permutations of specific concentrations and doses per cell. We now describe an experimental procedure of inducing differential feeder cell growth-arrest by titrating with such volumes and validating the best feeder batch through target cell growth assessment. A safe cell density of Swiss 3T3 tested for the exclusion of Mitomycin C resistant variants was titrated with a range of volumes of a Mitomycin C solution. The differentially growth-arrested feeder batches generated were tested for short-term and long-term viability and human epidermal keratinocyte growth supporting ability. The feeder cell extinction rate was directly proportional to the volume of Mitomycin C solution within a given concentration per se. The keratinocyte colony forming efficiency and the overall growth in mass cultures were maximal with a median extinction rate produced by an intermediate volume, while the faster and slower extinction rates by high and low volumes, respectively, were suboptimal. The described method could counter the inadequacies of growth-arrest with Mitomycin C.

  5. Differential regulation of vitamin D receptor expression in distinct leukemic cell lines upon phorbol ester-induced growth arrest

    Directory of Open Access Journals (Sweden)

    Folgueira M.A.A.K.

    2000-01-01

    Full Text Available A close correlation between vitamin D receptor (VDR abundance and cell proliferation rate has been shown in NIH-3T3 fibroblasts, MCF-7 breast cancer and in HL-60 myeloblastic cells. We have now determined if this association occurs in other leukemic cell lines, U937 and K562, and if VDR content is related to c-myc expression, which is also linked to cell growth state. Upon phorbol myristate acetate (PMA treatment, cells from the three lineages (HL-60, U937 and K562 differentiated and expressed specific surface antigens. All cell lines analyzed were growth inhibited by PMA and the doubling time was increased, mainly due to an increased fraction of cells in the G0/G1 phase, as determined by flow cytometry measurements of incorporated bromodeoxyuridine and cell DNA content. C-myc mRNA expression was down-regulated and closely correlated to cell growth arrest. However, VDR expression in leukemic cell lines, as determined by immunofluorescence and Northern blot assays, was not consistently changed upon inhibition of cell proliferation since VDR levels were down-regulated only in HL-60 cells. Our data suggest that VDR expression cannot be explained simply as a reflection of the leukemic cell growth state.

  6. A generic mechanism for adaptive growth rate regulation.

    Directory of Open Access Journals (Sweden)

    Chikara Furusawa

    2008-01-01

    Full Text Available How can a microorganism adapt to a variety of environmental conditions despite the existence of a limited number of signal transduction mechanisms? We show that for any growing cells whose gene expression fluctuate stochastically, the adaptive cellular state is inevitably selected by noise, even without a specific signal transduction network for it. In general, changes in protein concentration in a cell are given by its synthesis minus dilution and degradation, both of which are proportional to the rate of cell growth. In an adaptive state with a higher growth speed, both terms are large and balanced. Under the presence of noise in gene expression, the adaptive state is less affected by stochasticity since both the synthesis and dilution terms are large, while for a nonadaptive state both the terms are smaller so that cells are easily kicked out of the original state by noise. Hence, escape time from a cellular state and the cellular growth rate are negatively correlated. This leads to a selection of adaptive states with higher growth rates, and model simulations confirm this selection to take place in general. The results suggest a general form of adaptation that has never been brought to light--a process that requires no specific mechanisms for sensory adaptation. The present scheme may help explain a wide range of cellular adaptive responses including the metabolic flux optimization for maximal cell growth.

  7. A generic mechanism for adaptive growth rate regulation.

    Science.gov (United States)

    Furusawa, Chikara; Kaneko, Kunihiko

    2008-01-01

    How can a microorganism adapt to a variety of environmental conditions despite the existence of a limited number of signal transduction mechanisms? We show that for any growing cells whose gene expression fluctuate stochastically, the adaptive cellular state is inevitably selected by noise, even without a specific signal transduction network for it. In general, changes in protein concentration in a cell are given by its synthesis minus dilution and degradation, both of which are proportional to the rate of cell growth. In an adaptive state with a higher growth speed, both terms are large and balanced. Under the presence of noise in gene expression, the adaptive state is less affected by stochasticity since both the synthesis and dilution terms are large, while for a nonadaptive state both the terms are smaller so that cells are easily kicked out of the original state by noise. Hence, escape time from a cellular state and the cellular growth rate are negatively correlated. This leads to a selection of adaptive states with higher growth rates, and model simulations confirm this selection to take place in general. The results suggest a general form of adaptation that has never been brought to light--a process that requires no specific mechanisms for sensory adaptation. The present scheme may help explain a wide range of cellular adaptive responses including the metabolic flux optimization for maximal cell growth.

  8. Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis.

    Science.gov (United States)

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E; Gassmann, Walter; Schroeder, Julian I

    2012-12-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor-nucleotide binding-Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid-induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest.

  9. B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B lymphoma cells involve cyclic AMP and Epac proteins

    NARCIS (Netherlands)

    Grandoch, Maria; de Jesus, Maider Lopez; Weernink, Paschal A. Oude; Weber, Artur-Aron; Jakobs, Karl H.; Schmidt, Martina

    2009-01-01

    Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte homeostasis and immune function. In immature B cells, ligation of the BCR promotes growth arrest and apoptosis, and BCR-driven balancing between pro-apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and antia

  10. Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells

    NARCIS (Netherlands)

    Nicke, B.; Bastien, J.; Khanna, S.J.; Warne, P.H.; Cowling, V.; Cook, S.J.; Peters, G.; Delpuech, O.; Schulze, A.; Berns, K.; Mullenders, J.; Beijersbergen, R.L.; Bernards, R.A.; Ganesan, T.S.; Downward, J.; Hancock, D.C.

    2005-01-01

    The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kino

  11. Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility

    Directory of Open Access Journals (Sweden)

    Lazo John S

    2010-05-01

    Full Text Available Abstract Background Protein kinase D (PKD has been implicated in a wide range of cellular processes and pathological conditions including cancer. However, targeting PKD therapeutically and dissecting PKD-mediated cellular responses remains difficult due to lack of a potent and selective inhibitor. Previously, we identified a novel pan-PKD inhibitor, CID755673, with potency in the upper nanomolar range and high selectivity for PKD. In an effort to further enhance its selectivity and potency for potential in vivo application, small molecule analogs of CID755673 were generated by modifying both the core structure and side-chains. Results After initial activity screening, five analogs with equal or greater potencies as CID755673 were chosen for further analysis: kb-NB142-70, kb-NB165-09, kb-NB165-31, kb-NB165-92, and kb-NB184-02. Our data showed that modifications to the aromatic core structure in particular significantly increased potency while retaining high specificity for PKD. When tested in prostate cancer cells, all compounds inhibited PMA-induced autophosphorylation of PKD1, with kb-NB142-70 being most active. Importantly, these analogs caused a dramatic arrest in cell proliferation accompanying elevated cytotoxicity when applied to prostate cancer cells. Cell migration and invasion were also inhibited by these analogs with varying potencies that correlated to their cellular activity. Conclusions Throughout the battery of experiments, the compounds kb-NB142-70 and kb-NB165-09 emerged as the most potent and specific analogs in vitro and in cells. These compounds are undergoing further testing for their effectiveness as pharmacological tools for dissecting PKD function and as potential anti-cancer agents in the treatment of prostate cancer.

  12. Cell Growth Arrest Mediated by STAT Proteins in Breast Cancer Cells

    Science.gov (United States)

    1998-07-01

    pepstatin, and aprotinin (1 (Xg/ml each). Whole cell extracts were immediately subjected to electromobility shift assay. Preparation of membrane and...activation on the cytosol fraction (STAT protein) concentration. Electromobility shift assay (EMSA) The sample after in vitro activation (3 ul) (1 [il...transcription; EGF, epidermal growth factor; NGF, nerve growth factor; EMSA, electromobility shift assay; SIF, sis-inducible factor; SIE, sis

  13. Metformin Induces Growth Inhibition and Cell Cycle Arrest by Upregulating MicroRNA34a in Renal Cancer Cells

    Science.gov (United States)

    Xie, Wei; Wang, Lei; Sheng, Halei; Qiu, Jing; Zhang, Di; Zhang, Le; Yang, Fan; Tang, Dahai; Zhang, Kebin

    2017-01-01

    Background Metformin is a widely used biguanide drug for the treatment of type 2 diabetes. It has been revaluated as a potential anti-cancer drug with promising activity in various tumors. However, the precise mechanisms underlying the suppression of cancer cells by metformin remain not well understood. Material/Methods In this study, human renal cell carcinoma cell line ACHN was used to investigate the anti-proliferation effect of metformin. A cell counting kit-8 assay was used to detect the cell viability. The cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of cyclin D1 and p27KIP1 was detected by Western blot. The underlying mechanism involving miRNA34a was further investigated by quantitative RT-PCR and transfection with miRNA inhibitor specific for miRNA34a in ACHN, 769-P, and A498 cells. Results Metformin could significantly inhibit the proliferation of ACHN cells in a dose- and time-dependent manner. In addition, the results showed that metformin induced G0/G1 phase arrest and delayed entry into S phase in ACHN cells. It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level. Furthermore, metformin increased ACHN cell death. Lastly, miRNA34a was found to be upregulated by metformin in ACHN, 769-P, and A498 cells. Subsequently, it was demonstrated that inhibition of miRNA34a could partially attenuate the suppressive effect of metformin on renal cancer cell proliferation. Conclusions The study data revealed that metformin induced cell growth inhibition and cell cycle arrest partially by upregulating miRNA34a in renal cancer cells. PMID:28045889

  14. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide

    Institute of Scientific and Technical Information of China (English)

    Gao-Liang Ouyang; Qiu-Feng Cai; Min Liu; Rui-Chuan Chen; Zhi Huang; Rui-Sheng Jiang; Fu Chen; Shui-Gen Hong; Shi-Deng Bao

    2004-01-01

    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer.METHODS: Effects of HMBA on the growth of human hepatocellular carcinoma SMMC-7721 cells were assayed by MTT chronometry. Apoptosis induced by HMBA was detected by phase-contrast microscopy, flow cytometry,propidium iodide staining and immunocytochemical analysis.RESULTS: The growth of SMMC-7721 cells was significantly inhibited by HMBA, and the growth inhibitory rate was 51.1%, 62.6%, 68.7% and 73.9% respectively after treatment with 5.0, 7.5, 10.0 and 12.5 mmol/L of HMBA.In the cells treated with 10 mmol/L of HMBA for 72 h, the population of cells at sub-G1 phase significantly increased,and the apoptotic bodies and condensed nuclei were detected. Moreover, treatment of SMMC-7721 cells with 10 mmol/L of HMBA down-regulated the expression of Bcl2 anti-apoptotic protein, while slightly up-regulated the level of pro-apoptotic protein Bax.CONCLUSION: Treatment with 10.0 mmol/L of HMBA can significantly inhibit the growth and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells by decreasing the ratio of Bcl-2 to Bax.

  15. Arrest of myelination and reduced axon growth when Schwann cells lack mTOR.

    Science.gov (United States)

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J

    2012-02-01

    In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years, there has been an increased understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination, together with a growing appreciation of some of the signaling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete. The mammalian target of rapamycin (mTOR) is a core kinase in two major complexes, mTORC1 and mTORC2, that regulate cell growth and differentiation in a variety of mammalian cells. Here we show that elimination of mTOR from murine Schwann cells prevented neither radial sorting nor the initiation of myelination. However, normal postnatal growth of myelinating Schwann cells, both radially and longitudinally, was highly retarded. The myelin sheath in the mutant was much thinner than normal; nevertheless, sheath thickness relative to axon diameter (g-ratio) remained constant in both wild-type and mutant nerves from P14 to P90. Although axon diameters were normal in the mutant at the initiation of myelination, further growth as myelination proceeded was retarded, and this was associated with reduced phosphorylation of neurofilaments. Consistent with thinner axonal diameters and internodal lengths, conduction velocities in mutant quadriceps nerves were also reduced. These data establish a critical role for mTOR signaling in both the longitudinal and radial growth of the myelinating Schwann cell.

  16. Metformin inhibits salivary adenocarcinoma growth through cell cycle arrest and apoptosis

    OpenAIRE

    2015-01-01

    The inhibitory effects of metformin have been observed in many types of cancer. However, its effect on human salivary gland carcinoma is unknown. The effect of metformin alone or in combination with pp242 (an mTOR inhibitor) on salivary adenocarcinoma cells growth were determined in vitro and in vivo. We found that metformin suppressed HSY cell growth in vitro in a time and dose dependent manner associated with a reduced expression of MYC onco-protein, and the same inhibitory effect of metfor...

  17. Higher order nuclear organization in growth arrest of humanmammary epithelial cells: A novel role for telomere-associated proteinTIN2

    Energy Technology Data Exchange (ETDEWEB)

    Kaminker, Patrick; Plachot, Cedric; Kim, Sahn-Ho; Chung, Peter; Crippen, Danielle; Petersen, Ole W.; Bissell, Mina J.; Campisi, Judith; Lelievre, Sophie A.

    2004-12-15

    Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those which occur during differentiation and growth arrest. Using human mammary epithelial cells (HMECs) in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNAse, but not RNAse, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein l{gamma}. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in HMECs. Our findings reveal a novel extra-telomeric organization of TIN2 associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.

  18. Non-homologous end joining dependency of {gamma}-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, Erich [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

    2004-11-22

    There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by {gamma}-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the {gamma}-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development.

  19. Hinokitiol inhibits cell growth through induction of S-phase arrest and apoptosis in human colon cancer cells and suppresses tumor growth in a mouse xenograft experiment.

    Science.gov (United States)

    Lee, Youn-Sun; Choi, Kyeong-Mi; Kim, Wonkyun; Jeon, Young-Soo; Lee, Yong-Moon; Hong, Jin-Tae; Yun, Yeo-Pyo; Yoo, Hwan-Soo

    2013-12-27

    Hinokitiol (1), a tropolone-related natural compound, induces apoptosis and has anti-inflammatory, antioxidant, and antitumor activities. In this study, the inhibitory effects of 1 were investigated on human colon cancer cell growth and tumor formation of xenograft mice. HCT-116 and SW-620 cells derived from human colon cancers were found to be similarly susceptible to 1, with IC50 values of 4.5 and 4.4 μM, respectively. Compound 1 induced S-phase arrest in the cell cycle progression and decreased the expression levels of cyclin A, cyclin E, and Cdk2. Conversely, 1 increased the expression of p21, a Cdk inhibitor. Compound 1 decreased Bcl-2 expression and increased the expression of Bax, and cleaved caspase-9 and -3. The effect of 1 on tumor formation when administered orally was evaluated in male BALB/c-nude mice implanted intradermally separately with HCT-116 and SW-620 cells. Tumor volumes and tumor weights in the mice treated with 1 (100 mg/kg) were decreased in both cases. These results suggest that the suppression of tumor formation by compound 1 in human colon cancer may occur through cell cycle arrest and apoptosis.

  20. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masatoshi, E-mail: msuzuki@nagasaki-u.ac.jp [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan); Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

    2012-06-01

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO{sub 2}-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ss-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  1. Arrest of Myelination and Reduced Axon Growth when Schwann Cells Lack mTOR

    OpenAIRE

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J.

    2012-01-01

    In developing peripheral nerves differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years there has been an increasing understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination together with a growing appreciation of some of the signalling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete....

  2. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.

    Science.gov (United States)

    Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Fortner, Karen A; Viapiano, Mariano S; Jaworski, Diane M

    2015-08-01

    Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth.

  3. Solanum tuberosum lectin inhibits Ehrlich ascites carcinoma cells growth by inducing apoptosis and G2/M cell cycle arrest.

    Science.gov (United States)

    Kabir, Syed Rashel; Rahman, Md Musfikur; Amin, Ruhul; Karim, Md Rezaul; Mahmud, Zahid Hayat; Hossain, M Tofazzal

    2016-06-01

    Recently, a lectin was purified from the potato cultivated in Bangladesh locally known as Sheel. In the present study cytotoxicity of the lectin against Ehrlich ascites carcinoma (EAC) cells was studied by MTT assay in vitro in RPMI-1640 medium and 8.0-36.0 % cell growth inhibition was observed at the range of 2.5-160 μg/ml protein concentration when incubated for 24 h. The lectin-induced apoptosis in EAC cells was confirmed by fluorescence and optical microscope. The apoptotic cell death was also confirmed by using caspase inhibitors. Cells growth inhibition caused by the lectin (36 %) was remarkably decreased to 7.6 and 22.3 % respectively in the presence of caspase-3 and -8 inhibitors. RT-PCR was used to evaluate the expression of apoptosis-related genes Bcl-X, p53, and Bax. An intensive expression of Bcl-X gene was observed in untreated control EAC cells with the disappeared of the gene in Sheel-treated EAC cells. At the same time, Bax gene expression appeared only in Sheel-treated EAC cells and the expression level of the p53 gene was increased remarkable after the treatment of EAC cells with the lectin. The lectin showed strong agglutination activity against EAC cells. Flow cytometry was used to study the cell cycle phases of EAC cells and it was observed that the lectin arrested the G2/M phase. In conclusion, Sheel lectin inhibited EAC cells growth by inducing apoptosis.

  4. Interleukin-1beta can mediate growth arrest and differentiation via the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells.

    Science.gov (United States)

    Park, Jong-In; Strock, Christopher J; Ball, Douglas W; Nelkin, Barry D

    2005-02-01

    Interleukin-1beta (IL-1beta) is a pleiotropic cytokine that can induce several cellular signal transduction pathways. Here, we show that IL-1beta can induce cell cycle arrest and differentiation in the human medullary thyroid carcinoma (MTC) cell line, TT. IL-1beta induces cell cycle arrest accompanied by morphological changes and expression of the neuroendocrine marker calcitonin. These changes are blocked by the MEK1/2 specific inhibitor U0126, indicating that MEK1/2 is essential for IL-1beta signaling in TT cells. IL-1beta induces expression of leukemia inhibitory factor (LIF) and activation of STAT3 via the MEK/ERK pathway. This activation of STAT3 could be abrogated by treatment with anti-LIF neutralizing antibody or anti-gp130 blocking antibody, indicating that induction of LIF expression is sufficient and essential for STAT3 activation by IL-1beta. In addition to activation of the LIF/JAK/STAT pathway, IL-1beta also induced an MEK/ERK-mediated intracellular cell-autonomous signaling pathway that is independently sufficient for growth arrest and differentiation. Thus, IL-1beta activates the MEK/ERK pathway to induce growth arrest and differentiation in MTC cells via dual independent signaling mechanisms, the cell-extrinsic LIF/JAK/STAT pathway, and the cell-intrinsic autonomous signaling pathway.

  5. Growth arrest of vascular smooth muscle cells in suspension culture using low-acyl gellan gum.

    Science.gov (United States)

    Natori, Tomomi; Fujiyoshi, Masachika; Uchida, Masashi; Abe, Natsuki; Kanaki, Tatsuro; Fukumoto, Yasunori; Ishii, Itsuko

    2017-03-01

    The proliferation of vascular smooth muscle cells (SMCs) causes restenosis in biomaterial vascular grafts. The purposes of this study were to establish a suspension culture system for SMCs by using a novel substrate, low-acyl gellan gum (GG) and to maintain SMCs in a state of growth inhibition. When SMCs were cultured in suspension with GG, their proliferation was inhibited. Their viability was 70% at day 2, which was maintained at more than 50% until day 5. In contrast, the viability of cells cultured in suspension without GG was 5.6% at day 2. By cell cycle analysis, the ratio of SMCs in the S phase when cultured in suspension with GG was lower than when cultured on plastic plates. In SMCs cultured in suspension with GG, the ratio of phosphorylated retinoblastoma (Rb) protein to Rb protein was decreased and p27(Kip1) expression was unchanged in comparison with SMCs cultured on plastic plates. In addition, SMCs could be induced to proliferate again by changing the culture condition from suspension with GG to plastic plates. These results suggest that our established culturing method for SMCs is useful to maintain SMCs in a state of growth inhibition with high viability.

  6. Linear Growth Arrest Without Weight Gain Due to Overuse of Topical Clobetasol

    Directory of Open Access Journals (Sweden)

    Zahra Razavi

    2014-11-01

    Full Text Available Prolonged potent topical glucocorticoid therapy in infants can cause iatrogenic Cushing’s syndrome. This case highlights the rarity of poor weight gain in iatrogenic Cushing’s syndrome. A 17-month-old boy was referred to outpatients pediatric endocrine clinic for evaluation of growth failure. On presentation his weight was 9.7kg (5th percentile and height was 72cm (-3.6 SD below mean for age and sex. Systemic examination revealed grossly moon-like face, hypertrichosis and thin skin in the genital area. His mother reported using local clobetasol for the previous seven months for his diaper dermatitis. Baseline plasma cortisol was low (0.3ng/ml, normal range: 60 to 280ng/ml. During standard dose of synthetic adrenocorticotropic hormone test, the peak cortisol level was 0.4ng/ml (N>180ng/ml and was consistent with hypothalamic–pituitary–adrenal axis suppression. The patient’s clinical presentation and laboratory investigations confirmed the diagnosis of secondary adrenal insufficiency and iatrogenic Cushing’s syndrome. He was treated successfully by discontinuing use of clobetasol. His appearance and growth returned to normal within two months. Morning cortisol was 101.2ng/ml after stopping the oral physiologic dose of hydrocortisone. Our case differed from other reports of iatrogenic Cushing’s syndrome by presenting in poor weight gain rather than obesity.

  7. Inhibitor of growth 4 suppresses colorectal cancer growth and invasion by inducing G1 arrest, inhibiting tumor angiogenesis and reversing epithelial-mesenchymal transition.

    Science.gov (United States)

    Qu, Hui; Yin, Hong; Yan, Su; Tao, Min; Xie, Yufeng; Chen, Weichang

    2016-05-01

    Previous studies have found that inhibitor of growth 4 (ING4), a tumor suppressor, is reduced in human colorectal cancer (CRC), and is inversely correlated with clinical Dukes' stage, histological grade, lymph node metastasis and microvessel density (MVD). However, its underlying mechanism remains undetermined. In the present study, we analyzed ING4 expression in a panel of human CRC cells using low (LS174T and SW480) and high (LoVo and SW620) metastatic cell lines. We demonstrated that both the low and high metastatic CRC cells exhibited a lower level of ING4 compared to the level in normal human colorectal mucous epithelial FHC cells. Furthermore, ING4 expression in high metastatic CRC cells was less than that in low metastatic CRC cells. We then generated a lentivirus construct expressing ING4 and green fluorescent protein (GFP), established a ING4-stably transgenic LoVo CRC cell line, and investigated the effect of lentiviral-mediated ING4 expression on high metastatic LoVo CRC cells. Gain-of-function studies revealed that ING4 significantly inhibited LoVo CRC cell growth and invasion in vitro and induced cell cycle G1 phase arrest. Moreover, ING4 obviously suppressed LoVo CRC subcutaneously xenografted tumor growth and reduced tumor MVD in vivo in athymic BALB/c nude mice. Mechanistically, ING4 markedly upregulated P21 and E-cadherin but downregulated cyclin E, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), Snail1, N-cadherin and vimentin in the LoVo CRC cells. Our data provide compelling evidence that i) ING4 suppresses CRC growth possibly via induction of G1 phase arrest through upregulation of P21 cyclin-dependent kinase (CDK) inhibitor and downregulation of cyclin E as well as inhibition of tumor angiogenesis through reduction of IL-6, IL-8 and VEGF proangiogenic factors; ii) ING4 inhibits CRC invasion and metastasis probably via a switch from mesenchymal marker N-cadherin to epithelial marker E-cadherin through downregulation of

  8. Silica Nanoparticles Sensitize Human Multiple Myeloma Cells to Snake (Walterinnesia aegyptia Venom-Induced Apoptosis and Growth Arrest

    Directory of Open Access Journals (Sweden)

    Douaa Sayed

    2012-01-01

    Full Text Available Background. Multiple myeloma (MM, an almost incurable disease, is the second most common blood cancer. Initial chemotherapeutic treatment could be successful; however, resistance development urges the use of higher toxic doses accompanied by hematopoietic stem cell transplantation. The establishment of more effective treatments that can overcome or circumvent chemoresistance has become a priority. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV either alone or in combination with silica nanoparticles (WEV+NPs mediated the growth arrest and apoptosis of prostate cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on proliferation and apoptosis of MM cells. Methods. The impacts of WEV alone and WEV+NP were monitored in MM cells from 70 diagnosed patients. The influences of WEV and WEV+NP were assessed with flow cytometry analysis. Results. WEV alone and WEV+NP decreased the viability of MM cells. Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited MM cell proliferation. Furthermore, analysis of the cell cycle using the propidium iodide (PI staining method indicated that WEV+NP strongly altered the cell cycle of MM cells and enhanced the induction of apoptosis. Conclusions. Our data reveal the biological effects of WEV and WEV+NP on MM cells that enable these compounds to function as effective treatments for MM.

  9. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    Full Text Available Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1 as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  10. Aureobasidin A arrests growth of yeast cells through both ceramide intoxication and deprivation of essential inositolphosphorylceramides

    DEFF Research Database (Denmark)

    Cerantola, Vanessa; Guillas, Isabelle; Roubaty, Carole

    2009-01-01

    , 2Delta.YDC1 cells stop growing when exposed to Aureobasidin A (AbA), an inhibitor of the inositolphosphorylceramide synthase AUR1, yet their ceramide levels remain very low. This finding argues against a current hypothesis saying that yeast cells do not require inositolphosphorylceramides and die...... in the presence of AbA only because ceramides build up to toxic concentrations. Moreover, W303lag1Delta lac1Delta ypc1Delta ydc1Delta cells, reported to be AbA resistant, stop growing on AbA after a certain number of cell divisions, most likely because AbA blocks the biosynthesis of anomalous...... inositolphosphorylsphingosides. Thus, data argue that inositolphosphorylceramides of yeast, the equivalent of mammalian sphingomyelins, are essential for growth. Data also clearly confirm that wild-type strains, when exposed to AbA, immediately stop growing because of ceramide intoxication, long before...

  11. Overexpression of the promyelocytic leukemia gene suppresses growth of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis

    Institute of Scientific and Technical Information of China (English)

    HE Dalin 贺大林; NAN Xunyi 南勋义; Chang Kun-Song; WANG Yafeng 王亚峰; Chung Leland W.K.

    2003-01-01

    Objectives To examine the anti-oncogenic effects of promyelocytic leukemia (PML) on bladder cancer and to explore its molecular mechanisms of growth suppression.Methods Wild-type PML was transfected into bladder cancer cells (5637 cell) and expressed in a replication-deficient adenovirus-mediated gene delivery system and introduced into human bladder cancer cells (5637 cell) in vitro and in vivo. The effect and mechanisms of the PML gene in cell growth, clonogenicity, and tumorigenicity of bladder cancer cells were studied using in vitro and in vivo growth assays, soft agar colony-forming assay, cell cycle analysis, apoptosis assay and in vivo tumorigenicity assay.Results Overexpression of PML in 5637 cells significantly reduced their growth rate and clonogenicity on soft agar. PML suppressed bladder cancer cell growth by inducing G1 cell cycle arrest and apoptosis. Adenovirus-mediated PML (Ad-PML) significantly suppressed the tumorigenicity and growth of bladder cancer cells. Intratumoral injection of Ad-PML into tumors induced by 5637 cells dramatically suppressed their growth. Conclusions The results indicated that overexpression of PML protein may promote efficient growth inhibition of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis, and adenovirus-mediated PML (Ad-PML) expression efficiently suppresses human bladder cancer growth.

  12. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Bai-He Liu; Yao Li; Fang Liu; Jian Guo; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of growth inhibition ofhuman gastric cancer SGC-7901 cell with RRR-α-tocopherylsuccinate (VES), a derivative of natural Vitamin E, viainducing apoptosis and DNA synthesis arrest.METHODS: Human gastric cancer SGC-7901 cells wereregularly incubated in the presence of VES at 5, 10 and20mg@ L 1(VES was dissolved in absolute ethanol anddiluted in RPMI 1640 complete condition mediacorrespondingly to a final concentration of VES and 1mL@L-1 ethanol), succinic acid and ethanol equivalents asvehicle (VEH) control andcondition media only asuntreated (UT) control. Trypan blue dye exclusionanalysis and MTT assay were applied to detect the cellproliferation. 37kBq of tritiated thymidine was added tocells and [3H] TdR uptake was measured to observe DNAsynthesis. Apoptotic morphology was observed byelectron microscopy and DAPI staining. Flow cytometryand terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling (TUNEL) assay were performed to detectVES-triggered apoptosis.RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppressionby 24.7%, 49.2% and 68.7% following 24h of VEStreatment at 5, 10 and 20 mg@L 1, respectively, similar tothe findings from MTT assay. DNA synthesis wasevidently reduced by 35%, 45% and 98% after 24h VEStreatment at 20 mg@ L-1 and 48h at 10 and 20 mg@ L 1,respectively. VES induced SGC-7901 cells to undergoapoptosis with typically apoptotic characteristics,including morphological changes of chromatincondensation, chromatin crescent formation/margination,nucleus fragmentation and apoptotic body formation,typical apoptotic sub-G1 peak by flow cytometry andincrease of apoptotic cells by TUNEL assay in which 90%of cells underwent apoptosis after 48h of VES treatment at20 mcg@L-1.CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesisarrest. Inhibition of SGC-7901 cell growth by VES is dose-and time

  13. Growth arrest line mimicking lymphoma involvement: The findings of {sup 99m}Tc-MDP bone SPECT/CT and serial bone scan in a child with non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chan Woo; Kim, Ji Young; Choi, Yun Young; Lee, Seung Hun; Lee, Young Ho [Hanyang University Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on {sup 99m}Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.

  14. Growth Arrest Line Mimicking Lymphoma Involvement: The Findings of (99m)Tc-MDP Bone SPECT/CT and Serial Bone Scan in a Child with Non-Hodgkin's Lymphoma.

    Science.gov (United States)

    Kim, Chanwoo; Kim, Ji Young; Choi, Yun Young; Lee, Seunghun; Lee, Young-Ho

    2016-06-01

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on (99m)Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.

  15. Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis.

    Science.gov (United States)

    Chatterjee, Nirupama; Anwar, Tarique; Islam, Nashreen S; Ramasarma, T; Ramakrishna, Gayatri

    2016-09-01

    Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in GTPase activity of Rac1, accumulation of the reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV-mediated growth arrest was significantly abrogated in cells pre-treated with the N-acetylcysteine, Rac1 knocked down by siRNA and DPI an inhibitor of NADPH oxidase. In conclusion, our results show that polyacrylate derivative of peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1-NADPH oxidase leading to oxidative stress and DNA damage.

  16. Adaptation to optimal cell growth through self-organized criticality.

    Science.gov (United States)

    Furusawa, Chikara; Kaneko, Kunihiko

    2012-05-18

    A simple cell model consisting of a catalytic reaction network is studied to show that cellular states are self-organized in a critical state for achieving optimal growth; we consider the catalytic network dynamics over a wide range of environmental conditions, through the spontaneous regulation of nutrient transport into the cell. Furthermore, we find that the adaptability of cellular growth to reach a critical state depends only on the extent of environmental changes, while all chemical species in the cell exhibit correlated partial adaptation. These results are in remarkable agreement with the recent experimental observations of the present cells.

  17. Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis.

    Science.gov (United States)

    Qi, Runzi; An, Huazhang; Yu, Yizhi; Zhang, Minghui; Liu, Shuxun; Xu, Hongmei; Guo, Zhenghong; Cheng, Tao; Cao, Xuetao

    2003-12-01

    Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis; hence, perturbed Notch signaling may contribute to tumorigenesis. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in Africa and Asia. The mechanisms that orchestrate the multiple oncogenic insults required for initiation and progression of HCC are not clear. We constitutively overexpressed active Notch1 in human HCC to explore the effects of Notch1 signaling on HCC cell growth and to investigate the underlying molecular mechanisms. We show here that overexpression of Notch1 was able to inhibit the growth of HCC cells in vitro and in vivo. Biochemical analysis revealed the involvement of cell cycle regulated proteins in Notch1-mediated G(0)/G(1) arrest of HCC cells. Compared with green fluorescent protein (GFP) control, transient transfection of Notch1 ICN decreased expression of cyclin A (3.5-fold), cyclin D1 (2-fold), cyclin E (4.5-fold), CDK2 (2.8-fold), and the phosphorylated form of retinoblastoma protein (3-fold). Up-regulation of p21(waf/cip1) protein expression was observed in SMMC7721-ICN cells stably expressing active Notch1 but not in SMMC7721-GFP cells, which only express GFP. Furthermore, a 12-fold increase in p53 expression and an increase (4.8-fold) in Jun-NH(2)-terminal kinase activation were induced in SMMC7721-ICN cells compared with SMMC7721-GFP cells. In contrast, expression of the antiapoptotic Bcl-2 protein could not be detected in SMMC7721-ICN cells. These findings suggest that Notch1 signaling may participate in the development of HCC cells, affecting multiple pathways that control both cell proliferation and apoptosis.

  18. Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901

    Institute of Scientific and Technical Information of China (English)

    王宽; 张岂凡; 王锡山; 薛英威; 庞达; 傅松滨

    2004-01-01

    Background Peptide nucleic acid (PNA) has many characteristics useful in molecular biology. This paper described an effective way to raise the cell ingestion rate of PNA so as to kill gastric cancer cells.Methods Heteroduplexes of PNAs and oligonucleotides, wrapped by Lipofectamine 2000, were used to infect SGC7901 cells. The inhibitive effect of heteroduplexes was evaluated by analyzing cell clone forming and cell growth rate. Telomerase activity of SGC7901 cells was detected by polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) and silver staining assay.Results PNAs showed a dose-dependent inhibition of cell proliferation. The percentage of proliferation inhibition was 99.4% after 7 days; the rate of cloning inhibition was 98.2% after 8 days;whereas for oligonucleotide groups, at the same concentration, the percentages were 50. 1% and 67. 5% respectively. Antisense PNA-DNA-Lipofectamine 2000 group (AP-D-L group) exhibited significantly different percentages from the control groups (P<0.05). The test result indicated that telomerase activity of the AP-D-L group was inhibited (P<0.05). At the same time, the impact on cell morphology was observed.Conclusions The results showed that PNAs are potent antisense reagents. The telomeraseassociated therapies are very promising for the treatment of malignant tumours.

  19. Serum Growth Arrest Specific Protein 6 (Gas-6 Levels in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Fethullah Gerin

    2016-03-01

    Full Text Available Objective: We have investigated serum growth ar­rest-specific protein 6 (GAS-6 levels from patients with schizophrenia divided into acute phase remission phases as well as control group. Methods: This study was conducted in Psychiatry De­partment of Istanbul University Cerrahpasa Medical Fac­ulty. The patients who were diagnosed with schizophrenia after regular psychiatric examination according to DSM-IV criteria (n=22 as well as control subjects were includ­ed in the study. Schizophrenia patients with acute phase and remission phase were evaluated by Positive and Negative Syndrome Scale (PANSS and Clinical global Impression Scale (CGI-S. The serum GAS-6 levels of schizophrenia patients during acute phase and remission phase were compared with the serum GAS-6 levels of healthy controls. Serum GAS-6 levels were measured by commercial ELISA kits. Results: No difference was found in serum GAS-6 levels among the three groups; schizophrenia with acute phase, schizophrenia with remission phase, and controls. There were no correlations between serum GAS-6 levels and PANSS and CGI scores. Conclusion: To reach a definitive data and better in­terpretation about the relationship between GAS-6 and schizophrenia, future studies with larger groups of pa­tients with schizophrenia subdivided by drug naïve and treated with antipsychotics/other treatment modalities and controls are needed.

  20. Daily Arrests

    Data.gov (United States)

    Montgomery County of Maryland — This dataset provides the public with arrest information from the Montgomery County Central Processing Unit (CPU) systems. The data presented is derived from every...

  1. Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol

    Science.gov (United States)

    SONER, BURAK CEM; AKTUG, HUSEYIN; ACIKGOZ, EDA; DUZAGAC, FAHRIYE; GUVEN, UMMU; AYLA, SULE; CAL, CAG; OKTEM, GULPERI

    2014-01-01

    Flavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity, apoptosis and G1-phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)+high/CD44+high prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose- and time-dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere-forming assay. Flavopiridol was applied to monolayer cultures of CD133high/CD44high human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM. The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC50) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin-V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G0/G1 analysis showed a statistically significant difference between 100 and 500 nM (P<0.005), 100 and 1000 nM (P<0.001), 300 and 1000 nM (P<0.001), and 500 and 1000 nM (P<0.001). Flavopiridol also significantly influenced the cells in the G2/M phase, particularly at high-dose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC50 dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase-3, caspase-8 and p53. In conclusion, the present results indicated that flavopiridol could be a

  2. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Qinghe Chen

    Full Text Available BACKGROUND: Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Although resveratrol possesses chemopreventive properties against several cancers, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. The present study was carried out to examine whether PI3K/AKT/FOXO pathway mediates the biological effects of resveratrol. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors (LY294002 and Wortmannin and AKT inhibitor alone slightly induced apoptosis in LNCaP cells. These inhibitors further enhanced the apoptosis-inducing potential of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis. Wild type PTEN and PTEN-G129E enhanced resveratrol-induced apoptosis, whereas PTEN-G129R had no effect on proapoptotic effects of resveratrol. Furthermore, apoptosis-inducing potential of resveratrol was enhanced by dominant negative AKT, and inhibited by wild-type AKT and constitutively active AKT. Resveratrol has no effect on the expression of FKHR, FKHRL1 and AFX genes. The inhibition of FOXO phosphorylation by resveratrol resulted in its nuclear translocation, DNA binding and transcriptional activity. The inhibition of PI3K/AKT pathway induced FOXO transcriptional activity resulting in induction of Bim, TRAIL, p27/KIP1, DR4 and DR5, and inhibition of cyclin D1. Similarly, resveratrol-induced FOXO transcriptional activity was further enhanced when activation of PI3K/AKT pathway was blocked. Over-expression of phosphorylation deficient mutants of FOXO proteins (FOXO1-TM, FOXO3A-TM and FOXO4-TM induced FOXO transcriptional activity, which was further enhanced by resveratrol. Inhibition of FOXO transcription factors by shRNA blocked resveratrol-induced upregulation of Bim, TRAIL, DR4, DR5, p27/KIP1 and

  3. Proximate causes of adaptive growth rates: growth efficiency variation among latitudinal populations of Rana temporaria.

    Science.gov (United States)

    Lindgren, B; Laurila, A

    2005-07-01

    In ectothermic organisms, declining season length and lower temperature towards higher latitudes often select for latitudinal variation in growth and development. However, the energetic mechanisms underlying this adaptive variation are largely unknown. We investigated growth, food intake and growth efficiency of Rana temporaria tadpoles from eight populations along a 1500 km latitudinal gradient across Sweden. To gain an insight into the mechanisms of adaptation at organ level, we also examined variation in tadpole gut length. The tadpoles were raised at two temperatures (16 and 20 degrees C) in a laboratory common garden experiment. We found increased growth rate towards higher latitudes, regardless of temperature treatment. This increase in growth was not because of a higher food intake rate, but populations from higher latitudes had higher growth efficiency, i.e. they were more efficient at converting ingested food into body mass. Low temperature reduced growth efficiency most strongly in southern populations. Relative gut length increased with latitude, and tadpoles at low temperature tended to have longer guts. However, variation in gut length was not the sole adaptive explanation for increased growth efficiency as latitude and body length still explained significant amounts of variation in growth efficiency. Hence, additional energetic adaptations are probably involved in growth efficiency variation along the latitudinal gradient.

  4. Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Rui Zhao

    2016-01-01

    Full Text Available Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6, is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD. We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl−1 (P < 0.001 and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml−1 (P < 0.001 in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.

  5. Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification.

    Science.gov (United States)

    Son, Bo-Kyung; Akishita, Masahiro; Iijima, Katsuya; Ogawa, Sumito; Maemura, Koji; Yu, Jing; Takeyama, Kenichi; Kato, Shigeaki; Eto, Masato; Ouchi, Yasuyoshi

    2010-03-05

    Recent epidemiological studies have found that androgen deficiency is associated with a higher incidence of cardiovascular disease in men. However, little is known about the mechanism underlying the cardioprotective effects of androgens. Here we show the inhibitory effects of testosterone on vascular calcification and a critical role of androgen receptor (AR)-dependent transactivation of growth arrest-specific gene 6 (Gas6), a key regulator of inorganic phosphate (P(i))-induced calcification of vascular smooth muscle cells (VSMC). Testosterone and nonaromatizable androgen dihydrotestosterone inhibited P(i)-induced calcification of human aortic VSMC in a concentration-dependent manner. Androgen inhibited P(i)-induced VSMC apoptosis, an essential process for VSMC calcification. The effects on VSMC calcification were mediated by restoration of P(i)-induced down-regulation of Gas6 expression and a subsequent reduction of Akt phosphorylation. These effects of androgen were blocked by an AR antagonist, flutamide, but not by an estrogen receptor antagonist, ICI 182,780. We then explored the mechanistic role of the AR in Gas6 expression and found an abundant expression of AR predominantly in the nucleus of VSMC and two consensus ARE sequences in the Gas6 promoter region. Dihydrotestosterone stimulated Gas6 promoter activity, and this effect was abrogated by flutamide and by AR siRNA. Site-specific mutation revealed that the proximal ARE was essential for androgen-dependent transactivation of Gas6. Furthermore, chromatin immunoprecipitation assays demonstrated ligand-dependent binding of the AR to the proximal ARE of Gas6. These results indicate that AR signaling directly regulates Gas6 transcription, which leads to inhibition of vascular calcification, and provides a mechanistic insight into the cardioprotective action of androgens.

  6. LKB1 Haploinsufficiency Cooperates With Kras to Promote Pancreatic Cancer Through Suppression of p21-Dependent Growth Arrest

    Science.gov (United States)

    Morton, Jennifer P.; Jamieson, Nigel B.; Karim, Saadia A.; Athineos, Dimitris; Ridgway, Rachel A.; Nixon, Colin; McKay, Colin J.; Carter, Ross; Brunton, Valerie G.; Frame, Margaret C.; Ashworth, Alan; Oien, Karin A.; Evans, T.R. Jeffry; Sansom, Owen J.

    2010-01-01

    Background & Aims Patients carrying germline mutations of LKB1 have an increased risk of pancreatic cancer; however, it is unclear whether down-regulation of LKB1 is an important event in sporadic pancreatic cancer. In this study, we aimed to investigate the impact of LKB1 down-regulation for pancreatic cancer in mouse and human and to elucidate the mechanism by which Lkb1 deregulation contributes to this disease. Methods We first investigated the consequences of Lkb1 deficiency in a genetically modified mouse model of pancreatic cancer, both in terms of disease progression and at the molecular level. To test the relevance of our findings to human pancreatic cancer, we investigated levels of LKB1 and its potential targets in human pancreatic cancer. Results We definitively show that Lkb1 haploinsufficiency can cooperate with oncogenic KrasG12D to cause pancreatic ductal adenocarcinoma (PDAC) in the mouse. Mechanistically, this was associated with decreased p53/p21-dependent growth arrest. Haploinsufficiency for p21 (Cdkn1a) also synergizes with KrasG12D to drive PDAC in the mouse. We also found that levels of LKB1 expression were decreased in around 20% of human PDAC and significantly correlated with low levels of p21 and a poor prognosis. Remarkably, all tumors that had low levels of LKB1 had low levels of p21, and these tumors did not express mutant p53. Conclusions We have identified a novel LKB1-p21 axis that suppresses PDAC following Kras mutation in vivo. Down-regulation of LKB1 may therefore serve as an alternative to p53 mutation to drive pancreatic cancer in vivo. PMID:20452353

  7. Health, growth and psychosocial adaptation of immigrant children.

    Science.gov (United States)

    Gualdi-Russo, Emanuela; Toselli, Stefania; Masotti, Sabrina; Marzouk, Diaa; Sundquist, Kristina; Sundquist, Jan

    2014-08-01

    The increasing population diversity in Europe demands clarification of possible ethnic influences on the growth and health of immigrant children and their psychosocial adaptation to the host countries. This article assesses recent data on immigrant children in Europe in comparison to European natives by means of a systematic review of the literature on growth patterns and data on children's health and adaptation. There were wide variations across countries in growth patterns and development of immigrant children and natives, with different trends in Central and Northern Europe with respect to Southern Europe. In general, age at menarche was lower in immigrant girls, while male pubertal progression seemed faster in immigrants than in European natives, even when puberty began after. Owing to the significant differences in anthropometric traits (mainly stature and weight), new reference growth curves for immigrant children were constructed for the largest minority groups in Central Europe. Possible negative effects on growth, health and psychosocial adaptation were pointed out for immigrant children living in low income, disadvantaged communities with a high prevalence of poor lifestyle habits. In conclusion, this review provides a framework for the health and growth of immigrant children in Europe in comparison to native-born children: the differences among European countries in growth and development of migrants and non-migrants are closely related to the clear anthropological differences among the ethnic groups due to genetic influences. Higher morbidity and mortality was frequently associated with the minority status of these children and their low socio-economic status. The observed ethnic differences in health reveal the need for adequate health care in all groups. Therefore, we provide suggestions for the development of health care strategies in Europe.

  8. A class of DNA-binding peptides from wheat bud causes growth inhibition, G2 cell cycle arrest and apoptosis induction in HeLa cells

    Directory of Open Access Journals (Sweden)

    Elgjo Kjell

    2009-07-01

    Full Text Available Abstract Background Deproteinized DNA from eukaryotic and prokaryotic cells still contains a low-molecular weight peptidic fraction which can be dissociated by alkalinization of the medium. This fraction inhibits RNA transcription and tumor cell growth. Removal from DNA of normal cells causes amplification of DNA template activity. This effect is lower or absent in several cancer cell lines. Likewise, the amount of active peptides in cancer cell DNA extracts is lower than in DNA preparation of the corresponding normal cells. Such evidence, and their ubiquitous presence, suggests that they are a regulatory, conserved factor involved in the control of normal cell growth and gene expression. Results We report that peptides extracted from wheat bud chromatin induce growth inhibition, G2 arrest and caspase-dependent apoptosis in HeLa cells. The growth rate is decreased in cells treated during the S phase only and it is accompanied by DNA damage and DNA synthesis inhibition. In G2 cells, this treatment induces inactivation of the CDK1-cyclin B1 complex and an increase of active chk1 kinase expression. Conclusion The data indicate that the chromatin peptidic pool inhibits HeLa cell growth by causing defective DNA replication which, in turn, arrests cell cycle progression to mitosis via G2 checkpoint pathway activation.

  9. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    V. Vucic

    2006-02-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  10. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Vucic V.

    2006-01-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  11. Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1 in hepatic cell proliferation at mononucleosomal resolution.

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    Natalia Sacilotto

    Full Text Available BACKGROUND: Gas1 (growth arrest-specific 1 gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real time by quantifying the presence of RNA polymerase II in coding regions (RNApol-ChIP. It has been found that Gas1 is expressed not only in quiescent liver but also at the cell cycle G(1/S transition. The latter expression peak had not been previously reported. Two nucleosomes, flanking a nucleosome-free region, are positioned close to the transcription start site. Both nucleosomes slide in going from the active to the inactive state and vice versa. Nuc-ChIP analysis of the acquisition of histone epigenetic marks show distinctive features in both active states: H3K9ac and H3K4me2 are characteristic of transcription in G(0 and H4R3me2 in G(1/S transition. Sequential-ChIP analysis revealed that the "repressing" mark H3K9me2 colocalize with several "activating" marks at nucleosome N-1 when Gas1 is actively transcribed suggesting a greater plasticity of epigenetic marks than proposed until now. The recruitment of chromatin-remodeling or modifying complexes also displayed distinct characteristics in quiescence and the G(1/S transition. CONCLUSIONS/SIGNIFICANCE: The finding that Gas1 is transcribed at the G(1/S transition suggests that the gene may exert a novel function during cell proliferation. Transcription of this gene is modulated by specific "activating" and

  12. Sarsaparilla (Smilax Glabra Rhizome) Extract Inhibits Cancer Cell Growth by S Phase Arrest, Apoptosis, and Autophagy via Redox-Dependent ERK1/2 Pathway.

    Science.gov (United States)

    She, Tiantian; Qu, Like; Wang, Lixin; Yang, Xingxin; Xu, Shuo; Feng, Junnan; Gao, Yujing; Zhao, Chuanke; Han, Yong; Cai, Shaoqing; Shou, Chengchao

    2015-05-01

    Cancer is still the major cause of death across the world. Regular approaches cannot effectively solve the emerging problems, including drug/radiation resistance, side effects, and therapeutic ineffectiveness. Natural dietary supplements have shown effectiveness in the prevention and treatment of cancer. Sarsaparilla (Smilax Glabra Rhizome) has growth-inhibitory effects on several cancer cell lines in vitro and in vivo, with little toxicity on normal cells. However, the mechanism underlying its function remains elusive. In the present study, we examined the anticancer activity of the supernatant of the water-soluble extract (SW) from sarsaparilla. Liquid chromatography/mass spectrometry-ion trap-time-of-flight (LC/MS-IT-TOF) analysis identified flavonoids, alkaloids, and phenylpropanoids as the major bioactive components of SW. SW was shown to markedly inhibit the growth of a broad spectrum of cancer cell lines in the in vitro and in vivo assays. S phase arrest, autophagy, or/and apoptosis were partly responsible for SW-induced growth inhibition. Results of microarray analysis and validation by quantitative RT-PCR indicated the involvement of oxidative stress and the MAPK1 pathway in SW-treated cells. We further found that SW destroyed intracellular-reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and supplement with N-acetylcysteine (NAC) or glutathione (GSH) significantly antagonized SW-induced S phase arrest, apoptosis, and autophagy. In addition, SW-induced GSH/GSSG imbalance activated the ERK1/2 pathway, which contributed to SW-induced S phase arrest, apoptosis, autophagy, and resultant growth-inhibitory effect. Together, our results provide a molecular basis for sarsaparilla as an anticancer agent.

  13. Growth inhibitory effect of KYKZL-1 on Hep G{sub 2} cells via inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jing; Du, Yi-Fang; Xiao, Zhi-Yi; Pan, Li-Li; Li, Wei; Huan, Lin; Gong, Zhu-Nan [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Wei, Shao-Hua [College of Chemistry and Materials Science, Nanjing Normal University, Nanjing (China); Huang, Shi-Qian; Xun, Wei; Zhang, Yi; Chang, Lei-Lei; Xie, Meng-Yu [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Ao, Gui-Zhen [Department of Medicinal Chemistry, School of Pharmacy, Soochow University, Jiangsu (China); Cai, Jie; Qiu, Ting; Wu, Hao; Sun, Ting [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Xu, Guang-Lin, E-mail: xudunlop@126.com [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Department of Pharmacology, University of Michigan, Ann Arbor (United States)

    2014-01-01

    KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the inhibitory activity test on Hep G{sub 2} growth. We found that KYKZL-1 inhibited the growth of Hep G{sub 2} cells via inducing apoptosis. Further studies showed that KYKZL-1 activated caspase-3 through cytochrome c release from mitochondria and down regulation of Bcl-2/Bax ratio and reduced the high level of COX-2 and 5-LOX. As shown in its anti-inflammatory effect, KYKZL-1 also exhibited inhibitory effect on the PGE{sub 2} and LTB{sub 4} production in Hep G{sub 2} cells. Accordingly, exogenous addition of PGE{sub 2} or LTB{sub 4} reversed the decreases in cell viability. In addition, KYKZL-1 caused cell cycle arrest at the S–G{sub 2} checkpoint via the activation of p21{sup CIP1} protein and down-regulation of cyclin A expression. These data indicate that the growth inhibitory effect of KYKZL-1 is associated with inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest. Combined with our previous findings, KYKZL-1 exhibiting COX/5-LOX inhibition may be a promising potential agent not only for inflammation control but also for cancer prevention/therapy with an enhanced gastric safety profile. - Highlights: • KYKZL-1 is designed to exhibit COX/5-LOX dual inhibition. • KYKZL-1 resulted in apoptosis of Hep G{sub 2} cells. • KYKZL-1 activated caspase-3 through cytochrome c and bcl-2/bax ratio. • KYKZL-1 caused cell cycle arrest via modulation of p21{sup CIP1} and cyclin A level.

  14. Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.

    Science.gov (United States)

    Cai, Xianbin; Hu, Xi; Tan, Xiaojun; Cheng, Weijie; Wang, Qinjia; Chen, Xiaofeng; Guan, Yinghong; Chen, Chong; Jing, Xubin

    2015-01-01

    Esophageal squamous cell carcinomas (ESCC) have become a severe threat to health and the current treatments for ESCC are frequently not effective. Recent epidemiological studies suggest that the anti-hyperglycemic agent metformin may reduce the risk of developing cancer, including ESCC, among diabetic patients. However, the antitumor effects of metformin on ESCC and the mechanisms underlying its cell cycle regulation remain elusive. The findings reported herein show that the anti-proliferative action of metformin on ESCC cell lines is partially mediated by AMPK. Moreover, we observed that metformin induced G0/G1 phase arrest accompanied by the up-regulation of p21CIP1 and p27KIP1. In vivo experiments further showed that metformin inhibited tumor growth in a ESCC xenograft model. Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo. In conclusion, metformin inhibits the growth of ESCC cells both in cell cultures and in an animal model. AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC. These findings indicate that metformin has the potential for use in the treatment of ESCC.

  15. An Eden model for the growth of adaptive networks

    Science.gov (United States)

    Meakin, Paul

    1991-12-01

    An adaptive growth model based on the Eden model has been investigated using computer simulations. In this model a “score” associated with all the sites along the shortest path from the newly added site to the initial seed or growth site is incremented by an amount δ 1 ( δ1=1/( l+1) η where l is the path length) and the score associated with all the sites in the cluster is decreased by a fixed amount δ2 ( δ2=1/ Nm) after each growth event. If the score associated with a site falls below zero it is removed from the cluster. In the asymptotic limit ( t→∞ where t is the number of growth events) the cluster size fluctuates about a constant value proportional to N vm where the exponent v is given by the empirical relationship v=2/(2+ η), which is supported by simple theoretical considerations. The growth of the number of occupied sites, s( t), can be represented by the scaling form s( t) = N vm ƒ(t/N vm) .

  16. Effects of 50 Hz pulsed electromagnetic fields on the growth and cell cycle arrest of mesenchymal stem cells: an in vitro study.

    Science.gov (United States)

    Li, Xinping; Zhang, Mingsheng; Bai, Liming; Bai, Wenfang; Xu, Weicheng; Zhu, Hongxiang

    2012-12-01

    Mesenchymal stem cells (MSCs) are capable of self-renew and multipotent differatiation which allows them to be sensitive to microenvironment is altered. Pulsed electromagnetic fields (PEMF) can affect cellular physiology of some types of cells. This study was undertaken to investigate the effects of PEMF on the growth and cell cycle arrest of MSCs expanded in vitro. To achieve this, cultured of normal rat MSCs, the treatment groups were respectively irradiated by 50 Hz PEMF at 10 mT of flux densities for 3 or 6 h. The effects of PEMF on cell proliferation, cell cycle arrest, and cell surface antigen phenotype were investigated. Our results showed that exposed MSCs had a significant proliferative capacity (P cell growth was not different (P>0.05) at an earlier phase after PEMF treatment. Exposure to PEMF had a significant increase the percentage of MSCs in G1 phase compare with the control group, with a higher percentage of cells in G1 phase exposed for 6 h then that for 3 h. At the 16th hour after treatment, PEMF had no significant effect on cell proliferation and cell cycle (P>0.05). These results suggested that PEMF enhanced MSCs proliferation with time-independent and increased the percentage of cells at the G1 phase of the cell cycle in a time-dependent manner, and the effect of PEMF on the cell proliferation and cell cycle arrest of MSCs was temporal after PEMF treatment.

  17. Adapting to Population Growth: The Evolutionary Alternative to Malthus

    Directory of Open Access Journals (Sweden)

    Axel Kristinsson

    2016-06-01

    Full Text Available A long-standing debate on the dynamics of population growth in human history has become polarized between a Malthusian stance and a Boserupian one. The former tends to view population growth as limited by carrying capacity, dependent on environment and technology, whereas the latter sees population growth itself as a major inducement to social, economic and technological developments. In this paper the authors experiment with approaching this debate by using recent developments in evolutionary theory. According to these, evolutionary principles, as expounded by Charles Darwin and subsequent evolutionary scientists, apply not only to biological evolution but also to social or cultural evolution. Here, the role of genes is taken over by culture and, since culture is much more pliable than our DNA, evolution speeds up. As the only organisms on Earth whose evolution relies as heavily on culture as on genes, humans have become extremely adaptable. Their hyper-adaptability suggest that humans, through their cultural evolution, have managed increasingly to adapt to their own growing population, thus succeeding in accommodating ever-growing numbers. This hypothesis fits the Boserupian approach to population very well but less so the Malthusian one, perhaps indicating a gradual shift from a Malthusian regime to a Boserupian one in human history. The hypothesis is discussed and examined through four case studies: The beginning of farming around Göbekli Tepe in southeast Turkey, the productive farming systems of Tiwanaku in South America, the population crisis of late medieval and early modern Iceland, and the ‘collapse’ of Rapa Nui (Easter Island.

  18. Fibroblast growth factor 2 causes G2/M cell cycle arrest in ras-driven tumor cells through a Src-dependent pathway.

    Directory of Open Access Journals (Sweden)

    Jacqueline Salotti

    Full Text Available We recently reported that paracrine Fibroblast Growth Factor 2 (FGF2 triggers senescence in Ras-driven Y1 and 3T3(Ras mouse malignant cell lines. Here, we show that although FGF2 activates mitogenic pathways in these Ras-dependent malignant cells, it can block cell proliferation and cause a G2/M arrest. These cytostatic effects of FGF2 are inhibited by PD173074, an FGF receptor (FGFR inhibitor. To determine which downstream pathways are induced by FGF2, we tested specific inhibitors targeting mitogen-activated protein kinase (MEK, phosphatidylinositol 3 kinase (PI3K and protein kinase C (PKC. We show that these classical mitogenic pathways do not mediate the cytostatic activity of FGF2. On the other hand, the inhibition of Src family kinases rescued Ras-dependent malignant cells from the G2/M irreversible arrest induced by FGF2. Taken together, these data indicate a growth factor-sensitive point in G2/M that likely involves FGFR/Ras/Src pathway activation in a MEK, PI3K and PKC independent manner.

  19. The microRNA 424/503 cluster reduces CDC25A expression during cell cycle arrest imposed by transforming growth factor β in mammary epithelial cells.

    Science.gov (United States)

    Llobet-Navas, David; Rodriguez-Barrueco, Ruth; de la Iglesia-Vicente, Janis; Olivan, Mireia; Castro, Veronica; Saucedo-Cuevas, Laura; Marshall, Netonia; Putcha, Preeti; Castillo-Martin, Mireia; Bardot, Evan; Ezhkova, Elena; Iavarone, Antonio; Cordon-Cardo, Carlos; Silva, Jose M

    2014-12-01

    Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor β (TGF-β) in the mammary epithelium. Induction of this microRNA cluster impacts mammary epithelium fate by regulating apoptosis and insulin-like growth factor 1 (IGF1) signaling. Here, we expanded our finding to demonstrate that miR-424(322)/503 is an integral component of the cell cycle arrest mediated by TGF-β. Mechanistically, we showed that after TGF-β exposure, increased levels of miR-424(322)/503 reduce the expression of the cell cycle regulator CDC25A. miR-424(322)/503-dependent posttranscriptional downregulation of CDC25A cooperates with previously described transcriptional repression of the CDC25A promoter and proteasome-mediated degradation to reduce the levels of CDC25A expression and to induce cell cycle arrest. We also provide evidence that the TGF-β/miR-424(322)/503 axis is part of the mechanism that regulates the proliferation of hormone receptor-positive (HR(+)) mammary epithelial cells in vivo.

  20. The MicroRNA 424/503 Cluster Reduces CDC25A Expression during Cell Cycle Arrest Imposed by Transforming Growth Factor β in Mammary Epithelial Cells

    Science.gov (United States)

    Rodriguez-Barrueco, Ruth; de la Iglesia-Vicente, Janis; Olivan, Mireia; Castro, Veronica; Saucedo-Cuevas, Laura; Marshall, Netonia; Putcha, Preeti; Castillo-Martin, Mireia; Bardot, Evan; Ezhkova, Elena; Iavarone, Antonio; Cordon-Cardo, Carlos

    2014-01-01

    Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor β (TGF-β) in the mammary epithelium. Induction of this microRNA cluster impacts mammary epithelium fate by regulating apoptosis and insulin-like growth factor 1 (IGF1) signaling. Here, we expanded our finding to demonstrate that miR-424(322)/503 is an integral component of the cell cycle arrest mediated by TGF-β. Mechanistically, we showed that after TGF-β exposure, increased levels of miR-424(322)/503 reduce the expression of the cell cycle regulator CDC25A. miR-424(322)/503-dependent posttranscriptional downregulation of CDC25A cooperates with previously described transcriptional repression of the CDC25A promoter and proteasome-mediated degradation to reduce the levels of CDC25A expression and to induce cell cycle arrest. We also provide evidence that the TGF-β/miR-424(322)/503 axis is part of the mechanism that regulates the proliferation of hormone receptor-positive (HR+) mammary epithelial cells in vivo. PMID:25266660

  1. Analysis on environmental factors of embryo growth arrest%胚胎停止发育的环境影响因素分析

    Institute of Scientific and Technical Information of China (English)

    杨正爱; 田旭光

    2012-01-01

    目的:探讨各种环境因素对胚胎发育的影响,为预防胚胎停止发育提供依据.方法:采用自行设计的问卷进行调查,分析比较188例诊断为早期胚胎停止发育患者和281例正常流产妇女的一般情况、饮食习惯、生活习惯、家庭环境、职业环境、心理健康状况和人际关系对胚胎停止发育的影响.结果:单因素分析显示,年龄、怀孕次数、情绪控制能力、精神压力、值夜班、补充叶酸、是否饮茶、是否吸烟、携带手机时间、使用微波炉或电磁炉、接触震动及接触电磁辐射是胚胎停止发育的影响因素(P<0.05);多因素分析显示,补充叶酸(OR=2.514)、是否吸烟(OR=4.254)及接触电磁辐射(OR=4.998)是主要影响因素.结论:胚胎停止发育是多种因素综合影响的结果.孕期叶酸的补充、戒烟及远离电磁辐射是重要的预防措施.%Objective; To explore the effect of various environmental factors on embryonic development, provide a basis for preventing embryo growth arrest. Methods: A self - designed questionnaire was used to survey, analyze, and compare the effects of general condition, dietary habits, living habits, family environment, occupational environment, psychological health status, and interpersonal relationship of 188 patients diagnosed as early embryo growth arrest and 281 normal women undergoing abortion on embryo growth arrest Results: Univa-riate analysis showed that age, times of pregnancy, emotional control, stress, night shift, supplementing folic acid, tea - drinking or not, smoking or not, carrying mobile phones, using a microwave oven or cooker, exposure to vibration, and exposure to electromagnetic radiation were influencing factors of embryo growth arrest ( P < 0. 05 ) ; multivariate analysis showed that supplementing folic acid ( OR= 2. 514 ) , smoking or not ( OR = 4. 254) , and exposure to electromagnetic radiation ( OR = 4. 998 ) were main influencing factors. Conclusion

  2. Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress.

    Science.gov (United States)

    Yaffe, Paul B; Power Coombs, Melanie R; Doucette, Carolyn D; Walsh, Mark; Hoskin, David W

    2015-10-01

    Piperine, a piperidine alkaloid present in black pepper, inhibits the growth of cancer cells, although the mechanism of action is not well understood. In this study, we show that piperine (75-150 µM) inhibited the growth of several colon cancer cell lines but had little effect on the growth of normal fibroblasts and epithelial cells. Piperine inhibited HT-29 colon carcinoma cell proliferation by causing G1 phase cell cycle arrest that was associated with decreased expression of cyclins D1 and D3 and their activating partner cyclin-dependent kinases 4 and 6, as well as reduced phosphorylation of the retinoblastoma protein and up-regulation of p21/WAF1 and p27/KIP1 expression. In addition, piperine caused hydroxyl radical production and apoptosis that was partially dependent on the production of reactive oxygen species. Piperine-treated HT-29 cells showed loss of mitochondrial membrane integrity and cleavage of poly (ADP-ribose) polymerase-1, as well as caspase activation and reduced apoptosis in the presence of the pan-caspase inhibitor zVAD-FMK. Increased expression of the endoplasmic reticulum stress-associated proteins inositol-requiring 1α protein, C/EBP homologous protein, and binding immunoglobulin protein, and activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, as well as decreased phosphorylation of Akt and reduced survivin expression were also observed in piperine-treated HT-29 cells. Furthermore, piperine inhibited colony formation by HT-29 cells, as well as the growth of HT-29 spheroids. Cell cycle arrest and endoplasmic reticulum stress-associated apoptosis following piperine treatment of HT-29 cells provides the first evidence that piperine may be useful in the treatment of colon cancer.

  3. Tanshinone IIA Inhibits Growth of Keratinocytes through Cell Cycle Arrest and Apoptosis: Underlying Treatment Mechanism of Psoriasis

    Directory of Open Access Journals (Sweden)

    Fu-Lun Li

    2012-01-01

    Full Text Available The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE, and flow cytometry methods. Apoptosis was partially blocked by the caspase-3 inhibitor Ac-DEVD-CHO. Mitochondrial regulation of apoptosis further downstream was investigated, showing changes in the mitochondrial membrane potential, cytochrome c release into the cytoplasm, and enhanced activation of cleaved caspase-3 and Poly ADP-ribose polymerase (PARP. There was also no translocation of apoptosis-inducing factor (AIF from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. Our findings provide the molecular mechanisms by which Tan IIA can be used to treat psoriasis and support the traditional use of Salvia miltiorrhiza Bungee (Labiatae for psoriasis and related skin diseases.

  4. Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway.

    Science.gov (United States)

    Wu, Chien-Ting; Lin, Tung-Yi; Hsu, Hsien-Yeh; Sheu, Fuu; Ho, Chau-Mei; Chen, Edmund I-T

    2011-12-01

    Ling Zhi-8 (LZ-8), an immunomodulatory protein, is derived from and has been cloned from the medicinal mushroom Ganoderma lucidum (Reishi or Ling Zhi); this protein exhibits immunomodulating and antitumor properties. We investigated the effects of recombinant LZ-8 protein (rLZ-8) on the proliferation of A549 human lung cancer cells. Here, we showed that rLZ-8 inhibits cell growth and that this is correlated with increased G(1) arrest. The treatment of A549 cells with rLZ-8 activated p53 and p21 expression, and both the G(1) arrest and the antigrowth effect were found to be p53 dependent. It was further demonstrated that rLZ-8 inhibited tumor growth in mice transplanted with Lewis lung carcinoma cells. Interestingly, rLZ-8 treatment was found to lead to nucleolar stress (or ribosomal stress) as evidenced by inhibition of precursor ribosomal RNA synthesis and reduced polysome formation in A549 cells. These changes resulted in an increasing binding of ribosomal protein S7 to MDM2 and a decreased interaction between MDM2 and p53. Taking these results together, we have identified a novel rLZ-8 antitumor function that positively modulates p53 via ribosomal stress and inhibits lung cancer cell growth in vitro and in vivo. Our current results suggest that rLZ-8 may have potential as a therapeutic intervention for the treatment of cancers that contain wild-type p53 and high expression of MDM2.

  5. 6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest.

    Science.gov (United States)

    Lin, Ching-Bin; Lin, Chun-Che; Tsay, Gregory J

    2012-01-01

    6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27(Kip1) and p21(Cip1) were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS) and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27(Kip1), and p21(Cip1) levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.

  6. 6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

    Directory of Open Access Journals (Sweden)

    Ching-Bin Lin

    2012-01-01

    Full Text Available 6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs, and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27Kip1 and p21Cip1 were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27Kip1, and p21Cip1 levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.

  7. Wogonoside induces growth inhibition and cell cycle arrest via promoting the expression and binding activity of GATA-1 in chronic myelogenous leukemia cells.

    Science.gov (United States)

    Li, Hui; Hui, Hui; Xu, Jingyan; Yang, Hao; Zhang, Xiaoxiao; Liu, Xiao; Zhou, Yuxin; Li, Zhiyu; Guo, Qinglong; Lu, Na

    2016-06-01

    GATA-1, a zinc finger transcription factor, has been demonstrated to play a key role in the progression of leukemia. In this study, we investigate the effects of wogonoside, a naturally bioactive flavonoid derived from Scutellaria baicalensis Georgi, on cell growth and cell cycle in chronic myeloid leukemia (CML) cells, and uncover its underlying mechanisms. The experimental design comprised CML cell lines K562, imatinib-resistant K562 (K562r) cells, and primary CML cells, treated in vitro or in vivo, respectively, with wogonoside; growth and cell cycle were then evaluated. We found that wogonoside could induce growth inhibition and G0/G1 cell cycle arrest in both normal and K562r cells. Wogonoside promotes the expression of GATA-1 and facilitates the binding to methyl ethyl ketone (MEK) and p21 promoter, thus inhibiting MEK/extracellular signal-regulated kinase signaling and cell cycle checkpoint proteins, including CDK2, CDK4, cyclin A, and cyclin D1, and increasing p21 expression. Furthermore, in vivo studies showed that administration of wogonoside decreased CML cells and prolonged survival in NOD/SCID mice with CML cell xenografts. In conclusion, these results clearly revealed the inhibitory effect of wogonoside on the growth in CML cells and suggested that wogonoside may act as a promising drug for the treatment of imatinib-resistant CML.

  8. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

    Directory of Open Access Journals (Sweden)

    Nan Hua

    Full Text Available Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs. In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.

  9. UV-B inhibition of hypocotyl growth in etiolated Arabidopsis thaliana seedlings is a consequence of cell cycle arrest initiated by photodimer accumulation.

    Science.gov (United States)

    Biever, Jessica J; Brinkman, Doug; Gardner, Gary

    2014-06-01

    Ultraviolet (UV) radiation is an important constituent of sunlight that determines plant morphology and growth. It induces photomorphogenic responses but also causes damage to DNA. Arabidopsis mutants of the endonucleases that function in nucleotide excision repair, xpf-3 and uvr1-1, showed hypersensitivity to UV-B (280-320nm) in terms of inhibition of hypocotyl growth. SOG1 is a transcription factor that functions in the DNA damage signalling response after γ-irradiation. xpf mutants that carry the sog1-1 mutation showed hypocotyl growth inhibition after UV-B irradiation similar to the wild type. A DNA replication inhibitor, hydroxyurea (HU), also inhibited hypocotyl growth in etiolated seedlings, but xpf-3 was not hypersensitive to HU. UV-B irradiation induced accumulation of the G2/M-specific cell cycle reporter construct CYCB1;1-GUS in wild-type Arabidopsis seedlings that was consistent with the expected accumulation of photodimers and coincided with the time course of hypocotyl growth inhibition after UV-B treatment. Etiolated mutants of UVR8, a recently described UV-B photoreceptor gene, irradiated with UV-B showed inhibition of hypocotyl growth that was not different from that of the wild type, but they lacked UV-B-specific expression of chalcone synthase (CHS), as expected from previous reports. CHS expression after UV-B irradiation was not different in xpf-3 compared with the wild type, nor was it altered after HU treatment. These results suggest that hypocotyl growth inhibition by UV-B light in etiolated Arabidopsis seedlings, a photomorphogenic response, is dictated by signals originating from UV-B absorption by DNA that lead to cell cycle arrest. This process occurs distinct from UVR8 and its signalling pathway responsible for CHS induction.

  10. Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

    Science.gov (United States)

    Zhang, Jian; Wei, Wei; Jin, Hui-Cheng; Ying, Rong-Chao; Zhu, A-Kao; Zhang, Fang-Jie

    2015-01-01

    Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

  11. Neferine, an alkaloid from lotus seed embryo, inhibits human lung cancer cell growth by MAPK activation and cell cycle arrest.

    Science.gov (United States)

    Poornima, Paramasivan; Weng, Ching Feng; Padma, Viswanadha Vijaya

    2014-01-01

    Neferine is the major bisbenzylisoquinoline alkaloid isolated from the seed embryo of a traditional medicinal plant Nelumbo nucifera (Lotus). Epidemiological studies have revealed the therapeutic potential of lotus seed embryo. Although several mechanisms have been proposed, a clear anticancer action mechanism of neferine on lung cancer cells is still not known. Lung cancer is the most common cause of cancer death in the world, and the patients with advanced stage of nonsmall lung cancer require adjunct chemotherapy after surgical resection for the eradication of cancer cells. In this study, the effects of neferine were evaluated and characterized in A549 cells. Neferine induced apoptosis in a dose-dependent manner with the hypergeneration of reactive oxygen species, activation of MAPKs, lipid peroxidation, depletion of cellular antioxidant pool, loss of mitochondrial membrane potential, and intracellular calcium accumulation. Furthermore, neferine treatment leads to the inhibition of nuclear factor kappaB and Bcl2, upregulation of Bax and Bad, release of cytochrome C, activation of caspase cascade, and DNA fragmentation. In addition, neferine could induce p53 and its effector protein p21 and downregulation of cell cycle regulatory protein cyclin D1 thereby inducing G1 cell cycle arrest. These results suggest a novel function of neferine as an apoptosis inducer in lung cancer cells.

  12. The adenovirus E4orf4 protein induces growth arrest and mitotic catastrophe in H1299 human lung carcinoma cells.

    Science.gov (United States)

    Li, S; Szymborski, A; Miron, M-J; Marcellus, R; Binda, O; Lavoie, J N; Branton, P E

    2009-01-22

    The human adenovirus E4orf4 protein, when expressed alone, induces p53-independent death in a wide range of cancer cells. Earlier studies by our groups suggested that although in some cases cell death can be associated with some hallmarks of apoptosis, it is not always affected by caspase inhibitors. Thus it is unlikely that E4orf4-induced cell death occurs uniquely through apoptosis. In the present studies using H1299 human lung carcinoma cells as a model system we found that death is induced in the absence of activation of any of the caspases tested, accumulation of reactive oxygen species, or release of cytochrome c from mitochondria. E4orf4 caused a substantial change in cell morphology, including vigorous membrane blebbing, multiple nuclei in many cells and increased cell volume. Most of these characteristics are not typical of apoptosis, but they are of necrosis. FACS analysis and western blotting for cell cycle markers showed that E4orf4-expressing cells became arrested in G(2)/M and also accumulated high levels of cyclin E. The presence of significant numbers of tetraploid and polyploid cells and some cells with micronuclei suggested that E4orf4 appears to induce death in these cells through a process resulting from mitotic catastrophe.

  13. Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression.

    Science.gov (United States)

    Armistead, Joy; Patel, Nehal; Wu, Xiaoli; Hemming, Richard; Chowdhury, Biswajit; Basra, Gagandeep Singh; Del Bigio, Marc R; Ding, Hao; Triggs-Raine, Barbara

    2015-05-01

    Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G, p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to characterize the effects of EMG1 deficiency, particularly in the brain, where EMG1 expression is high. Embryos homozygous for the mutation in Emg1 were small for gestational age with neural tube defects, and died between embryonic days 8.5 and 12.5. These embryos exhibited dramatically reduced cell proliferation, which we also detected in autopsy brain tissue and bone marrow of BCS patients, consistent with a requirement for high levels of EMG1 in tissues with rapid cell proliferation. In fibroblasts derived from the BCS mouse embryos, we detected a high proportion of binucleated cells, indicating that a mitotic defect underlies the growth arrest in BCS. These studies add to growing evidence of a link between ribosome biogenesis, mitotic progression, and brain development that is currently unexplored.

  14. Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development

    DEFF Research Database (Denmark)

    Migliorini, Domenico; Lazzerini Denchi, Eros; Danovi, Davide

    2002-01-01

    characterized by overall growth deficiency, anemia, improper neural tube closure, and dilation of lateral ventricles. In situ analysis demonstrated increased levels of p21(CIP1/Waf1) and lower levels of Cyclin E and proliferating cell nuclear antigen expression. Consistent with lack of 5-bromo-2'-deoxyuridine...

  15. Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Solanki, Sumit; Salotra, Poonam; Nakhasi, Hira L

    2014-06-30

    Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis.

  16. 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.

  17. Newt orthologue of Growth arrest-specific 6 (NvGas6) is implicated in stress response during newt forelimb regeneration.

    Science.gov (United States)

    Beug, Shawn; Vascotto, Sandy G; Tsilfidis, Catherine

    2006-03-01

    Red-spotted newts are capable of regenerating various structures and organs through the process of epimorphic regeneration. Receptor tyrosine kinases (RTKs) and their ligands are important for normal cellular development and physiology but most have not yet been characterised during regeneration. We have isolated a newt orthologue of Growth arrest-specific 6 (NvGas6), and examined its expression during forelimb regeneration and within a blastema cell line (B1H1). During limb regeneration, NvGas6 expression increases upon amputation, peaks during maximal blastema cell proliferation, and is subsequently downregulated during redifferentiation. Transcripts are localised to the wound epithelium and distal mesenchymal cells during dedifferentiation and proliferative phases, and scattered within redifferentiating tissues during later stages. In B1H1 cultures, NvGas6 is upregulated under reduced serum conditions and myogenesis. Treatment with mimosine and colchicine or exposure to heat shock or anoxia results in upregulation of NvGas6 expression. Taken together, our findings suggest that during regeneration, NvGas6 expression may be upregulated in response to cellular stress.

  18. Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Xiao-Mei Wu; Bo Jiang; Chun-Yu Wang; Hai-Nan Zhang; Xiang-Min Shen

    2014-01-01

    Objective:To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34 (GADD34). Methods: A total of 108 healthy male Sprague-Dawley rats were randomly divided into sham operation group, model group and edaravone group (36 cases for each group). Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawley rats. Then, GADD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats. Results: The GADD34 expression was detected in the peri-infarct regions of rats 1 h after reperfusion, which reached its peak 24 h after reperfusion. And edaravone could significantly down-regulate the GADD34 expression. Conclusions:Edaravon could down-regulate GADD34 expression, which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

  19. Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Wei; Wang; Xiao-Mei; Wu; Bo; Jiang; Chun-Yu; Wang; Hai-Nan; Zhang; Xiang-Min; Shen

    2014-01-01

    Objective:To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34(GADD34).Methods:A total of 108 healthy male Sprague-Dawlcy rats were randomly divided into sham operation group,model group and edaravone.group(36 cases for each group).Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawlev rats.Then.GAOD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats.Results:The GADD34 expression was detected in the peri-infaret regions of rats 1 h after reperfusion,which reached its peak 24 h after reperfusion.And edaravone could significantly down-regulate the GAOD34 expression.Conclusions:Edaravon could down-regulate GADD34 expression,which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

  20. Intestinal growth adaptation and glucagon-like peptide 2 in rats with ileal-jejunal transposition or small bowel resection

    DEFF Research Database (Denmark)

    Thulesen, Jesper; Hartmann, B.; Kissow, H.;

    2001-01-01

    Anatomy, glucagon-like peptide 2, small intestine, short bowel, intestinal adaptation, growth factors, rat......Anatomy, glucagon-like peptide 2, small intestine, short bowel, intestinal adaptation, growth factors, rat...

  1. Inhibition of p38-MAPK potentiates cisplatin-induced apoptosis via GSH depletion and increases intracellular drug accumulation in growth-arrested kidney tubular epithelial cells.

    Science.gov (United States)

    Rodríguez-García, Maria Elena; Quiroga, Adoración G; Castro, José; Ortiz, Alberto; Aller, Patricio; Mata, Felicísima

    2009-10-01

    We were interested in analyzing the regulation by mitogen-activated protein kinases (MAPKs) of cisplatin-provoked toxicity in epithelial renal tubule cell lines, when assayed under culture conditions (cell confluence plus serum deprivation), which mimic the characteristics of a nonproliferating epithelium. Under these restrictive growth conditions, cisplatin induced apoptosis with lower efficacy than in exponentially growing cells, and decreased p38-MAPK phosphorylation in NRK-52E and other (LLC-PK1, MDCK, HK2) cell lines. Moreover, cisplatin-provoked apoptosis was potentiated by cotreatment with p38-MAPK-specific inhibitors (SB203580, SB220025) or transfection with a kinase-negative mutant of MKK6, whereas c-Jun NH2-terminal kinase or extracellular signal-regulated kinase/MAPK and ERK Kinase inhibitors were ineffective. By contrast, when applied to exponentially growing cells, cisplatin stimulated p38-MAPK phosphorylation and apoptosis, was attenuated by kinase inhibitors. Treatment of confluent/serum-deprived cells with cisplatin caused mitochondrial transmembrane potential disruption and activated the mitochondrial apoptotic pathway, as indicated by the decrease in Bcl-X(L) expression, increase in Bax expression and cytochrome c release, and these effects were potentiated by cotreatment with SB203580. Treatment of confluent/serum-deprived cells with cisplatin plus SB203580 decreased the intracellular reduced glutathione (GSH) content, and increased intracellular cisplatin accumulation as well as cisplatin binding to DNA. Cotreatment with the GSH-depleting agent D,L-buthionine-R,S-sulfoximine also potentiated cisplatin-provoked apoptosis. In summary, p38-MAPK inhibition potentiates cisplatin-provoked apoptosis in growth-arrested epithelial renal tubule cells, a result that may be explained at least in part by GSH depletion and drug transport alteration.

  2. The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis in Jurkat cells, a model of CD4⁺ T cells.

    Science.gov (United States)

    Wang, Heng; Wang, Yong; Jiang, Xiaoji; Wang, Zhizhong; Zhong, Bing; Fang, Yongfei

    2014-08-01

    CD4(+) T cells in rheumatoid arthritis (RA) express growth signaling pathway in association with deregulated growth and resistance to apoptosis. The janus kinase (Jak) 3 and signal transducer and activator of transcription (STAT) pathway play a critical role in interleukin-2 (IL-2)-induced CD4(+) T cell proliferation. The present study aimed to explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant Rhizoma curcumae. Cell proliferation was determined using WST-1 assay after curcumol treatment. The cell cycle distribution and Bcl-2 protein expression were assessed by flow cytometry. The cellular morphology of apoptosis was evaluated by Hoechst 33258 staining. The expressions of phosphorylated-Jak3 (p-Jak3), p-STAT3, and p-STAT5a following IL-2 stimulation were determined by western blot analysis. The Electrophoretic Mobility Shift Assay was used to detect the DNA binding activities of transcription factors STAT3 and STAT5. The study results showed that curcumol could inhibit the IL-2-induced Jurkat cell proliferation in a concentration- and time-dependent manner in vitro. Curcumol could cause cell cycle arrest at the S phase, induce cell apoptosis, and inhibit the expression of Bcl-2 in a dose-dependent manner. Curcumol at 50μg/mL and Jak3 inhibitor ZM39923 could inhibit the phosphorylation of Jak3 and STAT5a. In conclusion, the underlying mechanism of curcumol on suppressing CD4(+) T cell proliferation and inducing apoptosis might partly be mediated by inhibition of Jak3-STAT5-related molecular activities and Bcl-2 expression, respectively; further studies are required in vivo to test the use of curcumol as a promising therapeutic option for RA.

  3. Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3beta phosphorylation.

    Science.gov (United States)

    Kumar, Anil; Hou, Xu; Lee, Chunsik; Li, Yang; Maminishkis, Arvydas; Tang, Zhongshu; Zhang, Fan; Langer, Harald F; Arjunan, Pachiappan; Dong, Lijin; Wu, Zhijian; Zhu, Linda Y; Wang, Lianchun; Min, Wang; Colosi, Peter; Chavakis, Triantafyllos; Li, Xuri

    2010-05-14

    Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.

  4. Inositol Hexaphosphate Inhibits Growth and Induces G1 Arrest and Apoptotic Death of Androgen-Dependent Human Prostate Carcinoma LNCaP Cells

    Directory of Open Access Journals (Sweden)

    Chapla Agarwal

    2004-09-01

    Full Text Available Prostate cancer (PCA is the most common invasive malignancy and the second leading cause of cancerrelated deaths in the US male population. One approach to control this malignancy is its preventive intervention by dietary agents. Inositol hexaphosphate (IP6, a dietary constituent, has shown promising efficacy against various cancers; however, limited studies have been performed with IP6 against PCA. Here, we investigated the growth-inhibitory effect and associated mechanisms of IP6 in androgen-dependent human prostate carcinoma LNCaP cells. IP6 treatment of cells resulted in a strong growth inhibition and an increase in G1 cell population. In mechanistic studies, IP6 resulted in an increase in cyclin-dependent kinase inhibitors (CDKIs Cipi/p21 and Kip1/p27 levels, together with a decrease in cyclin-dependent kinase (CDK 4 and cyclin D1 protein levels. An increase in CDKI levels by IP6 also led to a concomitant increase in their interactions with CDK2 and CDK4, together with a strong decrease in the kinase activity of both CDKs. Downstream in CDKI-CDK-cyclin cascade, consistent with its inhibitory effect on CDK kinase activity, IP6 treatment of cells increased hypophosphorylated levels of retinoblastoma (Rb with a decrease in Rb phosphorylation at serine 780, 807, and 811 sites, and caused a moderate to strong decrease in the levels of transcription factors E2F1, E2F4, and E2F5. In other studies, IP6 caused a dose- and a time-dependent apoptotic death of LNCaP cells, and a decrease in Bcl2 levels, causing a strong increase in Bax versus Bcl2 ratio, as well as an inhibition of constitutively active AKT phosphorylation. Taken together, these molecular alterations provide an insight into IP6-caused growth inhibition, G1 arrest, and apoptotic death of human prostate carcinoma LNCaP cells. Because early clinical PCA growth is an androgen-dependent response, the results of the present study employing androgendependent LNCaP cells suggest that IP6 has

  5. Physeal arrest of the distal radius.

    Science.gov (United States)

    Abzug, Joshua M; Little, Kevin; Kozin, Scott H

    2014-06-01

    Fractures of the distal radius are among the most common pediatric fractures. Although most of these fractures heal without complication, some result in partial or complete physeal arrest. The risk of physeal arrest can be reduced by avoiding known risk factors during fracture management, including multiple attempts at fracture reduction. Athletes may place substantial compressive and shear forces across the distal radial physes, making them prone to growth arrest. Timely recognition of physeal arrest can allow for more predictable procedures to be performed, such as distal ulnar epiphysiodesis. In cases of partial arrest, physeal bar excision with interposition grafting can be performed. Once ulnar abutment is present, more invasive procedures may be required, including ulnar shortening osteotomy or radial lengthening.

  6. Hwanggeumchal sorghum induces cell cycle arrest, and suppresses tumor growth and metastasis through Jak2/STAT pathways in breast cancer xenografts.

    Directory of Open Access Journals (Sweden)

    Jin Hee Park

    Full Text Available BACKGROUND: Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model. CONCLUSIONS/SIGNIFICANCE: Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer.

  7. Suppression of growth arrest and DNA damage-inducible 45alpha expression confers resistance to sulindac and indomethacin-induced gastric mucosal injury.

    Science.gov (United States)

    Chiou, Shiun-Kwei; Hodges, Amy; Hoa, Neil

    2010-09-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin are a major cause of gastric erosions and ulcers. Induction of apoptosis by NSAIDs is an important mechanism involved. Understanding how NSAIDs affect genes that regulate apoptosis is useful for designing therapeutic or preventive strategies and for evaluating the efficacy of safer drugs being developed. We investigated whether growth arrest and DNA damage-inducible 45alpha (GADD45alpha), a stress signal response gene involved in regulation of DNA repair and induction of apoptosis, plays a part in NSAID-induced gastric mucosal injury and apoptosis in vivo in mice and in vitro in cultured human AGS and rat RGM-1 gastric epithelial cells. Intraperitoneal administration of sulindac and indomethacin both resulted in up-regulation of GADD45alpha expression and induction of significant injury and apoptosis in gastric mucosa of wild-type mice. GADD45alpha(-/-) mice were markedly more resistant to both sulindac- and indomethacin-induced gastric mucosal injury and apoptosis than wild-type mice. Sulindac sulfide and indomethacin treatments also concentration-dependently increased GADD45alpha expression and apoptosis in AGS and RGM-1 cells. Antisense suppression of GADD45alpha expression significantly reduced sulindac and indomethacin-induced activation of caspase-9 and apoptosis in AGS cells. Pretreatments with exogenous prostaglandins and small interfering RNA suppression of cyclooxygenase (COX)-1 and -2 did not affect up-regulation of GADD45alpha by sulindac sulfide and indomethacin in AGS cells. These findings indicate that GADD45alpha up-regulation is a COX-independent mechanism that is required for induction of severe gastric mucosal apoptosis and injury by NSAIDs, probably via a capase-9-dependent pathway of programmed cell death.

  8. Growth Arrest-Specific 6 Protein in Patients with Sjogren Syndrome: Determination of the Plasma Level and Expression in the Labial Salivary Gland.

    Directory of Open Access Journals (Sweden)

    Chen-Hung Chen

    Full Text Available Growth arrest-specific protein 6 (Gas6 is a vitamin K-dependent protein expressed by endothelial cells and leukocytes that are involved in cell survival, migration, and proliferation in response to inflammatory processes. The aim of this study was to assess the implications of Gas6 in Sjögren syndrome (SS and its expression in the labial salivary gland.A total of 254 adults, including 159 with primary Sjögren syndrome (pSS, 34 with secondary Sjögren syndrome (sSS, and 61 normal controls, were recruited. Plasma Gas6 concentrations were determined, and Gas6 expressions in labial salivary gland (LSG tissues from controls and pSS and sSS patients were also evaluated. Plasma Gas6 concentrations were significantly lower among patients with pSS than normal controls (13.5 ± 8.6 vs. 19.9 ± 13.4 ng/ml, p < 0.001. There were, however, no significant differences in plasma Gas6 levels between pSS and sSS patients (13.5 ± 8.6 vs. 16.9 ± 11.2 ng/ml, p = 0.068. In multivariate logistic regression analysis, after adjustment for white blood cell count, hemoglobin level, platelet count, lymphocyte count, and C3 and C4 levels, lower plasma Gas6 concentrations were significantly associated with an increased risk of SS. Moreover, by using a semi-quantitative scale to evaluate Gas6 expression in LSG tissues, Gas6 expression was found to be markedly lower in LSG tissues from pSS patients than in tissues from normal controls.Decreased plasma Gas6 concentration and LSG expression were associated with pSS. As such, Gas6 may represent a novel independent risk factor for pSS, with a potential role in salivary gland inflammation and dysfunction.

  9. Hedging Medical Spending Growth: An Adaptive Expectations Approach.

    Science.gov (United States)

    Lieberthal, Robert D

    2016-08-01

    Long-term health insurance provides consumers with protection against persistent, negative health shocks. While the stochastic rise in medical spending growth may make some health risks harder to insure, financial assets could act as a hedge for medical spending growth risk. The purpose of this research was to determine whether such hedges exist. The results of this study were two-fold. First, the asset classes with the strongest statistical evidence as hedges were bonds, not stocks. Second, any strategy to hedge medical spending growth involved shorting assets i.e. betting against the bond or stock market. Health insurers writing long-term contracts should combine the use of hedges in the bond market with of portfolio diversification, and may benefit from health policies to moderate the uncertainty of medical spending growth.

  10. Growth and adaptation of microorganisms on the cheese surface.

    Science.gov (United States)

    Monnet, Christophe; Landaud, Sophie; Bonnarme, Pascal; Swennen, Dominique

    2015-01-01

    Microbial communities living on cheese surfaces are composed of various bacteria, yeasts and molds that interact together, thus generating the typical sensory properties of a cheese. Physiological and genomic investigations have revealed important functions involved in the ability of microorganisms to establish themselves at the cheese surface. These functions include the ability to use the cheese's main energy sources, to acquire iron, to tolerate low pH at the beginning of ripening and to adapt to high salt concentrations and moisture levels. Horizontal gene transfer events involved in the adaptation to the cheese habitat have been described, both for bacteria and fungi. In the future, in situ microbial gene expression profiling and identification of genes that contribute to strain fitness by massive sequencing of transposon libraries will help us to better understand how cheese surface communities function.

  11. Adaptation of Lactococcus lactis to high growth temperature leads to a dramatic increase in acidification rate

    DEFF Research Database (Denmark)

    Chen, Jun; Shen, Jing; Hellgren, Lars;

    2015-01-01

    Lactococcus lactis is essential for most cheese making, and this mesophilic bacterium has its growth optimum around 30 °C. We have, through adaptive evolution, isolated a mutant TM29 that grows well up to 39 °C, and continuous growth at 40 °C is possible if pre-incubated at a slightly lower...

  12. ERK activation is required for CCK-mediated pancreatic adaptive growth in mice.

    Science.gov (United States)

    Holtz, Bryan J; Lodewyk, Kevin B; Sebolt-Leopold, Judith S; Ernst, Stephen A; Williams, John A

    2014-10-01

    High levels of cholecystokinin (CCK) can stimulate pancreatic adaptive growth in which mature acinar cells divide, leading to enhanced pancreatic mass with parallel increases in protein, DNA, RNA, and digestive enzyme content. Prolonged release of CCK can be induced by feeding trypsin inhibitor (TI) to disrupt normal feedback control. This leads to exocrine growth in a CCK-dependent manner. The extracellular signal-related kinase (ERK) pathway regulates many proliferative processes in various tissues and disease models. The aim of this study was to evaluate the role of ERK signaling in pancreatic adaptive growth using the MEK inhibitors PD-0325901 and trametinib (GSK-1120212). It was determined that PD-0325901 given two times daily by gavage or mixed into powdered chow was an effective and specific inhibitor of ERK signaling in vivo. TI-containing chow led to a robust increase in pancreatic mass, protein, DNA, and RNA content. This pancreatic adaptive growth was blocked in mice fed chow containing the MEK inhibitors. PD-0325901 blocked TI-induced ERK-regulated early response genes, cell-cycle proteins, and mitogenesis by acinar cells. It was determined that ERK signaling is necessary for the initiation of pancreatic adaptive growth but not necessary to maintain it. PD-0325901 blocked adaptive growth when given before cell-cycle initiation but not after mitogenesis had been established. Furthermore, GSK-1120212, a chemically distinct inhibitor of the ERK pathway that is now approved for clinical use, inhibited growth similar to PD-0325901. These data demonstrate that the ERK pathway is required for CCK-stimulated pancreatic adaptive growth.

  13. Adaptive growth responses of Listeria monocytogenes to acid and osmotic shifts above and across the growth boundaries.

    Science.gov (United States)

    Belessi, C-I A; Le Marc, Y; Merkouri, S I; Gounadaki, A S; Schvartzman, S; Jordan, K; Drosinos, E H; Skandamis, P N

    2011-01-01

    The effect of acid and osmotic shifts on the growth of Listeria monocytogenes was evaluated at 10°C. Two types of shifts were tested: (i) within the range of pH and water activity (a(w)) levels that allow growth of L. monocytogenes and (ii) after habituation at no-growth conditions back to growth-permitting conditions. A L. monocytogenes cheese isolate, with high survival capacity during cheesemaking, was inoculated (10(2) CFU/ml) in tryptic soy broth supplemented with 0.6% yeast extract at six pH levels (5.1 to 7.2; adjusted with lactic acid) and 0.5% NaCl (a(w) 0.995), or four a(w) levels (0.995 to 0.93, adjusted with 0.5 to 10.5% NaCl) at pH 7.2 and grown to early stationary phase. L. monocytogenes was then shifted (at 10(2) CFU/ml) to each of the aforementioned growth-permitting pH and a(w) levels and incubated at 10°C. Shifts from no-growth to growth-permitting conditions were carried out by transferring L. monocytogenes habituated at pH 4.9 or a(w) 0.90 (12.5% NaCl) for 1, 5, and 10 days to all pH and a(w) levels permitting growth. Reducing a(w) or pH at different levels in the range of 0.995 to 0.93 and 7.2 to 5.1, respectively, decreased the maximum specific growth rate of L. monocytogenes. The lag time of the organism increased with all osmotic downshifts, as well as by the reduction of pH to 5.1. Conversely, any type of shift within pH 5.5 to 7.2 did not markedly affect the lag times of L. monocytogenes. The longer the cells were incubated at no-growth a(w) (0.90), the faster they initiated growth subsequently, suggesting adaptation to osmotic stress. Conversely, extended habituation at pH 4.9 had the opposite effect on subsequent growth of L. monocytogenes, possibly due to cell injury. These results suggest that there is an adaptation or injury rate induced at conditions inhibiting the growth of the pathogen. Thus, quantifying adaptation phenomena under growth-limiting environments, such as in fermented dairy and meat products or products preserved in

  14. Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene.

    Science.gov (United States)

    Charusanti, Pep; Conrad, Tom M; Knight, Eric M; Venkataraman, Karthik; Fong, Nicole L; Xie, Bin; Gao, Yuan; Palsson, Bernhard Ø

    2010-11-04

    Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level. We investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of phosphoglucose isomerase (pgi) by adaptively evolving ten replicates of E. coli lacking pgi for 50 days in glucose M9 minimal medium and by characterizing endpoint clones through whole-genome re-sequencing and phenotype profiling. We found that 1) the growth rates for all ten endpoint clones increased approximately 3-fold over the 50-day period; 2) two to five mutations arose during adaptation, most frequently in the NADH/NADPH transhydrogenases udhA and pntAB and in the stress-associated sigma factor rpoS; and 3) despite similar growth rates, at least three distinct endpoint phenotypes developed as defined by different rates of acetate and formate secretion. These results demonstrate that E. coli can adapt to the loss of a major metabolic gene product with only a handful of mutations and that adaptation can result in multiple, alternative phenotypes.

  15. The MRL proteins: adapting cell adhesion, migration and growth.

    Science.gov (United States)

    Coló, Georgina P; Lafuente, Esther M; Teixidó, Joaquin

    2012-01-01

    MIG-10, RIAM and Lamellipodin (Lpd) are the founding members of the MRL family of multi-adaptor molecules. These proteins have common domain structures but display distinct functions in cell migration and adhesion, signaling, and in cell growth. The binding of RIAM with active Rap1 and with talin provides these MRL molecules with important regulatory roles on integrin-mediated cell adhesion and migration. Furthermore, RIAM and Lpd can regulate actin dynamics through their binding to actin regulatory Ena/VASP proteins. Recent data generated with the Drosophila MRL ortholog called Pico and with RIAM in melanoma cells indicate that these proteins can also regulate cell growth. As MRL proteins represent a relatively new family, many questions on their structure-function relationships remain unanswered, including regulation of their expression, post-translational modifications, new interactions, involvement in signaling and their knockout mice phenotype.

  16. Effect of Common Genetic Variants of Growth Arrest-Specific 6 Gene on Insulin Resistance, Obesity and Type 2 Diabetes in an Asian Population.

    Directory of Open Access Journals (Sweden)

    Chang-Hsun Hsieh

    Full Text Available Growth arrest-specific 6 (Gas6, a vitamin K-dependent protein, has been implicated in systemic inflammation, obesity, and insulin resistance (IR. Data from recent studies suggest that polymorphisms in the Gas6 gene are associated with cardiovascular disorders and type 2 diabetes (T2D. However, the association of Gas6 gene variants with obesity, IR, and T2D development has not been explored.Four common single nucleotide polymorphisms (SNPs in the Gas6 gene were genotyped in 984 participants from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe family cohort. An insulin suppression test was performed to determine IR based on steady-state plasma glucose (SSPG. Associations between IR indices and obesity, and SNP genotypes, based on previously-reported data for this cohort (Phase I, were analyzed. In the present follow-up study (Phase II, the effects of gene variants of Gas6 on the progression to T2D were explored in individuals who were free of T2D in Phase I. The mean follow-up period for Phase II was 5.7 years.The mean age of the study population in Phase I was 49.5 years and 16.7% of individuals developed T2D during follow-up. After adjusting for covariates, three SNPs (rs8191973, rs8197974, and rs7323932 were found to be associated with SSPG levels (p = 0.007, p = 0.03, and p = 0.011, respectively. This association remained significant after multiple testing and showed a significant interaction with physical activity for SNP rs8191973. However, no other significant correlations were observed between Gas6 polymorphisms and other indices of IR or obesity. A specific haplotype, AACG (from rs8191974, rs7323932, rs7331124, and rs8191973, was positively associated with SSPG levels (p = 0.0098. None of the polymorphisms were associated with an increased risk of T2D development.Our results suggest that Gas6 gene variants are associated with IR, although their effects on subsequent progression to T2D were minimal in

  17. OXIDATIVE STRESS IN MUSCLE GROWTH AND ADAPTATION TO PHYSICAL EXERCISE

    Directory of Open Access Journals (Sweden)

    Ihor Yurkevych

    2015-05-01

    Full Text Available In a few last decades oxidative stress detected in a variety of physiological processes where reactive oxygen species (ROS and reactive nitrogen species (RNS play a central role. They are directly involved in oxidation of proteins, lipids and nucleic acids. In certain concentrations they are necessary for cell division, proliferation and apoptosis. Contractile muscle tissue at aerobic conditions form high ROS flow that may modulate a variety of cell functions, for example proliferation. However, slight increase in ROS level provide hormetic effect which may participate in adaptation to heavy weight training resulted in hypertrophy and proliferation of skeletal muscle fibers. This review will discuss ROS types, sites of generation, strategies to increase force production and achieve skeletal muscle hypertrophy.

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

    Science.gov (United States)

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

    2016-04-01

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

  19. Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

    OpenAIRE

    Tseng, Ruo-Chia; Chang, Jer-Wei; Mao, Jiou-Shan; Tsai, Charng-Dar; Wu, Pei-Chen; Lin, Cuei-Jyuan; Lu, Yi-Lin; Liao, Sheng-You; Cheng, Hung-Chi; Hsu, Han-Shui; Wang, Yi-Ching

    2015-01-01

    Growth-arrest-specific 7 (GAS7) belongs to a group of adaptor proteins that coordinate the actin cytoskeleton. Among human GAS7 isoforms, only GAS7C possesses a Src homology 3 domain. We report here that GAS7C acts as a migration suppressor and can serve as a prognostic biomarker in lung cancer. GAS7C overexpression reduces lung cancer migration, whereas GAS7C knockdown enhances cancer cell migration. Importantly, ectopically overexpressed GAS7C binds tightly with N-WASP thus inactivates the ...

  20. Combination of Low Concentration of (−-Epigallocatechin Gallate (EGCG and Curcumin Strongly Suppresses the Growth of Non-Small Cell Lung Cancer in Vitro and in Vivo through Causing Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Wenbin Huang

    2013-06-01

    Full Text Available (−-Epigallocatechin gallate (EGCG and curcumin are two naturally derived agents that have been widely investigated worldwide. They exhibit their anti-tumor effects in many types of cancers. In the current study, the effect of the combination of the two agents on non-small cell lung cancer (NSCLC cells was investigated. The results revealed that at low concentrations, the combination of the EGCG and curcumin strongly enhanced cell cycle arrest. Flow cytometry analysis showed that the cells were arrested at G1 and S/G2 phases. Two main cell cycle related proteins cyclin D1 and cyclin B1 were significantly inhibited at the present of EGCG and curcumin. EdU (5-ethynyl-2'-deoxyuridine fluorescence staining showed that the DNA replication was significantly blocked. A clonal growth assay also confirmed a marked repression of cell growth. In a lung cancer xenograft node mice model, combination of EGCG and curcumin exhibited protective effect against weight loss due to tumor burden. Tumor growth was strongly repressed by the combination of the two agents, without causing any serious side-effect. Overall, these results strongly suggest that EGCG in combination with curcumin could be a candidate for chemoprevention agent of NSCLC.

  1. High-density growth arrest in Ras-transformed cells: low Cdk kinase activities in spite of absence of p27Kip Cdk-complexes

    DEFF Research Database (Denmark)

    Groth, Anja; Willumsen, Berthe Marie

    2005-01-01

    The ras oncogene transforms immortalized, contact-inhibited non-malignant murine fibroblasts into cells that are focus forming, exhibit increased saturation density, and are malignant in suitable hosts. Here, we examined changes in cell cycle control complexes as normal and Ras-transformed cells...... response to contact inhibition, a separate back-up mechanism enforced cell cycle arrest at higher cell density....... ceased to grow exponentially, to reveal the molecular basis for Ras-dependent focus formation. As normal cells entered density-dependent arrest, cyclin D1 decreased while cyclin D2 was induced and replaced D1 in Cdk4 complexes. Concomitantly, p27Kip1 levels rose and the inhibitor accumulated in both Cdk4...

  2. Climate Change Adaptation. Challenges and Opportunities for a Smart Urban Growth

    Directory of Open Access Journals (Sweden)

    Adriana Galderisi

    2014-04-01

    Full Text Available Climate change is one of the main environmental issues challenging cities in the 21th century. At present, more than half of the world population lives in cities and the latter are responsible for 60% to 80% of global energy consumption and greenhouse gas (GHG emissions, which are the main causes of the change in climate conditions. In the meantime, they are seriously threatened by the heterogeneous climate-related phenomena, very often exacerbated by the features of the cities themselves. In the last decade, international and European efforts have been mainly focused on mitigation rather than on adaptation strategies. Europe is one of the world leaders in global mitigation policies, while the issue of adaptation has gained growing importance in the last years. As underlined by the EU Strategy on adaptation to climate change, even though climate change mitigation still remains a priority for the global community, large room has to be devoted to adaptation measures, in order to effectively face the unavoidable impacts and related economic, environmental and social costs of climate change (EC, 2013. Thus, measures for adaptation to climate change are receiving an increasing financial support and a growing number of European countries are implementing national and urban adaptation strategies to deal with the actual and potential climate change impacts. According to the above considerations, this paper explores strengths and weaknesses of current adaptation strategies in European cities. First the main suggestions of the European Community to improve urban adaptation to climate change are examined; then, some recent Adaptation Plans are analyzed, in order to highlight challenges and opportunities arising from the adaptation processes at urban level and to explore the potential of Adaptation Plans to promote a smart growth in the European cities.

  3. Patterns of Growth in Adaptive Social Abilities among Children with Autism Spectrum Disorders

    Science.gov (United States)

    Anderson, Deborah K.; Oti, Rosalind S.; Lord, Catherine; Welch, Kathleen

    2009-01-01

    Adaptive social skills were assessed longitudinally at approximately ages 2, 3, 5, 9, and 13 years in a sample of 192 children with a clinical diagnosis of autism (n = 93), PDD-NOS (n = 51), or nonspectrum developmental disabilities (n = 46) at age 2. Growth curve analyses with SAS proc mixed were used to analyze social trajectories over time.…

  4. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

    DEFF Research Database (Denmark)

    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul

    2006-01-01

    Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are es...

  5. Pittsburgh Police Arrest Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Arrest data contains information on people taken into custody by City of Pittsburgh police officers. More serious crimes such as felony offenses are more likely to...

  6. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  7. Plasma membrane proteomics in the maize primary root growth zone: novel insights into root growth adaptation to water stress.

    Science.gov (United States)

    Voothuluru, Priyamvada; Anderson, Jeffrey C; Sharp, Robert E; Peck, Scott C

    2016-09-01

    Previous work on maize (Zea mays L.) primary root growth under water stress showed that cell elongation is maintained in the apical region of the growth zone but progressively inhibited further from the apex. These responses involve spatially differential and coordinated regulation of osmotic adjustment, modification of cell wall extensibility, and other cellular growth processes that are required for root growth under water-stressed conditions. As the interface between the cytoplasm and the apoplast (including the cell wall), the plasma membrane likely plays critical roles in these responses. Using a simplified method for enrichment of plasma membrane proteins, the developmental distribution of plasma membrane proteins was analysed in the growth zone of well-watered and water-stressed maize primary roots. The results identified 432 proteins with differential abundances in well-watered and water-stressed roots. The majority of changes involved region-specific patterns of response, and the identities of the water stress-responsive proteins suggest involvement in diverse biological processes including modification of sugar and nutrient transport, ion homeostasis, lipid metabolism, and cell wall composition. Integration of the distinct, region-specific plasma membrane protein abundance patterns with results from previous physiological, transcriptomic and cell wall proteomic studies reveals novel insights into root growth adaptation to water stress.

  8. Key techniques and applications of adaptive growth method for stiffener layout design of plates and shells

    Science.gov (United States)

    Ding, Xiaohong; Ji, Xuerong; Ma, Man; Hou, Jianyun

    2013-11-01

    The application of the adaptive growth method is limited because several key techniques during the design process need manual intervention of designers. Key techniques of the method including the ground structure construction and seed selection are studied, so as to make it possible to improve the effectiveness and applicability of the adaptive growth method in stiffener layout design optimization of plates and shells. Three schemes of ground structures, which are comprised by different shell elements and beam elements, are proposed. It is found that the main stiffener layouts resulted from different ground structures are almost the same, but the ground structure comprised by 8-nodes shell elements and both 3-nodes and 2-nodes beam elements can result in clearest stiffener layout, and has good adaptability and low computational cost. An automatic seed selection approach is proposed, which is based on such selection rules that the seeds should be positioned on where the structural strain energy is great for the minimum compliance problem, and satisfy the dispersancy requirement. The adaptive growth method with the suggested key techniques is integrated into an ANSYS-based program, which provides a design tool for the stiffener layout design optimization of plates and shells. Typical design examples, including plate and shell structures to achieve minimum compliance and maximum bulking stability are illustrated. In addition, as a practical mechanical structural design example, the stiffener layout of an inlet structure for a large-scale electrostatic precipitator is also demonstrated. The design results show that the adaptive growth method integrated with the suggested key techniques can effectively and flexibly deal with stiffener layout design problem for plates and shells with complex geometrical shape and loading conditions to achieve various design objectives, thus it provides a new solution method for engineering structural topology design optimization.

  9. Defining Old Growth for Fire-adapted Forests of the Western United States

    Directory of Open Access Journals (Sweden)

    Merrill R. Kaufmann

    2007-12-01

    Full Text Available There are varying definitions of old-growth forests because of differences in environment and differing fire influence across the Intermountain West. Two general types of forests reflect the role of fire: 1 forests shaped by natural changes in structure and species makeup - plant succession - that are driven by competitive differences among species and individual trees and by small-scale disturbances, and 2 forests where plant succession processes are disrupted by major biological disturbances (fire, insects, wind, or drought extending across larger areas. Some case examples of old-growth forests where fire was historically frequent are used. The examples sketch out the typical biophysical settings, fire regime, natural disturbance factors, spatial features of patches, and the processes and conditions that produce spatial changes of the landscape over time. These examples confirm the complexity of describing or defining old growth in frequent-fire forests. We define fire-adapted forests at three spatial scales, whereas the standard definition of old growth refers to a patch or stand condition. Our definition is based on ecological principles rather than on the cultural aspects of old growth. It focuses on central tendencies, given all the possible combinations of conditions and processes, that move forests toward old growth in the fire-adapted forests of the Intermountain West.

  10. Antrodia camphorata induces G(1) cell-cycle arrest in human premyelocytic leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice.

    Science.gov (United States)

    Yang, Hsin-Ling; Kumar, K J Senthil; Kuo, Ya-Ting; Chang, Hebron C; Liao, Jiunn-Wang; Hsu, Li-Sung; Hseu, You-Cheng

    2014-09-01

    Antrodia camphorata is a well-known medicinal mushroom in Taiwan. The broth from a fermented culture of Antrodia camphorata (AC) has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of AC on cell cycle arrest in vitro in HL-60 cells and on tumor regression in vivo using an athymic nude mouse model. We found that AC (20-80 μg mL(-1)) treatment significantly induced G1 cell-cycle arrest in HL-60 cells by reducing the levels of cyclin D1, CDK4, cyclin E, CDK2, cyclin A, and phosphorylation of retinoblastoma protein (p-Rb). Moreover, AC treatment led to significantly increased protein expression levels of CDK inhibitors, including p21(WAF1) and p15(NIK4B). Additionally, AC treatment markedly induced intracellular ROS generation and mitochondrial dysfunction in HL-60 cells. Furthermore, the in vivo study results revealed that AC treatment was effective in terms of delaying the tumor incidence in nude mice that had been inoculated with HL-60 cells as well as in reducing the tumor burden. Histological analysis confirmed that AC treatment significantly modulated the xenografted tumor progression as demonstrated by a reduction in mitotic cells. Our data strongly suggest that Antrodia camphorata could be an anti-cancer agent for human leukemia.

  11. The European Arrest Warrant

    Directory of Open Access Journals (Sweden)

    Minodora-Ioana Balan-Rusu

    2012-05-01

    Full Text Available In the paper it is generally examined the institution of the European arrest warrant according to the latest changes and additions through the adoption of a new European legislative act. The paper is a continuation of research in the area of judicial cooperation in criminal matters in the European Union. It may be useful to the judicial bodies with the responsibilities of issuing and executing a specific European arrest warrant and to academics and students in law schools. The research results, the essential contribution, the originality consist of the general examination of the institution, the critical remarks and proposals for amending and completing certain provisions insufficiently clear.

  12. IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis:contribution of the PI-3' kinase/AKT pathway

    Institute of Scientific and Technical Information of China (English)

    Gregory B Carey; Elena Semenova; Xiulan Qi; Achsah D Keegan

    2007-01-01

    Interleukin-4(IL-4)promotes lymphocyte survival and protects primary lymphomas from apoptosis.Previous studies reported differential requirements for the signal transducer and activator of transcription 6(STAT6)and IRS2/phosphatidylinositol 3 kinase(PI-3K)signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis.In this study,we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31,a model B-cell lymphoma line.In CH31,anti-IgM treatment leads to the loss of mitochondrial membrane potential,phospho-Akt,phospho-CDK2,and c-myc protein.These losses are followed by massive induction ofp27Kip1 protein expression,cell cycle arrest,and apoptosis.Strikingly,IL-4 treatment prevented or reversed these changes.Furthermore,IL-4 suppressed the activation of caspases 9 and 3,and,in contrast to previous reports,induced the phosphorylation(deactivation)of BAD.IL-4 treatment also induced expression of BclxL,a STAT6-dependent gene.Pharmacologic inhibitors and dominant inhibitory forms of PI-3K andAkt abrogated the anti-apoptotic function of IL-4.These results suggest that the IL-4 receptor activates several signaling pathways,with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.

  13. 4β-Hydroxywithanolide E from Physalis peruviana (golden berry inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

    Directory of Open Access Journals (Sweden)

    Guo Zong-Lun

    2010-02-01

    Full Text Available Abstract Background The crude extract of the fruit bearing plant, Physalis peruviana (golden berry, demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown. Methods Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299 using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE assay was used to evaluate the DNA damage due to the drug. Results It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p p 50 of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h. Conclusions In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.

  14. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats.

    Science.gov (United States)

    Nelson, David W; Liu, Xiaowen; Holst, Jens J; Raybould, Helen E; Ney, Denise M

    2006-11-01

    Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal mucosa was not significantly different; ileal mucosal sucrase specific activity was significantly increased by resection in capsaicin-treated rats. Capsaicin did not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in plasma concentration of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not essential for GLP-2 secretion when the ileum has direct contact with luminal nutrients after resection. In summary, vagal afferent neurons are essential for maximal resection-induced intestinal adaptation through a mechanism that appears to involve stimulation by luminal nutrients.

  15. GH3-mediated auxin homeostasis links growth regulation with stress adaptation response in Arabidopsis.

    Science.gov (United States)

    Park, Jung-Eun; Park, Ju-Young; Kim, Youn-Sung; Staswick, Paul E; Jeon, Jin; Yun, Ju; Kim, Sun-Young; Kim, Jungmook; Lee, Yong-Hwan; Park, Chung-Mo

    2007-03-30

    Plants constantly monitor environmental fluctuations to optimize their growth and metabolism. One example is adaptive growth occurring in response to biotic and abiotic stresses. Here, we demonstrate that GH3-mediated auxin homeostasis is an essential constituent of the complex network of auxin actions that regulates stress adaptation responses in Arabidopsis. Endogenous auxin pool is regulated, at least in part, through negative feedback by a group of auxin-inducible GH3 genes encoding auxin-conjugating enzymes. An Arabidopsis mutant, wes1-D, in which a GH3 gene WES1 is activated by nearby insertion of the (35)S enhancer, exhibited auxin-deficient traits, including reduced growth and altered leaf shape. Interestingly, WES1 is also induced by various stress conditions as well as by salicylic acid and abscisic acid. Accordingly, wes1-D was resistant to both biotic and abiotic stresses, and stress-responsive genes, such as pathogenesis-related genes and CBF genes, were upregulated in this mutant. In contrast, a T-DNA insertional mutant showed reduced stress resistance. We therefore propose that GH3-mediated growth suppression directs reallocation of metabolic resources to resistance establishment and represents the fitness costs of induced resistance.

  16. Runway Arrested Landing Site (RALS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Runway Arrested Landing Site includes an underground complex located on a Mod 2, Mod 3, and Mod 3+ arresting gear and are located under the runway and accurately...

  17. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction.

    Science.gov (United States)

    Shah, Nisarg J; Hyder, Md Nasim; Quadir, Mohiuddin A; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J; Nevins, Myron; Spector, Myron; Hammond, Paula T

    2014-09-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.

  18. Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV‐3 and A-2780 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Piotrowska, Hanna; Myszkowski, Krzysztof; Ziółkowska, Alicja [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kulcenty, Katarzyna [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Wierzchowski, Marcin [Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan (Poland); Kaczmarek, Mariusz [Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan (Poland); Murias, Marek [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kwiatkowska-Borowczyk, Eliza [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Poznan (Poland); Jodynis-Liebert, Jadwiga, E-mail: liebert@ump.edu.pl [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland)

    2012-08-15

    In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC{sub 50} = 0.71 μM) and SKOV-3 (IC{sub 50} = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.

  19. Evolution of the dragonfly head-arresting system

    Science.gov (United States)

    Gorb, S. N.

    1999-01-01

    The arrester or fixation system of the head in adult Odonata is unique among arthropods. This system involves the organs of two body segments: the head and the neck. It consists of a skeleton–muscle apparatus that sets the arrester parts in motion. The parts comprise formations covered with complicated microstructures: fields of microtrichia on the rear surface of the head and post-cervical sclerites of the neck. The arrester immobilizes the head during feeding or when the dragonfly is in tandem flight. Thus, it may serve as an adaptation to save the head from violent mechanical disturbance and to stabilize gaze in a variety of behavioural situations. This study shows the evolutionary trend of the arrester in the order Odonata by using scanning electron microscopy and measurements of arrester structures in 227 species from 26 odonate families. The arrester design occurring in the Epiophlebiidae, Gomphidae, Neopetaliidae, Petaluridae and Chlorogomphinae is suggested to be the basic one. Two convergent pathways of head-arrester evolution among Zygoptera and Anisoptera are proposed. The possible functional significance of the arrester system is discussed.

  20. Aqueous extracts of the edible Gracilaria tenuistipitata are protective against H₂O₂-induced DNA damage, growth inhibition, and cell cycle arrest.

    Science.gov (United States)

    Yang, Jing-Iong; Yeh, Chi-Chen; Lee, Jin-Ching; Yi, Szu-Cheng; Huang, Hurng-Wern; Tseng, Chao-Neng; Chang, Hsueh-Wei

    2012-06-13

    Potential antioxidant properties of an aqueous extract of the edible red seaweed Gracilaria tenuistipitata (AEGT) against oxidative DNA damage were evaluated. The AEGT revealed several antioxidant molecules, including phenolics, flavonoids and ascorbic acid. In a cell-free assay, the extract exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity that significantly reduced H₂O₂-induced plasmid DNA breaks in a dose-response manner (P < 0.001). The AEGT also suppressed H₂O₂-induced oxidative DNA damage in H1299 cells by reducing the percentage of damaged DNA in a dose-response manner (P < 0.001) as measured by a modified alkaline comet-nuclear extract (comet-NE) assay. The MTT assay results showed that AEGT confers significant protection against H₂O₂-induced cytotoxicity and that AEGT itself is not cytotoxic (P < 0.001). Moreover, H₂O₂-induced cell cycle G2/M arrest was significantly released when cells were co-treated with different concentrations of AEGT (P < 0.001). Taken together, these findings suggest that edible red algae Gracilaria water extract can prevent H₂O₂-induced oxidative DNA damage and its related cellular responses.

  1. Alpinia pricei Rhizome Extracts Induce Cell Cycle Arrest in Human Squamous Carcinoma KB Cells and Suppress Tumor Growth in Nude Mice

    Directory of Open Access Journals (Sweden)

    You-Cheng Hseu

    2011-01-01

    Full Text Available Alpinia pricei has been shown to induce apoptosis in human squamous carcinoma (KB cells. In this study, we report the effectiveness of the ethanol (70% extracts of A. pricei rhizome (AP extracts in terms of tumor regression as determined using both in vitro cell culture and in vivo athymic nude mice models of KB cells. We found that the AP extract (25–200 μg/mL treatment decreased the proliferation of KB cells by arresting progression through the G2/M phase of the cell cycle. This cell cycle blockade was associated with reductions in cyclin A and B1, Cdc2, and Cdc25C, and increased p21/WAF1, Wee1, p53 and phospho-p53 (p-p53 in a dose- and time-dependent manner. Moreover, we found that AP extract treatment decreased metalloproteinase-9 (MMP-9 and urokinase plasminogen activator (u-PA expression, while expression of their endogenous inhibitors, tissue inhibitor of MMP-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1, were increased in KB cells. Furthermore, AP extract treatment effectively delayed tumor incidence in nude mice inoculated with KB cells and reduced the tumor burden. AP extract treatment also induced apoptotic DNA fragmentation, as detected by in situ TUNEL staining. Thus, A. pricei may possess antitumor activity in human squamous carcinoma (KB cells.

  2. CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Hye-Jin Park

    2014-09-01

    Full Text Available Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox-treated group. An increase in life span (ILS% = 50.88% was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients.

  3. Dactylone inhibits epidermal growth factor-induced transformation and phenotype expression of human cancer cells and induces G1-S arrest and apoptosis.

    Science.gov (United States)

    Fedorov, Sergey N; Shubina, Larisa K; Bode, Ann M; Stonik, Valentin A; Dong, Zigang

    2007-06-15

    The marine natural chamigrane-type sesquiterpenoid, dactylone, is closely related to secondary metabolites of some edible species of red algae. In the present study, the effect of dactylone was tested on the mouse skin epidermal JB6 P+ Cl41 cell line and its stable transfectants as well as on several human tumor cell lines, including lung (H460), colon (HCT-116), and skin melanomas (SK-MEL-5 and SK-MEL-28). This natural product was effective at nontoxic doses as a cancer-preventive agent, which exerted its actions, at least in part, through the inhibition of cyclin D3 and Cdk4 expression and retinoblastoma tumor suppressor protein (Rb) phosphorylation. The inhibition of these cell cycle components was followed by cell cycle arrest at the G1-S transition with subsequent p53-independent apoptosis. Therefore, these data showed that application of dactylone and related compounds may lead to decreased malignant cell transformation and/or decreased tumor cell proliferation.

  4. Monitoring changes in proteome during stepwise adaptation of a MDCK cell line from adherence to growth in suspension.

    Science.gov (United States)

    Kluge, Sabine; Benndorf, Dirk; Genzel, Yvonne; Scharfenberg, Klaus; Rapp, Erdmann; Reichl, Udo

    2015-08-20

    Adaptation of continuous cell lines to growth in suspension in a chemically defined medium has significant advantages for design and optimization in manufacturing of biologicals. In this work, changes in the protein expression level during a step-wise adaptation of an adherent Madin Darby canine kidney (MDCK) cell line to suspension growth were analyzed. Therefore, three cell line adaptations were performed independently. Two adaptations were monitored closely to characterize short term changes in protein expression levels after serum deprivation. In addition, initial stages of suspension growth were analyzed for both adaptations. The third adaptation involved MDCK suspension cells (MDCKSUS2) grown over an extended time period to achieve robust growth characteristics. Here, cells of the final stage of adaptation were compared with their parental cell line (MDCKADH). A combination of two dimensional differential gel electrophoresis for relative protein quantification and tandem mass spectrometry for protein identification enabled insights into cellular physiology. The two closely monitored cell line adaptations followed different routes regarding specific changes in protein expression but resulted in similar proteome profiles at the initial stages of suspension growth analyzed. Compared to the MDCKADH cells more than 90% of all changes in the protein expression level were identified after serum deprivation and were related to cytoskeletal structure, genetic information processing and cellular metabolism. Myosin proteins, involved in cellular detachment by actin-myosin contractile mechanisms were also differentially expressed. Interestingly, for both of the two adaptations, proteins linked for tumorigenicity, like lactoylglutathione lyase and sulfotransferase 1A1 were differentially expressed. In contrast, none of these proteins were differentially expressed for the MDCKSUS2 cell line. Overall, proteomic monitoring allowed identification of key proteins involved in

  5. NF-kappa B signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells

    NARCIS (Netherlands)

    Yao, Jun; Duan, Li; Fan, Mingwen; Wu, Xinxing

    2006-01-01

    The HDAC inhibitor Trichostatin A (TSA) exhibits antiturnour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113

  6. Selection and adaptation of microalgae to growth in 100% unfiltered coal-fired flue gas.

    Science.gov (United States)

    Aslam, Ambreen; Thomas-Hall, Skye R; Mughal, Tahira Aziz; Schenk, Peer M

    2017-03-01

    Microalgae have been considered for biological carbon capture and sequestration to offset carbon emissions from fossil fuel combustion. This study shows that mixed biodiverse microalgal communities can be selected for and adapted to tolerate growth in 100% flue gas from an unfiltered coal-fired power plant that contained 11% CO2. The high SOx and NOx emissions required slow adaptation of microalgae over many months, with step-wise increases from 10% to 100% flue gas supplementation and phosphate buffering at higher concentrations. After a rapid decline in biodiversity over the first few months, community profiling revealed Desmodesmus spp. as the dominant microalgae. To the authors' knowledge this work is the first to demonstrate that up 100% unfiltered flue gas from coal-fired power generation can be used for algae cultivation. Implementation of serial passages over a range of photobioreactors may contribute towards the development of microalgal-mediated carbon capture and sequestration processes.

  7. Rice LTG1 is involved in adaptive growth and fitness under low ambient temperature.

    Science.gov (United States)

    Lu, Guangwen; Wu, Fu-Qing; Wu, Weixun; Wang, Hong-Jun; Zheng, Xiao-Ming; Zhang, Yunhui; Chen, Xiuling; Zhou, Kunneng; Jin, Mingna; Cheng, Zhijun; Li, Xueyong; Jiang, Ling; Wang, Haiyang; Wan, Jianmin

    2014-05-01

    Low temperature (LT) is one of the most prevalent factors limiting the productivity and geographical distribution of rice (Oryza sativa L.). Although significant progress has been made in elucidating the effect of LT on seed germination and reproductive development in rice, the genetic component affecting vegetative growth under LT remains poorly understood. Here, we report that rice cultivars harboring the dominant LTG1 (Low Temperature Growth 1) allele are more tolerant to LT (15-25°C, a temperature range prevalent in high-altitude, temperate zones and high-latitude areas), than those with the ltg1 allele. Using a map-based cloning strategy, we show that LTG1 encodes a casein kinase I. A functional nucleotide polymorphism was identified in the coding region of LTG1, causing a single amino acid substitution (I357K) that is associated with the growth rate, heading date and yield of rice plants grown at LT. We present evidence that LTG1 affects rice growth at LT via an auxin-dependent process(es). Furthermore, phylogenetic analysis of this locus suggests that the ltg1 haplotype arose before the domestication of rice in tropical climates. Together, our data demonstrate that LTG1 plays an important role in the adaptive growth and fitness of rice cultivars under conditions of low ambient temperature.

  8. Relation of spontaneous transformation in cell culture to adaptive growth and clonal heterogeneity.

    Science.gov (United States)

    Rubin, A L; Yao, A; Rubin, H

    1990-01-01

    Cell transformation in culture is marked by the appearance of morphologically altered cells that continue to multiply to form discrete foci in confluent sheets when the surrounding cells are inhibited. These foci occur spontaneously in early-passage NIH 3T3 cells grown to confluency in 10% calf serum (CS) but are not seen in cultures grown to confluency in 2% CS. However, repeated passage of the cells at low density in 2% CS gives rise to an adapted population that grows to increasingly higher saturation densities and produces large numbers of foci in 2% CS. The increased saturation density of the adapted population in 2% CS is retained upon repeated passage in 10% CS, but the number and size of the foci produced in 2% CS gradually decrease under this regime. Clonal analysis confirms that the focus-forming potential of most if not all of the cells in a population increases in response to a continuously applied growth constraint, although only a small fraction of the population may actually form foci in a given assay. The acquired capacity for focus formation varies widely in clones derived from the adapted population and changes in diverse ways upon further passage of the clones. We propose that the adaptive changes result from progressive selection of successive phenotypic variations in growth capacity that occur spontaneously. The process designated progressive state selection resolves the apparent dichotomy between spontaneous mutation with selection on the one hand and induction on the other, by introducing selection among fluctuating states or metabolic patterns rather than among genetically altered cells.

  9. Understanding the adaptive growth strategy of Lactobacillus plantarum by in silico optimisation.

    Science.gov (United States)

    Teusink, Bas; Wiersma, Anne; Jacobs, Leo; Notebaart, Richard A; Smid, Eddy J

    2009-06-01

    In the study of metabolic networks, optimization techniques are often used to predict flux distributions, and hence, metabolic phenotype. Flux balance analysis in particular has been successful in predicting metabolic phenotypes. However, an inherent limitation of a stoichiometric approach such as flux balance analysis is that it can predict only flux distributions that result in maximal yields. Hence, previous attempts to use FBA to predict metabolic fluxes in Lactobacillus plantarum failed, as this lactic acid bacterium produces lactate, even under glucose-limited chemostat conditions, where FBA predicted mixed acid fermentation as an alternative pathway leading to a higher yield. In this study we tested, however, whether long-term adaptation on an unusual and poor carbon source (for this bacterium) would select for mutants with optimal biomass yields. We have therefore adapted Lactobacillus plantarum to grow well on glycerol as its main growth substrate. After prolonged serial dilutions, the growth yield and corresponding fluxes were compared to in silico predictions. Surprisingly, the organism still produced mainly lactate, which was corroborated by FBA to indeed be optimal. To understand these results, constraint-based elementary flux mode analysis was developed that predicted 3 out of 2669 possible flux modes to be optimal under the experimental conditions. These optimal pathways corresponded very closely to the experimentally observed fluxes and explained lactate formation as the result of competition for oxygen by the other flux modes. Hence, these results provide thorough understanding of adaptive evolution, allowing in silico predictions of the resulting flux states, provided that the selective growth conditions favor yield optimization as the winning strategy.

  10. Understanding the adaptive growth strategy of Lactobacillus plantarum by in silico optimisation.

    Directory of Open Access Journals (Sweden)

    Bas Teusink

    2009-06-01

    Full Text Available In the study of metabolic networks, optimization techniques are often used to predict flux distributions, and hence, metabolic phenotype. Flux balance analysis in particular has been successful in predicting metabolic phenotypes. However, an inherent limitation of a stoichiometric approach such as flux balance analysis is that it can predict only flux distributions that result in maximal yields. Hence, previous attempts to use FBA to predict metabolic fluxes in Lactobacillus plantarum failed, as this lactic acid bacterium produces lactate, even under glucose-limited chemostat conditions, where FBA predicted mixed acid fermentation as an alternative pathway leading to a higher yield. In this study we tested, however, whether long-term adaptation on an unusual and poor carbon source (for this bacterium would select for mutants with optimal biomass yields. We have therefore adapted Lactobacillus plantarum to grow well on glycerol as its main growth substrate. After prolonged serial dilutions, the growth yield and corresponding fluxes were compared to in silico predictions. Surprisingly, the organism still produced mainly lactate, which was corroborated by FBA to indeed be optimal. To understand these results, constraint-based elementary flux mode analysis was developed that predicted 3 out of 2669 possible flux modes to be optimal under the experimental conditions. These optimal pathways corresponded very closely to the experimentally observed fluxes and explained lactate formation as the result of competition for oxygen by the other flux modes. Hence, these results provide thorough understanding of adaptive evolution, allowing in silico predictions of the resulting flux states, provided that the selective growth conditions favor yield optimization as the winning strategy.

  11. Intestinal adaptation after extensive small bowel resection: differential changes in growth and insulin-like growth factor system messenger ribonucleic acids in jejunum and ileum.

    Science.gov (United States)

    Ziegler, T R; Mantell, M P; Chow, J C; Rombeau, J L; Smith, R J

    1998-07-01

    The distal small bowel exhibits greater adaptive growth than proximal segments after partial small intestine resection. To explore this process, we evaluated adaptive cellularity, intestinal insulin-like growth factor (IGF) system messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno-ileal resection or intestinal transection and reanastomosis without resection, followed by infusion of human recombinant IGF-I (2.4 mg/kgXday) or vehicle. After 7 days, resected rats demonstrated modest adaptive growth in jejunum and marked cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum (183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues. IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly increased ileal cellularity after resection, but had no effect in jejunum. IGF-I markedly increased IGFBP-3 mRNA levels in jejunum after both transection and resection. These data confirm that bowel resection induces greater adaptive growth in ileum than jejunum. IGF-I administration modestly increases ileal, but not jejunal, growth after resection. Increased levels of intestinal IGF-I and IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited jejunal vs. ileal growth after extensive jejuno-ileal resection.

  12. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Qing Yang

    Full Text Available Resveratrol, a naturally occurring polyphenolic compound, has been reported to exert anticancer activity by affecting diverse molecular targets. In this study, we examined the effects and the underlying mechanisms of resveratrol on gastric cancer. We found that resveratrol inhibited the proliferation of gastric cancer cells in a dose-dependent manner. At the concentration of 25 and 50 µM, resveratrol inhibited the cell viability and diminished the clonogenic potential of gastric cancer cells. Resveratrol treatment arrested gastric cancer cells in the G1 phase and led to senescence instead of apoptosis. Regulators of the cell cycle and senescence pathways, including cyclin D1, cyclin-dependent kinase (CDK4 and 6, p21 and p16, were dysregulated by resveratrol treatment. The inhibitory effects of resveratrol on gastric cancer were also verified in vivo using a nude mice xenograft model. Resveratrol (40 mg/kg/d exerted inhibitory activities on gastric cancer development and significantly decreased the fractions of Ki67-positive cells in the tumor specimens from the nude mice. After resveratrol treatment, the induction of senescence and the changes in the expression of the regulators involved in the cell cycle and senescence pathways were similar to what we observed in vitro. However, the depletion of Sirtuin (Sirt1 reversed the above-described effects of resveratrol both in vitro and in vivo. Our data suggest that resveratrol inhibits gastric cancer in a Sirt1-dependent manner and provide detailed evidence for the possibility of applying resveratrol in gastric cancer prevention and therapy.

  13. Fisetin inhibits growth, induces G₂ /M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation.

    Science.gov (United States)

    Pal, Harish C; Sharma, Samriti; Elmets, Craig A; Athar, Mohammad; Afaq, Farrukh

    2013-07-01

    Non-melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5-80 μm) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G₂ /M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2; Bcl-xL and Mcl-1); (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP-ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs.

  14. Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

    Science.gov (United States)

    Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

    2017-02-01

    Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage.

  15. Brain serotonergic activation in growth-stunted farmed salmon: adaption versus pathology

    DEFF Research Database (Denmark)

    Vindas, Marco A.; Johansen, Ida B.; Folkedal, Ole

    2016-01-01

    Signalling systems activated under stress are highly conserved, suggesting adaptive effects of their function. Pathologies arising from continued activation of such systems may represent a mismatch between evolutionary programming and current environments. Here, we use Atlantic salmon (Salmo salar......) in aquaculture as a model to explore this stance of evolutionary-based medicine, for which empirical evidence has been lacking. Growth-stunted (GS) farmed fish were characterized by elevated brain serotonergic activation, increased cortisol production and behavioural inhibition. We make the novel observation...

  16. Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21(WAF1/CIP1) expression.

    Science.gov (United States)

    Tseng, Tsui-Hwa; Chien, Ming-Hsien; Lin, Wea-Lung; Wen, Yu-Ching; Chow, Jyh-Ming; Chen, Chi-Kuan; Kuo, Tsang-Chih; Lee, Wei-Jiunn

    2017-02-01

    Apigenin (4',5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21(WAF1/CIP1) and increased the interaction of p21(WAF1/CIP1) with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21(WAF1/CIP1) promoter region, resulting in the increase of p21(WAF1/CIP1) transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21(WAF1/CIP1) and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017.

  17. Physiological and cell morphology adaptation of Bacillus subtilis at near-zero specific growth rates: a transcriptome analysis

    NARCIS (Netherlands)

    Overkamp, W.; Ercan, O.; Herber, M.; Maris, van A.J.; Kleerebezem, M.; Kuipers, O.P.

    2015-01-01

    Nutrient scarcity is a common condition in nature, but the resulting extremely low growth rates (below 0.025 h-1) are an unexplored research area in B. subtilis. To understand microbial life in natural environments, studying the adaptation of B. subtilis to near-zero growth conditions is relevant. T

  18. Transcriptome adaptation of group B Streptococcus to growth in human amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Izabela Sitkiewicz

    Full Text Available BACKGROUND: Streptococcus agalactiae (group B Streptococcus is a bacterial pathogen that causes severe intrauterine infections leading to fetal morbidity and mortality. The pathogenesis of GBS infection in this environment is poorly understood, in part because we lack a detailed understanding of the adaptation of this pathogen to growth in amniotic fluid. To address this knowledge deficit, we characterized the transcriptome of GBS grown in human amniotic fluid (AF and compared it with the transcriptome in rich laboratory medium. METHODS: GBS was grown in Todd Hewitt-yeast extract medium and human AF. Bacteria were collected at mid-logarithmic, late-logarithmic and stationary growth phase. We performed global expression microarray analysis using a custom-made Affymetrix GeneChip. The normalized hybridization values derived from three biological replicates at each growth point were obtained. AF/THY transcript ratios representing greater than a 2-fold change and P-value exceeding 0.05 were considered to be statistically significant. PRINCIPAL FINDINGS: We have discovered that GBS significantly remodels its transcriptome in response to exposure to human amniotic fluid. GBS grew rapidly in human AF and did not exhibit a global stress response. The majority of changes in GBS transcripts in AF compared to THY medium were related to genes mediating metabolism of amino acids, carbohydrates, and nucleotides. The majority of the observed changes in transcripts affects genes involved in basic bacterial metabolism and is connected to AF composition and nutritional requirements of the bacterium. Importantly, the response to growth in human AF included significant changes in transcripts of multiple virulence genes such as adhesins, capsule, and hemolysin and IL-8 proteinase what might have consequences for the outcome of host-pathogen interactions. CONCLUSIONS/SIGNIFICANCE: Our work provides extensive new information about how the transcriptome of GBS responds

  19. Predator-induced phenotypic plasticity in metabolism and rate of growth: rapid adaptation to a novel environment.

    Science.gov (United States)

    Handelsman, Corey A; Broder, E Dale; Dalton, Christopher M; Ruell, Emily W; Myrick, Christopher A; Reznick, David N; Ghalambor, Cameron K

    2013-12-01

    Novel environments often impose directional selection for a new phenotypic optimum. Novel environments, however, can also change the distribution of phenotypes exposed to selection by inducing phenotypic plasticity. Plasticity can produce phenotypes that either align with or oppose the direction of selection. When plasticity and selection are parallel, plasticity is considered adaptive because it provides a better pairing between the phenotype and the environment. If the plastic response is incomplete and falls short of producing the optimum phenotype, synergistic selection can lead to genetic divergence and bring the phenotype closer to the optimum. In contrast, non-adaptive plasticity should increase the strength of selection, because phenotypes will be further from the local optimum, requiring antagonistic selection to overcome the phenotype-environment mismatch and facilitate adaptive divergence. We test these ideas by documenting predator-induced plasticity for resting metabolic rate and growth rate in populations of the Trinidadian guppy (Poecilia reticulata) adapted to high and low predation. We find reduced metabolic rates and growth rates when cues from a predator are present during development, a pattern suggestive of adaptive and non-adaptive plasticity, respectively. When we compared populations recently transplanted from a high-predation environment into four streams lacking predators, we found evidence for rapid adaptive evolution both in metabolism and growth rate. We discuss the implications for predicting how traits will respond to selection, depending on the type of plasticity they exhibit.

  20. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Directory of Open Access Journals (Sweden)

    Kuroda S

    2014-08-01

    Full Text Available Shinji Kuroda,1 Justina Tam,2 Jack A Roth,1 Konstantin Sokolov,2 Rajagopal Ramesh3–5 1Department of Thoracic and Cardiovascular Surgery, 2Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Pathology, 4Graduate Program in Biomedical Sciences, 5Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Background: We have previously demonstrated the epidermal growth factor receptor (EGFR-targeted hybrid plasmonic magnetic nanoparticles (225-NP produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods: The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results: The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the

  1. E. coli 6S RNA: a universal transcriptional regulator within the centre of growth adaptation.

    Science.gov (United States)

    Geissen, René; Steuten, Benedikt; Polen, Tino; Wagner, Rolf

    2010-01-01

    Bacterial 6S RNA has been shown to bind with high affinity to σ(70)-containing RNA polymerase, suppressing σ(70)-dependent transcription during stationary phase, when 6S RNA concentrations are highest. We recently reported a genome-wide transcriptional comparison of wild-type and 6S RNA deficient E. coli strains. Contrary to the expected σ(70)- and stationary phase-specific regulatory effect of 6S RNA it turned out that mRNA levels derived from many alternative sigma factors, including σ(38) or σ(32), were affected during exponential and stationary growth. Among the most noticeably down-regulated genes at stationary growth are ribosomal proteins and factors involved in translation. In addition, a striking number of mRNA levels coding for enzymes involved in the purine metabolism, for transporters and stress regulators are altered both during log- and stationary phase. During the study we discovered a link between 6S RNA and the general stress alarmone ppGpp, which has a higher basal level in cells deficient in 6S RNA. This finding points to a functional interrelation of 6S RNA and the global network of stress and growth adaptation.

  2. Key physiological properties contributing to rhizosphere adaptation and plant growth promotion abilities of Azospirillum brasilense.

    Science.gov (United States)

    Fibach-Paldi, Sharon; Burdman, Saul; Okon, Yaacov

    2012-01-01

    Azospirillum brasilense is a plant growth promoting rhizobacterium (PGPR) that is being increasingly used in agriculture in a commercial scale. Recent research has elucidated key properties of A. brasilense that contribute to its ability to adapt to the rhizosphere habitat and to promote plant growth. They include synthesis of the auxin indole-3-acetic acid, nitric oxide, carotenoids, and a range of cell surface components as well as the ability to undergo phenotypic variation. Storage and utilization of polybetahydroxyalkanoate polymers are important for the shelf life of the bacteria in production of inoculants, products containing bacterial cells in a suitable carrier for agricultural use. Azospirillum brasilense is able to fix nitrogen, but despite some controversy, as judging from most systems evaluated so far, contribution of fixed nitrogen by this bacterium does not seem to play a major role in plant growth promotion. In this review, we focus on recent advances in the understanding of physiological properties of A. brasilense that are important for rhizosphere performance and successful interactions with plant roots.

  3. Redox state, reactive oxygen species and adaptive growth in colonial hydroids.

    Science.gov (United States)

    Blackstone, N W

    2001-06-01

    Colonial metazoans often encrust surfaces over which the food supply varies in time or space. In such an environment, adaptive colony development entails adjusting the timing and spacing of feeding structures and gastrovascular connections to correspond to this variable food supply. To investigate the possibility of such adaptive growth, within-colony differential feeding experiments were carried out using the hydroid Podocoryna carnea. Indeed, such colonies strongly exhibited adaptive growth, developing dense arrays of polyps (feeding structures) and gastrovascular connections in areas that were fed relative to areas that were starved, and this effect became more consistent over time. To investigate mechanisms of signaling between the food supply and colony development, measurements were taken of metabolic parameters that have been implicated in signal transduction in other systems, particularly redox state and levels of reactive oxygen species. Utilizing fluorescence microscopy of P. carnea cells in vivo, simultaneous measurements of redox state [using NAD(P)H] and hydrogen peroxide (using 2',7'-dichlorofluorescin diacetate) were taken. Both measures focused on polyp epitheliomuscular cells, since these exhibit the greatest metabolic activity. Colonies 3-5h after feeding were relatively oxidized, with low levels of peroxide, while colonies 24h after feeding were relatively reduced, with high levels of peroxide. The functional role of polyps in feeding and generating gastrovascular flow probably produced this dichotomy. Polyps 3-5h after feeding contract maximally, and this metabolic demand probably shifts the redox state in the direction of oxidation and diminishes levels of reactive oxygen species. In contrast, 24h after feeding, polyps are quiescent, and this lack of metabolic demand probably shifts the redox state in the direction of reduction and increases levels of reactive oxygen species. Within-colony differential feeding experiments were carried out on

  4. Physiological and cell morphology adaptation of Bacillus subtilis at near-zero specific growth rates: a transcriptome analysis.

    Science.gov (United States)

    Overkamp, Wout; Ercan, Onur; Herber, Martijn; van Maris, Antonius J A; Kleerebezem, Michiel; Kuipers, Oscar P

    2015-02-01

    Nutrient scarcity is a common condition in nature, but the resulting extremely low growth rates (below 0.025 h(-1) ) are an unexplored research area in Bacillus subtilis. To understand microbial life in natural environments, studying the adaptation of B. subtilis to near-zero growth conditions is relevant. To this end, a chemostat modified for culturing an asporogenous B. subtilis sigF mutant strain at extremely low growth rates (also named a retentostat) was set up, and biomass accumulation, culture viability, metabolite production and cell morphology were analysed. During retentostat culturing, the specific growth rate decreased to a minimum of 0.00006 h(-1) , corresponding to a doubling time of 470 days. The energy distribution between growth and maintenance-related processes showed that a state of near-zero growth was reached. Remarkably, a filamentous cell morphology emerged, suggesting that cell separation is impaired under near-zero growth conditions. To evaluate the corresponding molecular adaptations to extremely low specific growth, transcriptome changes were analysed. These revealed that cellular responses to near-zero growth conditions share several similarities with those of cells during the stationary phase of batch growth. However, fundamental differences between these two non-growing states are apparent by their high viability and absence of stationary phase mutagenesis under near-zero growth conditions.

  5. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Science.gov (United States)

    Kuroda, Shinji; Tam, Justina; Roth, Jack A; Sokolov, Konstantin; Ramesh, Rajagopal

    2014-01-01

    Background We have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. Conclusion The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth

  6. β-Arrestin1/miR-326 Transcription Unit Is Epigenetically Regulated in Neural Stem Cells Where It Controls Stemness and Growth Arrest

    Science.gov (United States)

    Begalli, Federica; Abballe, Luana; Catanzaro, Giuseppina; Vacca, Alessandra; Napolitano, Maddalena; Tafani, Marco; Giangaspero, Felice; Locatelli, Franco

    2017-01-01

    Cell development is regulated by a complex network of mRNA-encoded proteins and microRNAs, all funnelling onto the modulation of self-renewal or differentiation genes. How intragenic microRNAs and their host genes are transcriptionally coregulated and their functional relationships for the control of neural stem cells (NSCs) are poorly understood. We propose here the intragenic miR-326 and its host gene β-arrestin1 as novel players whose epigenetic silencing maintains stemness in normal cerebellar stem cells. Such a regulation is mediated by CpG islands methylation of the common promoter. Epigenetic derepression of β-arrestin1/miR-326 by differentiation signals or demethylating agents leads to suppression of stemness features and cell growth and promotes cell differentiation. β-Arrestin1 inhibits cell proliferation by enhancing the nuclear expression of the cyclin-dependent kinase inhibitor p27. Therefore, we propose a new mechanism for the control of cerebellar NSCs where a coordinated epigenetic mechanism finely regulates β-arrestin1/miR-326 expression and consequently NSCs stemness and cell growth. PMID:28298929

  7. Theracurmin® efficiently inhibits the growth of human prostate and bladder cancer cells via induction of apoptotic cell death and cell cycle arrest.

    Science.gov (United States)

    Kang, Minyong; Ho, Jin-Nyoung; Kook, Ha Rim; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2016-03-01

    In the present study, we aimed to investigate the anticancer properties of Theracurmin®, a novel form of the yellow curry pigment curcumin, as well as explore the molecular mechanisms of the potential anticancer effects of Theracurmin® on human prostate cancer and bladder cancer cells in vitro. The proliferation of cancer cells was examined by using the Cell Counting Kit-8. The clonogenic growth potential was determined by clonogenic assay. Cell cycle distribution was evaluated by flow cytometry using propidium iodide staining. Western blot analysis was applied to explore the expression patterns of molecules associated with apoptotic cell death and cell cycle checkpoint. We noted that Theracurmin® and curcumin exhibited similar anticancer effects in both androgen-dependent and -independent human prostate cancer cells in a dose- and time-dependent manner. These agents reduced cell viability and clonogenic growth potential by inducing apoptosis and cell cycle disturbance in human prostate cancer cells. Theracurmin® and curcumin also exerted marked anticancer effects on human bladder cancer cells, even in cisplatin-resistant T24R2 cells, in a dose- and time-dependent manner. Moreover, Theracurmin® and curcumin treatment decreased cell viability and clonogenicity via induction of apoptotic cell death and cell cycle dysregulation in human bladder cancer cells. In conclusion, our study suggests that Theracurmin® has potential as an anticancer agent in complementary and alternative medicine for these urological cancers.

  8. Adaptive strategies for graph state growth in the presence of monitored errors

    CERN Document Server

    Campbell, E T; Benjamin, S C; Kok, P; Campbell, Earl T.; Fitzsimons, Joseph; Benjamin, Simon C.; Kok, Pieter

    2006-01-01

    Graph states, also known as cluster states, are the entanglement resource that enables one-way quantum computing. They can be grown by a series of projective measurements on the component qubits. Such measurements typically carry a significant failure probability. Moreover, even upon success they may generate imperfect entanglement. Here we describe strategies to adapt growth operations in order to cancel incurred errors. Nascent states that initially deviate from the ideal graph states evolve toward the desired high fidelity resource without incurring an impractical overhead. Our analysis extends the diagrammatic language of graph states to include characteristics such as tilted vertices, weighted edges, and partial fusion, which may arise due to experimental imperfections. The strategies we present are relevant to parity projection schemes such as optical `path erasure' with distributed matter qubits.

  9. Adaptive growth of tree root systems in response to wind action and site conditions.

    Science.gov (United States)

    Nicoll, Bruce C.; Ray, Duncan

    1996-01-01

    Soil-root plate dimensions and structural root architecture were examined on 46-year-old Sitka spruce (Picea sitchensis (Bong.) Carr.) trees that had been mechanically uprooted. Rooting depth was restricted by a water table, and root system morphology had adapted to resist the wind movement associated with shallow rooting. The spread of the root system and the ratio of root mass to shoot mass (root/shoot ratio) were both negatively related to soil-root plate depth. Root systems had more structural root mass on the leeward side than the windward side of the tree relative to the prevailing wind direction. Cross sections of structural roots were obtained at distances of 0.5, 0.75, 1.0, and 1.25 m from the tree center. Buttressed parts of roots had greater lateral and vertical secondary thickening above rather than below the biological center. This uneven growth, which produced a shape similar in cross section to a T-beam, was greater on the leeward side of the tree, and was greatest at 0.5 m from the tree center of shallow rooted trees. Further from the tree, particularly on the windward side, many roots developed eccentric cross-sectional shapes comparable to I-beams, which would efficiently resist vertical flexing. Roots became more ovoid in shape with increasing distance from the tree, especially on deep rooted trees where lateral roots tapered rapidly to a small diameter. We conclude that these forms of adaptive growth in response to wind movement improve the rigidity of the soil-root plate and counteract the increasing vulnerability to windthrow as the tree grows.

  10. Universal approximation of extreme learning machine with adaptive growth of hidden nodes.

    Science.gov (United States)

    Zhang, Rui; Lan, Yuan; Huang, Guang-Bin; Xu, Zong-Ben

    2012-02-01

    Extreme learning machines (ELMs) have been proposed for generalized single-hidden-layer feedforward networks which need not be neuron-like and perform well in both regression and classification applications. In this brief, we propose an ELM with adaptive growth of hidden nodes (AG-ELM), which provides a new approach for the automated design of networks. Different from other incremental ELMs (I-ELMs) whose existing hidden nodes are frozen when the new hidden nodes are added one by one, in AG-ELM the number of hidden nodes is determined in an adaptive way in the sense that the existing networks may be replaced by newly generated networks which have fewer hidden nodes and better generalization performance. We then prove that such an AG-ELM using Lebesgue p-integrable hidden activation functions can approximate any Lebesgue p-integrable function on a compact input set. Simulation results demonstrate and verify that this new approach can achieve a more compact network architecture than the I-ELM.

  11. High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Jay W.; Stouffer, Richard L.; Rodland, Karin D.

    2005-06-09

    Ovarian cancer is the most lethal gynecological cancer affecting women. Hormone-based therapies are variably successful in treating ovarian cancer, but the reasoning behind these therapies is paradoxical. Clinical reagents such as tamoxifen are considered to inhibit or reverse tumor growth by competitive inhibition of the estrogen receptor (ER); however high dose estrogen is as clinically effective as tamoxifen, and it is unlikely that estrogen is acting by blocking ER activity; however, it may be activating a unique function of the ER that is nonmitogenic. For poorly defined reasons, 90% of varian cancers derive from the ovarian surface epithelium (OSE). In vivo the ER-positive OSE is exposed to high estrogen levels, reaching micromolar concentrations in dominant ovarian follicles. Using cultured OSE cells in vitro, we show that these levels of estradiol (1 ug/ml; {approx}3um) block the actions of serum growth factors, activate the G1 phase retinoblastoma AQ:A checkpoint, and induce p21, an inhibitor of kinases that normally inactivate the retinoblastoma checkpoint. We also show that estradiol increases p53 levels, which may contribute to p21 induction. Supporting the hypothesis that clinical selective ER modulators activate this novel ER function, we find that micromolar doses of tamoxifen and the ''pure antiestrogen'' ICI 182,780 elicit the same effects as estradiol. We propose that, in the context of proliferation, these data clarify some paradoxical aspects of hormone-based therapy and suggest that fuller understanding of normal ER function is necessary to improve therapeutic strategies that target the ER. (J Clin Endocrinol Metab 90: 0000-0000, 2005)

  12. RhoA/phosphatidylinositol 3-kinase/protein kinase B/mitogen-activated protein kinase signaling after growth arrest-specific protein 6/mer receptor tyrosine kinase engagement promotes epithelial cell growth and wound repair via upregulation of hepatocyte growth factor in macrophages.

    Science.gov (United States)

    Lee, Ye-Ji; Park, Hyun-Jung; Woo, So-Youn; Park, Eun-Mi; Kang, Jihee Lee

    2014-09-01

    Growth arrest-specific protein 6 (Gas6)/Mer receptor tyrosine kinase (Mer) signaling modulates cytokine secretion and helps to regulate the immune response and apoptotic cell clearance. Signaling pathways that activate an epithelial growth program in macrophages are still poorly defined. We report that Gas6/Mer/RhoA signaling can induce the production of epithelial growth factor hepatic growth factor (HGF) in macrophages, which ultimately promotes epithelial cell proliferation and wound repair. The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal-regulated protein kinase, and Jun NH2-terminal kinase axis in RAW 264.7 cells, was identified as Gas6/Mer downstream signaling pathway for the upregulation of HGF mRNA and protein. Conditioned medium from RAW 264.7 cells that had been exposed to Gas6 or apoptotic cells enhanced epithelial cell proliferation of the epithelial cell line LA-4 and wound closure. Cotreatment with an HGF receptor-blocking antibody or c-Met antagonist downregulated this enhancement. Inhibition of Mer with small interfering RNA (siRNA) or the RhoA/Rho kinase pathway by RhoA siRNA or Rho kinase pharmacologic inhibitor suppressed Gas6-induced HGF mRNA and protein expression in macrophages and blocked epithelial cell proliferation and wound closure induced by the conditioned medium. Our data provide evidence that macrophages can be reprogrammed by Gas6 to promote epithelial proliferation and wound repair via HGF, which is induced by the Mer/RhoA/Akt/MAP kinase pathway. Thus, defects in Gas6/Mer/RhoA signaling in macrophages may delay tissue repair after injury to the alveolar epithelium.

  13. Hydrogen peroxide inhibits transforming growth factor-β1-induced cell cycle arrest by promoting Smad3 linker phosphorylation through activation of Akt-ERK1/2-linked signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jiyeon; Park, Seong Ji; Jo, Eun Ji [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Hui-Young [Department of Internal Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Hong, Suntaek [Laboratory of Cancer Cell Biology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840 (Korea, Republic of); Kim, Seong-Jin [CHA Cancer Institute, CHA University of Medicine and Science, Seoul 135-081 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-06-14

    Highlights: •H{sub 2}O{sub 2} inhibits TGF-β1-induced cell cycle arrest. •H{sub 2}O{sub 2} induces Smad3 linker phosphorylation through Akt-ERK1/2 pathway. •H{sub 2}O{sub 2}-mediated suppression of TGF-β signal requires Smad3 linker phosphorylation. •This is a first report about interplay between H{sub 2}O{sub 2} and growth inhibition pathway. -- Abstract: Hydrogen peroxide (H{sub 2}O{sub 2}) functions as a second messenger in growth factor receptor-mediated intracellular signaling cascade and is tumorigenic by virtue of its ability to promote cell proliferation; however, the mechanisms underlying the growth stimulatory action of H{sub 2}O{sub 2} are less understood. Here we report an important mechanism for antagonistic effects of H{sub 2}O{sub 2} on growth inhibitory response to transforming growth factor-β1 (TGF-β1). In Mv1Lu and HepG2 cells, pretreatment of H{sub 2}O{sub 2} (0.05–0.2 mM) completely blocked TGF-β1-mediated induction of p15{sup INK4B} expression and increase of its promoter activity. Interestingly, H{sub 2}O{sub 2} selectively suppressed the transcriptional activation potential of Smad3, not Smad2, in the absence of effects on TGF-β1-induced phosphorylation of the COOH-tail SSXS motif of Smad3 and its nuclear translocation. Mechanism studies showed that H{sub 2}O{sub 2} increases the phosphorylation of Smad3 at the middle linker region in a concentration- and time-dependent manner and this effect is mediated by activation of extracellular signal-activated kinase 1/2 through Akt. Furthermore, expression of a mutant Smad3 in which linker phosphorylation sites were ablated significantly abrogated the inhibitory effects of H{sub 2}O{sub 2} on TGF-β1-induced increase of p15{sup INK4B}-Luc reporter activity and blockade of cell cycle progression from G1 to S phase. These findings for the first time define H{sub 2}O{sub 2} as a signaling molecule that modulate Smad3 linker phosphorylation and its transcriptional activity, thus providing

  14. ADAPTATION TO UNFAVORABLE CONDITIONS OF GROWTH: PATHOGENICITY OF ACHOLEPLASMA LAIDLAWII PG8

    Directory of Open Access Journals (Sweden)

    Maxim V. Trushin

    2006-11-01

    Full Text Available ABSTRACT:As a result of cultivation of A. laidlawii PG8 cells on the deficient medium during 480 days, the mycoplasma culture adapted in vitro to unfavorable growth conditions was obtained. The culture consisted of cells with sizes less than 0.2 µm and features of A. laidlawii PG8 ultramicroforms, nanocells. A. laidlawii PG8 culture adapted in vitro to unfavorable growth conditions shows more evident phytopathogenicity than the unadapted one. Infecting plants V. minor L. by A. laidlawii PG8 culture adapted in vitro to UGC resulted in the appearance of chloroses in 75%, necrosis – 50%, leaves marcescence – 50% and abnormalities of bine development in 30% of plants through 12 days, while infecting plants by A. laidlawii PG8 culture unadapted to UGC led to respective signs in 40%, 25%, 25% and 0% of samples, respectively, through 30 days. The ability of A. laidlawii PG8 to form UMF resistant to stress factors in UGC with high phytopathogenic potential seems to demand a new approach to investigate the precise mechanisms of interacting the mycoplasma with host organisms.RESUMENComo resultado del cultivo de células de A. laidlawii PG8 en medio deficiente durante 480 días, fue obtenido un cultivo de mycoplasma adaptado in vitro a las condiciones desfavorables del crecimiento. El cultivo consistió en células con tamaño menor de 0.2 µm y características PG8 ultramicroformas de A. laidlawii nanocélulas. El cultivo de A. laidlawii PG8 adaptado in vitro a condiciones desfavorables del crecimiento muestra más evidente fitopatogenicidad que el inadaptado. Plantas infectadas V. minor L. por el cultivo del A. laidlawii PG8 adaptado in vitro a UGC dio como resultado la aparición de clorosis en el 75%, necrosis en el 50%, marcescencia de las hojas en el 50% y anormalidades del desarrollo del bine en el 30% de plantas a los 12 días, mientras que las plantas infectadas por el cultivo del A. laidlawii PG8 inadaptado a UGC, condujo a dichos signos en

  15. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells.

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M; Pyne, Nigel J; Pyne, Susan

    2016-03-29

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest.

  16. An adaptive ARX model to estimate the RUL of aluminum plates based on its crack growth

    Science.gov (United States)

    Barraza-Barraza, Diana; Tercero-Gómez, Víctor G.; Beruvides, Mario G.; Limón-Robles, Jorge

    2017-01-01

    A wide variety of Condition-Based Maintenance (CBM) techniques deal with the problem of predicting the time for an asset fault. Most statistical approaches rely on historical failure data that might not be available in several practical situations. To address this issue, practitioners might require the use of self-starting approaches that consider only the available knowledge about the current degradation process and the asset operating context to update the prognostic model. Some authors use Autoregressive (AR) models for this purpose that are adequate when the asset operating context is constant, however, if it is variable, the accuracy of the models can be affected. In this paper, three autoregressive models with exogenous variables (ARX) were constructed, and their capability to estimate the remaining useful life (RUL) of a process was evaluated following the case of the aluminum crack growth problem. An existing stochastic model of aluminum crack growth was implemented and used to assess RUL estimation performance of the proposed ARX models through extensive Monte Carlo simulations. Point and interval estimations were made based only on individual history, behavior, operating conditions and failure thresholds. Both analytic and bootstrapping techniques were used in the estimation process. Finally, by including recursive parameter estimation and a forgetting factor, the ARX methodology adapts to changing operating conditions and maintain the focus on the current degradation level of an asset.

  17. Stiffener Layout Optimization of Inlet Structure for Electrostatic Precipitator by Improved Adaptive Growth Method

    Directory of Open Access Journals (Sweden)

    Jin Ji

    2014-11-01

    Full Text Available The inlet structure is the main part of an electrostatic precipitator, so its mechanical properties, including the static strength, stiffness, and vibration characteristics, play an important role in the structural safety. In order to achieve good mechanical performance and lightweight of the inlet structure, an optimal design method, which is based on growth mechanism of the branching systems in nature and optimality criteria, named the improved adaptive growth method, is suggested. The method is applied to optimize the stiffener layout of the inlet structure, and the multiobjective optimization mathematical model which consists of the minimum compliance and the maximum natural frequency is considered. The optimality criteria method is applied to solve the design problem. The design result shows that the suggested method is effective, compared with the empirical design of the inlet structure, the weight of the optimal structure is reduced by 3.0%, while the global stiffness and the first natural frequency are increased by 18.83% and 4.66%, respectively.

  18. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

    Science.gov (United States)

    Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

    2010-09-01

    The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications.

  19. The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth of Erwinia amylovora and acts as a seed germination-arrest factor.

    Science.gov (United States)

    Lee, Xiaoyun; Azevedo, Mark D; Armstrong, Donald J; Banowetz, Gary M; Reimmann, Cornelia

    2013-02-01

    The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) shares biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P. aeruginosa strain overproducing AMB weakly interfered with seed germination of the grassy weed Poa annua and strongly inhibited growth of Erwinia amylovora, the causal agent of the devastating orchard crop disease known as fire blight. AMB was active against a 4-formylaminooxyvinylglycine-resistant isolate of E. amylovora, suggesting that the molecular targets of the two oxyvinylglycines in Erwinia do not, or not entirely, overlap. The AMB biosynthesis and transport genes were shown to be organized in two separate transcriptional units, ambA and ambBCDE, which were successfully expressed from IPTG-inducible tac promoters in the heterologous host P. fluorescens CHA0. Engineered AMB production enabled this model biocontrol strain to become inhibitory against E. amylovora and to weakly interfere with the germination of several graminaceous seeds. We conclude that AMB production requires no additional genes besides ambABCDE and we speculate that their expression in marketed fire blight biocontrol strains could potentially contribute to disease control.

  20. IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms.

    Directory of Open Access Journals (Sweden)

    Brian Wan-Chi Tse

    Full Text Available Interleukin(IL-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM/B4H7-luc. RM1 and RM1(BM/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4. IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4(+ and CD8(+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/- mice or in mice depleted of CD4(+ and/or CD8(+ cells than in normal mice. The tumors in RAG1(-/- mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

  1. Intestinal growth adaptation and glucagon-like peptide 2 in rats with ileal--jejunal transposition or small bowel resection

    DEFF Research Database (Denmark)

    Thulesen, J; Hartmann, B; Kissow, Hannelouise;

    2001-01-01

    , and twofold in the distally resected group. Tissue GLP-2 levels were unchanged in resected rats. The data indicate that transposition of a distal part of the small intestine, and thereby exposure of L cells to a more nutrient-rich chyme, leads to intestinal growth. The adaptive intestinal growth is associated......Glucagon-like peptide 2 (GLP-2), produced by enteroendocrine L-cells, regulates intestinal growth. This study investigates circulating and intestinal GLP-2 levels in conditions with altered L-cell exposure to nutrients. Rats were allocated to the following experimental groups: ileal...... GLP-2 levels in the intestinal segments were unchanged. In resected rats with reduced intestinal capacity, adaptive small bowel growth was more pronounced following proximal resection than distal small bowel resection. Circulating GLP-2 levels increased threefold in proximally resected animals...

  2. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest.

    Science.gov (United States)

    Chiao, Jen Wei; Wu, Hongyan; Ramaswamy, Gita; Conaway, C Clifford; Chung, Fung-Lung; Wang, Longgui; Liu, Delong

    2004-08-01

    Epidemiological surveys indicate that intake of cruciferous vegetables is inversely related to prostate cancer incidence, although the responsible dietary factors have not been identified. Our studies demonstrated that exposure of human prostate cancer cells in culture to the N-acetylcysteine (NAC) conjugate of phenethyl isothiocyanate (PEITC-NAC), the major metabolite of PEITC that is abundant in watercress, inhibited proliferation and tumorigenesis. The PEITC-NAC is known to mediate cytoprotection at initiation of carcinogenesis. The relevance of PEITC-NAC in diets on the growth of prostate tumor cells has been evaluated in immunodeficient mice with xenografted tumors of human prostate cancer PC-3 cells. The daily PEITC-NAC (8 micromol/g) supplemented diet group showed a significant reduction in tumor size in 100% of the mice during the 9-week treatment period. Tumor weight at autopsy was reduced by 50% compared with mice on the diet without PEITC-NAC (P = 0.05). Mitosis and in vivo 5-bromo-2'-deoxyuridine labeled proliferating cells were reduced in these tumors. The PEITC-NAC diet up-regulated the inhibitors of cyclin-dependent kinases p21WAF-1/Cip-1 and p27Kip1, and reduced the expression of cyclins D and E, indicating they were potential molecular targets. As a result, phosphorylated Rb was significantly decreased and the G1- to S-phase transition retarded. The treated tumors also showed a significant increase in apoptosis as determined by in situ end-labeling, and by poly ADP-ribose polymerase cleavage. This study demonstrates the first in vivo evidence of dietary PEITC-NAC inhibiting tumorigenesis of prostate cancer cells. PEITC-NAC may prevent initiation of carcinogenesis and modulate the post-initiation phase by targeting cell cycle regulators and apoptosis induction.

  3. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  4. [Arrest of maturation in spermatogenesis].

    Science.gov (United States)

    Francavilla, S; Bellocci, M; Martini, M; Bruno, B; Moscardelli, S; Fabbrini, A; Properzi, G

    1982-07-30

    The ultrastructural aspects of the germinal epithelium of 10 infertile men affected by maturative arrest of spermatogenesis were studied. We noted an increased number of malformed germinal cells. Marginal nuclear vescicles were present in spermatogonia of patients affected by spermatogonial arrest. The few spermatid present in the germinal epithelium of the patients affected by a spermatidic arrest presented changes of the nuclear condensation, the acrosome, and the tail. The Sertoli cells presented an immature aspect of the nucleus and changes of the "mantle". A possible correlation between the Sertoli cells changes and the altered spermatogenesis was proposed.

  5. Fronts under arrest: Nonlocal boundary dynamics in biology.

    Science.gov (United States)

    McCalla, Scott G; von Brecht, James H

    2016-12-01

    We introduce a minimal geometric partial differential equation framework to understand pattern formation from interacting, counterpropagating fronts. Our approach concentrates on the interfaces between different states in a system, and relies on both nonlocal interactions and mean-curvature flow to track their evolution. As an illustration, we use this approach to describe a phenomenon in bacterial colony formation wherein sibling colonies can arrest each other's growth. This arrested motion leads to static separations between healthy, growing colonies. As our minimal model faithfully recovers the geometry of these competing colonies, it captures and elucidates the key leading-order mechanisms responsible for such patterned growth.

  6. A palmitoyl conjugate of insect pentapeptide Yamamarin arrests cell proliferation and respiration

    OpenAIRE

    2010-01-01

    A palmitoyl conjugate of an insect pentapeptide that occurs in diapausing insects causes a reversible cell-cycle arrest and suppresses mitochondrial respiration. This peptide compound also causes growth arrest in murine leukemic cell line expressing human gene Bcr/Abl and a farnesoyl peptide induces embryonic diapause in Bombyx mori. These results demonstrate that the insect peptide compounds can lead to the understanding of a common pathway in developmental arrest in animals and may provide ...

  7. Seedling growth dynamic of Haloxylon ammodendron and its adaptation strategy to habitat condition in hinterland of desert

    Institute of Scientific and Technical Information of China (English)

    WEI Jiang; ZHANG XiMing; SHAN LiShan; YAN HaiLong; LIANG ShaoMing

    2007-01-01

    Through measuring the above/below-ground growth data of Haloxylon ammodendron seedlings at different stages in hinterland of the desert the results show that the H. ammodendron seedling growth has demonstrated different adaptation characteristics in the continued arid environment with time and space. In May, July, September and October, the growth speed of vertical root is 0.607 cm/d, 0.809 cm/d, 0.155 cm/d and 0.394 cm/d, respectively; the growth speed of height is 0.093 cm/d, 0.076 cm/d,0.408 cm/d and 136 cm/d, respectively. It is explained that seedlings root system has the growth superiority in space. The maximum growth speed of below-ground (vertical root and horizontal root) of seedling is earlier than that of above-ground (height and horizontal of shoot). In the different periods,the vertical growth speed and the horizontal growth speed of below-ground is 2-10 times and 3-5 times than the height increase speed and the shoot growth speed, respectively. In the whole season,the growth speed of above/below-ground of seedlings shows the alternation growth tendency. At the different periods, the root/shoot ratio of H. ammodendron seedlings is 0.41, 0.3, 0.39 and 0.88. All these characteristics are the comprehensive performance of seedlings' strategy selection to adapt to the continued arid environment.

  8. Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors.

    Science.gov (United States)

    Fleming, Michael S; Vysochan, Anna; Paixão, Sόnia; Niu, Jingwen; Klein, Rüdiger; Savitt, Joseph M; Luo, Wenqin

    2015-04-02

    RET can be activated in cis or trans by its co-receptors and ligands in vitro, but the physiological roles of trans signaling are unclear. Rapidly adapting (RA) mechanoreceptors in dorsal root ganglia (DRGs) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth. Here, we show that Ret and Gfrα2 null mice display comparable early central projection deficits, but Gfrα2 null RA mechanoreceptors recover later. Loss of Gfrα1, the co-receptor implicated in activating RET in trans, causes no significant central projection or cell survival deficit, but Gfrα1;Gfrα2 double nulls phenocopy Ret nulls. Finally, we demonstrate that GFRα1 produced by neighboring DRG neurons activates RET in RA mechanoreceptors. Taken together, our results suggest that trans and cis RET signaling could function in the same developmental process and that the availability of both forms of activation likely enhances but not diversifies outcomes of RET signaling.

  9. ADAPTATION OF CRACK GROWTH DETECTION TECHNIQUES TO US MATERIAL TEST REACTORS

    Energy Technology Data Exchange (ETDEWEB)

    A. Joseph Palmer; Sebastien P. Teysseyre; Kurt L. Davis; Gordon Kohse; Yakov Ostrovsky; David M. Carpenter; Joy L. Rempe

    2015-04-01

    A key component in evaluating the ability of Light Water Reactors to operate beyond 60 years is characterizing the degradation of materials exposed to radiation and various water chemistries. Of particular concern is the response of reactor materials to Irradiation Assisted Stress Corrosion Cracking (IASCC). Some test reactors outside the United States, such as the Halden Boiling Water Reactor (HBWR), have developed techniques to measure crack growth propagation during irradiation. The basic approach is to use a custom-designed compact loading mechanism to stress the specimen during irradiation, while the crack in the specimen is monitored in-situ using the Direct Current Potential Drop (DCPD) method. In 2012 the US Department of Energy commissioned the Idaho National Laboratory and the MIT Nuclear Reactor Laboratory (MIT NRL) to take the basic concepts developed at the HBWR and adapt them to a test rig capable of conducting in-pile IASCC tests in US Material Test Reactors. The first two and half years of the project consisted of designing and testing the loader mechanism, testing individual components of the in-pile rig and electronic support equipment, and autoclave testing of the rig design prior to insertion in the MIT Reactor. The load was applied to the specimen by means of a scissor like mechanism, actuated by a miniature metal bellows driven by pneumatic pressure and sized to fit within the small in-core irradiation volume. In addition to the loader design, technical challenges included developing robust connections to the specimen for the applied current and voltage measurements, appropriate ceramic insulating materials that can endure the LWR environment, dealing with the high electromagnetic noise environment of a reactor core at full power, and accommodating material property changes in the specimen, due primarily to fast neutron damage, which change the specimen resistance without additional crack growth. The project culminated with an in

  10. Effects of ecological differentiation on Lotka-Volterra systems for species with behavioral adaptation and variable growth rates.

    Science.gov (United States)

    Lacitignola, D; Tebaldi, C

    2005-03-01

    We study the properties of a n2-dimensional Lotka-Volterra system describing competing species that include behaviorally adaptive abilities. We indicate as behavioral adaptation a mechanism, based on a kind of learning, which is not viewed in the evolutionary sense but is intended to occur over shorter time scales. We consider a competitive adaptive n species Lotka-Volterra system, n > or = 3, in which one species is made ecologically differentiated with respect to the others by carrying capacity and intrinsic growth rate. The symmetry properties of the system and the existence of a certain class of invariant subspaces allow the introduction of a 7-dimensional reduced model, where n appears as a parameter, which gives full account of existence and stability of equilibria in the complete system. The reduced model is effective also in describing the time-dependent regimes for a large range of parameter values. The case in which one species has a strong ecological advantage (i.e. with a carrying capacity higher than the others), but with a varying growth rate, has been analyzed in detail, and time-dependent behaviors have been investigated in the case of adaptive competition among four species. Relevant questions, as species survival/exclusion, are addressed focusing on the role of adaptation. Interesting forms of species coexistence are found (i.e. competitive stable equilibria, periodic oscillations, strange attractors).

  11. The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation.

    Science.gov (United States)

    Ferrezuelo, Francisco; Colomina, Neus; Palmisano, Alida; Garí, Eloi; Gallego, Carme; Csikász-Nagy, Attila; Aldea, Martí

    2012-01-01

    Budding yeast cells are assumed to trigger Start and enter the cell cycle only after they attain a critical size set by external conditions. However, arguing against deterministic models of cell size control, cell volume at Start displays great individual variability even under constant conditions. Here we show that cell size at Start is robustly set at a single-cell level by the volume growth rate in G1, which explains the observed variability. We find that this growth-rate-dependent sizer is intimately hardwired into the Start network and the Ydj1 chaperone is key for setting cell size as a function of the individual growth rate. Mathematical modelling and experimental data indicate that a growth-rate-dependent sizer is sufficient to ensure size homeostasis and, as a remarkable advantage over a rigid sizer mechanism, it reduces noise in G1 length and provides an immediate solution for size adaptation to external conditions at a population level.

  12. Sculpting Pickering Emulsion Droplets by Arrest and Jamming

    Science.gov (United States)

    Burke, Christopher; Wei, Zengyi; Caggioni, Marco; Spicer, Patrick; Atherton, Tim

    Pickering emulsion droplets can be arrested into non-spherical shapes--useful for applications such as active delivery--through a general mechanism of deformation followed by absorption of additional colloidal particles onto the interface, relaxation of the droplet caused by surface tension and arrest at some point due to crowding of the particles. We perform simulations of the arrest process to clarify the relative importance of diffusive rearrangement of particles and collective forcing due to surface evolution. Experiment and theory are compared, giving insight into the stability of the resulting capsules and the robustness of the production process for higher-throughput production in, for example, microfluidic systems. We adapt theoretical tools from the jamming literature to better understand the arrested configurations and long timescale evolution of the system: using linear programming and a penalty function approach, we identify unjamming motions in kinetically arrested states. We propose a paradigm of ``metric jamming'' to describe the limiting behavior of this class of system: a structure is metric-jammed if it is stable with respect to collective motion of the particles as well as evolution of the hypersurface on which the packing is embedded. Supported by a Cottrell Award from the Research Corporation for Science Advancement.

  13. The influence of the social thermoregulation on the cold-adaptive growth of BAT in hairless and furred mice.

    Science.gov (United States)

    Heldmaier, G

    1975-03-26

    When mice were living in groups they developed less brown adipose tissue (BAT) during cold adaptation as compared with single mice. This effect of social aggregation was more pronounced in genetically hairless mice than in furred mice. In both races of mice the most significant difference in BAT growth was found between single mice and pairs of mice, indicating that the formation of pairs causes the relatively most effective improvement of thermal balance.

  14. Features of Localization of ARG-X Protease-processing in the Suprastructures of Interphase Chromatin under Conditions of Cell Cycle Arrest by Sodium Butyrate, upon Induction of Growth Morphogenesis of Mature Embryos of Winter and Spring Wheat

    Directory of Open Access Journals (Sweden)

    Ivanov R.S.

    2016-08-01

    Full Text Available A fundamental property of many organisms is the ability to feel, to assess direction of the signal action and respond to the environmental conditions. It is known that chromatin plays a major role in organizing the regulation of gene activity. However, our understanding of how state of the suprastructure organization of chromatin and its proteins reacts not only to changes in the environment, but also on the development of specific signals remains largely unclear. In the course of this work, we have analyzed the result of the various ways of chromatin modifications: the regulatory Arg-X protease-processing and inhibition of protein deacetylation with sodium butyrate. Sodium butyrate causes cell cycle arrest in the G0/G1 phase, and promotes of duration of the transcriptional activity of chromatin. Experiments on molecular-genetic state of the chromatin matrix were carried out at the induction of growth morphogenesis in the physiological period of active water absorption of mature seeds and wheat germs, which were purposefully transformed and formed in different environmental conditions. During focused, long-term transforming of spring wheat Artemovka into winter wheat Mironovskaya 808 and the last of them again into Mironovskaya Spring wheat while stopping of the cell cycle in the G0/G1 phase, mainly occurs the active Arg-X protease-processing at the level of non-histone proteins, and linker histones of suprastructures chromatin. We assume that the regulatory proteolytic processing and prolongation of acetylation of proteins can be interconnected in the regulation of conformational transitions of chromatin at the different levels of its organization: both suprastructures and at the more profound proteomic level of non-histone and histone blocks, and have its peculiarities during the period of transcriptional activation. We hope that the study peculiarities of locations of regulatory proteolysis in the conditions of inhibition of deacetylation in

  15. Analysis of Crack Arrest Toughness.

    Science.gov (United States)

    1988-01-15

    vload(m) vp tn(m) Vertical Source Load (kN) on wedge HY80 Finite Element 0.0122 0.0099 3.81x10 -4 144 Steel Calculations Experiment 0.0122 --- 3.74x10-4...curve, are bona fide measures of the fracture arrest capability of tough ductile steels . The second is that the J-values represent the crack driving...fibrous mode of crack extension. (b) A new test method for studying fast fracture and arrest in tough steels . (c) Measurements of fast fracture and crack

  16. Effects of somatostatin on the growth hormone-insulin-like growth factor axis and seawater adaptation of rainbow trout (Oncorhynchus mykiss)

    Science.gov (United States)

    Poppinga, J.; Kittilson, J.; McCormick, S.D.; Sheridan, M.A.

    2007-01-01

    Growth hormone (GH) has been shown to contribute to the seawater (SW) adaptability of euryhaline fish both directly and indirectly through insulin-like growth factor-1 (IGF-1). This study examined the role of somatostatin-14 (SS-14), a potent inhibitor of GH, on the GH-IGF-1 axis and seawater adaptation. Juvenile rainbow trout (Oncorhynchus mykiss) were injected intraperitoneally with SS-14 or saline and transferred to 20??ppt seawater. A slight elevation in plasma chloride levels was accompanied by significantly reduced gill Na+, K+-ATPase activity in SS-14-treated fish compared to control fish 12??h after SW transfer. Seawater increased hepatic mRNA levels of GH receptor 1 (GHR 1; 239%), GHR 2 (48%), and IGF-1 (103%) in control fish 12??h after transfer. Levels of GHR 1 (155%), GHR 2 (121%), IGF-1 (200%), IGF-1 receptor A (IGFR1A; 62%), and IGFR1B (157%) increased in the gills of control fish 12??h after transfer. SS-14 abolished or attenuated SW-induced changes in the expression of GHR, IGF-1, and IGFR mRNAs in liver and gill. These results indicate that SS-14 reduces seawater adaptability by inhibiting the GH-IGF-1 axis. ?? 2007 Elsevier B.V. All rights reserved.

  17. Adaptation to low pH and lignocellulosic inhibitors resulting in ethanolic fermentation and growth of Saccharomyces cerevisiae.

    Science.gov (United States)

    Narayanan, Venkatachalam; Sànchez I Nogué, Violeta; van Niel, Ed W J; Gorwa-Grauslund, Marie F

    2016-12-01

    Lignocellulosic bioethanol from renewable feedstocks using Saccharomyces cerevisiae is a promising alternative to fossil fuels owing to environmental challenges. S. cerevisiae is frequently challenged by bacterial contamination and a combination of lignocellulosic inhibitors formed during the pre-treatment, in terms of growth, ethanol yield and productivity. We investigated the phenotypic robustness of a brewing yeast strain TMB3500 and its ability to adapt to low pH thereby preventing bacterial contamination along with lignocellulosic inhibitors by short-term adaptation and adaptive lab evolution (ALE). The short-term adaptation strategy was used to investigate the inherent ability of strain TMB3500 to activate a robust phenotype involving pre-culturing yeast cells in defined medium with lignocellulosic inhibitors at pH 5.0 until late exponential phase prior to inoculating them in defined media with the same inhibitor cocktail at pH 3.7. Adapted cells were able to grow aerobically, ferment anaerobically (glucose exhaustion by 19 ± 5 h to yield 0.45 ± 0.01 g ethanol g glucose(-1)) and portray significant detoxification of inhibitors at pH 3.7, when compared to non-adapted cells. ALE was performed to investigate whether a stable strain could be developed to grow and ferment at low pH with lignocellulosic inhibitors in a continuous suspension culture. Though a robust population was obtained after 3600 h with an ability to grow and ferment at pH 3.7 with inhibitors, inhibitor robustness was not stable as indicated by the characterisation of the evolved culture possibly due to phenotypic plasticity. With further research, this short-term adaptation and low pH strategy could be successfully applied in lignocellulosic ethanol plants to prevent bacterial contamination.

  18. Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1

    NARCIS (Netherlands)

    Collado, M.; Medema, R.H.; Garcia-Cao, I.; Dubuisson, M.L.N.; Barradas, M.; Glassford, J.; Rivas, C.; Burgering, B.M.T.; Serrano, M.; Lam, E.W.-F.

    2000-01-01

    A senescence-like growth arrest is induced in mouse primary embryo fibroblasts by inhibitors of phosphoinositide 3-kinase (PI3K). We observed that senescence-like growth arrest is correlated with an increase in p27Kip1 but that down-regulation of other cyclin-dependent kinase (CDK) inhibitors, inclu

  19. The stringent response and cell cycle arrest in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Daniel J Ferullo

    2008-12-01

    Full Text Available The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions.

  20. Cognitive and Adaptive Advantages of Growth Hormone Treatment in Children with Prader-Willi Syndrome

    Science.gov (United States)

    Dykens, Elisabeth M.; Roof, Elizabeth; Hunt-Hawkins, Hailee

    2017-01-01

    Background: People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient…

  1. Diabetic intestinal growth adaptation and glucagon-like peptide 2 in the rat

    DEFF Research Database (Denmark)

    Thulesen, J; Hartmann, B; Nielsen, C;

    1999-01-01

    Dietary fibre influence growth and function of the upper gastrointestinal tract. This study investigates the importance of dietary fibre in intestinal growth in experimental diabetes, and correlates intestinal growth with plasma levels of the intestinotrophic factor, glucagon-like peptide 2 (GLP-2)....

  2. COMBINED DELAUNAY TRIANGULATION AND ADAPTIVE FINITE ELEMENT METHOD FOR CRACK GROWTH ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    Pramote DECHAUMPHAI; Sutthisak PHONGTHANAPANICH; Thanawat SRICHAROENCHAI

    2003-01-01

    The paper presents the utilization of the adaptive Delaunay triangulation in the finite element modeling of two dimensional crack propagation problems, including detailed description of the proposed procedure which consists of the Delaunay triangulation algorithm and an adaptive remeshing technique. The adaptive remeshing technique generates small elements around crack tips and large elements in the other regions. The resulting stress intensity factors and simulated crack propagation behavior are used to evaluate the effectiveness of the procedure. Three sample problems of a center cracked plate, a single edge cracked plate and a compact tension specimen, are simulated and their results assessed.

  3. MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth by integrating multiple hormonal pathways.

    Science.gov (United States)

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Obata, Toshihiro; Fernie, Alisdair R; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2013-10-01

    Growth regulation is an important aspect of plant adaptation during environmental perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB transcription factor of rice, was explored. OsMPS is induced by salt stress and expressed in vegetative and reproductive tissues. Over-expression of OsMPS reduces growth under non-stress conditions, while knockdown plants display increased biomass. OsMPS expression is induced by abscisic acid and cytokinin, but is repressed by auxin, gibberellin and brassinolide. Growth retardation caused by OsMPS over-expression is partially restored by auxin application. Expression profiling revealed that OsMPS negatively regulates the expression of EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling genes. Furthermore, the expression of OsMPS-dependent genes is regulated by auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its target genes to various hormones suggest an integrative function of OsMPS in the cross-talk between phytohormones and the environment to regulate adaptive growth.

  4. Growth parameter components of adaptive specificity during experimental evolution of the UVR-inducible mutator Pseudomonas cichorii 302959.

    Directory of Open Access Journals (Sweden)

    Michael R Weigand

    Full Text Available BACKGROUND: Mutagenic DNA repair (MDR transiently increases mutation rate through the activation of low-fidelity repair polymerases in response to specific, DNA-damaging environmental stress conditions such as ultraviolet radiation (UVR exposure. These repair polymerases also confer UVR tolerance, intimately linking mutability and survival in bacteria that colone habitats subject to regular UVR exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigate adaptive specificity in experimental lineages of the highly UVR-mutable epiphytic plant pathogen Pseudomonas cichorii 302959. Relative fitness measurements of isolates and population samples from replicate lineages indicated that adaptive improvements emerged early in all lineages of our evolution experiment and specific increases in relative fitness correlated with distinct improvements in doubling and lag times. Adaptive improvements gained under UVR and non-UVR conditions were acquired preferentially, and differentially contributed to relative fitness under varied growth conditions. CONCLUSIONS: These results support our earlier observations that MDR activation may contribute to gains in relative fitness without impeding normal patterns of adaptive specificity in P. cichorii 302959.

  5. 14 CFR 1203b.103 - Arrest authority.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Arrest authority. 1203b.103 Section 1203b.103 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SECURITY PROGRAMS; ARREST AUTHORITY AND USE OF FORCE BY NASA SECURITY FORCE PERSONNEL § 1203b.103 Arrest authority. (a) NASA...

  6. 33 CFR 154.822 - Detonation arresters, flame arresters, and flame screens.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Detonation arresters, flame arresters, and flame screens. 154.822 Section 154.822 Navigation and Navigable Waters COAST GUARD... BULK Vapor Control Systems § 154.822 Detonation arresters, flame arresters, and flame screens. (a)...

  7. Different transcriptional responses from slow and fast growth rate strains of Listeria monocytogenes adapted to low temperature

    Directory of Open Access Journals (Sweden)

    Ninoska eCordero

    2016-03-01

    Full Text Available Listeria monocytogenes has become one of the principal foodborne pathogens worldwide. The capacity of this bacterium to grow at low temperatures has opened an interesting field of study in terms of the identification and classification of new strains of L. monocytogenes with different growth capacities at low temperatures. We determined the growth rate at 8 ºC of 110 strains of L. monocytogenes isolated from different food matrices. We identified a group of slow and fast strains according to their growth rate at 8 °C and performed a global transcriptomic assay in strains previously adapted to low temperature. We then identified shared and specific transcriptional mechanisms, metabolic and cellular processes of both groups; bacterial motility was the principal process capable of differentiating the adaptation capacity of L. monocytogenes strains with different ranges of tolerance to low temperatures. Strains belonging to the fast group were less motile, which may allow these strains to achieve a greater rate of proliferation at low temperature.

  8. 超声对宫内胚胎停止发育诊断的应用观察%Application of ultrasound in the diagnosis of intrauterine embryo growth arrest

    Institute of Scientific and Technical Information of China (English)

    侯树新

    2015-01-01

    Objective: To analyze the characteristics of intrauterine embryo growth arrest, stop the application effect observa-tion of ultrasound in the diagnosis of intrauterine embryo development.Methods:From 2013 to 2014 in our hospital for treat-ment of 30 cases of diagnosed intrauterine embryos stop development of ultrasonic testing images were analyzed retrospectively. Results: 30 cases of embryonic images with different characteristics, in the ultrasonic observation, air sac type 11 cases, accounting for 24.4%, in the ultrasonic observation, no echo area inside the uterus appears irregular oval sacs, and the pregnancy pregnant sac is larger, the size of gestational sac size is 3~4cm. With favorable pregnancy pregnancy, the inner wall of uterus of pregnant women was clear, and the wall of the uterus pregnancy pregnant sac some separation. Pregnancy pregnant sac deformation type is 5 cases, accounting for 11%, patients with intrauterine pregnancies were more irregular shape, with a flat, C, and presents the bleak rough pregnancy pregnant sac state, no embryo. Light spot, wide type in 12 cases, accounting for 26.6%, in the acoustic observation, showed a light or facula echo obvious.Conclusion:Ultrasonic observation on development has a direct, accurate, rapid for intra-uterine embryo stops, miscarriage prevention and treatment of pregnant women without meaning, providing the reliable basis for the clinical treatment of.%目的:分析宫内胚胎停止发育的特点,观察超声在宫内胚胎停止发育诊断中的应用效果。方法选取2013到2014年在本院治疗的30例被诊断为宫内胚胎停止发育的患者的超声检测图片进行回顾分析。结果30例胚胎停止发育的图片各有特点,在超声观察下,空囊型的为11例,占36.6%,在超声观测下,子宫内部呈现出来的椭圆形的不规则囊状物无回声区,而且它的孕娠囊较大,妊娠囊大小为3~4cm,妊娠大小基本与怀孕周期一致,孕妇的

  9. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    Science.gov (United States)

    Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth. PMID:7959223

  10. The transcriptome of the nosocomial pathogen Enterococcus faecalis V583 reveals adaptive responses to growth in blood.

    Directory of Open Access Journals (Sweden)

    Heidi C Vebø

    Full Text Available BACKGROUND: Enterococcus faecalis plays a dual role in human ecology, predominantly existing as a commensal in the alimentary canal, but also as an opportunistic pathogen that frequently causes nosocomial infections like bacteremia. A number of virulence factors that contribute to the pathogenic potential of E. faecalis have been established. However, the process in which E. faecalis gains access to the bloodstream and establishes a persistent infection is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: To enhance our understanding of how this commensal bacterium adapts during a bloodstream infection and to examine the interplay between genes we designed an in vitro experiment using genome-wide microarrays to investigate what effects the presence of and growth in blood have on the transcriptome of E. faecalis strain V583. We showed that growth in both 2xYT supplemented with 10% blood and in 100% blood had a great impact on the transcription of many genes in the V583 genome. We identified several immediate changes signifying cellular processes that might contribute to adaptation and growth in blood. These include modulation of membrane fatty acid composition, oxidative and lytic stress protection, acquisition of new available substrates, transport functions including heme/iron transporters and genes associated with virulence in E. faecalis. CONCLUSIONS/SIGNIFICANCE: The results presented here reveal that cultivation of E. faecalis in blood in vitro has a profound impact on its transcriptome, which includes a number of virulence traits. Observed regulation of genes and pathways revealed new insight into physiological features and metabolic capacities which enable E. faecalis to adapt and grow in blood. A number of the regulated genes might potentially be useful candidates for development of new therapeutic approaches for treatment of E. faecalis infections.

  11. Fetal hemodynamic adaptive changes related to intrauterine growth the generation R study

    NARCIS (Netherlands)

    B.O. Verburg (Bero Olof); V.W.V. Jaddoe (Vincent); J.W. Wladimiroff (Juriy); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); R.P.M. Steegers-Theunissen (Régine)

    2008-01-01

    textabstractBackground-It has been suggested that an adverse fetal environment increases susceptibility to hypertension and cardiovascular disease in adult life. This increased risk may result from suboptimal development of the heart and main arteries in utero and from adaptive cardiovascular change

  12. Simulation and Evaluation of Urban Growth for Germany Including Climate Change Mitigation and Adaptation Measures

    Directory of Open Access Journals (Sweden)

    Jana Hoymann

    2016-06-01

    Full Text Available Decision-makers in the fields of urban and regional planning in Germany face new challenges. High rates of urban sprawl need to be reduced by increased inner-urban development while settlements have to adapt to climate change and contribute to the reduction of greenhouse gas emissions at the same time. In this study, we analyze conflicts in the management of urban areas and develop integrated sustainable land use strategies for Germany. The spatial explicit land use change model Land Use Scanner is used to simulate alternative scenarios of land use change for Germany for 2030. A multi-criteria analysis is set up based on these scenarios and based on a set of indicators. They are used to measure whether the mitigation and adaptation objectives can be achieved and to uncover conflicts between these aims. The results show that the built-up and transport area development can be influenced both in terms of magnitude and spatial distribution to contribute to climate change mitigation and adaptation. Strengthening the inner-urban development is particularly effective in terms of reducing built-up and transport area development. It is possible to reduce built-up and transport area development to approximately 30 ha per day in 2030, which matches the sustainability objective of the German Federal Government for the year 2020. In the case of adaptation to climate change, the inclusion of extreme flood events in the context of spatial planning requirements may contribute to a reduction of the damage potential.

  13. Neurologic management following cardiac arrest.

    Science.gov (United States)

    Bircher, N G

    1989-10-01

    Optimal neurologic outcome after cardiac arrest requires careful attention to the details of both intracranial and extracranial homeostasis. A high index of suspicion regarding the potential causes and complications of cardiac arrest facilitates discovery and treatment of problems before they adversely affect neurologic outcome. The future is bright for resuscitation research: Our fundamental understanding of cerebral ischemia and its consequences has dramatically improved, and this knowledge can hopefully be transferred to clinical useful modes of therapy. However, the transition from a promising, therapeutically effective intervention in animals to the demonstration that treatment is effective following cardiac arrest in humans is an important and difficult step. The patient population is heterogeneous before the insult, the duration and severity of the insult are variable, and the effectiveness of cardiopulmonary resuscitation varies among institutions. Therefore, the only means of demonstrating clinical efficacy is the performance of a large clinical trial. The Resuscitation Research Center at the University of Pittsburgh has developed and coordinated a multicenter, multinational team of investigators who have completed one definitive trial of postarrest barbiturate therapy and are currently completing a similar trial using a calcium entry blocker. Despite the formidable obstacles posed by such comprehensive efforts, they provide the mechanism for determining whether the cost of a new treatment modality is justified by the likelihood of improved mortality or morbidity.

  14. Replicatively senescent cells are arrested in G1 and G2 phases

    Science.gov (United States)

    Mao, Zhiyong; Ke, Zhonghe; Gorbunova, Vera; Seluanov, Andrei

    2012-01-01

    Most human somatic cells do not divide indefinitely but enter a terminal growth arrest termed replicative senescence. Replicatively senescent cells are generally believed to arrest in G1 or G0 stage of the cell cycle. While doing cell cycle analysis on three different lines of normal human fibroblasts we observed that 36-60% of the replicatively senescent cells had 4N DNA content. Only up to 5% of senescent cells had more than one nucleus ruling out the possibility that the 4N cell population were G1-arrested bi-nucleated cells. Furthermore, it is unlikely that the 4N cells are tetraploids, because actively dividing pre-senescent cultures lacked the 8N tetraploid G2 population. Collectively these results suggest that the 4N population consists of G2 arrested cells. The notion that a large fraction of senescent cell population is arrested in G2 is important for understanding the biology of replicative senescence. PMID:22745179

  15. A transcription factor links growth rate and metabolism in the hypersaline adapted archaeon Halobacterium salinarum.

    Science.gov (United States)

    Todor, Horia; Dulmage, Keely; Gillum, Nicholas; Bain, James R; Muehlbauer, Michael J; Schmid, Amy K

    2014-09-01

    Co-ordinating metabolism and growth is a key challenge for all organisms. Despite fluctuating environments, cells must produce the same metabolic outputs to thrive. The mechanisms underlying this 'growth homeostasis' are known in bacteria and eukaryotes, but remain unexplored in archaea. In the model archaeon Halobacterium salinarum, the transcription factor TrmB regulates enzyme-coding genes in diverse metabolic pathways in response to glucose. However, H. salinarum is thought not to catabolize glucose. To resolve this discrepancy, we demonstrate that TrmB regulates the gluconeogenic production of sugars incorporated into the cell surface S-layer glycoprotein. Additionally, we show that TrmB-DNA binding correlates with instantaneous growth rate, likely because S-layer glycosylation is proportional to growth. This suggests that TrmB transduces a growth rate signal to co-regulated metabolic pathways including amino acid, purine, and cobalamin biosynthesis. Remarkably, the topology and function of this growth homeostatic network appear conserved across domains despite extensive alterations in protein components.

  16. Lysine63-linked ubiquitylation of PIN2 auxin carrier protein governs hormonally controlled adaptation of Arabidopsis root growth.

    Science.gov (United States)

    Leitner, Johannes; Petrášek, Jan; Tomanov, Konstantin; Retzer, Katarzyna; Pařezová, Markéta; Korbei, Barbara; Bachmair, Andreas; Zažímalová, Eva; Luschnig, Christian

    2012-05-22

    Cross-talk between plant cells and their surroundings requires tight regulation of information exchange at the plasma membrane (PM), which involves dynamic adjustments of PM protein localization and turnover to modulate signal perception and solute transport at the interface between cells and their surroundings. In animals and fungi, turnover of PM proteins is controlled by reversible ubiquitylation, which signals endocytosis and delivery to the cell's lytic compartment, and there is emerging evidence for related mechanisms in plants. Here, we describe the fate of Arabidopsis PIN2 protein, required for directional cellular efflux of the phytohormone auxin, and identify cis- and trans-acting mediators of PIN2 ubiquitylation. We demonstrate that ubiquitin acts as a principal signal for PM protein endocytosis in plants and reveal dynamic adjustments in PIN2 ubiquitylation coinciding with variations in vacuolar targeting and proteolytic turnover. We show that control of PIN2 proteolytic turnover via its ubiquitylation status is of significant importance for auxin distribution in root meristems and for environmentally controlled adaptations of root growth. Moreover, we provide experimental evidence indicating that PIN2 vacuolar sorting depends on modification specifically by lysine(63)-linked ubiquitin chains. Collectively, our results establish lysine(63)-linked PM cargo ubiquitylation as a regulator of polar auxin transport and adaptive growth responses in higher plants.

  17. Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading

    Science.gov (United States)

    Adams, G. R.

    1998-01-01

    Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.

  18. Adaptation of the QoL-AGHDA scale for adults with growth hormone deficiency in four Slavic languages

    Directory of Open Access Journals (Sweden)

    McKenna Stephen P

    2011-08-01

    Full Text Available Abstract Purpose The Quality of Life in Adult Growth Hormone Deficiency Assessment (QoL-AGHDA is a disease-specific quality of life measure specific to individuals who are growth hormone deficient. The present study describes the adaptation of the QoL-AGHDA for use in the following four Slavic languages; Czech, Polish, Serbian and Slovakian. Methods The study involved three stages in each language; translation, cognitive debriefing and validation. The validation stage assessed internal consistency (Cronbach's alpha, reproducibility (test-retest reliability using Spearman's rank correlations, convergent and divergent validity (Correlations with the NHP and known group validity. Results The QoL-AGHDA was successfully translated into the target languages with minimal problems. Cognitive debriefing interviewees (n = 15-18 found the measures easy to complete and identified few problems with the content. Internal consistency (Czech Republic = 0.91, Poland = 0.91, Serbia = 0.91 and Slovakia = 0.89 and reproducibility (Czech Republic = 0.91, Poland = 0.91, Serbia = 0.88 and Slovakia = 0.93 were good in all adaptations. Convergent and divergent validity and known group validity data were not available for Slovakia. The QoL-AGHDA correlated as expected with the NHP scales most relevant to GHD. The QoL-AGHDA was able to distinguish between participants based on a range of variables. Conclusions The QoL-AGHDA was successfully adapted for use in the Czech Republic, Poland, Serbia and Slovakia. Further validation of the Slovakian version would be beneficial. The addition of these new lanaguage versions will prove valuable to multinational clinical trials and to clinical practice in the respective countries.

  19. Programmed cell cycle arrest is required for infection of corn plants by the fungus Ustilago maydis.

    Science.gov (United States)

    Castanheira, Sónia; Mielnichuk, Natalia; Pérez-Martín, José

    2014-12-01

    Ustilago maydis is a plant pathogen that requires a specific structure called infective filament to penetrate the plant tissue. Although able to grow, this filament is cell cycle arrested on the plant surface. This cell cycle arrest is released once the filament penetrates the plant tissue. The reasons and mechanisms for this cell cycle arrest are unknown. Here, we have tried to address these questions. We reached three conclusions from our studies. First, the observed cell cycle arrest is the result of the cooperation of at least two distinct mechanisms: one involving the activation of the DNA damage response (DDR) cascade; and the other relying on the transcriptional downregulation of Hsl1, a kinase that modulates the G2/M transition. Second, a sustained cell cycle arrest during the infective filament step is necessary for the virulence in U. maydis, as a strain unable to arrest the cell cycle was severely impaired in its ability to infect corn plants. Third, production of the appressorium, a structure required for plant penetration, is incompatible with an active cell cycle. The inability to infect plants by strains defective in cell cycle arrest seems to be caused by their failure to induce the appressorium formation process. In summary, our findings uncover genetic circuits to arrest the cell cycle during the growth of this fungus on the plant surface, thus allowing the penetration into plant tissue.

  20. DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest.

    Science.gov (United States)

    Baugh, L Ryan; Sternberg, Paul W

    2006-04-18

    Development is typically studied as a continuous process under laboratory conditions, but wild animals often develop in variable and stressful environments. C. elegans larvae hatch in a developmentally arrested state (L1 arrest) and initiate post-embryonic development only in the presence of food (E. coli in lab). In contrast to the well-studied dauer arrest, L1 arrest occurs without morphological modification, although larvae in L1 arrest are more resistant to environmental stress than developing larvae . Consistent with its role in dauer formation and aging, we show that insulin/insulin-like growth factor (IGF) signaling regulates L1 arrest. daf-2 insulin/IGF receptor mutants have a constitutive-L1-arrest phenotype when fed and extended survival of L1 arrest when starved. Conversely, daf-16/FOXO mutants have a defective-arrest phenotype, failing to arrest development and dying rapidly when starved. We show that DAF-16 is required for transcription of the cyclin-dependent kinase inhibitor cki-1 in stem cells in response to starvation, accounting for the failure of daf-16/FOXO mutants to arrest cell division during L1 arrest. Other developmental events such as cell migration, cell fusion, and expression of the microRNA lin-4, a temporal regulator of post-embryonic development, are also observed in starved daf-16/FOXO mutants. These results suggest that DAF-16/FOXO promotes developmental arrest via transcriptional regulation of numerous target genes that control various aspects of development.

  1. Allometric growth in juvenile marine turtles: possible role as an antipredator adaptation.

    Science.gov (United States)

    Salmon, Michael; Scholl, Joshua

    2014-04-01

    Female marine turtles produce hundreds of offspring during their lifetime but few survive because small turtles have limited defenses and are vulnerable to many predators. Little is known about how small turtles improve their survival probabilities with growth though it is assumed that they do. We reared green turtles (Chelonia mydas) and loggerheads (Caretta caretta) from hatchlings to 13 weeks of age and documented that they grew wider faster than they grew longer. This pattern of allometric growth might enable small turtles to more quickly achieve protection from gape-limited predators, such as the dolphinfish (Coryphaena hippurus). As a test of that hypothesis, we measured how dolphinfish gape increased with length, reviewed the literature to determine how dolphinfish populations were size/age structured in nearby waters, and then determined the probability that a small turtle would encounter a fish large enough to consume it if it grew by allometry vs. by isometry (in which case it retained its hatchling proportions). Allometric growth more quickly reduced the probability of a lethal encounter than did isometric growth. On that basis, we suggest that allometry during early ontogeny may have evolved because it provides a survival benefit for small turtles.

  2. Insertion-Sequence-Mediated Mutations Isolated During Adaptation to Growth and Starvation in Lactococcus lactis.

    NARCIS (Netherlands)

    Visser, de J.A.G.M.; Akkermans, A.D.L.; Hoekstra, R.F.; Vos, de W.M.

    2004-01-01

    We studied the activity of three multicopy insertion sequence (IS) elements in 12 populations of Lactococcus lactis IL1403 that evolved in the laboratory for 1000 generations under various environmental conditions (growth or starvation and shaken or stationary). Using RFLP analysis of single-clone r

  3. Daily patterns and adaptation of the ghrelin, growth hormone and insulin-like growth factor-1 system under daytime food synchronisation in rats.

    Science.gov (United States)

    Arellanes-Licea, E del C; Báez-Ruiz, A; Carranza, M E; Arámburo, C; Luna, M; Díaz-Muñoz, M

    2014-05-01

    Daytime restricted feeding promotes the re-alignment of the food entrained oscillator (FEO). Endocrine cues which secretion is regulated by the transition of fasting and feeding cycles converge in the FEO. The present study aimed to investigate the ghrelin, growth hormone (GH) and insulin-like growth factor (IGF)-1 system because their release depends on rhythmic and nutritional factors, and the output from the system influences feeding and biochemical status. In a daily sampling approach, rats that were fed ad lib. were compared with rats on a reversed (daytime) and restricted feeding schedule by 3 weeks (dRF; food access for 2 h), also assessing the effect of acute fasting and refeeding. We undertook measurements of clock protein BMAL1 and performed somatometry of peripheral organs and determined the concentration of total, acylated and unacylated ghrelin, GH and IGF-1 in both serum and in its main synthesising organs. During dRF, BMAL1 expression was synchronised to mealtime in hypophysis and liver; rats exhibited acute hyperphagia, stomach distension with a slow emptying, a phase shift in liver mass towards the dark period and decrease in mass perigonadal white adipose tissue. Total ghrelin secretion during the 24-h period increased in the dRF group as a result of elevation of the unacylated form. By contrast, GH and IGF-1 serum concentration fell, with a modification of GH daily pattern after mealtime. In the dRF group, ghrelin content in the stomach and pituitary GH content decreased, whereas hepatic IGF-1 remained equal. The daily patterns and synthesis of these hormones had a rheostatic adaptation. The endocrine adaptive response elicited suggests that it may be associated with the regulation of metabolic, behavioural and physiological processes during the paradigm of daytime restricted feeding and associated FEO activity.

  4. A palmitoyl conjugate of insect pentapeptide Yamamarin arrests cell proliferation and respiration.

    Science.gov (United States)

    Sato, Yosinori; Yang, Ping; An, Ying; Matsukawa, Kazushige; Ito, Kikukatsu; Imanishi, Shigeo; Matsuda, Hirokazu; Uchiyama, Yusuke; Imai, Kunio; Ito, Shigeki; Ishida, Yoji; Suzuki, Koichi

    2010-05-01

    A palmitoyl conjugate of an insect pentapeptide that occurs in diapausing insects causes a reversible cell-cycle arrest and suppresses mitochondrial respiration. This peptide compound also causes growth arrest in murine leukemic cell line expressing human gene Bcr/Abl and a farnesoyl peptide induces embryonic diapause in Bombyx mori. These results demonstrate that the insect peptide compounds can lead to the understanding of a common pathway in developmental arrest in animals and may provide a new peptidominetic analog in the development of biopharmaceuticals and pest management.

  5. Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

    Directory of Open Access Journals (Sweden)

    Yu-Fen Tseng

    Full Text Available Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14, a reassortant virus between A/Vietnam/1194/2004 (H5N1 virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15 was generated and can grow over 10(8 TCID(50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes.

  6. Cognitive impairment after sudden cardiac arrest

    OpenAIRE

    Jaszke-Psonka, Magdalena; Piegza, Magdalena; Ścisło, Piotr; Pudlo, Robert; Piegza, Jacek; Badura-Brzoza, Karina; Leksowska, Aleksandra; Hese, Robert T.; Gorczyca, Piotr W.

    2016-01-01

    Aim To evaluate the incidence and severity of the impairment of selected cognitive functions in patients after sudden cardiac arrest (SCA) in comparison to patients after myocardial infarction without SCA and healthy subjects and to analyze the influence of sociodemographic and clinical parameters and the duration of cardiac arrest on the presence and severity of the described disorders. Material and methods The study group comprised 30 cardiac arrest survivors, the reference group comprised ...

  7. Cyclooxygenase 2,pS2,inducible nitric oxide synthase and transforming growth factor alpha in gastric adaptation to stress

    Institute of Scientific and Technical Information of China (English)

    Shi-Nan Nie; Hai-Chen Sun; Xue-Hao Wu; Xiao-Ming Qian

    2004-01-01

    AIM: To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides),inducible nitric oxide synthase (iNOS) and transforming growth factor alpha (TGFα) in gastric adaptation to water immersion and restraint stress (WRS) in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 d. Gastric mucosal blood flow (GMBF) was measured by laser Doppler fiowmeter3. The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFα were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot.RESULTS: The damage to the surface of gastric epithelium with focal areas of deep haemorrhagic necrosis was induced by repeated WRS.The adaptative cytoprotection against stress was developed with activation of cell proliferation in the neck regions of gastric glands. The ulcer index (UI) in groups Ⅱ, Ⅲ and Ⅳ was markedly reduced as compared with group Ⅰ (Ⅰ: 47.23±1.20; Ⅳ: 10.39±1.18,P<0.01). GMBF significantly decreased after first exposure to WRS with an adaptive increasement of GMBF in experimental groups after repetitive challenges with WRS. After the 4th WRS,the value of GMBF almost restored to normal level (Ⅰ:321.87±8.85; Ⅳ: 455.95±11.81,P<0.01). First WRS significantly decreased the expression of pS2 and significantly increased the expressions of COX-2, iNOS and TGFα. After repeated WRS, pS2 and TGFα expressions gradually increased (pS2: Ⅰ: 0.37±0.02; Ⅳ: 0.77±0.01; TGFα: Ⅰ:0.86±0.01; Ⅳ: 0.93±0.03, P<0.05) with a decrease in the expressions of COX-2 and iNOS (COX-2: Ⅰ: 0.45±0.02; Ⅳ:0.22±0.01; iNOS: Ⅰ: 0.93±0.01; Ⅳ: 0.56±0.01, P<0.01).Expressions of pS2, COX-2, iNOS and TGFα showed regular changes with a good relationship among them.CONCLUSION: Gastric adaptation to WRS injury involves enhanced cell proliferation, increased expression of pS2 and

  8. Arresting relaxation in Pickering Emulsions

    Science.gov (United States)

    Atherton, Tim; Burke, Chris

    2015-03-01

    Pickering emulsions consist of droplets of one fluid dispersed in a host fluid and stabilized by colloidal particles absorbed at the fluid-fluid interface. Everyday materials such as crude oil and food products like salad dressing are examples of these materials. Particles can stabilize non spherical droplet shapes in these emulsions through the following sequence: first, an isolated droplet is deformed, e.g. by an electric field, increasing the surface area above the equilibrium value; additional particles are then adsorbed to the interface reducing the surface tension. The droplet is then allowed to relax toward a sphere. If more particles were adsorbed than can be accommodated by the surface area of the spherical ground state, relaxation of the droplet is arrested at some non-spherical shape. Because the energetic cost of removing adsorbed colloids exceeds the interfacial driving force, these configurations can remain stable over long timescales. In this presentation, we present a computational study of the ordering present in anisotropic droplets produced through the mechanism of arrested relaxation and discuss the interplay between the geometry of the droplet, the dynamical process that produced it, and the structure of the defects observed.

  9. Cholera toxin, a typical protein kinase A activator, induces G1 phase growth arrest in human bladder transitional cell carcinoma cells via inhibiting the c-Raf/MEK/ERK signaling pathway.

    Science.gov (United States)

    Zheng, Xiaoke; Ou, Yanqiu; Shu, Minfeng; Wang, Youqiong; Zhou, Yuxi; Su, Xingwen; Zhu, Wenbo; Yin, Wei; Li, Shifeng; Qiu, Pengxin; Yan, Guangmei; Zhang, Jingxia; Hu, Jun; Xu, Dong

    2014-05-01

    The biotoxin cholera toxin has been demonstrated to have anti-tumor activity in numerous types of cancer, including glioma. However, the role of cholera toxin in the tumorigenesis of transitional cell carcinoma (TCC), the most common malignant tumor of the bladder, remains to be elucidated. To address this, in the present study, two TCC cell lines, T24 and UM-UC-3, were treated with cholera toxin [protein kinase A (PKA) activator] and KT5720 (PKA inhibitor). Cell survival and proliferation, cell cycle alterations and apoptosis were analyzed using Hoechst staining, the MTT assay, fluorescence microscopy and flow cytometry. Western blot analysis was used to detect the expression of proteins involved in cell cycle regulation. The results revealed that cholera toxin significantly induced G1 arrest and downregulated the expression of cyclin D1 and cyclin-dependent kinase 4/6 in the TCC cell lines, and this was rescued by KT5720. Furthermore, it was demonstrated that cholera toxin downregulated the activation of the c-Raf/Mek/Erk cascade, an important mediator of tumor cell proliferation, via the PKA-dependent c-Raf phosphorylation at Ser-43. Furthermore, inhibition of Mek activity with UO126 mimicked the effects of cholera toxin. In conclusion, these results confirmed that cholera toxin specifically inhibited proliferation and induced G1 phase arrest in human bladder TCC cells. This effect was due to PKA-dependent inactivation of the c-Raf/Mek/Erk pathway. This suggested that cholera toxin may be a viable therapeutic treatment against tumorigenesis and proliferation in bladder cancer.

  10. Ent-11α-Hydroxy-15-oxo-kaur-16-en-19-oic-acid Inhibits Growth of Human Lung Cancer A549 Cells by Arresting Cell Cycle and Triggering Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Li Li; George G Chen; Ying-nian Lu; Yi Liu; Ke-feng Wu; Xian-ling Gong; Zhan-ping Gou; Ming-yue Li; Nian-ci Liang

    2012-01-01

    Objective:To examine the apoptotic effect of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F),a compound isolated from Pteris semipinnata L(PsL),in human lung cancer A549 cells.Methods:A549 cells were treated with 5F (0-80 μg/ml) for different time periods.Cytotoxicity was examined using a MTT method.Cell cycle was examined using propidium iodide staining.Apoptosis was examined using Hoechst 33258 staining,enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis.Expression of representative apoptosis-related proteins was evaluated by Western blot analysis.Reactive oxygen species (ROS) level was measured using standard protocols.Potential interaction of 5F with cisplatin was also examined.Results:5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner.5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase.Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis.The expression of p21 was increased.5F exposure also increased Bax expression,release of cytochrome c and apoptosis inducing factor (AIF),and activation of caspase-3.5F significantly sensitized the cells to cisplatin toxicity Interestingly,treatment with 5F did not increase ROS,but reduced ROS production induced by cisplatin.Conclusion:SF could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis.

  11. Dual role of tree florigen activation complex component FD in photoperiodic growth control and adaptive response pathways.

    Science.gov (United States)

    Tylewicz, Szymon; Tsuji, Hiroyuki; Miskolczi, Pál; Petterle, Anna; Azeez, Abdul; Jonsson, Kristoffer; Shimamoto, Ko; Bhalerao, Rishikesh P

    2015-03-10

    A complex consisting of evolutionarily conserved FD, flowering locus T (FT) proteins is a regulator of floral transition. Intriguingly, FT orthologs are also implicated in developmental transitions distinct from flowering, such as photoperiodic control of bulbing in onions, potato tuberization, and growth cessation in trees. However, whether an FT-FD complex participates in these transitions and, if so, its mode of action, are unknown. We identified two closely related FD homologs, FD-like 1 (FDL1) and FD-like 2 (FDL2), in the model tree hybrid aspen. Using gain of function and RNAi-suppressed FDL1 and FDL2 transgenic plants, we show that FDL1 and FDL2 have distinct functions and a complex consisting of FT and FDL1 mediates in photoperiodic control of seasonal growth. The downstream target of the FT-FD complex in photoperiodic control of growth is Like AP1 (LAP1), a tree ortholog of the floral meristem identity gene APETALA1. Intriguingly, FDL1 also participates in the transcriptional control of adaptive response and bud maturation pathways, independent of its interaction with FT, presumably via interaction with abscisic acid insensitive 3 (ABI3) transcription factor, a component of abscisic acid (ABA) signaling. Our data reveal that in contrast to its primary role in flowering, FD has dual roles in the photoperiodic control of seasonal growth and stress tolerance in trees. Thus, the functions of FT and FD have diversified during evolution, and FD homologs have acquired roles that are independent of their interaction with FT.

  12. Survival and growth patterns of white spruce (Picea glauca [Moench] Voss) rangewide provenances and their implications for climate change adaptation.

    Science.gov (United States)

    Lu, Pengxin; Parker, William H; Cherry, Marilyn; Colombo, Steve; Parker, William C; Man, Rongzhou; Roubal, Ngaire

    2014-06-01

    Intraspecific assisted migration (ISAM) through seed transfer during artificial forest regeneration has been suggested as an adaptation strategy to enhance forest resilience and productivity under future climate. In this study, we assessed the risks and benefits of ISAM in white spruce based on long-term and multilocation, rangewide provenance test data. Our results indicate that the adaptive capacity and growth potential of white spruce varied considerably among 245 range-wide provenances sampled across North America; however, the results revealed that local populations could be outperformed by nonlocal ones. Provenances originating from south-central Ontario and southwestern Québec, Canada, close to the southern edge of the species' natural distribution, demonstrated superior growth in more northerly environments compared with local populations and performed much better than populations from western Canada and Alaska, United States. During the 19-28 years between planting and measurement, the southern provenances have not been more susceptible to freezing damage compared with local populations, indicating they have the potential to be used now for the reforestation of more northerly planting sites; based on changing temperature, these seed sources potentially could maintain or increase white spruce productivity at or above historical levels at northern sites. A universal response function (URF), which uses climatic variables to predict provenance performance across field trials, indicated a relatively weak relationship between provenance performance and the climate at provenance origin. Consequently, the URF from this study did not provide information useful to ISAM. The ecological and economic importance of conserving white spruce genetic resources in south-central Ontario and southwestern Québec for use in ISAM is discussed.

  13. Food viscosity as determinant for adaptive growth responses in rat intestine: long-term feeding of different hydroxyethyl celluloses.

    Science.gov (United States)

    Elsenhans, B; Caspary, W F

    2000-07-01

    Carbohydrate gelling agents can be regarded as being representative for the soluble and viscous fractions of dietary fibre. Their dietary concentration affects the consistency of the ingested food as well as the dilution of nutrients and energy. By feeding hydroxyethyl cellulose (HEC) differing in molecular mass, and thus in its viscosity properties, only the consistency of the diet was modified. Three HEC (of low (LV), medium (MV) and high viscosity (HV)) were employed in a 6-week feeding study with female rats to evaluate the effect of the viscosity on adaptive responses of intestinal growth variables. Each of the HEC was added in three increasing concentrations (8, 16, and 32%, w/w) to a fibre-free control diet to yield nine test groups besides a fibre-free and an additional, fibre-rich, cereal-based control group. Except for the highest concentration of the high viscosity product (32% HV-HEC), the dilution of the energy density of the diet was almost completely compensated by an increased food intake. With the same exception, energy utilisation was not impaired and, therefore, body-weight gains in the test groups were not significantly different from that in the control. Most other changes, e.g. increases in small intestinal length, mucosal DNA content, caecal and colonic weight, not only depended on the dietary concentration but also on the viscosity of HEC in a manner that either increasing the viscosity at a given dietary concentration or increasing the dietary concentration at a given viscosity led to the same results. These findings clearly prove the important role of the viscosity of the lumen content, as a mere physico-chemical factor, in determining adaptative growth responses in the intestinal tract of rats.

  14. Growth and Collapse of a Resource System: an Adaptive Cycle of Change in Public Lands Governance and Forest Management in Alaska

    OpenAIRE

    2009-01-01

    Large-scale government efforts to develop resources for societal benefit have often experienced cycles of growth and decline that leave behind difficult social and ecological legacies. To understand the origins and outcomes of these failures of resource governance, scholars have applied the framework of the adaptive cycle. In this study, we used the adaptive cycle as a diagnostic approach to trace the drivers and dynamics of forest governance surrounding a boom–bust sequence of industri...

  15. Natural variation in Arabidopsis adaptation to growth at low nitrogen conditions.

    Science.gov (United States)

    North, Kathryn Anne; Ehlting, Barbara; Koprivova, Anna; Rennenberg, Heinz; Kopriva, Stanislav

    2009-10-01

    Improving nutrient use efficiency of crop plants, especially at low input, is essential to ensure sustainable food production in the future. In order to address the genetic basis of nutrient use efficiency in a model system, growth of Arabidopsis ecotypes at normal and low nitrogen (N) supply was compared. The ecotypes differed significantly in the extent of growth reduction in limiting conditions. The fresh weight of Shahdara and Ws grown at 1mM nitrate was reduced by 30% compared to control, whereas Col-0 and Ga-0 were almost unaffected. Total N content was reduced in all ecotypes by 10-30%. The capacity to store nitrate correlated with the tolerance to low N; in Shahdara and Ws, but not in Col-0 and Ga-0, nitrate content on low N was significantly reduced compared to control nutrition. The mRNA levels for genes of nitrate uptake and assimilation were only moderately affected by the treatment. The transcript levels of nitrate reductase NIA1 and nitrite reductase were higher in the ecotypes tolerant to low N (Col-0 and Ga-0) with normal N nutrition but on low N they were reduced to a much higher extent than the sensitive ecotypes (Shahdara and Ws). It seems that a higher capacity to keep nitrate reserves at low N, perhaps due to the ability to turn down nitrate reduction rate, is responsible for a better tolerance of Col-0 and Ga-0 to low N supply.

  16. A novel parameter estimation method for metal oxide surge arrester models

    Indian Academy of Sciences (India)

    Mehdi Nafar; Gevork B Gharehpetian; Taher Niknam

    2011-12-01

    Accurate modelling and exact determination of Metal Oxide (MO) surge arrester parameters are very important for arrester allocation, insulation coordination studies and systems reliability calculations. In this paper, a new technique, which is the combination of Adaptive Particle Swarm Optimization (APSO) and Ant Colony Optimization (ACO) algorithms and linking the MATLAB and EMTP, is proposed to estimate the parameters of MO surge arrester models. The proposed algorithm is named Modified Adaptive Particle Swarm Optimization (MAPSO). In the proposed algorithm, to overcome the drawback of the PSO algorithm (convergence to local optima), the inertia weight is tuned by using fuzzy rules and the cognitive and the social parameters are self-adaptively adjusted. Also, to improve the global search capability and prevent the convergence to local minima, ACO algorithm is combined to the proposed APSO algorithm. The transient models of MO surge arrester have been simulated by using ATP-EMTP. The results of simulations have been applied to the program, which is based on MAPSO algorithm and can determine the fitness and parameters of different models. The validity and the accuracy of estimated parameters of surge arrester models are assessed by comparing the predicted residual voltage with experimental results.

  17. Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

    DEFF Research Database (Denmark)

    Zhang, Yiming; Liu, Guodong; Engqvist, Martin K. M.

    2015-01-01

    DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase...... further increased the maximum specific growth rate to 0.069 h-1. Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing...... expression of several hexose transporter genes. The non-synonymous mutations in HXT2 and CIT1 may function in the presence of mutated MTH1 alleles and could be related to an altered central carbon metabolism in order to ensure production of cytosolic acetyl-CoA in the Pdc negative strain....

  18. Global Optimization, Local Adaptation, and the Role of Growth in Distribution Networks

    Science.gov (United States)

    Ronellenfitsch, Henrik; Katifori, Eleni

    2016-09-01

    Highly optimized complex transport networks serve crucial functions in many man-made and natural systems such as power grids and plant or animal vasculature. Often, the relevant optimization functional is nonconvex and characterized by many local extrema. In general, finding the global, or nearly global optimum is difficult. In biological systems, it is believed that such an optimal state is slowly achieved through natural selection. However, general coarse grained models for flow networks with local positive feedback rules for the vessel conductivity typically get trapped in low efficiency, local minima. In this work we show how the growth of the underlying tissue, coupled to the dynamical equations for network development, can drive the system to a dramatically improved optimal state. This general model provides a surprisingly simple explanation for the appearance of highly optimized transport networks in biology such as leaf and animal vasculature.

  19. Global optimization, local adaptation and the role of growth in distribution networks

    CERN Document Server

    Ronellenfitsch, Henrik

    2016-01-01

    Highly-optimized complex transport networks serve crucial functions in many man-made and natural systems such as power grids and plant or animal vasculature. Often, the relevant optimization functional is non-convex and characterized by many local extrema. In general, finding the global, or nearly global optimum is difficult. In biological systems, it is believed that natural selection slowly guides the network towards an optimized state. However, general coarse grained models for flow networks with local positive feedback rules for the vessel conductivity typically get trapped in low efficiency, local minima. In this work we show how the growth of the underlying tissue, coupled to the dynamical equations for network development, can drive the system to a dramatically improved optimal state. This general model provides a surprisingly simple explanation for the appearance of highly optimized transport networks in biology such as leaf and animal vasculature.

  20. The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.

    Science.gov (United States)

    Bell, Ryan A V; Al-Khalaf, Mohammad; Megeney, Lynn A

    2016-01-01

    Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature of proteolytic systems in maintaining normal cellular function. Here, we discuss the major cellular proteolysis machinery-the ubiquitin/proteosome system, the autophagy/lysosomal system, and caspase-mediated protein cleavage-and the critical role of these protein machines in establishing and preserving muscle health. We examine how ordered degradation modifies (1) the spatiotemporal expression of myogenic regulatory factors during myoblast differentiation, (2) membrane fusion during myotube formation, (3) sarcomere remodeling and muscle growth following physical stress, and (4) energy homeostasis during nutrient deprivation. Finally, we review the origin and etiology of a number of myopathies and how these devastating conditions arise from inborn errors in proteolysis.

  1. Growth curve of locally adapted pantaneiro cows raised under natural conditions

    Directory of Open Access Journals (Sweden)

    Eleonora Araújo Barbosa

    2013-11-01

    Full Text Available The objective of this study was to use morphometric and ultrasound evaluations to estimate the growth curve of the Pantaneiro cattle breed, raised in its natural habitat, aiming at the re-insertion of this breed in production systems. One hundred and three females, aging from months to 11 years, and raised on native pastures, were evaluated. The animals belonged to the Conservation Nucleus of Embrapa Pantanal, located in the Pantanal of Mato Grosso do Sul (Brazil. Weight, thoracic perimeter (TP, body length (BL, rump height (RH, height at withers (HW, hip height (HH, depth (DP, distance between the ilia (DI (cm and rib-eye area (REA were measured. To relate the measurements with the age of the animals, the univariate regression model was used, assigning the variable response to gamma distribution. The Pearson correlation between variables was also estimated. The inflection point of the growth curve was 37 months for HH; between 38 and 39 months for TP and HW; between 40 and 41 months for DI, HH and DP; and 45 months for BL. The REA results could not fit in a statistical model. The majority of the variables presented a correlation above 60% among themselves, except for REA × Age, of 15.81%; REA × HW, of 34.44%; HH × Age, of 46.19; HH × DI, of 58.07%; REA × HH, of 24.57%; and REA × TP, of 39.9%. The cows showed maturity age at 40 months, which may have occurred because they were raised in natural farming conditions. In Pantaneiro cows reared in extensive systems only on natural pastures, the use of ultrasound is not effective to estimate the curve of muscular development, perhaps because this breed was not selected for weight gain.

  2. Arabidopsis COPPER MODIFIED RESISTANCE1/PATRONUS1 is essential for growth adaptation to stress and required for mitotic onset control.

    Science.gov (United States)

    Juraniec, Michal; Heyman, Jefri; Schubert, Veit; Salis, Pietrino; De Veylder, Lieven; Verbruggen, Nathalie

    2016-01-01

    The mitotic checkpoint (MC) guards faithful sister chromatid segregation by monitoring the attachment of spindle microtubules to the kinetochores. When chromosome attachment errors are detected, MC delays the metaphase-to-anaphase transition through the inhibition of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. In contrast to yeast and mammals, our knowledge on the proteins involved in MC in plants is scarce. Transient synchronization of root tips as well as promoter-reporter gene fusions were performed to analyze temporal and spatial expression of COPPER MODIFIED RESISTANCE1/PATRONUS1 (CMR1/PANS1) in developing Arabidopsis thaliana seedlings. Functional analysis of the gene was carried out, including CYCB1;2 stability in CMR1/PANS1 knockout and overexpressor background as well as metaphase-anaphase chromosome status. CMR1/PANS1 is transcriptionally active during M phase. Its deficiency provokes premature cell cycle exit and in consequence a rapid consumption of the number of meristematic cells in particular under stress conditions that are known to affect spindle microtubules. Root growth impairment is correlated with a failure to delay the onset of anaphase, resulting in anaphase bridges and chromosome missegregation. CMR1/PANS1 overexpression stabilizes the mitotic CYCB1;2 protein. Likely, CMR1/PANS1 coordinates mitotic cell cycle progression by acting as an APC/C inhibitor and plays a key role in growth adaptation to stress.

  3. Contrasting growth and adaptive responses of two oak species to flooding stress: role of non-symbiotic haemoglobin.

    Science.gov (United States)

    Parent, Claire; Crèvecoeur, Michèle; Capelli, Nicolas; Dat, James F

    2011-07-01

    Soil flooding is an environmental constraint that is increasingly important for forest ecosystems, affecting tree growth and regeneration. As a result, selection pressure will alter forest diversity and distribution by favouring tree species tolerant of soil oxygen deprivation. Sessile and pedunculate oaks are the most abundant oak species and they exhibit a strong differential tolerance to waterlogging. In order to gain some understanding of the mechanisms of tolerance of both species to hypoxia, we undertook the characterization of the physiological, morphological, cellular and molecular responses of both species to flooding stress. Our results indicate that pedunculate oak, the more tolerant species, succeeded in maintaining its growth, water status and photosynthetic activity at a higher level than sessile oak. Furthermore, pedunculate oak developed aerenchyma in its root cortex as well as adventitious roots. The later exhibited a strong accumulation of class1 non-symbiotic haemoglobin localized by in situ hybridization in the protoderm and in some cortical cells. In conclusion, the higher tolerance of pedunculate oak to flooding was associated with an enhanced capacity to maintain photosynthesis and water homeostasis, coupled with the development of adaptive features (aerenchyma, adventitious roots) and with a higher expression of non-symbiotic haemoglobin in the roots.

  4. Adaptation of Trichoderma Species to Pesticide Confidor and Evaluation of their Growth Ability in the Media Containing Confidor

    Directory of Open Access Journals (Sweden)

    Farnaz Ershadfath

    2015-12-01

    Full Text Available Introduction: Contamination caused by pesticides is considered as one of the environmental problems. Bioremediation is exploiting the ability of microorganisms to remove pollutants. Trichoderma species are free-living fungi that exist naturally in the environment. These fungi have the ability to uptake some contaminants biologically. The aim of this study is to evaluate the effect of Confidor, as an environmental contaminant, on the growth ability of Trichoderma sp. as a contaminant absorber. Materials and methods: Five species of Trichoderma fungi were cultured in PDA media. Then the fungi were adapted with 3 different concentrations of Confidor gradually (5, 10 and 20 mg/l. The diameter of the fungal colonies growing in different concentrations of the toxin, were measured after 24 hr and were compared with the control samples (medium without toxin. Results: Results showed that in all species of fungi the colony diameters increased significantly with increasing toxin concentrations. The largest colony diameter was related to T.tomentosum, T.asperellum and T.harzianum (88.88, 87.5 and 86.95%, respectively at the concentration of 20 mg of toxic. Also, in all studied fungal species, in the medium containing 20 (mg/ l of toxic, the aerial hyphae expanded much thicker and faster than other concentrations. Discussion and conclusion: The results indicate a significant increase in the growth ability of Trichoderma strains with increasing Confidor concentration. Therefore it could be concluded that Trichoderma fungi have a high potentiality for biodegradation of Confidor.

  5. Psychopathology in Women Arrested for Domestic Violence

    Science.gov (United States)

    Stuart, Gregory L.; Moore, Todd M.; Gordon, Kristina Coop; Ramsey, Susan E.; Kahler, Christopher W.

    2006-01-01

    This study examined the prevalence of psychopathology among women arrested for violence and whether the experience of intimate partner violence (IPV) was associated with Axis I psychopathology. Women who were arrested for domestic violence perpetration and court referred to violence intervention programs (N=103) completed measures of IPV…

  6. Adaptation of Crack Growth Detection Techniques to US Material Test Reactors

    Energy Technology Data Exchange (ETDEWEB)

    A. Joseph Palmer; Sebastien P. Teysseyre; Kurt L. Davis; Joy L. Rempe; Gordon Kohse; Yakov Ostrovsky; David M. Carpenter

    2014-04-01

    A key component in evaluating the ability of Light Water Reactors to operate beyond 60 years is characterizing the degradation of materials exposed to radiation and various water chemistries. Of particular concern is the response of reactor materials to Irradiation Assisted Stress Corrosion Cracking (IASCC). Some materials testing reactors (MTRs) outside the U.S., such as the Halden Boiling Water Reactor (HBWR), have deployed a technique to measure crack growth propagation during irradiation. This technique incorporates a compact loading mechanism to stress the specimen during irradiation. A crack in the specimen is monitored using the Direct Current Potential Drop (DCPD) method. A project is underway to develop and demonstrate the performance of a similar type of test rig for use in U.S. MTRs. The first year of this three year project was devoted to designing, analyzing, fabricating, and bench top testing a mechanism capable of applying a controlled stress to specimens while they are irradiated in a pressurized water loop (simulating PWR reactor conditions). During the second year, the mechanism will be tested in autoclaves containing high pressure, high temperature water with representative water chemistries. In addition, necessary documentation and safety reviews for testing in a reactor environment will be completed. In the third year, the assembly will be tested in the Massachusetts Institute of Technology Reactor (MITR) and Post Irradiation Examinations (PIE) will be performed.

  7. [Growth responses of six leguminous plants adaptable in Northern Shaanxi to petroleum contaminated soil].

    Science.gov (United States)

    Shan, Bao-Qin; Zhang, Yong-Tao; Cao, Qiao-Ling; Kang, Zhen-Yan; Li, Shu-Yuan

    2014-03-01

    To select appropriate native species in Northern Shaanxi for phytoremediation, the growth index of six kinds of leguminous plants planted in petroleum contaminated soils were investigated through pot culture. Petroleum concentrations were set at 0, 5 000, 10 000, 20 000, 40 000 mg x kg(-1) respectively with three replicates. Using different levels of seed germination rate, germination time, individual height, wilting rate, dry weight and chlorophyll content in leaves of tested plants as the ecological indicator. The results showed that tested plants have significantly different responses to petroleum pollution. Compared with those planted in clean soils, seed germination rate and individual height were promoted when petroleum concentration was lower than 5000 mg x kg(-1), but inhibition occurred when petroleum concentrations were higher than 10000 mg x kg(-1). Strong endurance of Medicago sativa was observed to petroleum polluted soil, especially at lower petroleum concentration. Leaf wilting of Robinia pseudoacacia was unobserved even when petroleum concentration was 40 000 mg x kg(-1), thus displaying the potential of remediating petroleum contaminated soils. The petroleum concentration was significantly and negatively correlated with seed germination rate, individual height and dry weight, but positively correlated with chlorophyll content in leaves.

  8. Interfacial Crack Arrest in Sandwich Panels with Embedded Crack Stoppers Subjected to Fatigue Loading

    Science.gov (United States)

    Martakos, G.; Andreasen, J. H.; Berggreen, C.; Thomsen, O. T.

    2017-02-01

    A novel crack arresting device has been implemented in sandwich panels and tested using a special rig to apply out-of-plane loading on the sandwich panel face-sheets. Fatigue crack propagation was induced in the face-core interface of the sandwich panels which met the crack arrester. The effect of the embedded crack arresters was evaluated in terms of the achieved enhancement of the damage tolerance of the tested sandwich panels. A finite element (FE) model of the experimental setup was used for predicting propagation rates and direction of the crack growth. The FE simulation was based on the adoption of linear fracture mechanics and a fatigue propagation law (i.e. Paris law) to predict the residual fatigue life-time and behaviour of the test specimens. Finally, a comparison between the experimental results and the numerical simulations was made to validate the numerical predictions as well as the overall performance of the crack arresters.

  9. Interfacial Crack Arrest in Sandwich Panels with Embedded Crack Stoppers Subjected to Fatigue Loading

    Science.gov (United States)

    Martakos, G.; Andreasen, J. H.; Berggreen, C.; Thomsen, O. T.

    2016-08-01

    A novel crack arresting device has been implemented in sandwich panels and tested using a special rig to apply out-of-plane loading on the sandwich panel face-sheets. Fatigue crack propagation was induced in the face-core interface of the sandwich panels which met the crack arrester. The effect of the embedded crack arresters was evaluated in terms of the achieved enhancement of the damage tolerance of the tested sandwich panels. A finite element (FE) model of the experimental setup was used for predicting propagation rates and direction of the crack growth. The FE simulation was based on the adoption of linear fracture mechanics and a fatigue propagation law (i.e. Paris law) to predict the residual fatigue life-time and behaviour of the test specimens. Finally, a comparison between the experimental results and the numerical simulations was made to validate the numerical predictions as well as the overall performance of the crack arresters.

  10. Quick adaptation of Ralstonia Solanacearum to copper stress to recover culturability and growth in water and soil

    Directory of Open Access Journals (Sweden)

    Sergio Daniel Moreira Ascarrunz

    2011-06-01

    Full Text Available Cells of Ralstonia solanacearum were exposed to Cu in distilled water, and the resulting Cu-stressed non-culturable cells were inoculated to natural (non-pasteurized and pasteurized soils in order to examine their culturability and recovery. Exposing the cells to 20 µM CuSO4 produced transitory non-culturable cells, which exhibited a remarkable recovery in culturability after incubation in the solution for 36 h, reaching a density near the initial level by 108 h. To determine whether such non-culturable cells actually "resuscitated" or multiplied after adapting to Cu toxicity, growth curves were constructed in order to contrast the rates of increase in culturable cell numbers between Cu-stressed or non-stressed inocula. Additionally, fresh non-stressed cells were exposed to CuSO4 in the presence of nalidixic acid by adding the antibiotic at different times after the onset of Cu stress to verify any cell multiplication during the population increase. The results revealed that the non-culturable cells surviving Cu toxicity adapted very quickly to Cu and began multiplying within 12 h, because only the Cu-stressed cells that were increasing in the exponential growth phase, but not those in the stationary phase, were killed by the antibiotic. Such cells exhibited an apparent tolerance to this metal when inoculated to a freshly prepared solution of CuSO4, and also detoxified the ion in the solution in which they grew. The presence of nutrients greatly counteracted the effect of Cu in water microcosms, since culturable cells were detected and increased in number even when exposed to 40 µM CuSO4. In contrast, when inoculated to non-pasteurized soil, Cu-stressed cells showed no such recoveries. However, when the soil was pasteurized before inoculation or added with nutrients, culturable cells were recovered and increased in number. This indicates that increased nutrient availability in soil allows Cu-stressed cells to quickly overcome the stress and

  11. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  12. [Cardiopulmonary resuscitation in cardiac arrest following trauma].

    Science.gov (United States)

    Leidel, B A; Kanz, K-G

    2016-11-01

    For decades, survival rates of cardiac arrest following trauma were reported between 0 and 2 %. Since 2005, survival rates have increased with a wide range up to 39 % and good neurological recovery in every second person injured for unknown reasons. Especially in children, high survival rates with good neurologic outcomes are published. Resuscitation following traumatic cardiac arrest differs significantly from nontraumatic causes. Paramount is treatment of reversible causes, which include massive bleeding, hypoxia, tension pneumothorax, and pericardial tamponade. Treatment of reversible causes should be simultaneous. Chest compression is inferior following traumatic cardiac arrest and should never delay treatment of reversible causes of the traumatic cardiac arrest. In massive bleeding, bleeding control has priority. Damage control resuscitation with permissive hypotension, aggressive coagulation therapy, and damage control surgery represent the pillars of initial treatment. Cardiac arrest due to hypoxia should be resolved by airway management and ventilation. Tension pneumothorax should be decompressed by finger thoracostomy, pericardial tamponade by resuscitative thoracotomy. In addition, resuscitative thoracotomy allows direct and indirect bleeding control. Untreated impact brain apnea may rapidly lead to cardiac arrest and requires quick opening of the airway and effective oxygenation. Established algorithms for treatment of cardiac arrest following trauma enable a safe, structured, and effective management.

  13. Theory of dynamic arrest in colloidal mixtures.

    Science.gov (United States)

    Juárez-Maldonado, R; Medina-Noyola, M

    2008-05-01

    We present a first-principles theory of dynamic arrest in colloidal mixtures based on the multicomponent self-consistent generalized Langevin equation theory of colloid dynamics [M. A. Chávez-Rojo and M. Medina-Noyola, Phys. Rev. E 72, 031107 (2005); M. A. Chávez-Rojo and M. Medina-Noyola, Phys. Rev. E76, 039902 (2007)]. We illustrate its application with a description of dynamic arrest in two simple model colloidal mixtures: namely, hard-sphere and repulsive Yukawa binary mixtures. Our results include observation of the two patterns of dynamic arrest, one in which both species become simultaneously arrested and the other involving the sequential arrest of the two species. The latter case gives rise to mixed states in which one species is arrested while the other species remains mobile. We also derive the ("bifurcation" or fixed-point") equations for the nonergodic parameters of the system, which takes the surprisingly simple form of a system of coupled equations for the localization length of the particles of each species. The solution of this system of equations indicates unambiguously which species is arrested (finite localization length) and which species remains ergodic (infinite localization length). As a result, we are able to draw the entire ergodic-nonergodic phase diagram of the binary hard-sphere mixture.

  14. Aqueous Extracts of the Edible Gracilaria tenuistipitata are Protective Against H2O2-Induced DNA Damage, Growth Inhibition, and Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Chi-Chen Yeh

    2012-06-01

    Full Text Available Potential antioxidant properties of an aqueous extract of the edible red seaweed Gracilaria tenuistipitata (AEGT against oxidative DNA damage were evaluated. The AEGT revealed several antioxidant molecules, including phenolics, flavonoids and ascorbic acid. In a cell-free assay, the extract exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging activity that significantly reduced H2O2-induced plasmid DNA breaks in a dose-response manner (P < 0.001. The AEGT also suppressed H2O2-induced oxidative DNA damage in H1299 cells by reducing the percentage of damaged DNA in a dose-response manner (P < 0.001 as measured by a modified alkaline comet-nuclear extract (comet-NE assay. The MTT assay results showed that AEGT confers significant protection against H2O2-induced cytotoxicity and that AEGT itself is not cytotoxic (P < 0.001. Moreover, H2O2-induced cell cycle G2/M arrest was significantly released when cells were co-treated with different concentrations of AEGT (P < 0.001. Taken together, these findings suggest that edible red algae Gracilaria water extract can prevent H2O2-induced oxidative DNA damage and its related cellular responses.

  15. Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP.

    Science.gov (United States)

    Mantena, Sudheer K; Sharma, Som D; Katiyar, Santosh K

    2006-10-01

    Chemotherapeutic approach using non-toxic botanicals may be one of the strategies for the management of the skin cancers. Here we report that in vitro treatment of human epidermoid carcinoma A431 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability (3-77%, P berberine-induced G(1) cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), a simultaneous decrease in Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and enhanced binding of Cdki-Cdk. In additional studies, treatment of A431 cells with berberine (15-75 microM) for 72 h resulted in a significant dose-dependent increase in apoptosis (31-60%, P berberine-treated control (11.7%), which was associated with an increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose) polymerase. Pretreatment of A431 cells with the pan-caspase inhibitor (z-VAD-fmk) significantly blocked the berberine-induced apoptosis in A431 cells confirmed that berberine-induced apoptosis is mediated through activation of caspase 3-dependent pathway. Together, this study for the first time identified berberine as a chemotherapeutic agent against human epidermoid carcinoma A431 cells in vitro, further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of non-melanoma skin cancers.

  16. Cardiac Arrest: Obstetric CPR/ACLS.

    Science.gov (United States)

    Cobb, Benjamin; Lipman, Steven

    2017-01-10

    In contrast with other high-resource countries, maternal mortality has seen an increase in the United States. Caring for pregnant women in cardiac arrest may prove uniquely challenging given the rarity of the event coupled by the physiological changes of pregnancy. Optimization of resuscitative efforts warrants special attention as described in the 2015 American Heart Association's "Scientific Statement on Maternal Cardiac Arrest." Current recommendations address a variety of topics ranging from the basic components of chest compressions and airway management to some of the logistical complexities and operational challenges involved in maternal cardiac arrest.

  17. Energy balance, nitrogen balance, and growth in preterm infants fed expressed breast milk, a premature infant formula, and two low-solute adapted formulae.

    Science.gov (United States)

    Brooke, O G; Wood, C; Barley, J

    1982-12-01

    Energy balance, nitrogen balance, and growth studies were done in 37 preterm infants (20 of very low birthweight) who were fed on expressed breast milk or on one of 3 formulae each of different composition, including a special premature formula and a highly adapted 'humanised' formula. The variability of breast milk composition was such that it would have been difficult to predict the infants' protein and energy intakes under normal nursing conditions. All measured parameters of nutritional performance were best in infants fed on the 'premature' formula and were reflected in greater weight gain, linear growth, and head growth. The nitrogen balance data suggest that the highly adapted formula, which had a protein content comparable with that of mature human milk, contained too little protein for small preterm infants.

  18. Analysis of different strategies adapted by two cassava cultivars in response to drought stress: ensuring survival or continuing growth.

    Science.gov (United States)

    Zhao, Pingjuan; Liu, Pei; Shao, Jiaofang; Li, Chunqiang; Wang, Bin; Guo, Xin; Yan, Bin; Xia, Yiji; Peng, Ming

    2015-03-01

    Cassava is one of the most drought-tolerant crops, however, the underlying mechanism for its ability to survive and produce under drought remains obscure. In this study, two cassava cultivars, SC124 and Arg7, were treated by gradually reducing the soil water content. Their responses to the drought stress were examined through their morphological and physiological traits and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. SC124 plants adapted a 'survival' mode under mild drought stress as evidenced by early stomatal closure and a reduction in the levels of various photosynthetic proteins and photosynthetic capacity, resulting in early growth quiescence. In contrast, Arg7 plants underwent senescence of older leaves but continued to grow, although at a reduced rate, under mild drought. SC124 plants were more capable of surviving prolonged severe drought than Arg7. The iTRAQ analysis identified over 5000 cassava proteins. Among the drought-responsive proteins identified in the study were an aquaporin, myo-inositol 1-phosphate synthases, and a number of proteins involved in the antioxidant systems and secondary metabolism. Many proteins that might play a role in signalling or gene regulation were also identified as drought-responsive proteins, which included several protein kinases, two 14-3-3 proteins, several RNA-binding proteins and transcription factors, and two histone deacetylases. Our study also supports the notion that linamarin might play a role in nitrogen reallocation in cassava under drought.

  19. Extracellular enzymatic activities of cold-adapted bacteria from polar oceans and effect of temperature and salinity on cell growth

    Institute of Scientific and Technical Information of China (English)

    Zeng Yinxin; Yu Yong; Chen Bo; Li Huirong

    2004-01-01

    The potential of 324 bacteria isolated from different habitats in polar oceans to produce a variety of extracellular enzymatic activities at low temperature was investigated. By plate assay, lipase, protease, amylase, gelatinase, agarase, chitinase or cellulase were detected. Lipases were generally present by bacteria living in polar oceans. Protease-producing bacteria held the second highest proportion in culturable isolates. Strains producing amylase kept a relative stable proportion of around 30% in different polar marine habitats. All 50 Arctic sea-ice bacteria producing proteases were cold-adapted strains, however, only 20% were psychrophilic. 98% of them could grow at 3% NaCl, and 56% could grow without NaCl. On the other hand, 98% of these sea-ice bacteria produced extracellular proteases with optimum temperature at or higher than 35℃, well above the upper temperature limit of cell growth. Extracellular enzymes including amylase, agarase, cellulase and lipase released by bacteria from seawater or sediment in polar oceans, most expressed maximum activities between 25 and 35℃. Among extracellular enzymes released by bacterial strain BSw20308, protease expressed maximum activity at 40℃, higher than 35℃ of polysaccharide hydrolases and 25℃ of lipase.

  20. Different Expression and Clinical Significance of DNA Methyltransferases in the Chorionic Villi of Early Embryo Growth Arrest%DNA甲基转移酶在胚胎停育绒毛组织中的表达差异及临床意义

    Institute of Scientific and Technical Information of China (English)

    郭为伟; 高静; 周磊; 黄维清; 孔庆暖

    2016-01-01

    Objective:To study the expression of DNMT1, DNMT3A, DNMT3B and DNMT3L mRNA and protein in the chorionic villi of early embryo growth arrest and explore its clinical significance. Methods:We randomly selected 40 women as observational group in which were diagnosed with early embryo growth arrest by B ultrasound and accepted complete curettage of uterine cavity after visiting the Obstetrical Department of the Qingdao Municipal Hospital between January 2013 and June 2014, during the same period, select another 40 women who performed induced abortion with normal early pregnancy as control group.①Real-time quantitative PCR (qRT-PCR) was used on the normal groups (40 cases) and the early embryo growth arrest group (40 cases) to quantitatively determine DNMT1, DNMT3A, DNMT3B and DNMT3L mRNA expression in the chorionic villi tissues. ②Streptavidin- Perosidase (SP) immunochemistry and Western blot were performed on the two groups to detect the expression and distribution of DNMT1, DNMT3A, DNMT3B and DNMT3L. Results: ①qRT-PCR showed there were no statistically significant difference of DNMT1, DNMT3A, DNMT3B and DNMT3L expression in two groups (P>0.05).②Immuno-chemistry showed DNMTs were predominately distributed on the villous trophoblasts which the cytoplasm and nuclear had varying degrees of positive staining. And semi-quantitative analysis indicated that the expression of DNMT3A of early embryo growth arrest was significantly lower, compared with that of the normal group (P0.05). Conclusions:The lower expression of the DNMT3A protein might be involved in the pathogenesis of early embryo growth arrest.%目的:探讨胚胎停育绒毛组织中DNA甲基转移酶(DNMTs)4种亚型DNMT1、DNMT3A、DNMT3B与DNMT3L的mRNA及蛋白表达差异,并探讨其临床意义。方法:随机选取2013年1月-2014年6月在青岛市立医院妇产科门诊就诊的经B型超声(B超)证实为胚胎停育而行清宫术的40例患者为观察组,并选取同期

  1. The obesity paradox in cardiac arrest patients.

    Science.gov (United States)

    Chalkias, Athanasios; Xanthos, Theodoros

    2014-02-01

    Evidence from clinical cohorts indicates an obesity paradox in overweight and obese patients who seem to have a more favorable short-term and long-term prognosis than leaner patients. Although obese cardiac arrest victims are theoretically more difficult to be resuscitated due to difficulties in providing adequate chest compressions, ventilation, and oxygenation, research so far has shown that there is an obesity paradox in cardiac arrest.

  2. Surface Electrocardiogram Predictors of Sudden Cardiac Arrest

    Science.gov (United States)

    Abdelghani, Samy A.; Rosenthal, Todd M.; Morin, Daniel P.

    2016-01-01

    Background: Heart disease is a major cause of death in industrialized nations, with approximately 50% of these deaths attributable to sudden cardiac arrest. If patients at high risk for sudden cardiac arrest can be identified, their odds of surviving fatal arrhythmias can be significantly improved through prophylactic implantable cardioverter defibrillator placement. This review summarizes the current knowledge pertaining to surface electrocardiogram (ECG) predictors of sudden cardiac arrest. Methods: We conducted a literature review focused on methods of predicting sudden cardiac arrest through noninvasive electrocardiographic testing. Results: Several electrocardiographic-based methods of risk stratification of sudden cardiac arrest have been studied, including QT prolongation, QRS duration, fragmented QRS complexes, early repolarization, Holter monitoring, heart rate variability, heart rate turbulence, signal-averaged ECG, T wave alternans, and T-peak to T-end. These ECG findings have shown variable effectiveness as screening tools. Conclusion: At this time, no individual ECG finding has been found to be able to adequately stratify patients with regard to risk for sudden cardiac arrest. However, one or more of these candidate surface ECG parameters may become useful components of future multifactorial risk stratification calculators. PMID:27660578

  3. Sex Disparities in Arrest Outcomes for Domestic Violence

    Science.gov (United States)

    Hamilton, Melissa; Worthen, Meredith G. F.

    2011-01-01

    Domestic violence arrests have been historically focused on protecting women and children from abusive men. Arrest patterns continue to reflect this bias with more men arrested for domestic violence compared to women. Such potential gender variations in arrest patterns pave the way to the investigation of disparities by sex of the offender in…

  4. Functional analysis of a biosynthetic cluster essential for production of 4-formylaminooxyvinylglycine, a germination-arrest factor from Pseudomonas fluorescens WH6

    Science.gov (United States)

    Rhizosphere-associated Pseudomonas fluorescens WH6 produces the germination-arrest factor, 4-formylaminooxyvinylglycine (FVG). FVG has previously been shown to both arrest the germination of weedy grasses and to inhibit the growth of the bacterial plant pathogen Erwinia amylovora. Very little is kno...

  5. Contributions of Two-Component Regulatory Systems, Alternative σ Factors, and Negative Regulators to Listeria monocytogenes Cold Adaptation and Cold Growth

    Science.gov (United States)

    Chan, Yvonne C.; Hu, Yuewei; Chaturongakul, Soraya; Files, Kali D.; Bowen, Barbara M.; Boor, Kathryn J.; Wiedmann, Martin

    2011-01-01

    The ability of Listeria monocytogenes to grow at refrigeration temperatures is critical for transmission of this foodborne pathogen. We evaluated the contributions of different transcriptional regulators and two-component regulatory systems to L. monocytogenes cold adaptation and cold growth. L. monocytogenes parent strain 10403S and selected isogenic null mutants in genes encoding four alternative σ factors (sigB, sigH, sigC, and sigL), two regulators of σB (rsbT and rsbV), two negative regulators (ctsR and hrcA), and 15 two-component response regulators were grown in brain heart infusion broth at 4°C with (i) a high-concentration starting inoculum (108 CFU/ml), (ii) a low-concentration starting inoculum (102 CFU/ml), and (iii) a high-concentration starting inoculum of cold-adapted cells. With a starting inoculum of 108 CFU/ml, null mutants in genes encoding selected alternative σ factors (ΔsigH, ΔsigC, and ΔsigL), a negative regulator (ΔctsR), regulators of σB (ΔrsbT and ΔrsbV), and selected two-component response regulators (ΔlisR, Δlmo1172, and Δlmo1060) had significantly reduced growth (P < 0.05) compared with the parent strain after 12 days at 4°C. The growth defect for ΔsigL was limited and was not confirmed by optical density (OD600) measurement data. With a starting inoculum of 102 CFU/ml and after monitoring growth at 4°C over 84 days, only the ΔctsR strain had a consistent but limited growth defect; the other mutant strains had either no growth defects or limited growth defects apparent at only one or two of the nine sampling points evaluated during the 84-day growth period (ΔsigB, ΔsigC, and Δlmo1172). With a 108 CFU/ml starting inoculum of cold-adapted cells, none of the mutant strains that had a growth defect when inoculation was performed with cells pregrown at 37°C had reduced growth as compared with the parent strain after 12 days at 4°C, suggesting a specific defect in the ability of these mutant strains to adapt to 4

  6. A Multi-Moment Bulkwater Ice Microphysics Scheme with Consideration of the Adaptive Growth Habit and Apparent Density for Pristine Ice in the WRF Model

    Science.gov (United States)

    Tsai, T. C.; Chen, J. P.; Dearden, C.

    2014-12-01

    The wide variety of ice crystal shapes and growth habits makes it a complicated issue in cloud models. This study developed the bulk ice adaptive habit parameterization based on the theoretical approach of Chen and Lamb (1994) and introduced a 6-class hydrometeors double-moment (mass and number) bulk microphysics scheme with gamma-type size distribution function. Both the proposed schemes have been implemented into the Weather Research and Forecasting model (WRF) model forming a new multi-moment bulk microphysics scheme. Two new moments of ice crystal shape and volume are included for tracking pristine ice's adaptive habit and apparent density. A closure technique is developed to solve the time evolution of the bulk moments. For the verification of the bulk ice habit parameterization, some parcel-type (zero-dimension) calculations were conducted and compared with binned numerical calculations. The results showed that: a flexible size spectrum is important in numerical accuracy, the ice shape can significantly enhance the diffusional growth, and it is important to consider the memory of growth habit (adaptive growth) under varying environmental conditions. Also, the derived results with the 3-moment method were much closer to the binned calculations. A field campaign of DIAMET was selected to simulate in the WRF model for real-case studies. The simulations were performed with the traditional spherical ice and the new adaptive shape schemes to evaluate the effect of crystal habits. Some main features of narrow rain band, as well as the embedded precipitation cells, in the cold front case were well captured by the model. Furthermore, the simulations produced a good agreement in the microphysics against the aircraft observations in ice particle number concentration, ice crystal aspect ratio, and deposition heating rate especially within the temperature region of ice secondary multiplication production.

  7. Sequence adaptations during growth of rescued classical swine fever viruses in cell culture and within infected pigs

    DEFF Research Database (Denmark)

    Hadsbjerg, Johanne; Friis, Martin Barfred; Fahnøe, Ulrik

    2016-01-01

    RNA could be detected. However, the animals inoculated with these mutant viruses seroconverted against CSFV. Thus, these mutant viruses were highly attenuated in vivo. All 4 rescued viruses were also passaged up to 20 times in cell culture. Using full genome sequencing, the same two adaptations within...... adaptation and to identify key determinants of viral replication efficiency in cells and within host animals....

  8. 科技型中小企业适应性成长路径研究%Towards an adaptive growth path of medium and small technological enterprises

    Institute of Scientific and Technical Information of China (English)

    黄春萍; 刘奎颖; 曾珍香

    2011-01-01

    Medium and small technological enterprises are the main force of national economic development. Their healthy growth is the common concern of both the business and academic circles. The adaptation of these enterprises and their adaptive growth stages are analyzed and a model for their adaptive growth path is established. Finally, cluster analysis is applied in an empirical study.%科技型中小企业是国民经济发展的主力军,其健康成长是企业界和学术界共同关心的热点问题.本文首先分析了科技型中小企业的适应性及其适应性成长阶段,分别是创业阶段、发展阶段、成熟阶段和蜕变阶段;进而基于企业适应性这一视角,提出了科技型中小企业适应性成长路径为自主发展型、动态模仿型和创新涌现型,并构建了其适应性成长路径模型,最后应用聚类分析进行了实证研究.

  9. Up-regulation of stathmin induces growth arrest of esophageal squamous cell carcinoma EC9706 cell%上调stathmin基因表达对食管鳞癌EC9706细胞的作用

    Institute of Scientific and Technical Information of China (English)

    王峰; 王留兴; 何炜; 李克; 王瑞林; 赵培荣; 樊青霞

    2010-01-01

    proliferation of transfected cells was measured by cell counting, MTT and in vitro formation assay of flat Flow cytometry was used to detect the cell cycle. Nude mice were adopted to investigate the in vivo tumorigenic characteristics of the transfected cells. Results A 450 bp coding sequence of stathmin cDNA was amplified by RT-PCR and then cloned into pcDNA3. 1 ( + ) plasmid to harvest the recombinant plasmid pcDNA3. 1-stathmin. The recombinant plasmid pcDNA3. 1-stathmin and blank vector were transfected respectively into EC9706 cells. The up-regulated expression of stathmin protein was validated by Western blot ( P < 0. 01 ) . Compared with control, EC9706 cells transfected with pcDNA3. 1-stathmin appeared swollen and multi-nuclear with a cell mitotic arrest; doubling generation time of pcDNA3. 1stathmin transfectants was prolonged(25 -28 h); The in vitro cell proliferation ability and clone formation rate (34.5% +-6.9%) decreased, cell cleavage was blocked at G2/M phase (21. 7% +- 3. 4% ) and the oncogenicity of inoculated cells in nude mice decreased ( all P < 0. 01). Conclusions The up-regulated expression of stathmin protein triggered by the recombinant plasmid pcDNA3. 1-stathmin can inhibit the proliferation and oncogenicity of ESCC EC9706 cells. TTiis molecule may be a promising therapeutic target in ESCC patients.

  10. Cell cycle arrest and cell survival induce reverse trends of cardiolipin remodeling.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chao

    Full Text Available Cell survival from the arrested state can be a cause of the cancer recurrence. Transition from the arrest state to the growth state is highly regulated by mitochondrial activity, which is related to the lipid compositions of the mitochondrial membrane. Cardiolipin is a critical phospholipid for the mitochondrial integrity and functions. We examined the changes of cardiolipin species by LC-MS in the transition between cell cycle arrest and cell reviving in HT1080 fibrosarcoma cells. We have identified 41 cardiolipin species by MS/MS and semi-quantitated them to analyze the detailed changes of cardiolipin species. The mass spectra of cardiolipin with the same carbon number form an envelope, and the C64, C66, C68, C70 C72 and C74 envelopes in HT1080 cells show a normal distribution in the full scan mass spectrum. The cardiolipin quantity in a cell decreases while entering the cell cycle arrest, but maintains at a similar level through cell survival. While cells awakening from the arrested state and preparing itself for replication, the groups with short acyl chains, such as C64, C66 and C68 show a decrease of cardiolipin percentage, but the groups with long acyl chains, such as C70 and C72 display an increase of cardiolipin percentage. Interestingly, the trends of the cardiolipin species changes during the arresting state are completely opposite to cell growing state. Our results indicate that the cardiolipin species shift from the short chain to long chain cardiolipin during the transition from cell cycle arrest to cell progression.

  11. A synthetic circuit for selectively arresting daughter cells to create aging populations.

    Science.gov (United States)

    Afonso, Bruno; Silver, Pamela A; Ajo-Franklin, Caroline M

    2010-05-01

    The ability to engineer genetic programs governing cell fate will permit new safeguards for engineered organisms and will further the biological understanding of differentiation and aging. Here, we have designed, built and implemented a genetic device in the budding yeast Saccharomyces cerevisiae that controls cell-cycle progression selectively in daughter cells. The synthetic device was built in a modular fashion by combining timing elements that are coupled to the cell cycle, i.e. cell-cycle specific promoters and protein degradation domains, and an enzymatic domain which conditionally confers cell arrest. Thus, in the presence of a drug, the device is designed to arrest growth of only newly-divided daughter cells in the population. Indeed, while the engineered cells grow normally in the absence of drug, with the drug the engineered cells display reduced, linear growth on the population level. Fluorescence microscopy of single cells shows that the device induces cell arrest exclusively in daughter cells and radically shifts the age distribution of the resulting population towards older cells. This device, termed the 'daughter arrester', provides a blueprint for more advanced devices that mimic developmental processes by having control over cell growth and death.

  12. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    Science.gov (United States)

    Puzzanchera, Charles

    2009-01-01

    This Bulletin summarizes 2007 juvenile crime and arrest data reported by local law enforcement agencies across the country and cited in the FBI report, "Crime in the United States 2007." The Bulletin describes the extent and nature of juvenile crime that comes to the attention of the justice system. It serves as a baseline for comparison for…

  13. Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development

    Directory of Open Access Journals (Sweden)

    Bhattacharya Abhishek

    2010-03-01

    Full Text Available Abstract Background The secreted morphogen Dpp plays important roles in spatial regulation of gene expression and cell cycle progression in the developing Drosophila eye. Dpp signaling is required for timely cell cycle arrest ahead of the morphogenetic furrow as a prelude to differentiation, and is also important for eye disc growth. The dpp gene is expressed at multiple locations in the eye imaginal disc, including the morphogenetic furrow that sweeps across the eye disc as differentiation initiates. Results Studies of Brinker and Dad expression, and of Mad phosphorylation, establish that there is a gradient of Dpp signaling in the eye imaginal disc anterior to the morphogenetic furrow, predominantly in the anterior-posterior axis, and also Dpp signaling at the margins of the disc epithelium and in the dorsal peripodial membrane. Almost all signaling activity seems to spread through the plane of the epithelia, although peripodial epithelium cells can also respond to underlying disc cells. There is a graded requirement for Dpp signaling components for G1 arrest in the eye disc, with more stringent requirements further anteriorly where signaling is lower. The signaling level defines the cell cycle response, because elevated signaling through expression of an activated Thickveins receptor molecule arrested cells at more anterior locations. Very anterior regions of the eye disc were not arrested in response to activated receptor, however, and evidence is presented that expression of the Homothorax protein may contribute to this protection. By contrast to activated Thickveins, ectopic expression of processed Dpp leads to very high levels of Mad phosphorylation which appear to have non-physiological consequences. Conclusions G1 arrest occurs at a threshold level of Dpp signaling within a morphogen gradient in the anterior eye. G1 arrest is specific for one competent domain in the eye disc, allowing Dpp signaling to promote growth at earlier

  14. Functional csdA is needed for effective adaptation and initiation of growth of Clostridium botulinum ATCC 3502 at suboptimal temperature.

    Science.gov (United States)

    Söderholm, Henna; Derman, Yağmur; Lindström, Miia; Korkeala, Hannu

    2015-09-02

    The activity of RNA helicase csdA (cbo2802) after temperature downshift was compared to its activity at optimal growth temperature, and the effect of sense and antisense oriented insertional inactivation of cbo2802 on the growth of ATCC 3502 at suboptimal temperature was evaluated. The relative cbo2802 transcript level was significantly induced for 30min to 5h after cold shock. In contrast, a significant decrease in the relative transcript level of cbo2802 was observed within the same time frame at 37°C. Inactivation of cbo2802 led to an extensive delay in initiation of exponential growth at 20°C but not at 37°C. In addition, the mean minimum growth temperatures of the mutant strains were higher than those of the wild-type strain. During a 24-hour incubation at 37°C, all strains were motile, whereas at 20°C the mutant strains showed severely impaired motility compared to the wild-type strain. This study shows that a functional csdA is needed for effective adaptation and initiation of growth and motility of Clostridium botulinum ATCC 3502 at suboptimal temperature.

  15. Cardiac arrest: comparison of paramedic and conventional ambulance services.

    OpenAIRE

    1983-01-01

    A prospective study conducted in the Greater Vancouver area compared survival rates in prehospital cardiac arrest managed by an advanced life support (paramedic) service with those in cardiac arrest managed by conventional ambulance service. Management by the paramedic service was associated with higher survival rates for patients found in cardiac arrest but not for patients who suffered the arrest while the ambulance was present. Cardiopulmonary resuscitation by bystanders was associated wit...

  16. Modes of induced cardiac arrest: hyperkalemia and hypocalcemia - Literature review

    OpenAIRE

    Oliveira,Marcos Aurélio Barboza de; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseini; Cortez, José Luis Lasso; Braile, Domingo Marcolino

    2014-01-01

    The entry of sodium and calcium play a key effect on myocyte subjected to cardiac arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused by hypocalcemia maintains intracellular adenosine triphosphate levels, improves diastolic performance and reduces oxygen consumption, which can be translated into better protection to myocyte injury induced by cardiac arrest.

  17. Next-generation transcriptome profiling reveals insights into genetic factors contributing to growth differences and temperature adaptation in Australian populations of barramundi (Lates calcarifer).

    Science.gov (United States)

    Newton, James R; Zenger, Kyall R; Jerry, Dean R

    2013-09-01

    Identification of genetically-regulated adaptation in fish is a precursor to understanding how populations will respond to future climate induced stressors like temperature. Australian populations of barramundi (Lates calcarifer) show strong evidence of local adaptation to temperature. However, the phenotypic consequences of this adaptation are unknown and the genetic mechanisms underlying this response are poorly understood. In the current study, two populations of barramundi from temperature extremes of the species Australian distribution were communally reared at cool (22°C), control (28°C) and hot (36°C) water temperatures for 3.5months. Southern populations of barramundi originating from a cooler environment grew significantly faster at 22°C than northern populations of warm adapted barramundi. However, no difference in population growth was present at either 28°C or 36°C. The underlying transcriptome profile of barramundi was examined via Illumina mRNA deep sequencing to determine the major contributing gene categories giving rise to phenotypic differences in barramundi population growth. Gene ontology (GO) analysis revealed enrichment in categories relating to the regulation of peptidase activity as well as microtubule, cytoplasmic and cellular metabolic based processes. Further analysis of the GO category "microtubule based process" with associated genes from the "response to stress" category revealed an apparent re-organization of cytoskeletal elements in response to an induced cold stress in northern barramundi reared at 22°C, when compared with northern barramundi reared at 36°C. Between southern barramundi and northern barramundi reared at 36°C, an analysis of the "endopeptidase inhibitor activity" GO category in conjunction with stress genes indicated a suppression of the complement system in southern barramundi along with an increase in the cellular stress response. The results of the present study show that southern populations of barramundi

  18. 生长停滞特异性基因产物6的2个单核苷酸多态性与缺血性脑卒中的相关性%Relation between two single nucleotide polymorphisms of growth arrest-specific gene 6 and ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    高永俊; 李晓峰; 杨旭; 李新毅

    2012-01-01

    目的 探讨生长停滞特异性基因产物6(growth arrest-specific gene 6,Gas 6)单核苷酸多态性(single nucleotide polymorphisms,SNP)与缺血性脑卒中(ischemic stroke,IS)及其亚型发生的相关性.方法 选择IS患者119例作为病例组,同期随机抽取无心、脑及周围动脉粥样硬化史的健康体检者217例作为对照组.根据既往研究的阳性结果及HapMap数据库,选择Gas6 rs8191974及rs7400722位点分析.采用PCR-RFLP技术进行2个SNP基因分型.采用logistic多元回归分析IS及其亚型的危险因素.结果 2组2个SNP基因型(P=0.80、0.79)、等位基因频率(P=0.57、0.50)及不同模型基因频率(显性:P=0.93、0.58;隐性:P=0.51、0.58)比较,差异均无统计学意义;以连锁不平衡系数>0.5为判断标准,共构建4个单体型(G-C,G-T,A-C,A-T),2组4个单体型分布频率差异均无统计学意义(P>0.05);校正相关危险因素后,差异仍无统计学意义(P>0.05).结论 Gas6 rs8191974及rs7400722位点基因型、等位基因频率及单体型与IS无明显相关性.%Objective To study the relation of single nucleotide polymorphisms(SNP) of growth arrest-specific gene 6(Gas6) with ischemic stroke (IS) and its subtypes. Methods One hundred and nineteen IS patients served as a patient group and 217 subjects with no history of cardiac,cerebral and peripheral athrosclerosis served as a control group in this study. The rs8191974 and rs7400722 polymorphisms of Gas6, selected according to the positive findings in previous studies and in HapMap database,were detected by PCR-RFLP. Risk factors for IS and its subtypes were analyzed by multivariate logistic regression analysis. Results No significant difference was found in the 2 ingle nucleotide SNP,frequency of allele and Gas6 gene in different models,and in the 4 haplotypes(G-C, G-T, A-C, AT) we established with the chain-imbalance factor >0. 05 as a judge criterion between the two groups, even after the related risk factors were

  19. Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients

    DEFF Research Database (Denmark)

    D'Argenio, D.A.; Wu, M.H.; Hoffman, L.R.

    2007-01-01

    contribute to selection of lasR mutants both on rich medium and within the CF airway, supporting a key role for bacterial metabolic adaptation during chronic infection. Inactivation of lasR also resulted in increased beta-lactamase activity that increased tolerance to ceftazidime, a widely used beta-lactam...

  20. Adaptation and growth kinetics study of an Indian isolate of virulent duck enteritis virus in Vero cells.

    Science.gov (United States)

    Aravind, S; Kamble, Nitin M; Gaikwad, Satish S; Shukla, Sanjeev Kumar; Dey, Sohini; Mohan, C Madhan

    2015-01-01

    Duck virus enteritis, also known as duck plague, is a viral infection of ducks caused by duck enteritis virus (DEV). The control of the disease is mainly done by vaccination with chicken embryo adapted live virus that is known to be poorly immunogenic and elicits only partial protection. Further, the embryo propagated vaccine virus pose a threat of harboring other infectious agents. Seeing these limitations, the present study reports for the first time regarding propagation and adaptation of a virulent Indian isolate of duck enteritis virus in Vero cell line. In this study isolation of an outbreak virus from Kerala state was done in chicken embryo fibroblast cell culture (CEF). Then adapted the DEV isolate in the Vero cell line. The characteristic cytopathic effects (CPE) of clumping and fusion of Vero cells were observed starting from the 7th passage onwards. The presence of the virus and its multiplication in Vero cells was confirmed by detection of viral specific DNA and antigen by using polymerase chain reaction (PCR) and indirect immuno fluorescent assay (IIFA), respectively. PCR detection of DEV using self designed primers for US4 (gD) and UL30 (DNA Polymerase) gene has been reported for the in the present study. The kinetics of DEV in Vero cells revealed a maximum infectivity titer of 10(5.6) TCID 50/ml after 48hr of viral infection. Compared to chicken embryo adapted DVE vaccine virus, the Vero cell culture system is free from other infectious agents. So it will be a good candidate for cultivation and propagation of duck enteritis virus vaccine strain. Further research studies are suggested to explore the feasibility of utilizing this Vero cell culture adapted DEV isolate for developing an attenuated vaccine virus against duck virus enteritis.

  1. 基于自适应成长法的散热通道构建技术%Construction Technology of Cooling Channel Based on Adaptive Growth Method

    Institute of Scientific and Technical Information of China (English)

    杨东升; 丁晓红; 季学荣; 刘炜

    2012-01-01

    应用自然界生物分枝网形态成长机理的自适应成长法对体-点问题进行求解,以每一单元的材料热导率作为设计变量,以设计区域的最高温度最低为设计目标,根据设计领域的温度梯度,逐步将高导热材料填充到设计区域,实现自适应成长。以若干典型体-点问题为算例,通过与现有设计方法的结果进行比较,说明提出的自适应成长技术可有效地应用于散热通道的构建。%The adaptive growth method based on the growth mechanism of branch systems mor- phologies in nature was applied to solve volume--point problem. The thermal conductivity of each ele ment was selected to be as design variable and minimization of the maximum temperature in the de- sign area was the objective. The material with high thermal conductivity was distributed gradually to the design area and the adaptive growth of cooling channel was realized. Several typical volume--point problems were analyzed and compared with the results of current methods. It is found that the adap- tive growth method can be used to construct cooling channel effectively.

  2. First permanent molar root development arrest associated with compound odontoma.

    Science.gov (United States)

    Gunda, Sachin A; Patil, Anil; Varekar, Aniruddha

    2013-07-04

    Trauma or infection to the primary tooth may have deleterious effects on the underlying developing tooth buds. Anatomically the root apices of primary teeth are in close proximity to the developing permanent tooth buds; hence spread of infection originating from pulp necrosis of primary tooth may not only affect the underlying tooth bud but may also affect the adjacent tooth buds. The extent of malformation depends on the developmental stage of tooth or the age of patient. Presented here is a rare case of complete arrest of maxillary first permanent molar root growth due to spread of periapical infection originating from second primary molar leading to failure of its eruption and finally extraction. Histopathlogical analysis revealed compound odontoma associated with maxillary first permanent molar.

  3. Nuclear reactor melt arrest and coolability device

    Energy Technology Data Exchange (ETDEWEB)

    Theofanous, Theo G.; Dinh, Nam Truc; Wachowiak, Richard M.

    2016-06-14

    Example embodiments provide a Basemat-Internal Melt Arrest and Coolability device (BiMAC) that offers improved spatial and mechanical characteristics for use in damage prevention and risk mitigation in accident scenarios. Example embodiments may include a BiMAC having an inclination of less than 10-degrees from the basemat floor and/or coolant channels of less than 4 inches in diameter, while maintaining minimum safety margins required by the Nuclear Regulatory Commission.

  4. Dental Calculus Arrest of Dental Caries

    Science.gov (United States)

    Keyes, Paul H.; Rams, Thomas E.

    2016-01-01

    Background An inverse relationship between dental calculus mineralization and dental caries demineralization on teeth has been noted in some studies. Dental calculus may even form superficial layers over existing dental caries and arrest their progression, but this phenomenon has been only rarely documented and infrequently considered in the field of Cariology. To further assess the occurrence of dental calculus arrest of dental caries, this study evaluated a large number of extracted human teeth for the presence and location of dental caries, dental calculus, and dental plaque biofilms. Materials and methods A total of 1,200 teeth were preserved in 10% buffered formal saline, and viewed while moist by a single experienced examiner using a research stereomicroscope at 15-25× magnification. Representative teeth were sectioned and photographed, and their dental plaque biofilms subjected to gram-stain examination with light microscopy at 100× magnification. Results Dental calculus was observed on 1,140 (95%) of the extracted human teeth, and no dental carious lesions were found underlying dental calculus-covered surfaces on 1,139 of these teeth. However, dental calculus arrest of dental caries was found on one (0.54%) of 187 evaluated teeth that presented with unrestored proximal enamel caries. On the distal surface of a maxillary premolar tooth, dental calculus mineralization filled the outer surface cavitation of an incipient dental caries lesion. The dental calculus-covered carious lesion extended only slightly into enamel, and exhibited a brown pigmentation characteristic of inactive or arrested dental caries. In contrast, the tooth's mesial surface, without a superficial layer of dental calculus, had a large carious lesion going through enamel and deep into dentin. Conclusions These observations further document the potential protective effects of dental calculus mineralization against dental caries. PMID:27446993

  5. Rheology and structural arrest of casein suspensions

    OpenAIRE

    Dahbi, Louisa; Alexander, M.; Trappe, Véronique; Dhont, J. K. G.; Schurtenberger, Peter

    2010-01-01

    The rheology of milk powder suspensions is investigated up to very high concentrations, where structural arrest occurs. The main component of the milk powder investigated is casein, so that the suspensions can be regarded as casein suspensions. Four concentration regimes are identified. For effective casein volume fractions less than 0.54 the concentration dependence of the zero-shear viscosity is similar to that of hard-sphere suspensions. However, due to the elastic deformation of the casei...

  6. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.

    Directory of Open Access Journals (Sweden)

    Neel M Fofaria

    Full Text Available In this study, we determined the cytotoxic effects of piperine, a major constituent of black and long pepper in melanoma cells. Piperine treatment inhibited the growth of SK MEL 28 and B16 F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest by piperine treatment was associated with DNA damage as indicated by phosphorylation of H2AX at Ser139, activation of ataxia telangiectasia and rad3-related protein (ATR and checkpoint kinase 1 (Chk1. Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Similarly, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine. Piperine treatment caused down-regulation of E2F1 and phosphorylation of retinoblastoma protein (Rb. Apoptosis induced by piperine was associated with down-regulation of XIAP, Bid (full length and cleavage of Caspase-3 and PARP. Furthermore, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS by tiron protected the cells from piperine mediated cell cycle arrest and apoptosis. These results suggest that piperine mediated ROS played a critical role in inducing DNA damage and activation of Chk1 leading to G1 cell cycle arrest and apoptosis.

  7. Aerodynamically generated noise by lightning arrester

    Directory of Open Access Journals (Sweden)

    Váchová J.

    2007-10-01

    Full Text Available This paper presents the general solution of aerodynamically generated noise by lightning arrester. Governing equations are presented in form of Lighthill acoustic analogy, as embodied in the Ffowcs Williams-Hawkings (FW-H equation. This equation is based on conservation laws of fluid mechanics rather than on the wave equation. Thus, the FW-H equation is valid even if the integration surface is in nonlinear region. That’s why the FWH method is superior in aeroacoustics. The FW-H method is implemented in program Fluent and the numerical solution is acquired by Fluent code.The general solution of acoustic signal generated by lightning arrester is shown and the results in form of acoustic pressure and frequency spectrum are presented. The verification of accuracy was made by evaluation of Strouhal number. A comparison of Strouhal number for circumfluence of a cylinder and the lightning arrester was done, because the experimental data for cylinder case are known and these solids are supposed to be respectively in shape relation.

  8. Bud phenology and growth are subject to divergent selection across a latitudinal gradient in Populus angustifolia and impact adaptation across the distributional range and associated arthropods.

    Science.gov (United States)

    Evans, Luke M; Kaluthota, Sobadini; Pearce, David W; Allan, Gerard J; Floate, Kevin; Rood, Stewart B; Whitham, Thomas G

    2016-07-01

    Temperate forest tree species that span large geographical areas and climatic gradients often have high levels of genetic variation. Such species are ideal for testing how neutral demographic factors and climate-driven selection structure genetic variation within species, and how this genetic variation can affect ecological communities. Here, we quantified genetic variation in vegetative phenology and growth traits in narrowleaf cottonwood, Populus angustifolia, using three common gardens planted with genotypes originating from source populations spanning the species' range along the Rocky Mountains of North America (ca. 1700 km). We present three main findings. First, we found strong evidence of divergent selection (Q ST > F ST) on fall phenology (bud set) with adaptive consequences for frost avoidance. We also found evidence for selection on bud flush duration, tree height, and basal diameter, resulting in population differentiation. Second, we found strong associations with climate variables that were strongly correlated with latitude of origin. More strongly differentiated traits also showed stronger climate correlations, which emphasizes the role that climate has played in divergent selection throughout the range. We found population × garden interaction effects; for some traits, this accounted for more of the variance than either factor alone. Tree height was influenced by the difference in climate of the source and garden locations and declined with increasing transfer distance. Third, growth traits were correlated with dependent arthropod community diversity metrics. Synthesis. Overall, we conclude that climate has influenced genetic variation and structure in phenology and growth traits and leads to local adaptation in P. angustifolia, which can then impact dependent arthropod species. Importantly, relocation of genotypes far northward or southward often resulted in poor growth, likely due to a phenological mismatch with photoperiod, the proximate

  9. Root proteome response to growth on tannery waste in three different poplar species with various adaptation abilities

    Directory of Open Access Journals (Sweden)

    Zemleduch-Barylska A.

    2013-04-01

    Full Text Available In our study we compared growth of three poplar clones (Populus tremula ×alba, P. alba ‘Villafranca” and P. nigra on chromium-containing solid tannery waste. Tolerance index of saplings ranged from only 25% for P. nigra up to 80% for P. tremula x alba. Standard morphological, chemical and biochemical analyses also confirmed significant differences in reaction of all tested clones to such growth conditions. Preliminary proteomic study showed an unequal level of changes in protein profiles from roots in different poplars.

  10. Arrest scenarios in concentrated protein solutions - from hard sphere glasses to arrested spinodal decomposition

    Science.gov (United States)

    Stradner, Anna; Bucciarelli, Saskia; Casal, Lucia; Foffi, Giuseppe; Thurston, George; Farago, Bela; Schurtenberger, Peter

    2014-03-01

    The occurrence of an arrest transition in concentrated colloid suspensions and its dependence on the interaction potential is a hot topic in soft matter. Such arrest transitions can also occur in concentrated protein solutions, as they exist e.g. in biological cells or are increasingly used in pharmaceutical formulations. Here we demonstrate the applicability of concepts from colloid science to understand the dynamics of concentrated protein solutions. In this presentation we report a combination of 3D light scattering, small-angle X-ray scattering and neutron spin echo measurements to study the structural properties as well as the collective and self diffusion of proteins in highly concentrated solutions on the relevant length and time scales. We demonstrate that various arrest scenarios indeed exist for different globular proteins. The proteins chosen are different bovine lens crystallins. We report examples of hard and attractive glass transitions and arrested spinodal decomposition directly linked to the effective pair potentials determined in static scattering experiments for the different proteins. We discuss these different arrest scenarios in view of possible applications of dense protein solutions as well as in view of their possible relevance for living systems.

  11. Growth and Collapse of a Resource System: an Adaptive Cycle of Change in Public Lands Governance and Forest Management in Alaska

    Directory of Open Access Journals (Sweden)

    Colin M. Beier

    2009-12-01

    Full Text Available Large-scale government efforts to develop resources for societal benefit have often experienced cycles of growth and decline that leave behind difficult social and ecological legacies. To understand the origins and outcomes of these failures of resource governance, scholars have applied the framework of the adaptive cycle. In this study, we used the adaptive cycle as a diagnostic approach to trace the drivers and dynamics of forest governance surrounding a boom-bust sequence of industrial forest management in one of the largest-scale resource systems in U.S. history: the Tongass National Forest in southeastern Alaska. Our application of the adaptive cycle combined a historical narrative tracing dynamics in political, institutional, and economic subsystems and a longitudinal analysis of an indicator of overall system behavior (timber harvests. We found that federal policies in concert with global market changes drove transformative change in both forest governance (policy making and forest management (practices, through creation and dissolution of subsidized long-term lease contracts. Evidence of the systemic resilience provided by these leases was found in the analysis of industry responses to market volatility before and after Tongass-specific federal reforms. Although the lease contracts stabilized the Tongass system for a period of time, they fostered a growing degree of rigidity that contributed to a severe industrial collapse and the subsequent emergence of complex social traps. Broader lessons from the Tongass suggest that large-scale changes occurred only when the nested economic and policy cycles were in coherence, and a systemic effort to minimize social and ecological variability ultimately resulted in catastrophic collapse of governance. This collapse resulted in a pervasive and challenging legacy that prevents Tongass reorganization and limits the adaptive capacity of the larger social-ecological system of southeastern Alaska

  12. Arrest History and Intimate Partner Violence Perpetration in a Sample of Men and Women Arrested for Domestic Violence.

    Science.gov (United States)

    Shorey, Ryan C; Ninnemann, Andrew; Elmquist, Joanna; Labrecque, Lindsay; Zucosky, Heather; Febres, Jeniimarie; Brasfield, Hope; Temple, Jeff R; Stuart, Gregory L

    2012-01-01

    Intimate partner violence (IPV) is a serious and prevalent problem throughout the United States. Currently, individuals arrested for domestic violence are often court mandated to batterer intervention programs (BIPs). However, little is known about the arrest histories of these individuals, especially women. The current study examined the arrest histories of men (n = 303) and women (n = 82) arrested for domestic violence and court-referred to BIPs. Results demonstrated that over 30% of the entire sample had been previously arrested for a non-violent offense, and over 25% of the participants had been previously arrested for a violent offense other than domestic violence. Moreover, men were arrested significantly more frequently for violence-related and non-violent offenses than their female counterparts. In addition, men were more likely than women to have consumed binge-levels of alcohol prior to the offense that led to their most recent arrest and court-referral to a BIP. Lastly, arrest history was positively associated with physical and psychological aggression perpetration against an intimate partner for men only, such that more previous arrests were associated with more frequent aggression. These results provide evidence that many men and women arrested for domestic violence have engaged in a number of diverse criminal acts during their lifetimes, suggesting that BIPs may need to address general criminal behavior.

  13. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Guo Chun; Zhu Faliang [Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Yang Qiaozi [Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States); Gao Guimin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn; Shao Changshun [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)], E-mail: shao@biology.rutgers.edu

    2009-03-09

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis.

  14. Mind your errors: evidence for a neural mechanism linking growth mind-set to adaptive posterror adjustments.

    Science.gov (United States)

    Moser, Jason S; Schroder, Hans S; Heeter, Carrie; Moran, Tim P; Lee, Yu-Hao

    2011-12-01

    How well people bounce back from mistakes depends on their beliefs about learning and intelligence. For individuals with a growth mind-set, who believe intelligence develops through effort, mistakes are seen as opportunities to learn and improve. For individuals with a fixed mind-set, who believe intelligence is a stable characteristic, mistakes indicate lack of ability. We examined performance-monitoring event-related potentials (ERPs) to probe the neural mechanisms underlying these different reactions to mistakes. Findings revealed that a growth mind-set was associated with enhancement of the error positivity component (Pe), which reflects awareness of and allocation of attention to mistakes. More growth-minded individuals also showed superior accuracy after mistakes compared with individuals endorsing a more fixed mind-set. It is critical to note that Pe amplitude mediated the relationship between mind-set and posterror accuracy. These results suggest that neural mechanisms indexing on-line awareness of and attention to mistakes are intimately involved in growth-minded individuals' ability to rebound from mistakes.

  15. Temperature-dependent growth and emergence of functional leaves: an adaptive mechanism in the seedlings of the western Himalayan plant Podophyllum hexandrum.

    Science.gov (United States)

    Kushwaha, Rekha; Pandey, Subedar; Chanda, Sanjoy; Bhattacharya, Amita; Ahuja, Paramvir Singh

    2008-05-01

    As an adaptive mechanism, hypocotyl dormancy delays emergence of functional leaf until favorable season of growth in Podophyllum hexandrum, an endangered medicinal plant of the western Himalayas. However, upon exposure of the freshly germinated seedlings to favorable temperature (25 degrees C), functional leaves emerged within 20 days. Therefore, we examined regulation mechanisms of growth and development of this alpine plant by temperature under laboratory conditions. The seedlings were exposed to (1) 25 degrees C (temperature prevailing at the time of maximum vegetative growth), (2) 4 degrees C (mean temperature at the onset of winter in its natural habitat), and (3) 10 degrees C (an intermediate temperature). Slackened growth at 4 degrees C was followed by senescence of aerial parts and quiescence of roots and predetermined leaf primordia. Rapid development of leaf primordia at 25 degrees C was associated with increased starch hydrolysis. This was evident from higher alpha-amylase activity and reducing sugars. These parameters decreased on sudden exposure to 4 degrees C. In contrast, the roots (perennating organs) showed a slight increase (1.36-fold) in alpha-amylase activity. Growth and development in seedlings growing at 10 degrees C (temperature less adverse than 4 degrees C) were comparatively faster. The content of reducing sugars and alpha-amylase activity were also higher in all the seedling parts at 10 degrees C as compared to 4 degrees C. This indicated larger requirements for sugar by the seedlings at 10 degrees C. Irrespective of temperature, maximum changes in nitrate and nitrate reductase occurred during the initial 10 days, i.e., when the readily available form of sugars (reducing sugar) was highest. This indicated that a temperature-dependent availability of carbon, but not temperature itself, was an important regulator of uptake and reduction of nitrogen.

  16. Adaptability to climate change in forestry species: drought effects on growth and wood anatomy of ponderosa pines growing at different competition levels

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, M. E.; Gyenge, J. E.; Urquiza, M. M.; Varela, S.

    2012-11-01

    More stressful conditions are expected due to climatic change in several regions, including Patagonia, South-America. In this region, there are no studies about the impact of severe drought events on growth and wood characteristics of the most planted forestry species, Pinus ponderosa (Doug. ex-Laws). The objective of this study was to quantify the effect of a severe drought event on annual stem growth and functional wood anatomy of pines growing at different plantation densities aiming to understand how management practices can help to increase their adaptability to climate change. Growth magnitude and period, specific hydraulic conductivity, and anatomical traits (early- and late wood proportion, lumen diameter, cell-wall thickness, tracheid length and bordered pit dimensions) were measured in the ring 2008-2009, which was formed during drought conditions. This drought event decreased annual stem growth by 30-38% and 58-65% respect to previous mean growth, in open vs. closed stand trees, respectively, indicating a higher sensitivity of the latter, which is opposite to reports from the same species growing in managed native forests in USA. Some wood anatomical variables did differ in more water stressed trees (lower cell wall thickness of early wood cells and higher proportion of small-lumen cells in late wood), which in turn did not affect wood function (hydraulic conductivity and resistance to implosion). Other anatomical variables (tracheid length, pit dimensions, early- and late wood proportion, lumen diameter of early wood cells) did not differ between tree sizes and plantation density. The results suggest that severe drought affects differentially the amount but not the function and quality of formed wood in ponderosa pine growing at different competition levels. (Author) 41 refs.

  17. Arresting developments: trends in female arrests for domestic violence and proposed explanations.

    Science.gov (United States)

    Deleon-Granados, William; Wells, William; Binsbacher, Ruddyard

    2006-04-01

    This article represents an effort to generate more systematic and specified discussion on the topic of unintended consequences in the movement to decrease violence against women. In this case, the consequence is increases in female arrests for domestic violence. This article builds on recent discussions by first using a sample of data to examine felony domestic violence arrest rates for men and women. The data support the conclusion that domestic violence arrests of women have increased. Second, the article presents six explanations that are derived from existing literature. Although the authors do not offer empirical tests of these explanations, this presentation can play an important part in better understanding the outcomes of criminal justice policies that are aimed at increasing victim safety.

  18. Adaptive evolution for fast growth on glucose and the effects on the regulation of glucose transport system in Clostridium tyrobutyricum.

    Science.gov (United States)

    Jiang, Ling; Li, Shuang; Hu, Yi; Xu, Qing; Huang, He

    2012-03-01

    Laboratory adaptive evolution of microorganisms offers the possibility of relating acquired mutations to increased fitness of the organism under the conditions used. By combining a fibrous-bed bioreactor, we successfully developed a simple and valuable adaptive evolution strategy in repeated-batch fermentation mode with high initial substrate concentration and evolved Clostridium tyrobutyricum mutant with significantly improved butyric acid volumetric productivity up to 2.25 g/(L h), which is the highest value in batch fermentation reported so far. Further experiments were conducted to pay attention to glucose transport system in consideration of the high glucose consumption rate resulted from evolution. Complete characterization and comparison of the glucose phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) were carried out in the form of toluene-treated cells and cell-free extracts derived from both C. tyrobutyricum wide-type and mutant, while an alternative glucose transport route that requires glucokinase was confirmed by the phenomena of resistance to the glucose analogue 2-deoxyglucose and ATP-dependent glucose phosphorylation. Our results suggest that C. tyrobutyricum mutant is defective in PTS activity and compensates for this defect with enhanced glucokinase activity, resulting in the efficient uptake and consumption of glucose during the whole metabolism.

  19. Arrests of women for driving under the influence.

    Science.gov (United States)

    Shore, E R; McCoy, M L; Toonen, L A; Kuntz, E J

    1988-01-01

    Police records of arrests of women in Wichita, Kansas for driving under the influence (DUI) of alcohol for a 5-year period (1980-1984) were studied. The proportion of arrests of women increased from 10.6 to 14.5% of total arrested. Women in their 20s comprised the largest age group; single women were greatly overrepresented. More than one-half of the arrested women were employed outside the home; a substantial proportion (30.8%) were unemployed at the time of arrest. The average blood alcohol level of those tested was 183 mg/dl. Characteristics of arrestees are discussed in terms of changes in the social roles and expectations of women. Although time of arrest was similar to that of men (i.e., night), arrests of women were more evenly spread across the days of the week. Within the 5-year period, the rate of recidivism for DUI was 7.43%. The implications of arrest and recidivism patterns are discussed. A change in legal and arrest procedures was found to have the same effect on arrests of women as it had on those of men, suggesting that the changes did not produce differential treatment by police.

  20. Verification at the protein level of the PIF4-mediated external coincidence model for the temperature-adaptive photoperiodic control of plant growth in Arabidopsis thaliana.

    Science.gov (United States)

    Yamashino, Takafumi; Nomoto, Yuji; Lorrain, Séverine; Miyachi, Miki; Ito, Shogo; Nakamichi, Norihito; Fankhauser, Christian; Mizuno, Takeshi

    2013-03-01

    Plant circadian clock controls a wide variety of physiological and developmental events, which include the short-days (SDs)-specific promotion of the elongation of hypocotyls during de-etiolation and also the elongation of petioles during vegetative growth. In A. thaliana, the PIF4 gene encoding a phytochrome-interacting basic helix-loop-helix (bHLH) transcription factor plays crucial roles in this photoperiodic control of plant growth. According to the proposed external coincidence model, the PIF4 gene is transcribed precociously at the end of night specifically in SDs, under which conditions the protein product is stably accumulated, while PIF4 is expressed exclusively during the daytime in long days (LDs), under which conditions the protein product is degraded by the light-activated phyB and also the residual proteins are inactivated by the DELLA family of proteins. A number of previous reports provided solid evidence to support this coincidence model mainly at the transcriptional level of the PIF 4 and PIF4-traget genes. Nevertheless, the diurnal oscillation profiles of PIF4 proteins, which were postulated to be dependent on photoperiod and ambient temperature, have not yet been demonstrated. Here we present such crucial evidence on PIF4 protein level to further support the external coincidence model underlying the temperature-adaptive photoperiodic control of plant growth in A. thaliana.

  1. Adaptability comparison of E. fetida in vermicomposting against sludge from livestock wastewater treatment plant based on their several growth stages.

    Science.gov (United States)

    Hao, Xiaoxia; Hu, Hongwen; Li, Xuewei; Jiang, Dongmei; Zhu, Li; Bai, Lin

    2016-08-01

    Vermicomposting is a low-cost, eco-efficient process to deal with organic wastes. Mixtures of swine manure (SM), cow dung (CD), and animal wastewater treatment plant sludge (S) were applied as feeds, and Eisenia fetida was employed in this study to investigate the vermicomposting efficiency based on their several growth stages. The hatching test resulted in a 100 % hatching rate in S60SM40 (60 % S + 40 % SM) mixture, while 4.40 hatchlings per cocoon were observed. The growth of infancy performed best in 0-20 % CD mixtures (0.05 ± 0.002 g), followed by in SM + CD (0.04 ± 0.003 g). The highest growth rate of young and adult E. fetida was noticed in CD + S mixtures (11.14 ± 0.01 and 6.00 ± 0.02 mg/d/worm, respectively), while the higher cocoon production of adults was noticed in S + SM mixtures especially in S40SM60 (537 ± 5 worms). Moreover, the conversion of solids; the modified pH value; the reduction in total organic carbon (TOC); total Kjeldahl nitrogen (TKN), NH4-N, NO3-N, and C:N ratio; and the rich in total available phosphorus (TAP) and total potassium (TK) content by young and adult E. fetida were related to the growth of worms. Such work would benefit understanding and to increase the efficiency of vermicompost processing of different wastes.

  2. Adaptation of seedling growth to the altitude: a case of the Norway spruce from the polish Sudety mountains

    Directory of Open Access Journals (Sweden)

    Robakowski, Piotr

    1997-12-01

    Full Text Available Seedlings of five Norway spruce [Picea abies (L. Karst.] populations originating from different altitudes in the massif of Snieznik Klodzki in the Sudety Mountains (Poland were grown in the greenhouse. Height, root length, and weight of root, shoot, needles and bud, as well as biomass allocation were studied. A good correlation of seedling traits and the altitude of mother stands was found. This indicates a rather good ecological adaptation of these, probably introduced populations. Some ecological and silvicultural aspects of the results are discussed.

    [fr] Les plantes de cinq populations de l'épicéa commun [Picea abies (L. Karst.] provenant des différentes altitudes du massif de Snieznik Klodzki dans les Sudètes (une chaîne des montagnes en Pologne ont été cultivées dans la serre. Leurs paramètres suivants ont été analysés: la hauteur, la longueur des racines, le poids frais et le poids sec des racines, des tiges, des aiguilles, des bourgeons et l'allocation de la biomasse. La haute corrélation a été notée entre les paramètres des plantes et l'altitude des stations des arbres ayant été les semenciers des graines. Ce résultat montre une plutôt bonne adaptation écologique de ces populations, probablement introduites dans le massif de Snieznik Klodzki. Les aspects écologiques et les conséquences de l'adaptation de l'épicéa commun aux conditions montagneuses pour la sylviculture sont discutés.
    [es] Plántulas de cinco poblaciones de abeto rojo [Picea abies (L. Karst.] procedentes de diferente altitud en el macizo de Snieznik Klodzki, en los Montes Sudetes, (Polonia se cultivaron en invernadero. Se han analizado los parámetros siguientes: altura y longitud de las raíces, pesos fresco y seco de raíces, tallos, hojas y yemas, así como la distribución de la biomasa. Como resultado se obtuvo una correlación alta entre los parámetros de las plántidas y la altitud de las estaciones donde se colectaron las

  3. Comprehensive analysis of an Antarctic bacterial community with the adaptability of growth at higher temperatures than those in Antarctica.

    Science.gov (United States)

    Hosoi-Tanabe, Shoko; Zhang, Hongyan; Zhu, Daochen; Nagata, Shinichi; Ban, Syuhei; Imura, Satoshi

    2010-06-01

    To investigate the adaptability to higher temperatures of Antarctic microorganisms persisting in low temperature conditions for a long time, Antarctic lake samples were incubated in several selection media at 25 degrees C and 30 degrees C. The microorganisms did not grow at 30 degrees C; however, some of them grew at 25 degrees C, indicating that the bacteria in Antarctic have the ability to grow at a wide range of temperatures. Total DNA was extracted from these microorganisms and amplified using the bacteria-universal primers. The amplified fragments were cloned, and randomly selected 48 clones were sequenced. The sequenced clones showed high similarity to the alpha-subdivision of the Proteobacteria with specific affinity to the genus Agrobacterium, Caulobacter and Brevundimonas, the ss-subdivision of Proteobacteria with specific affinity to the genus Cupriavidus, and Bacillus of the phylum Firmicutes. These results showed the presence of universal genera, suggesting that the bacteria in the Antarctic lake were not specific to this environment.

  4. Hydroxylated PBDEs induce developmental arrest in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Usenko, Crystal Y., E-mail: Crystal_usenko@baylor.edu; Hopkins, David C.; Trumble, Stephen J., E-mail: Stephen_trumble@baylor.edu; Bruce, Erica D., E-mail: Erica_bruce@baylor.edu

    2012-07-01

    The ubiquitous spread of polybrominated diphenyl ethers (PBDEs) has led to concerns regarding the metabolites of these congeners, in particular hydroxylated PBDEs. There are limited studies regarding the biological interactions of these chemicals, yet there is some concern they may be more toxic than their parent compounds. In this study three hydroxylated PBDEs were assessed for toxicity in embryonic zebrafish: 3-OH-BDE 47, 5-OH-BDE 47, and 6-OH-BDE 47. All three congeners induced developmental arrest in a concentration-dependent manner; however, 6-OH-BDE 47 induced adverse effects at lower concentrations than the other congeners. Furthermore, all three induced cell death; however apoptosis was not observed. In short-term exposures (24–28 hours post fertilization), all hydroxylated PBDEs generated oxidative stress in the region corresponding to the cell death at 5 and 10 ppm. To further investigate the short-term effects that may be responsible for the developmental arrest observed in this study, gene regulation was assessed for embryos exposed to 0.625 ppm 6-OH-BDE 47 from 24 to 28 hpf. Genes involved in stress response, thyroid hormone regulation, and neurodevelopment were significantly upregulated compared to controls; however, genes related to oxidative stress were either unaffected or downregulated. This study suggests that hydroxylated PBDEs disrupt development, and may induce oxidative stress and potentially disrupt the cholinergic system and thyroid hormone homeostasis. -- Highlights: ► OH-PBDEs induce developmental arrest in a concentration-dependent manner. ► Hydroxyl group location influences biological interaction. ► OH-PBDEs induce oxidative stress. ► Thyroid hormone gene regulation was disrupted following exposure. ► To our knowledge, this is the first whole organism study of OH-PBDE toxicity.

  5. Predictors for outcome among cardiac arrest patients

    DEFF Research Database (Denmark)

    Wibrandt-Johansen, Ida Maria; Norsted, Kristine; Schmidt, Henrik;

    2015-01-01

    BackgroundIn the past decade, early treatment of cardiac arrest (CA) victims has been improved in several ways, leading to more optimistic over all prognoses. However, the global survival rate after out-of-hospital CA (OHCA) is still not more than 5-10%. With a better knowledge of the predictors...... determined the 90-day mortality and neurological outcome at discharge for CA patients treated with therapeutic hypothermia (TH), in regard to determine the importance of the predictors for mortality and neurological outcome, with emphasize on combining initial rhythm and time to return of spontaneous...

  6. Glucose starvation as a selective tool for the study of adaptive mutations in Saccharomyces cerevisiae.

    Science.gov (United States)

    Heidenreich, Erich; Steinboeck, Ferdinand

    2017-01-01

    Mutations not only arise in proliferating cells but also in resting - thus non-replicating - cells. Such stationary-phase mutations may occasionally enable an escape from growth repression and e.g. contribute to cancerogenesis or development of drug resistance. The most widely used condition for the study of such adaptive mutations in the eukaryotic model organism Saccharomyces cerevisiae is the starvation for a single amino acid. To overcome some limitations of this experimental setup we developed a new adaptive mutation assay that allows a screening for mutagenic processes during a more regular cell cycle arrest induced by the lack of a fermentable carbon source. We blocked one essential step of gluconeogenesis by inactivation of the FBP1 gene. This drives the cells into a cell cycle arrest when glucose is not available in the medium although a non-fermentable carbon source is present. As another component of the new mutation assay, we established a custom-designed test allele that contains a microsatellite sequence as a target for mutations. We demonstrated the feasibility and validity of this novel experimental setup by the observation and characterization of adaptive mutants.

  7. A case of thyroid storm with cardiac arrest

    Directory of Open Access Journals (Sweden)

    Nakashima Y

    2014-05-01

    Full Text Available Yutaka Nakashima,1 Tsuneaki Kenzaka,2 Masanobu Okayama,3 Eiji Kajii31Department for Support of Rural Medicine, Yamaguchi Grand Medical Center, 2Division of General Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan; 3Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke, JapanAbstract: A 23-year-old man became unconscious while jogging. He immediately received basic life support from a bystander and was transported to our hospital. On arrival, his spontaneous circulation had returned from a state of ventricular fibrillation and pulseless electrical activity. Following admission, hyperthyroidism led to a suspicion of thyroid storm, which was then diagnosed as a possible cause of the cardiac arrest. Although hyperthyroidism-induced cardiac arrest including ventricular fibrillation is rare, it should be considered when diagnosing the cause of treatable cardiac arrest.Keywords: hyperthyroidism, ventricular fibrillation, treatable cardiac arrest, cardiac arrest, cardiopulmonary arrest

  8. Possible role of growth regulators in adaptation to heat stress affecting partitioning of photosynthates in tomato plants

    OpenAIRE

    Zofia Starck; Elżbieta Cieśla

    2014-01-01

    Tomato plants of two cultivars: Roma - sensitive and Robin - tolerant to heat stress were grown in greenhouse up to the flowering stage and then under controlled environmen­tal conditions. The partitioning of recently fixed 14CO2 by mature tomato leaves was examined as a posteffect of 24-h heat stress (38/25°C day/night) with the interaction of growth regulators (GR) sprayed on the flowers with solution of β-naphthoxyacetic (NOA) and gibberellic (GA3) acid (denoted as NG), or Zeatin + NOA + G...

  9. Genetic changes during a laboratory adaptive evolution process that allowed fast growth in glucose to an Escherichia coli strain lacking the major glucose transport system

    Directory of Open Access Journals (Sweden)

    Aguilar César

    2012-08-01

    Full Text Available Abstract Background Escherichia coli strains lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS, which is the major bacterial component involved in glucose transport and its phosphorylation, accumulate high amounts of phosphoenolpyruvate that can be diverted to the synthesis of commercially relevant products. However, these strains grow slowly in glucose as sole carbon source due to its inefficient transport and metabolism. Strain PB12, with 400% increased growth rate, was isolated after a 120 hours adaptive laboratory evolution process for the selection of faster growing derivatives in glucose. Analysis of the genetic changes that occurred in the PB12 strain that lacks PTS will allow a better understanding of the basis of its growth adaptation and, therefore, in the design of improved metabolic engineering strategies for enhancing carbon diversion into the aromatic pathways. Results Whole genome analyses using two different sequencing methodologies: the Roche NimbleGen Inc. comparative genome sequencing technique, and high throughput sequencing with Illumina Inc. GAIIx, allowed the identification of the genetic changes that occurred in the PB12 strain. Both methods detected 23 non-synonymous and 22 synonymous point mutations. Several non-synonymous mutations mapped in regulatory genes (arcB, barA, rpoD, rna and in other putative regulatory loci (yjjU, rssA and ypdA. In addition, a chromosomal deletion of 10,328 bp was detected that removed 12 genes, among them, the rppH, mutH and galR genes. Characterization of some of these mutated and deleted genes with their functions and possible functions, are presented. Conclusions The deletion of the contiguous rppH, mutH and galR genes that occurred simultaneously, is apparently the main reason for the faster growth of the evolved PB12 strain. In support of this interpretation is the fact that inactivation of the rppH gene in the parental PB11 strain substantially increased

  10. Adaptive Significance of Quorum Sensing-dependent Regulation of Rhamnolipids by Integration of Growth Rate in Burkholderia glumae: A Trade-off between Survival and Efficiency

    Directory of Open Access Journals (Sweden)

    Arvin Nickzad

    2016-08-01

    Full Text Available Quorum sensing (QS is a cell density-dependent mechanism which enables a population of bacteria to coordinate cooperative behaviors in response to the accumulation of self-produced autoinducer signals in their local environment. An emerging framework is that the adaptive significance of QS in the regulation of production of costly extracellular metabolites («public goods» is to maintain the homeostasis of cooperation. We investigated this model using the phytopathogenic bacterium Burkholderia glumae, which we have previously demonstrated uses QS to regulate the production of rhamnolipids, extracellular surface-active glycolipids promoting the social behavior called «swarming motility». Using mass spectrometric quantification and chromosomal lux-based gene expression, we made the unexpected finding that when unrestricted nutrient resources are provided, production of rhamnolipids is carried out completely independently of QS regulation. This is a unique observation among known QS-controlled factors in bacteria. On the other hand, under nutrient-limited conditions, QS then becomes the main regulating mechanism, significantly enhancing the specific rhamnolipids yield. Accordingly, decreasing nutrient concentrations amplifies rhamnolipid biosynthesis gene expression, revealing a system where QS-dependent regulation is specifically triggered by the growth rate of the population, rather than by its cell density. Furthermore, a gradual increase in QS signal specific concentration upon decrease of specific growth rate suggests a reduction in quorum threshold, which reflects an increase in cellular demand for production of QS-dependent target gene product at low density populations. Integration of growth rate with QS as a decision-making mechanism for biosynthesis of costly metabolites, such as rhamnolipids, could serve to assess the demand and timing for expanding the carrying capacity of a population through spatial expansion mechanisms, such as

  11. The Genome Sequence of Psychrobacter arcticus 273-4, a Psychroactive Siberian Permafrost Bacterium, Reveals Mechanisms for Adaptation to Low-Temperature Growth

    Energy Technology Data Exchange (ETDEWEB)

    Ayala-del-Rio, Hector L. [Michigan State University, East Lansing; Chain, Patrick S. G. [Lawrence Livermore National Laboratory (LLNL); Grzymski, Joseph J. [Desert Research Institute, Reno, NV; Ponder, Monica [Michigan State University, East Lansing; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Bergholz, Peter [Michigan State University, East Lansing; Bartolo, Genevive [U.S. Department of Energy, Joint Genome Institute; Hauser, Loren John [ORNL; Land, Miriam L [ORNL; Bakermans, Corien [Michigan State University, East Lansing; Rodrigues, Debora [Michigan State University, East Lansing; Klappenbach, Joel [Michigan State University, East Lansing; Zarka, Dan [Michigan State University, East Lansing; Larimer, Frank W [ORNL; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Murray, Alison [Desert Research Institute, Reno, NV; Thomashow, Michael [Michigan State University, East Lansing; Tiedje, James M. [Michigan State University, East Lansing

    2010-01-01

    Psychrobacter arcticus strain 273-4, which grows at temperatures as low as -10 degrees C, is the first cold-adapted bacterium from a terrestrial environment whose genome was sequenced. Analysis of the 2.65-Mb genome suggested that some of the strategies employed by P. arcticus 273-4 for survival under cold and stress conditions are changes in membrane composition, synthesis of cold shock proteins, and the use of acetate as an energy source. Comparative genome analysis indicated that in a significant portion of the P. arcticus proteome there is reduced use of the acidic amino acids and proline and arginine, which is consistent with increased protein flexibility at low temperatures. Differential amino acid usage occurred in all gene categories, but it was more common in gene categories essential for cell growth and reproduction, suggesting that P. arcticus evolved to grow at low temperatures. Amino acid adaptations and the gene content likely evolved in response to the long-term freezing temperatures (-10 degrees C to -12 degrees C) of the Kolyma (Siberia) permafrost soil from which this strain was isolated. Intracellular water likely does not freeze at these in situ temperatures, which allows P. arcticus to live at subzero temperatures.

  12. Electrothermal model for complete metal-oxide surge arresters

    Energy Technology Data Exchange (ETDEWEB)

    Costa, E. Guedes da; Naidu, S.R. [UFPB, Dept. of Electrical Engineering, Campina Grande, PB (Brazil); Lima, A. Guedes de [CEFET-PB, Dept. of Mechanical Engineering, Joao Pessoa, PB (Brazil)

    2001-01-01

    A computational, electrothermal model for a complete metal-oxide surge arrester based on the implicit form of the finite-differences method is presented. The model is used to calculate the cooling curve after the application of overvoltages and the temperature variations during standard test. The model has been checked against experiments carried out on a test section and a complete surge arrester and the behaviour of a hypothetical surge arrester during standard tests simulated. (Author)

  13. Postoperative cardiac arrest in children with congenital heart abnormalities

    OpenAIRE

    2013-01-01

    BACKGROUND The exact survival rates and markers of survival after postoperative cardiac arrest in children with congenital heart abnormalities are unknown. METHODS In this one-year study, we identified children younger than seven years of age with postoperative cardiac arrest in our pediatric cardiac intensive care unit database. Parameters from perioperative, pre-arrest, and resuscitation periods were analyzed for these patients. Comparisons were made between survivors and non-survivors afte...

  14. Possible role of growth regulators in adaptation to heat stress affecting partitioning of photosynthates in tomato plants

    Directory of Open Access Journals (Sweden)

    Zofia Starck

    2014-01-01

    Full Text Available Tomato plants of two cultivars: Roma - sensitive and Robin - tolerant to heat stress were grown in greenhouse up to the flowering stage and then under controlled environmen­tal conditions. The partitioning of recently fixed 14CO2 by mature tomato leaves was examined as a posteffect of 24-h heat stress (38/25°C day/night with the interaction of growth regulators (GR sprayed on the flowers with solution of β-naphthoxyacetic (NOA and gibberellic (GA3 acid (denoted as NG, or Zeatin + NOA + GA3 (denoted as ZNG. In both cuitivars GR strongly stimulated fruit growth and transport of 14C-photosynthates to the clusters at the expense of vegetative organs. Heat stress decreased export of 14C-phoiosynthates from the blades in plants not treated with GR, but even more in cv. Roma. In Roma plants not treated with GR (with very small fruitlets and fruits the heat stress retarded 14C-transport just in the petioles, diminishing the 14C-supply to the fruits. Reduction of the current photosynthate supplied to the fruits seems to be causally connected with inhibition of the specific activity of acid invertase in that organ. Growth regulators reduced the negative effect of high temperature - they alleviated depression of 14C-export from the blades and increased invertase activity. 14C-photosynthate transport to the fruits, presumably owing to their higher sink strength, was less affected by heat stress. In Robin plants (which had bigger fruits during the experiment high temperature depressed 14C-fruit supply only in the NG-series, in contrast to enhacement of 14C-Movement to that sink in the control and ZNG-series. In spite of these facts, after heat stress, the specific activity of acid invertase decreased in all the experimental series, but much less in the GR-treated series. Therefore, in the Robin cv. there was no relation between invertase activity and 14C-mobilization by fruits, as was observed in Roma plants. The possible explanation of the different

  15. Bile acids are "homeotrophic" sensors of the functional hepatic capacity and regulate adaptive growth during liver regeneration.

    Science.gov (United States)

    Geier, Andreas; Trautwein, Christian

    2007-01-01

    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.

  16. Staphylococcus aureus Alters Growth Activity, Autolysis, and Antibiotic Tolerance in a Human Host-Adapted Pseudomonas aeruginosa Lineage

    DEFF Research Database (Denmark)

    Frydenlund Michelsen, Charlotte; Christensen, Anne-Mette; Bojer, Martin Saxtorph

    2014-01-01

    Interactions among members of polymicrobial infections or between pathogens and the commensal flora may determine disease outcomes. Pseudomonas aeruginosa and Staphylococcus aureus are important opportunistic human pathogens and are both part of the polymicrobial infection communities in human....... aeruginosa DK2 strains outcompeted S. aureus during coculture on agar plates, we found that later P. aeruginosa DK2 strains showed a commensal-like interaction, where S. aureus was not inhibited by P. aeruginosa and the growth activity of P. aeruginosa was enhanced in the presence of S. aureus. This effect...... is mediated by one or more extracellular S. aureus proteins greater than 10 kDa, which also suppressed P. aeruginosa autolysis and prevented killing by clinically relevant antibiotics through promoting small-colony variant (SCV) formation. The commensal interaction was abolished with S. aureus strains mutated...

  17. Developing European operational oceanography for Blue Growth, climate change adaptation and mitigation, and ecosystem-based management

    Science.gov (United States)

    She, Jun; Allen, Icarus; Buch, Erik; Crise, Alessandro; Johannessen, Johnny A.; Le Traon, Pierre-Yves; Lips, Urmas; Nolan, Glenn; Pinardi, Nadia; Reißmann, Jan H.; Siddorn, John; Stanev, Emil; Wehde, Henning

    2016-07-01

    Operational approaches have been more and more widely developed and used for providing marine data and information services for different socio-economic sectors of the Blue Growth and to advance knowledge about the marine environment. The objective of operational oceanographic research is to develop and improve the efficiency, timeliness, robustness and product quality of this approach. This white paper aims to address key scientific challenges and research priorities for the development of operational oceanography in Europe for the next 5-10 years. Knowledge gaps and deficiencies are identified in relation to common scientific challenges in four EuroGOOS knowledge areas: European Ocean Observations, Modelling and Forecasting Technology, Coastal Operational Oceanography and Operational Ecology. The areas "European Ocean Observations" and "Modelling and Forecasting Technology" focus on the further advancement of the basic instruments and capacities for European operational oceanography, while "Coastal Operational Oceanography" and "Operational Ecology" aim at developing new operational approaches for the corresponding knowledge areas.

  18. Pre-arrest diversion of people with mental illness: Literature review and international survey.

    Science.gov (United States)

    Hartford, Kathleen; Carey, Robert; Mendonca, James

    2006-01-01

    Mental health diversion is a process where alternatives to criminal sanctions are made available to persons with mental illness (PMI) who have come into contact with the law. One form of mental health diversion is pre-arrest, in which the police use their discretion in laying charges. Concomitant with the growth of pre-arrest diversion programs is a growing body of research devoted to the phenomenon. The purpose of this paper is to review the existing literature of pre-arrest diversion, and to report the results of an international survey of pre-arrest diversion programs we conducted to identify evidence-based practices. On the basis of our review and survey, we note that successful pre-trial programs appear to integrate relevant mental health, substance abuse and criminal justice agencies by having regular meetings between key personnel from the various agencies. Often, a liaison person with a mandate to effect strong leadership plays a key role in the coordination of various agencies. Streamlining services through the creation of an emergency drop-off center with a no-refusal policy for police cases is seen as crucial. While there is some indication that mentally ill offenders benefit from their participation in this form of diversion, the evaluative literature has not yet achieved the "critical mass" necessary to create generalizable, evidence-based knowledge. The absence of generally agreed-upon outcomes could lead to the inequitable application of basic principles of diversion. We suggest that indicators, benchmarks, and outcomes must be agreed upon if a comprehensive understanding of pre-arrest programs is to emerge.

  19. Altered Cell Cycle Arrest by Multifunctional Drug-Loaded Enzymatically-Triggered Nanoparticles.

    Science.gov (United States)

    Huang, Can; Sun, Ying; Shen, Ming; Zhang, Xiangyu; Gao, Pei; Duan, Yourong

    2016-01-20

    cRGD-targeting matrix metalloproteinase (MMP)-sensitive nanoparticles [PLGA-PEG1K-cRGD/PLGA-peptide-PEG5K (NPs-cRGD)] were successfully developed. Au-Pt(IV) nanoparticles, PTX, and ADR were encapsulated into NPs-RGD separately. The effects of the drug-loaded nanoparticles on the cell cycle were investigated. Here, we showed that higher cytotoxicity of drug-loaded nanoparticles was related to the cell cycle arrest, compared to that of free drugs. The NPs-cRGD studied here did not disrupt cell cycle progression. The cell cycle of Au-Pt(IV)@NPs-cRGD showed a main S phase arrest in all phases of the cell cycle phase, especially in G0/G1 phase. PTX@NPs-cRGD and ADR@NPs-cRGD showed a higher ratio of G2/M and S phase arrest than the free drugs, respectively. Cells in G0/G1 and S phases of the cell cycle had a higher uptake ratio of NPs-cRGD. A nutrient deprivation or an increase in the requirement of nutrients in tumor cells could promote the uptake of nanoparticles from the microenvironments. In vivo, NPs-cRGD could efficiently accumulate at tumor sites. The inhibition of tumor growth coupled with cell cycle arrest is in line with that in vitro. On the basis of our results, we propose that future studies on nanoparticle action mechanism should consider the cell cycle, which could be different from free drugs. Understanding the actions of cell cycle arrest could affect the application of nanomedicine in the clinic.

  20. Differentiated dynamics of bud dormancy and growth in temperate fruit trees relating to bud phenology adaptation, the case of apple and almond trees

    Science.gov (United States)

    El Yaacoubi, Adnane; Malagi, Gustavo; Oukabli, Ahmed; Citadin, Idemir; Hafidi, Majida; Bonhomme, Marc; Legave, Jean-Michel

    2016-11-01

    Few studies have focused on the characterization of bud dormancy and growth dynamics for temperate fruit species in temperate and mild cropping areas, although this is an appropriate framework to anticipate phenology adaptation facing future warming contexts which would potentially combine chill declines and heat increases. To examine this issue, two experimental approaches and field observations were used for high- and low-chill apple cultivars in temperate climate of southern France and in mild climates of northern Morocco and southern Brazil. Low-chill almond cultivars offered an additional relevant plant material for comparison with apple in northern Morocco. Divergent patterns of dormancy and growth dynamics were clearly found in apple tree between southern France and southern Brazil. Divergences were less pronounced between France and Morocco. A global view outlined main differences in the dormancy chronology and intensity, the transition between endordormancy and ecodormancy and the duration of ecodormancy. A key role of bud rehydration in the transition period was shown. High-chill cultivars would be submitted in mild conditions to heterogeneous rehydration capacities linked to insufficient chill fulfillment and excessive forcing linked to high temperatures. This would favor bud competitions and consequently excessive flowering durations and weak flowering. Low chilling requirements in apple and almond would conversely confer biological capacities to tolerate superficial dormancy and abrupt transition from endordormancy to ecodormancy without important heterogeneous rehydration states within buds. It may also assume that low-chill cultivars can also tolerate high temperatures during ecodormancy as well as extended flowering durations.

  1. Differentiated dynamics of bud dormancy and growth in temperate fruit trees relating to bud phenology adaptation, the case of apple and almond trees

    Science.gov (United States)

    El Yaacoubi, Adnane; Malagi, Gustavo; Oukabli, Ahmed; Citadin, Idemir; Hafidi, Majida; Bonhomme, Marc; Legave, Jean-Michel

    2016-04-01

    Few studies have focused on the characterization of bud dormancy and growth dynamics for temperate fruit species in temperate and mild cropping areas, although this is an appropriate framework to anticipate phenology adaptation facing future warming contexts which would potentially combine chill declines and heat increases. To examine this issue, two experimental approaches and field observations were used for high- and low-chill apple cultivars in temperate climate of southern France and in mild climates of northern Morocco and southern Brazil. Low-chill almond cultivars offered an additional relevant plant material for comparison with apple in northern Morocco. Divergent patterns of dormancy and growth dynamics were clearly found in apple tree between southern France and southern Brazil. Divergences were less pronounced between France and Morocco. A global view outlined main differences in the dormancy chronology and intensity, the transition between endordormancy and ecodormancy and the duration of ecodormancy. A key role of bud rehydration in the transition period was shown. High-chill cultivars would be submitted in mild conditions to heterogeneous rehydration capacities linked to insufficient chill fulfillment and excessive forcing linked to high temperatures. This would favor bud competitions and consequently excessive flowering durations and weak flowering. Low chilling requirements in apple and almond would conversely confer biological capacities to tolerate superficial dormancy and abrupt transition from endordormancy to ecodormancy without important heterogeneous rehydration states within buds. It may also assume that low-chill cultivars can also tolerate high temperatures during ecodormancy as well as extended flowering durations.

  2. AMPK Causes Cell Cycle Arrest in LKB1-deficient Cells via Activation of CAMKK2

    Science.gov (United States)

    Fogarty, Sarah; Ross, Fiona A.; Ciruelos, Diana Vara; Gray, Alexander; Gowans, Graeme J.; Hardie, D. Grahame

    2017-01-01

    The AMP-activated protein kinase (AMPK) is activated by phosphorylation at Thr172, either by the tumor suppressor kinase LKB1 or by an alternate pathway involving the Ca2+/calmodulin-dependent kinase, CAMKK2. Increases in AMP:ATP and ADP:ATP ratios, signifying energy deficit, promote allosteric activation and net Thr172 phosphorylation mediated by LKB1, so that the LKB1-AMPK pathway acts as an energy sensor. Many tumor cells carry loss-of-function mutations in the STK11 gene encoding LKB1, but LKB1 re-expression in these cells causes cell cycle arrest. Therefore, it was investigated as to whether arrest by LKB1 is caused by activation of AMPK or of one of the AMPK-related kinases, which are also dependent on LKB1 but are not activated by CAMKK2. In three LKB1-null tumor cell lines, treatment with the Ca2+ ionophore A23187 caused a G1-arrest that correlated with AMPK activation and Thr172 phosphorylation. In G361 cells, expression of a truncated, CAMKK2 mutant also caused G1-arrest similar to that caused by expression of LKB1, while expression of a dominant negative AMPK mutant, or a double knockout of both AMPK-α subunits, also prevented the cell cycle arrest caused by A23187. These mechanistic findings confirm that AMPK activation triggers cell cycle arrest, and also suggest that the rapid proliferation of LKB1-null tumor cells is due to lack of the restraining influence of AMPK. However, cell cycle arrest can be restored by re-expressing LKB1 or a constitutively active CAMKK2, or by pharmacological agents that increase intracellular Ca2+ and thus activate endogenous CAMKK2. Implications Evidence here reveals that the rapid growth and proliferation of cancer cells lacking the tumor suppressor LKB1 is due to reduced activity of AMPK, and suggests a therapeutic approach by which this block might be circumvented. PMID:27141100

  3. Aspartate Rescues S-phase Arrest Caused by Suppression of Glutamine Utilization in KRas-driven Cancer Cells.

    Science.gov (United States)

    Patel, Deven; Menon, Deepak; Bernfeld, Elyssa; Mroz, Victoria; Kalan, Sampada; Loayza, Diego; Foster, David A

    2016-04-22

    During G1-phase of the cell cycle, normal cells respond first to growth factors that indicate that it is appropriate to divide and then later in G1 to the presence of nutrients that indicate sufficient raw material to generate two daughter cells. Dividing cells rely on the "conditionally essential" amino acid glutamine (Q) as an anaplerotic carbon source for TCA cycle intermediates and as a nitrogen source for nucleotide biosynthesis. We previously reported that while non-transformed cells arrest in the latter portion of G1 upon Q deprivation, mutant KRas-driven cancer cells bypass the G1 checkpoint, and instead, arrest in S-phase. In this study, we report that the arrest of KRas-driven cancer cells in S-phase upon Q deprivation is due to the lack of deoxynucleotides needed for DNA synthesis. The lack of deoxynucleotides causes replicative stress leading to activation of the ataxia telangiectasia and Rad3-related protein (ATR)-mediated DNA damage pathway, which arrests cells in S-phase. The key metabolite generated from Q utilization was aspartate, which is generated from a transaminase reaction whereby Q-derived glutamate is converted to α-ketoglutarate with the concomitant conversion of oxaloacetate to aspartate. Aspartate is a critical metabolite for both purine and pyrimidine nucleotide biosynthesis. This study identifies the molecular basis for the S-phase arrest caused by Q deprivation in KRas-driven cancer cells that arrest in S-phase in response to Q deprivation. Given that arresting cells in S-phase sensitizes cells to apoptotic insult, this study suggests novel therapeutic approaches to KRas-driven cancers.

  4. Involvement of p53 in cell death following cell cycle arrest and mitotic catastrophe induced by rotenone

    OpenAIRE

    Gonçalves, António Pedro; Máximo, Valdemar; Lima, Jorge; Keshav K Singh; Soares, Paula; Videira, Arnaldo

    2011-01-01

    In order to investigate the cell death-inducing effects of rotenone, a plant extract commonly used as a mitochondrial complex I inhibitor, we studied cancer cell lines with different genetic backgrounds. Rotenone inhibits cell growth through the induction of cell death and cell cycle arrest, associated with the development of mitotic catastrophe. The cell death inducer staurosporine potentiates the inhibition of cell growth by rotenone in a dose-dependent synergistic manner. The tumor suppres...

  5. PP2A-mediated dephosphorylation of p107 plays a critical role in chondrocyte cell cycle arrest by FGF.

    Directory of Open Access Journals (Sweden)

    Victoria Kolupaeva

    Full Text Available FGF signaling inhibits chondrocyte proliferation, a cell type-specific response that is the basis for several genetic skeletal disorders caused by activating FGFR mutations. This phenomenon requires the function of the p107 and p130 members of the Rb protein family, and p107 dephosphorylation is one of the earliest distinguishing events in FGF-induced growth arrest. To determine whether p107 dephoshorylation played a critical role in the chondrocyte response to FGF, we sought to counteract this process by overexpressing in RCS chondrocytes the cyclin D1/cdk4 kinase complex. CyclinD/cdk4-expressing RCS cells became resistant to FGF-induced p107 dephosphorylation and growth arrest, and maintained significantly high levels of cyclin E/cdk2 activity and of phosphorylated p130 at later times of FGF treatment. We explored the involvement of a phosphatase in p107 dephosphorylation. Expression of the SV40 small T-Ag, which inhibits the activity of the PP2A phosphatase, or knockdown of the expression of the PP2A catalytic subunit by RNA interference prevented p107 dephosphorylation and FGF-induced growth arrest of RCS cells. Furthermore, an association between p107 and PP2A was induced by FGF treatment. Our data show that p107 dephosphorylation is a key event in FGF-induced cell cycle arrest and indicate that in chondrocytes FGF activates the PP2A phosphatase to promote p107 dephosphorylation.

  6. Resuscitation, prolonged cardiac arrest, and an automated chest compression device

    DEFF Research Database (Denmark)

    Risom, Martin; Jørgensen, Henrik; Rasmussen, Lars S;

    2010-01-01

    The European Resuscitation Council's 2005 guidelines for cardiopulmonary resuscitation (CPR) emphasize the delivery of uninterrupted chest compressions of adequate depth during cardiac arrest.......The European Resuscitation Council's 2005 guidelines for cardiopulmonary resuscitation (CPR) emphasize the delivery of uninterrupted chest compressions of adequate depth during cardiac arrest....

  7. Thermodynamic coarsening arrested by viscous fingering in partially miscible binary mixtures

    Science.gov (United States)

    Fu, Xiaojing; Cueto-Felgueroso, Luis; Juanes, Ruben

    2016-09-01

    We study the evolution of binary mixtures far from equilibrium, and show that the interplay between phase separation and hydrodynamic instability can arrest the Ostwald ripening process characteristic of nonflowing mixtures. We describe a model binary system in a Hele-Shaw cell using a phase-field approach with explicit dependence of both phase fraction and mass concentration. When the viscosity contrast between phases is large (as is the case for gas and liquid phases), an imposed background flow leads to viscous fingering, phase branching, and pinch off. This dynamic flow disorder limits phase growth and arrests thermodynamic coarsening. As a result, the system reaches a regime of statistical steady state in which the binary mixture is permanently driven away from equilibrium.

  8. Predictive Value of Brain Arrest Neurological Outcome Scale (BrANOS) on Mortality and Morbidity After Cardiac Arrest

    Science.gov (United States)

    Şahutoğlu, Cengiz; Uyar, Mehmet; Demirağ, Kubilay; İsayev, Hasan; Moral, Ali Reşat

    2016-01-01

    Objective There are several prediction scales and parameters for prognosis after a cardiac arrest. One of these scales is the brain arrest neurological outcome scale (BrANOS), which consists of duration of cardiac arrest, Glasgow Coma Scale score and Hounsfield unit measured on cranial computed tomography (CT) scan. The objective of this study is to investigate the effectiveness of BrANOS on predicting the mortality and disability after a cardiac arrest. Methods We retrospectively investigated cardiac arrest patients who were hospitalized in our intensive care unit (ICU) within a 3-year period. Inclusion criteria were age over 18 years old, survival of more than 24 hours after cardiac arrest and availability of cranial CT. We recorded the age, sex, diagnosis, duration of cardiac arrest and hospital stay, mortality, Glasgow Outcome Score (GOS) and BrANOS score. The primary endpoint of the study was to establish the relationship between mortality and BrANOS score in patients who survived for more than 24 hours after a cardiac arrest. The secondary endpoint of the study was to determine the 2-year life expectancy and GOS after cardiac arrest. Results The mean age of the patients was 57±17 years (33 females, 67 males). ICU mortality rate was 57%. The BrANOS mean score was 10.3±3.2. There was a significant difference between survivors and non-survivors in terms of the BrANOS score (8.8±3.2 vs. 11.6±2.7; p14 predicted death with 100% accuracy. All the patients without disability had a BrANOS score of <10. The BrANOS score also correlated well with GOS (p<0.001). The 2-year life expectancy rate was 31% in patients who survived more than 24 hours after a cardiac arrest. Conclusion In this study, we demonstrated that BrANOS provided reliable data for prognostic evaluation after a cardiac arrest. PMID:28058140

  9. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Lippert, Freddy K.; Folke, Fredrik

    2013-01-01

    resuscitation was attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac Arrest Registry. Of 29 111 patients with cardiac arrest, we excluded those with presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests witnessed by emergency medical services personnel (n...

  10. Internally damped, self-arresting vertical drop-weight impact test apparatus

    Science.gov (United States)

    Ambur, Damodar R. (Inventor); Prasad, Chunchu B. (Inventor); Stockum, Robert W. (Inventor)

    1996-01-01

    A vertical dropped-weight impact test machine has a dropped-weight barrel vertically supported on upper and lower support brackets. The dropped-weight barrel is chambered to receive a dropped-weight assembly having a latch pin at its upper end, a damping unit in the middle, and a tup at its lower end. The tup is adapted for gathering data during impact testing. The latch pin releasably engages a latch pin coupling assembly. The latch pin coupling assembly is attached to a winch via a halyard for raising and lowering the dropped-weight assembly. The lower end of the dropped-weight barrel is provided with a bounce-back arresting mechanism which is activated by the descending passage of the dropped-weight assembly. After striking the specimen, the dropped-weight assembly rebounds vertically and is caught by the bounce-back arresting mechanism. The damping unit of the dropped-weight assembly serves to dissipate energy from the rebounding dropped-weight assembly and prevents the dropped-weight assembly from rebounding from the self-arresting mechanism.

  11. Prediction of the potential clinical outcomes for post-resuscitated patients after cardiac arrest

    Science.gov (United States)

    Hong, Sungmin; Kwon, Bojun; Yun, Il Dong; Lee, Sang Uk; Kim, Kyuseok; Kim, Joonghee

    2013-02-01

    Cerebral injuries after cardiac arrest are serious causes for morbidity. Many previous researches in the medical society have been proposed to prognosticate the functional recoveries of post-resuscitated patients after cardiac arrest, but the validity of suggested features and the automation of prognostication have not been made yet. This paper presents the automatic classification method which predicts the potential clinical outcomes of post-resuscitated patients who suffered from cardiac arrest. The global features and the local features are adapted from the researches from the medical society. The global features, which are consisted of the percentage of the partial volume under the uniformly increasing thresholds, represent the global tendency of apparent diffusion coefficient value in a DWI. The local features are localized and measured on the refined local apparent diffusion coefficient minimal points. The local features represent the ischemic change of small areas in a brain. The features are trained and classified by the random forest method, which have been widely used in the machine learning society for classification. The validity of features is automatically evaluated during the classification process. The proposed method achieved the 0.129 false-positive rate while maintaining the perfect true-positive rate. The area-under-curve of the proposed method was 0.9516, which showed the feasibility and the robustness of the proposed method.

  12. Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes

    Science.gov (United States)

    Wigglesworth, Karen; Lee, Kyung-Bon; O’Brien, Marilyn J.; Peng, Jia; Matzuk, Martin M.; Eppig, John J.

    2013-01-01

    Coordinated regulation of oocyte and ovarian follicular development is essential for fertility. In particular, the progression of meiosis, a germ cell-specific cell division that reduces the number of chromosomes from diploid to haploid, must be arrested until just before ovulation. Follicular somatic cells are well-known to impose this arrest, which is essential for oocyte–follicle developmental synchrony. Follicular somatic cells sustain meiotic arrest via the natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system, and possibly also via high levels of the purine hypoxanthine in the follicular fluid. Upon activation by the ligand NPPC, NPR2, the predominant guanylyl cyclase in follicular somatic cells, produces cyclic guanosine monophosphate (cGMP), which maintains meiotic arrest after transfer to the oocyte via gap junctions. Here we report that both the NPPC/NPR2 system and hypoxanthine require the activity of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme required for the production of guanylyl metabolites and cGMP. Furthermore, oocyte-derived paracrine factors, particularly the growth differentiation factor 9–bone morphogenetic protein 15 heterodimer, promote expression of Impdh and Npr2 and elevate cGMP levels in cumulus cells. Thus, although the somatic compartment of ovarian follicles plays an essential role in the maintenance of oocyte meiotic arrest, as has been known for many years, this function of the somatic cells is surprisingly regulated by signals from the oocyte itself. PMID:23980176

  13. Sublingual Microcirculation is Impaired in Post-cardiac Arrest Patients

    DEFF Research Database (Denmark)

    G. Omar, Yasser; Massey, Michael; Wiuff Andersen, Lars;

    2013-01-01

    AIM: We hypothesized that microcirculatory dysfunction, similar to that seen in sepsis, occurs in post-cardiac arrest patients and that better microcirculatory flow will be associated with improved outcome. We also assessed the association between microcirculatory dysfunction and inflammatory...... markers in the post-cardiac arrest state. METHODS: We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield microscopy. Microcirculatory flow was assessed using...... the microcirculation flow index (MFI) at 6 and 24h in the cardiac arrest patients, and within 6h of emergency department admission in the sepsis and control patients. RESULTS: We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual...

  14. Out-of-Hospital Cardiac Arrest in Denmark

    DEFF Research Database (Denmark)

    Wissenberg Jørgensen, Mads

    challenges, due to the victim’s physical location, which brings an inherent risk of delay (or altogether absence) of recognition and treatment of cardiac arrest. A low frequency of bystander cardiopulmonary resuscitation and low 30-day survival after out-of-hospital cardiac arrest were identified nearly ten......BACK COVER TEXT Cardiac arrest is an emergency medical condition characterized by the cessation of cardiac mechanical activity; without immediate and decisive treatment, a victim’s chances of survival are minimal. Out-of-hospital cardiac arrest is a particular arrest subgroup that poses additional...... years ago in Denmark. These findings led to several national initiatives to strengthen bystander resuscitation attempts and advance care. Despite these nationwide efforts, it was unknown prior to this project whether these efforts resulted in changes in resuscitation attempts by bystanders and changes...

  15. 杜泊羊的适应性生长规律观察报告%Observation Report on the Growth Law of Adaptability of Dorper

    Institute of Scientific and Technical Information of China (English)

    乌兰其其格; 钮河

    2011-01-01

    The environmental adaptability of 50 embryo progenies of Dorper sheep in Baotou region of Inner Mongolia which were introduced from Australia were observed, and their growth and development status were also determined. Results showed that some indexes like rectal temperature, heartbeat, respiration, unhairing and ingestion, etc. of lamb, young and adult Dorper sheep had no obvious significance with them in origin place, furthermore some indexes like body weight, withers height, body length and chest width, etc. of them also met the characteristic requirements of Dorper sheep varieties. It is indicated that Dorper sheep show a good adaptability in Baotou region of Inner Mongolia. It provides relative theoretical basis for the feasibility of introducing Dorper sheep varieties and also has practical significance in guiding the crossbreeding and improvement of meat sheep breeds.%对内蒙古包头市从澳大利亚引进的50只杜泊羊胚胎后代进行环境适应性观察,并对其生长发育状况进行了测试。结果表明,杜泊羔羊、青年羊和成年羊在肛温、心跳、呼吸、脱毛和采食等指标与在原产地时无明显差异;体重、体高、体长和胸宽等指标也达到杜泊羊的品种特性要求。说明杜泊羊在内蒙古包头地区具有较好的适应性,这就对引进杜泊羊品种的可行性提供了相关的理论依据,并对指导肉用羊杂交改良具有现实意义。

  16. Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells.

    Science.gov (United States)

    Lee, Min Ho; Cho, Yoonjung; Jung, Byung Chul; Kim, Sung Hoon; Kang, Yeo Wool; Pan, Cheol-Ho; Rhee, Ki-Jong; Kim, Yoon Suk

    2015-08-14

    Parkin is a known tumor suppressor. However, the mechanism by which parkin acts as a tumor suppressor remains to be fully elucidated. Previously, we reported that parkin expression induces caspase-dependent apoptotic cell death in TNF-α-treated HeLa cells. However, at that time, we did not consider the involvement of parkin in cell cycle control. In the current study, we investigated whether parkin is involved in cell cycle regulation and suppression of cancer cell growth. In our cell cycle analyses, parkin expression induced G2/M cell cycle arrest in TNF-α-treated HeLa cells. To elucidate the mechanism(s) by which parkin induces this G2/M arrest, we analyzed cell cycle regulatory molecules involved in the G2/M transition. Parkin expression induced CDC2 phosphorylation which is known to inhibit CDC2 activity and cause G2/M arrest. Cyclin B1, which is degraded during the mitotic transition, accumulated in response to parkin expression, thereby indicating parkin-induced G2/M arrest. Next, we established that Myt1, which is known to phosphorylate and inhibit CDC2, increased following parkin expression. In addition, we found that parkin also induces increased Myt1 expression, G2/M arrest, and reduced cell viability in TNF-α-treated HCT15 cells. Furthermore, knockdown of parkin expression by parkin-specific siRNA decreased Myt1 expression and phosphorylation of CDC2 and resulted in recovered cell viability. These results suggest that parkin acts as a crucial molecule causing cell cycle arrest in G2/M, thereby suppressing tumor cell growth.

  17. Performance of metal oxide gapless surge arresters for HVDC systems

    Energy Technology Data Exchange (ETDEWEB)

    Diseko, N.L.

    1990-09-01

    An examination of the electrical stresses which may be imposed upon metal oxide surge arresters in a dc converter station is undertaken by means of simulation of the dc system and associated ac systems in the time domain using a digital computer program. Detailed models of a dc link are developed for temporary overvoltage stresses and steep front stresses. The most critical stresses for each type of dc station arrester due to converter faults and converter malfunctions are identified. The energy stresses were generally determined to be dependent on the converter control and protection strategies adopted during the faults. The arrester energy stresses for faults on both the line side and valve side busses of the converter transformer were determined to be sensitive to the instant of fault application and the duration of the fault. The arrester stresses for ac bus faults were analyzed in detail to determine their statistical distribution relative to the point on wave at which the fault occurred in each affected phase, and to the instant of fault clearance in each phase. Generally, the highest stresses occur for sequential fault occurrence in the phases compared with simultaneous faults. The studies indicate that the stresses in the arresters in a dc pile experiencing the worst duty depend on the number of arresters represented. Modelling only one arrester of a series-connected group does not provide correct results when the fault condition imposes duty on more than one of the arresters in the group. The study also indicates that the highest stresses do not necessarily occur in the single arrester connected across the valve with the highest prospective overvoltage. Hence the capability to represent all valve arresters within one pole is necessary when determining the most onerous stresses. 11 refs., 79 figs., 28 tabs.

  18. Allometric growth in the extant coelacanth lung during ontogenetic development.

    Science.gov (United States)

    Cupello, Camila; Brito, Paulo M; Herbin, Marc; Meunier, François J; Janvier, Philippe; Dutel, Hugo; Clément, Gaël

    2015-09-15

    Coelacanths are lobe-finned fishes known from the Devonian to Recent that were long considered extinct, until the discovery of two living species in deep marine waters of the Mozambique Channel and Sulawesi. Despite extensive studies, the pulmonary system of extant coelacanths has not been fully investigated. Here we confirm the presence of a lung and discuss its allometric growth in Latimeria chalumnae, based on a unique ontogenetic series. Our results demonstrate the presence of a potentially functional, well-developed lung in the earliest known coelacanth embryo, and its arrested growth at later ontogenetic stages, when the lung is clearly vestigial. The parallel development of a fatty organ for buoyancy control suggests a unique adaptation to deep-water environments. Furthermore, we provide the first evidence for the presence of small, hard, flexible plates around the lung in L. chalumnae, and consider them homologous to the plates of the 'calcified lung' of fossil coelacanths.

  19. A mutation-promotive role of nucleotide excision repair in cell cycle-arrested cell populations following UV irradiation.

    Science.gov (United States)

    Heidenreich, Erich; Eisler, Herfried; Lengheimer, Theresia; Dorninger, Petra; Steinboeck, Ferdinand

    2010-01-01

    Growing attention is paid to the concept that mutations arising in stationary, non-proliferating cell populations considerably contribute to evolution, aging, and pathogenesis. If such mutations are beneficial to the affected cell, in the sense of allowing a restart of proliferation, they are called adaptive mutations. In order to identify cellular processes responsible for adaptive mutagenesis in eukaryotes, we study frameshift mutations occurring during auxotrophy-caused cell cycle arrest in the model organism Saccharomyces cerevisiae. Previous work has shown that an exposure of cells to UV irradiation during prolonged cell cycle arrest resulted in an increased incidence of mutations. In the present work, we determined the influence of defects in the nucleotide excision repair (NER) pathway on the incidence of UV-induced adaptive mutations in stationary cells. The mutation frequency was decreased in Rad16-deficient cells and further decreased in Rad16/Rad26 double-deficient cells. A knockout of the RAD14 gene, the ortholog of the human XPA gene, even resulted in a nearly complete abolishment of UV-induced mutagenesis in cell cycle-arrested cells. Thus, the NER pathway, responsible for a normally accurate repair of UV-induced DNA damage, paradoxically is required for the generation and/or fixation of UV-induced frameshift mutations specifically in non-replicating cells.

  20. High efficiency light harvesting by carotenoids in the LH2 complex from photosynthetic bacteria: unique adaptation to growth under low-light conditions.

    Science.gov (United States)

    Magdaong, Nikki M; LaFountain, Amy M; Greco, Jordan A; Gardiner, Alastair T; Carey, Anne-Marie; Cogdell, Richard J; Gibson, George N; Birge, Robert R; Frank, Harry A

    2014-09-25

    Rhodopin, rhodopinal, and their glucoside derivatives are carotenoids that accumulate in different amounts in the photosynthetic bacterium, Rhodoblastus (Rbl.) acidophilus strain 7050, depending on the intensity of the light under which the organism is grown. The different growth conditions also have a profound effect on the spectra of the bacteriochlorophyll (BChl) pigments that assemble in the major LH2 light-harvesting pigment-protein complex. Under high-light conditions the well-characterized B800-850 LH2 complex is formed and accumulates rhodopin and rhodopin glucoside as the primary carotenoids. Under low-light conditions, a variant LH2, denoted B800-820, is formed, and rhodopinal and rhodopinal glucoside are the most abundant carotenoids. The present investigation compares and contrasts the spectral properties and dynamics of the excited states of rhodopin and rhodopinal in solution. In addition, the systematic differences in pigment composition and structure of the chromophores in the LH2 complexes provide an opportunity to explore the effect of these factors on the rate and efficiency of carotenoid-to-BChl energy transfer. It is found that the enzymatic conversion of rhodopin to rhodopinal by Rbl. acidophilus 7050 grown under low-light conditions results in nearly 100% carotenoid-to-BChl energy transfer efficiency in the LH2 complex. This comparative analysis provides insight into how photosynthetic systems are able to adapt and survive under challenging environmental conditions.

  1. Comparative Study on the Adaptation and Growth Dynamics of the Helix pomatia and Helix aspersa Muller Terrestrial Snails Under Different Feeding Regimes

    Directory of Open Access Journals (Sweden)

    Adrian Toader-Williams

    2010-05-01

    Full Text Available We used Helix pomatia and Helix aspersa species and measure their growth as the snails were approaching the hibernation season. Helix pomatia 2yo shown a decrease in weight while being raised in enclosed parcels of 4sqm the younger Helix pomatia 1yo as well as Helix aspersa Muller demonstrated the ability to adapt relatively fast to the same conditions. We established 5 experimental lots in a Helix pomatia farm, GPS coordinates N46.606040 E23.599950. Control lot contained Taraxacum officinales, Sonchus oleraceus, Equisetum arvense and Atriplex hortensis, wild flora found within the farm. The other lots contained the same plants as the control lot plus different combinations of imported plants from other areals. The H. pomatia 2yo weight decreased in the control lot by a mean of -3.86% while H. aspersa 1yo marked an increase of +16.89% in the same lot during the same period. The lot containing lupinus polyphyllus delivered snails with weight gain of +24.66% for H. pomatia 2yo and an increase of only +1.98% for H. aspersa 1yo. As a contrast, H. pomatia 2yo gained only +7.72% while H. aspersa 1yo gained +28.89%, in the lot containing Lavanda officinalis, Foeniculum vulgare and Hyssopus officinalis among the other plants.

  2. Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest

    Institute of Scientific and Technical Information of China (English)

    Shao-Fei Yan; Xin-Yan Liu; Yun-Fei Cheng; Zhi-Yi Li; Jie Ou; Wei Wang; Feng-Qin Li

    2016-01-01

    Background:Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy.The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear.This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest.Methods:Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group).Results:Intrauterine bacterial infection was discovered in both groups.The infection rate was 24.44% (11/45) in the early embryonic developmental arrest group and 9.09% (3/33) in the artificial abortion group.Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% (6/45),and none was detected in the artificial abortion group.M.luteus infection was significantly different between the groups (P < 0.05 as shown by Fisher's exact test).In addition,no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest.Conclusions:M.luteus infection is related to early embryonic developmental arrest and might be one of its causative factors.

  3. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  4. Pollution performance of 110 kV metal oxide arresters

    Energy Technology Data Exchange (ETDEWEB)

    Chrzan, K.; Pohl, Z. [Technical Univ. of Wroclaw (Poland). Dept. of Electrical Engineering; Grzybowski, S. [Mississippi State Univ., MS (United States). Dept. of Electrical and Computer Engineering; Koehler, W. [Univ. of Stuttgart (Germany). Dept. of Electrical Engineering

    1997-04-01

    Pollution test results of single unit 110 kV metal oxide surge arresters with porcelain housing according to the solid layer and salt fog methods are presented. During 6 hours of testing, the internal and external charge and maximum temperature along the varistor column were measured. The formation of single stable dry bands on the housing was often observed, especially during salt fog tests. In such cases, the varistor temperature can reach about 70 C. The simple electrical model of the arrester enabling calculations of voltages and currents as a function of arrester and pollution parameters is shown.

  5. Evolution of the dragonfly head-arresting system

    OpenAIRE

    Gorb, S. N.

    1999-01-01

    The arrester or fixation system of the head in adult Odonata is unique among arthropods. This system involves the organs of two body segments: the head and the neck. It consists of a skeleton–muscle apparatus that sets the arrester parts in motion. The parts comprise formations covered with complicated microstructures: fields of microtrichia on the rear surface of the head and post-cervical sclerites of the neck. The arrester immobilizes the head during feeding or when the dragonfly is in tan...

  6. Cross-talk between the fat body and brain regulates insect developmental arrest

    Science.gov (United States)

    Xu, Wei-Hua; Lu, Yu-Xuan; Denlinger, David L.

    2012-01-01

    Developmental arrest, a critical component of the life cycle in animals as diverse as nematodes (dauer state), insects (diapause), and vertebrates (hibernation), results in dramatic depression of the metabolic rate and a profound extension in longevity. Although many details of the hormonal systems controlling developmental arrest are well-known, we know little about the interactions between metabolic events and the hormones controlling the arrested state. Here, we show that diapause is regulated by an interplay between blood-borne metabolites and regulatory centers within the brain. Gene expression in the fat body, the insect equivalent of the liver, is strongly suppressed during diapause, resulting in low levels of tricarboxylic acid (TCA) intermediates circulating within the blood, and at diapause termination, the fat body becomes activated, releasing an abundance of TCA intermediates that act on the brain to stimulate synthesis of regulatory peptides that prompt production of the insect growth hormone ecdysone. This model is supported by our success in breaking diapause by injecting a mixture of TCA intermediates and upstream metabolites. The results underscore the importance of cross-talk between the brain and fat body as a regulator of diapause and suggest that the TCA cycle may be a checkpoint for regulating different forms of animal dormancy. PMID:22912402

  7. Desacetyluvaricin induces S phase arrest in SW480 colorectal cancer cells through superoxide overproduction.

    Science.gov (United States)

    Xue, Jun-Yi; Zhou, Guang-Xiong; Chen, Tianfeng; Gao, Si; Choi, Mei-Yuk; Wong, Yum-Shing

    2014-03-01

    Annonaceous acetogenins (ACGs) are a group of fatty acid-derivatives with potent anticancer effects. In the present study, we found desacetyluvaricin (Dau) exhibited notable in vitro antiproliferative effect on SW480 human colorectal carcinoma cells with IC50 value of 14 nM. The studies on the underlying mechanisms revealed that Dau inhibited the cancer cell growth through induction of S phase cell cycle arrest from 11.3% (control) to 33.2% (160 nM Dau), which was evidenced by the decreased protein expression of cyclin A Overproduction of superoxide, intracellular DNA damage, and inhibition of MEK/ERK signaling pathway, were also found involved in cells exposed to Dau. Moreover, pre-treatment of the cells with ascorbic acid significantly prevented the Dau-induced overproduction of superoxide, DNA damage and cell cycle arrest. Taken together, our results suggest that Dau induces S phase arrest in cancer cells by firstly superoxide overproduction and subsequently the involvement of various signaling pathways.

  8. Cross-talk between the fat body and brain regulates insect developmental arrest.

    Science.gov (United States)

    Xu, Wei-Hua; Lu, Yu-Xuan; Denlinger, David L

    2012-09-04

    Developmental arrest, a critical component of the life cycle in animals as diverse as nematodes (dauer state), insects (diapause), and vertebrates (hibernation), results in dramatic depression of the metabolic rate and a profound extension in longevity. Although many details of the hormonal systems controlling developmental arrest are well-known, we know little about the interactions between metabolic events and the hormones controlling the arrested state. Here, we show that diapause is regulated by an interplay between blood-borne metabolites and regulatory centers within the brain. Gene expression in the fat body, the insect equivalent of the liver, is strongly suppressed during diapause, resulting in low levels of tricarboxylic acid (TCA) intermediates circulating within the blood, and at diapause termination, the fat body becomes activated, releasing an abundance of TCA intermediates that act on the brain to stimulate synthesis of regulatory peptides that prompt production of the insect growth hormone ecdysone. This model is supported by our success in breaking diapause by injecting a mixture of TCA intermediates and upstream metabolites. The results underscore the importance of cross-talk between the brain and fat body as a regulator of diapause and suggest that the TCA cycle may be a checkpoint for regulating different forms of animal dormancy.

  9. Solanine inhibits prostate cancer Du145 xenograft growth in nude mice by inducing cell cycle arrest in G1/S phase%龙葵素通过诱导细胞周期G1/S阻滞抑制裸鼠前列腺癌细胞Du145移植瘤生长

    Institute of Scientific and Technical Information of China (English)

    钟伟枫; 刘思平; 潘斌; 唐兆烽; 钟锦光; 周芳坚

    2016-01-01

    Objective To investigate the effect of solanine on the growth of human prostate cancer cell xenograft in nude mice. Methods Human prostate cancer Du145 cells were injected into the subcutaneous layers on the back of nude mice. After a week, the mice bearing subcutaneous tumor graft were randomly divided into solanine treatment group and saline control group for treatment for 3 weeks. The tumor grafts were then harvested to evaluate the inhibition rate. The mRNA and protein expressions of cell cycle-related genes in the tumors were detected by qRT-PCR and Western blotting, respectively, and tumor cell apoptosis was detected using TUNEL method. Results The tumor growth rate in solanine-treated group was significantly slower than that in the control group (P<0.01). The mRNA and protein expressions of C-myc, cyclin D1, cyclin E1, CDK2, CDK4 and CDK6 were significantly inhibited by solanine. Solanine significantly up-regulated p21 mRNA and protein expression in the tumors and induced a higher apoptosis rate of the tumor cells than saline (P<0.01). Conclusion The tumor-inhibition effect of solanine is probably mediated by regulating the expressions of genes related with G1/S cell cycle arrest and cell apoptosis.%目的:探讨龙葵素对前列腺癌细胞Du145裸鼠移植瘤生长的影响及分子机制。方法采用高度恶性的转移前列腺癌细胞株Du145作为动物体内实验的模型,裸鼠皮下接种Du145细胞建立裸鼠皮下瘤模型。1周后将接种的裸鼠随机分为2组:龙葵素实验组和生理盐水空白对照组,每3 d分别向实体瘤中间部位注射0.2 mL龙葵素(50μg/mL)和生理盐水,观察裸鼠体内肿瘤生长,3周后颈椎脱臼处死裸鼠,剥离肿瘤组织,测量肿瘤的重量并根据肿瘤重量计算抑瘤率。实时荧光定量PCR和Western blotting技术检测各组裸鼠瘤体细胞周期相关基因mRNA和蛋白表达。Tunel原位检测各组裸鼠瘤体组织凋亡情况。结果龙葵素

  10. Neurological and circulatory outcomes of cardiopulmonary resuscitation in progress: influence of pre-arrest and arrest factors.

    Science.gov (United States)

    Jørgensen, E O

    1998-01-01

    Possible correlations between the circulatory and neurological responses to cardiopulmonary resuscitation (CPR) and the influence of pre-arrest factors (demographic data, medical history and aetiology of circulatory arrest) and arrest factors (location of arrest, ECG configurations, and duration of resuscitation) on the course of circulatory and neurological recovery were investigated in 111 victims of circulatory arrest. At the start of resuscitation 57 patients (Group I) had some brain function and 54 (Group II) had no brain function. Sixty nine patients (62%) had circulation restored but 54 (78%) were left with heart failure. Forty one patients (39%) survived the first day, 26 (63%) with heart failure; only 34 (31%) were alive after 48 h, 17 (50%) with heart failure. Half of the patients surviving 24 or 48 h had awakened. Consciousness returned in 32 patients (29%) during the first 48 h, more frequently in Group I than in Group II. Patients in Group I had a higher incidence of in-hospital arrest and had their circulation restored more often than those in Group II. Survival and post-resuscitation heart failure was alike in the groups. The pre-arrest factors explored did not modify the circulatory or neurological outcome whereas initial ventricular fibrillation was significantly related to recovery of consciousness. The revivability of spontaneous circulation and of neurological functions was found thus mainly to be determined by global ischaemia sustained prior to and during CPR.

  11. Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells.

    Science.gov (United States)

    Yan, Keqiang; Zhang, Cheng; Feng, Jinbo; Hou, Lifang; Yan, Lei; Zhou, Zunlin; Liu, Zhaoxu; Liu, Cheng; Fan, Yidon; Zheng, Baozhong; Xu, Zhonghua

    2011-07-01

    Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth.

  12. Hybrid simulation of metal oxide surge-arrester thermal behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Huang, L.; Raghuveer, M.R. [Manitoba Univ., Winnipeg, MB (Canada). Dept. of Electrical and Computer Engineering

    1996-01-01

    A finite-difference-based technique for simulating the thermal behaviour of a metal oxide surge arrester (MOSA) was described. The improved hybrid thermal modelling technique was claimed to accurately represent heat-transfer modes. Fin theory was used to represent arrester sheds. The proposed model, which relies on simple measurements at the arrester terminals, yields the temporal variation of temperature in a MOSA in both the axial and radial direction. The thermal behaviour of a MOSA under steady-state and transient conditions can be simulated using such a model under different environmental conditions. The accuracy of the modelling technique was demonstrated experimentally by measurements conducted on an arrester. 15 refs., 7 figs.

  13. Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA)

    DEFF Research Database (Denmark)

    Meyer, Anna Sina P; Ostrowski, Sisse R; Kjaergaard, Jesper;

    2016-01-01

    BACKGROUND: Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients...... resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery...... and AMI. Thus, a study is pertinent to investigate if prostacyclin infusion as a therapeutic intervention reduces endothelial damage without compromising, or even improving, the hemostatic competence in resuscitated cardiac arrest patients. Post-cardiac arrest patients frequently have a need...

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

    Directory of Open Access Journals (Sweden)

    Toshiyuki Takahashi

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

  15. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  16. Usage of Lightning Arrester Line to Feed Light Electrical Loads

    Directory of Open Access Journals (Sweden)

    Hani B. Odeh

    2009-01-01

    Full Text Available In remote areas, light loads (tens of kilowatts are scattered and situated in the field of high voltage lines (66KV and above. These loads are very far from the main feeders/sub-stations (33KV-0.380KV. Feeding such loads in the traditional ways like provision of Diesel-Powered Stations, installation of new distribution lines from the Feeding Centers, or building new Sub-Stations are not practical ways from the economical point of view, because it requires huge additional expenses and will increase electrical power losses. These expenses are not worthy for such loads and therefore, it is necessary to search for other methods to supply them. One of these methods is to use the lightning arrester line as capacitive divider to supply the light loads. In this research, the induced voltage of the lightning arrester line was calculated when it is isolated from the earth. We found the capacitance between lightning arrester line versus the phases and lightning arrester. It was also found the selective power out of the lightning arrester line and the required length which is to be isolated from the earth keeping the main function of the lightning arrester line. When economically comparing between supplying the light electrical loads by traditional ways and the method of lightning arrester, it was found the advantage of using lightning arresters to supply such loads. Also, by using the traditional methods, it was noted that there is a power loss in the power transmission lines by a percentage of 1.8%.

  17. Al-Qaeda arrest casts shadow over the LHC

    CERN Multimedia

    Dacey, James

    2010-01-01

    "Cern remains on course for the imminent switch-on of the Large Hadron Collider (LHC) despite the media frenzy following the recent arrest of a physicist who had been working at the facility. The researcher in question is a 32-year-old man of Algerian descent who is expected to face trail in France - the country in which he was arrested" (0.5 page)

  18. TRICHOSTATIN A INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND CELL CYCLE ARREST IN HELA CELLS

    Institute of Scientific and Technical Information of China (English)

    XU Zhou-min; WANG Yi-qun; MEI Qi; CHEN Jian; DU Jia; WEI Yan; XU Ying-chun

    2006-01-01

    Objective: The histone deacetylase inhibitors (HDACIS) have been shown to inhibit cancer cell proliferation, stimulate apoptosis, an induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of a HDACI, trichostatin A (TSA), against human cervical cancer cells (HeLa). Methods: HeLa cells were treated in vitro with various concentrations of TSA. The inhibitory effect of TSA on the growth of HeLa cells was measured by MTT assay. To detect the characteristic of apoptosis chromatin condensation, HeLa cells were stained with Hoechst 33258 in the presence of TSA. Induction of cell cycle arrest was studied by flow cytometry. Changes in gene expression of p53, p21Waf1 and p27Kip1 were studied by semiquantitative RT-PCR. Results: TSA inhibited cell growth in a time- and dose-dependent manner. Hoechst 33258 staining assay showed that TSA induced apoptosis. Cell cycle analysis indicated that treatment with TSA decreased the proportion of cells in S phase and increased the proportion of cells in G0/G1 and/or G2/M phases of the cell cycle. This was concomitant with overexpression of genes related to malignant phenotype, including an increase in p53, p21Waf1 and p27Kip1. Conclusion: These results suggest that TSA is effective in inhibiting growth of HeLa cells in vitro. The findings raise the possibility that TSA may prove particularly effective in treatment of cervical cancers.

  19. Respiratory Arrest in an Obese Pregnant Woman with Hyperemesis Gravidarum

    Directory of Open Access Journals (Sweden)

    Ayumi Iwashita

    2015-01-01

    Full Text Available A pregnant, non-Japanese-speaking Peruvian, and, thus, with communication difficulty, suffered hyperemesis gravidarum and had respiratory arrest, requiring cardiopulmonary resuscitation. The obese pregnant woman (prepregnancy weight: 107 kg had vomited and lost 15 kg in bodyweight over appropriately 2 weeks prior to the arrest but had not complained due to communication difficulty, which, together with her obesity, prevented a Japanese obstetrician from noticing her severe condition. 1,000 mL of low potassium fluid plus thiamine was administered. She became unable to stand, suggesting lower-extremity-proximal-muscle weakness, and then respiratory arrest occurred. Hypopotassemia (2.3 mEq/L, pulseless electrical activity, and muscle weakness suggested the presence of severe potassium deficiency, which may have caused respiratory muscle paralysis, leading to the respiratory arrest. Hypercapnea was severer than expected for compensatory hypoventilation, indicating the presence of concomitant severe hypoventilation, which may also have contributed to respiratory arrest. She recovered with electrolyte and volume replacement. Respiratory arrest can occur with hyperemesis gravidarum, and obesity and communication difficulties can prevent the early detection of severe conditions.

  20. Cardiac arrest due to lymphocytic colitis: a case report

    Directory of Open Access Journals (Sweden)

    Groth Kristian A

    2012-03-01

    Full Text Available Abstract Introduction We present a case of cardiac arrest due to hypokalemia caused by lymphocytic colitis. Case presentation A 69-year-old Caucasian man presented four months prior to a cardiac arrest with watery diarrhea and was diagnosed with lymphocytic colitis. Our patient experienced a witnessed cardiac arrest at his general practitioner's surgery. Two physicians and the emergency medical services resuscitated our patient for one hour and four minutes before arriving at our university hospital. Our patient was defibrillated 16 times due to the recurrence of ventricular tachyarrhythmias. An arterial blood sample revealed a potassium level of 2.0 mmol/L (reference range: 3.5 to 4.6 mmol/L and pH 6.86 (reference range: pH 7.37 to 7.45. As the potassium level was corrected, the propensity for ventricular tachyarrhythmias ceased. Our patient recovered from his cardiac arrest without any neurological deficit. Further tests and examinations revealed no other reason for the cardiac arrest. Conclusion Diarrhea can cause life-threatening situations due to the excretion of potassium, ultimately causing cardiac arrest due to hypokalemia. Physicians treating patients with severe diarrhea should consider monitoring their electrolyte levels.

  1. Associates of Cardiopulmonary Arrest in the Perihemodialytic Period

    Directory of Open Access Journals (Sweden)

    Jennifer E. Flythe

    2014-01-01

    Full Text Available Cardiopulmonary arrest during and proximate to hemodialysis is rare but highly fatal. Studies have examined peridialytic sudden cardiac event risk factors, but no study has considered associates of cardiopulmonary arrests (fatal and nonfatal events including cardiac and respiratory causes. This study was designed to elucidate patient and procedural factors associated with peridialytic cardiopulmonary arrest. Data for this case-control study were taken from the hemodialysis population at Fresenius Medical Care, North America. 924 in-center cardiopulmonary events (cases and 75,538 controls were identified. Cases and controls were 1 : 5 matched on age, sex, race, and diabetes. Predictors of cardiopulmonary arrest were considered for logistic model inclusion. Missed treatments due to hospitalization, lower body mass, coronary artery disease, heart failure, lower albumin and hemoglobin, lower dialysate potassium, higher serum calcium, greater erythropoietin stimulating agent dose, and normalized protein catabolic rate (J-shaped were associated with peridialytic cardiopulmonary arrest. Of these, lower albumin, hemoglobin, and body mass index; higher erythropoietin stimulating agent dose; and greater missed sessions had the strongest associations with outcome. Patient health markers and procedural factors are associated with peridialytic cardiopulmonary arrest. In addition to optimizing nutritional status, it may be prudent to limit exposure to low dialysate potassium (<2 K bath and to use the lowest effective erythropoietin stimulating agent dose.

  2. Exploration of the arrest peptide sequence space reveals arrest-enhanced variants.

    Science.gov (United States)

    Cymer, Florian; Hedman, Rickard; Ismail, Nurzian; von Heijne, Gunnar

    2015-04-17

    Translational arrest peptides (APs) are short stretches of polypeptides that induce translational stalling when synthesized on a ribosome. Mechanical pulling forces acting on the nascent chain can weaken or even abolish stalling. APs can therefore be used as in vivo force sensors, making it possible to measure the forces that act on a nascent chain during translation with single-residue resolution. It is also possible to score the relative strengths of APs by subjecting them to a given pulling force and ranking them according to stalling efficiency. Using the latter approach, we now report an extensive mutagenesis scan of a strong mutant variant of the Mannheimia succiniciproducens SecM AP and identify mutations that further increase the stalling efficiency. Combining three such mutations, we designed an AP that withstands the strongest pulling force we are able to generate at present. We further show that diproline stretches in a nascent protein act as very strong APs when translation is carried out in the absence of elongation factor P. Our findings highlight critical residues in APs, show that certain amino acid sequences induce very strong translational arrest and provide a toolbox of APs of varying strengths that can be used for in vivo force measurements.

  3. Genotypic Variation in Growth and Physiological Response to Drought Stress and Re-Watering Reveals the Critical Role of Recovery in Drought Adaptation in Maize Seedlings

    OpenAIRE

    Chen, Daoqian; Wang, Shiwen; Cao, Beibei; Cao, Dan; Leng, Guohui; Li, Hongbing; Yin, Lina; Shan, Lun; Deng, Xiping

    2016-01-01

    Non-irrigated crops in temperate climates and irrigated crops in arid climates are subjected to continuous cycles of water stress and re-watering. Thus, fast and efficient recovery from water stress may be among the key determinants of plant drought adaptation. The present study was designed to comparatively analyze the roles of drought resistance and drought recovery in drought adaptation and to investigate the physiological basis of genotypic variation in drought adaptation in maize (Zea ma...

  4. Genotypic variation in growth and physiological response to drought stress and re-watering reveals the critical role of recovery in drought adaptation in maize seedlings

    OpenAIRE

    Daoqian eChen; Shiwen eWang; Beibei eCao; Dan eCao; Guohui eLeng; Hongbing eLi; Lina eYin; Lun eShan; Xiping eDeng

    2016-01-01

    Non-irrigated crops in temperate climates and irrigated crops in arid climates are subjected to continuous cycles of water stress and re-watering. Thus, fast and efficient recovery from water stress may be among the key determinants of plant drought adaptation. The present study was designed to comparatively analyze the roles of drought resistance and drought recovery in drought adaptation and to investigate the physiological basis of genotypic variation in drought adaptation in maize (Zea ma...

  5. Requirement of MgtC for Brucella suis Intramacrophage Growth: a Potential Mechanism Shared by Salmonella enterica and Mycobacterium tuberculosis for Adaptation to a Low-Mg2+ Environment

    Science.gov (United States)

    Lavigne, Jean-Philippe; O'Callaghan, David; Blanc-Potard, Anne-Béatrice

    2005-01-01

    A Brucella suis mgtC mutant is defective for growth within macrophages and in low-Mg2+ medium. These phenotypes are strikingly similar to those observed with mgtC mutants from Salmonella enterica and Mycobacterium tuberculosis, two other pathogens that proliferate within phagosomes. MgtC appears as a remarkable virulence factor that would have been acquired by distantly related intracellular pathogens to contribute to the adaptation to a low-Mg2+ environment in the phagosome. PMID:15845525

  6. Role of the retinoblastoma protein in cell cycle arrest mediated by a novel cell surface proliferation inhibitor

    Science.gov (United States)

    Enebo, D. J.; Fattaey, H. K.; Moos, P. J.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    A novel cell regulatory sialoglycopeptide (CeReS-18), purified from the cell surface of bovine cerebral cortex cells has been shown to be a potent and reversible inhibitor of proliferation of a wide array of fibroblasts as well as epithelial-like cells and nontransformed and transformed cells. To investigate the possible mechanisms by which CeReS-18 exerts its inhibitory action, the effect of the inhibitor on the posttranslational regulation of the retinoblastoma susceptibility gene product (RB), a tumor suppressor gene, has been examined. It is shown that CeReS-18 mediated cell cycle arrest of both human diploid fibroblasts (HSBP) and mouse fibroblasts (Swiss 3T3) results in the maintenance of the RB protein in the hypophosphorylated state, consistent with a late G1 arrest site. Although their normal nontransformed counterparts are sensitive to cell cycle arrest mediated by CeReS-18, cell lines lacking a functional RB protein, through either genetic mutation or DNA tumor virus oncoprotein interaction, are less sensitive. The refractory nature of these cells is shown to be independent of specific surface receptors for the inhibitor, and another tumor suppressor gene (p53) does not appear to be involved in the CeReS-18 inhibition of cell proliferation. The requirement for a functional RB protein product, in order for CeReS-18 to mediate cell cycle arrest, is discussed in light of regulatory events associated with density-dependent growth inhibition.

  7. Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells.

    Science.gov (United States)

    García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A; Muñoz, Eduardo

    2016-01-26

    Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.

  8. Nursing students’ knowledge about arrest rhythms and their treatment

    Directory of Open Access Journals (Sweden)

    Aikaterini Kyrgianidou

    2014-04-01

    Full Text Available Cardiovascular diseases are one of the leading causes of death worldwide. Knowledge of health professionals for the arrest rhythms, is considered particularly important for the early recognition and proper treatment. Aim: The purpose of the present study was to assess the knowledge of nursing students on arrest rhythms and how to treat them. Material and Methods: The sample studied included 151 students from the Department of Nursing A' (n = 60, 40% and B' (n = 91, 60%, TEI of Athens, of whom 83% (n=125 were women and 17% (n=26 were men with a mean age of 23 years. Data collection was performed with specially designed questionnaire, that apart from demographics and students’ education level, it included ten questions about arrest rhythms’ knowledge and also self-assessment questions of their level of knowledge. The data were analyzed with the SPSS package v.19, using the criteria t-Test and χ2. Results: Of all the participants in the research, 95% (n = 144 did not answer correctly more than 6 questions from a total of 10. The students of the Department of Nursing A’ recognized with greater accuracy the arrest rhythms (p = 0.003. Those studying in lower semester acknowledged best the arrest rhythms (p = 0.002. Students who had recently attended course in basic or advanced resuscitation recognized best the arrest rhythms (p = 0.006. Older students knew better right treatment of the arrest rhythms (p = 0.037. Also, students who had attended the course of cardiac nursing in the last year, knew better the right treatment (p <0.001. Finally, the level of self-assessment was in line with the actual level of knowledge of students (p = 0.05. Conclusions: Continuous attendance of courses, education on certified programs and refresh courses help to maintain a good level of knowledge for longer periods.

  9. Changing the guard: Polymer replaces porcelain for surge arresters

    Energy Technology Data Exchange (ETDEWEB)

    Skytt, T.; Gleimar, H. E. G.

    2002-07-01

    Surge arresters are safety devices which quickly and effectively limit the over voltages that can arise in transmission networks following lightning, switching and other transient events. The earliest forms of overvoltage protection, a simple air gap between electrodes, have long since been replaced by a new generation of gapless arresters with series-connected, non-linear zinc oxide varistors contained in a porcelain housing. Now these porcelain type surge arresters are being replaced by a new type, called PEXLIM (Polymeric EXcellent LIMiter), which uses the same block of zinc oxide as the porcelain type, but its housing is made of silicon rubber, a polymer. The new lightweight insulation material shows a number of properties superior to the porcelain, such as enhanced product safety and ease of handling. It is also more durable, resilient, yet solid and compact, water-repellent, lightweight, resistant to aging or light or ultra-violet radiation, as well as fire, has good electrical properties, and is environmentally friendly since it does not contain any substances harmful to the environment. These properties make this new type of surge arrester highly suitable for use in earthquake-prone areas; it can also replace more expensive and maintenance-intensive equipment. Having successfully broken into the lower voltage systems, these new type of surge arresters are now rapidly gaining ground at the higher voltage levels. ABB, the developer of PEXLIM, has already supplied these arresters to North America for use in an 800-kV grid. As further proof of its growing popularity, last year PEXLIM made up over half of the surge arrester production for applications up to and including 245 kV. 1 tab., 6 figs.

  10. Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, A.; Zapf, J.; Eckardt, K.U.; Clemons, G.; Froesch, E.R.; Bauer, C. (Universitaet Zurich (Switzerland))

    1988-10-01

    Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. The authors have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 {mu}g of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, {sup 59}Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and {sup 59}Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production.

  11. Visualizing Vpr-induced G2 arrest and apoptosis.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Murakami

    Full Text Available Vpr is an accessory protein of human immunodeficiency virus type 1 (HIV-1 with multiple functions. The induction of G2 arrest by Vpr plays a particularly important role in efficient viral replication because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. The regulation of apoptosis by Vpr is also important for immune suppression and pathogenesis during HIV infection. However, it is not known whether Vpr-induced apoptosis depends on the ability of Vpr to induce G2 arrest, and the dynamics of Vpr-induced G2 arrest and apoptosis have not been visualized. We performed time-lapse imaging to examine the temporal relationship between Vpr-induced G2 arrest and apoptosis using HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator2 (Fucci2. The dynamics of G2 arrest and subsequent long-term mitotic cell rounding in cells transfected with the Vpr-expression vector were visualized. These cells underwent nuclear mis-segregation after prolonged mitotic processes and then entered G1 phase. Some cells subsequently displayed evidence of apoptosis after prolonged mitotic processes and nuclear mis-segregation. Interestingly, Vpr-induced apoptosis was seldom observed in S or G2 phase. Likewise, visualization of synchronized HeLa/Fucci2 cells infected with an adenoviral vector expressing Vpr clearly showed that Vpr arrests the cell cycle at G2 phase, but does not induce apoptosis at S or G2 phase. Furthermore, time-lapse imaging of HeLa/Fucci2 cells expressing SCAT3.1, a caspase-3-sensitive fusion protein, clearly demonstrated that Vpr induces caspase-3-dependent apoptosis. Finally, to examine whether the effects of Vpr on G2 arrest and apoptosis were reversible, we performed live-cell imaging of a destabilizing domain fusion Vpr, which enabled rapid stabilization and destabilization by Shield1. The effects of Vpr on G2 arrest and subsequent apoptosis were reversible. This study is the first to

  12. Investigating Different ZnO Arresters Models against Transient Waves

    Directory of Open Access Journals (Sweden)

    A. Babaee

    2011-12-01

    Full Text Available Metal oxide surge arresters have dynamic characteristics that are significant for over voltage coordination studies involving fast front surges. Several models with acceptable accuracy have been proposed to simulate this frequency-dependent behavior. In this paper, various electrical models are presented for surge arrester performance simulation against lightning impulse. The desirable model is obtained by using simulation results of the existing models and experimental tests. The IEEE proposed model is a proportional model can give satisfactory results for discharge currents within a range of time to crest for 0.5 to 45 :s but due to no existing residual voltage resulting switching current on the manufacture's datasheets decrease its performance generally. In this study the maximum residual voltage due to current impulse is analyzed too. In additional, the amount of discharged energy by surge arrester is focused.

  13. Numerical study of fracture arrest on snow cover

    Directory of Open Access Journals (Sweden)

    B. Frigo

    2010-10-01

    Full Text Available Under the hypothesis of a perfectly brittle phenomenon, avalanche triggering can be investigated numerically by means of Linear Elastic Fracture Mechanics (LEFM. Since, however, the real phenomenon is intrinsically dynamical, another aspect to investigate is represented by dynamic fracture propagation. In this paper, we model dynamic crack propagation into a dry snow slab and we investigate the possibility to arrest the crack propagation through the presence of weak zones distributed along the extension of the snow slope. Assuming that the weak layer is almost collapsed, we simulate the efficiency of artificial voids in the slab to arrest fracture propagation, into the framework of Dynamical Fracture Mechanics. We put forward here a new philosophy for the use of artificial discontinuities (void into the snowpack able to perform as crack arresters distributed along the snow slope area: the target is to split a large avalanche slab into smaller slabs, causing small avalanches to propagate with less catastrophic effects.

  14. Alphaherpesvirus Subversion of Stress-Induced Translational Arrest

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    Renée L. Finnen

    2016-03-01

    Full Text Available In this article, we provide an overview of translational arrest in eukaryotic cells in response to stress and the tactics used specifically by alphaherpesviruses to overcome translational arrest. One consequence of translational arrest is the formation of cytoplasmic compartments called stress granules (SGs. Many viruses target SGs for disruption and/or modification, including the alphaherpesvirus herpes simplex virus type 2 (HSV-2. Recently, it was discovered that HSV-2 disrupts SG formation early after infection via virion host shutoff protein (vhs, an endoribonuclease that is packaged within the HSV-2 virion. We review this discovery and discuss the insights it has provided into SG biology as well as its potential significance in HSV-2 infection. A model for vhs-mediated disruption of SG formation is presented.

  15. Alphaherpesvirus Subversion of Stress-Induced Translational Arrest

    Science.gov (United States)

    Finnen, Renée L.; Banfield, Bruce W.

    2016-01-01

    In this article, we provide an overview of translational arrest in eukaryotic cells in response to stress and the tactics used specifically by alphaherpesviruses to overcome translational arrest. One consequence of translational arrest is the formation of cytoplasmic compartments called stress granules (SGs). Many viruses target SGs for disruption and/or modification, including the alphaherpesvirus herpes simplex virus type 2 (HSV-2). Recently, it was discovered that HSV-2 disrupts SG formation early after infection via virion host shutoff protein (vhs), an endoribonuclease that is packaged within the HSV-2 virion. We review this discovery and discuss the insights it has provided into SG biology as well as its potential significance in HSV-2 infection. A model for vhs-mediated disruption of SG formation is presented. PMID:26999187

  16. Estramustine-binding protein (EMBP) content in four different cell lines and its correlation to estramustine induced metaphase arrest.

    Science.gov (United States)

    Eklöv, S; Mahdy, E; Wester, K; Björk, P; Malmström, P U; Busch, C; Nilsson, S

    1996-01-01

    It is known that estramustine (EM) accumulates in cells at the G2/M-phase and causes metaphase arrest of various cell types. The inhibitory effect is mediated by interaction with microtubule-associated proteins (MAPs) and/or tubulin. Estramustine-binding protein (EMBP) is a secretory protein which has been found in a number of different tumor cells and has been shown to faciliate the uptake of EM into cells. In this study the efficacy of EM in arresting cells at metaphase was studied, using four different human cell lines; the prostatic cancer cell line DU 145, the breast cancer cell line MDA 231, the colon cancer cell line Colon 320, and the urinary bladder cancer cell line RT4. The cells were incubated with EM at a concentration of 10 micrograms/ml for 24 hours. The data reveal an increase in metaphase arrests in the DU 145 and in Colon 320 cell lines. Both of these cell lines were found to contain high amounts of EMBP using a dot-blot assay. The other two cell lines, MDA 231 and RT4 had undetectable intracellular amounts of the protein and exhibited a low increase in metaphase arrests. The cell lines were analysed regarding S-phase fraction with flow-cytometry (FCM) to exclude the growth rate of the cells as a limiting factor. The results from the FCM confirmed the cytogenic analysis, that is a higher percentage of cells were in the G2/M phase in both the DU 145 and Colon 320 cell line compared to MDA 231 and RT4. EM causes mitotic arrest in those cell lines that contain detectable amounts of EMBP.

  17. Effects of hormone agonists on Sf9 cells, proliferation and cell cycle arrest.

    Science.gov (United States)

    Giraudo, Maeva; Califano, Jérôme; Hilliou, Frédérique; Tran, Trang; Taquet, Nathalie; Feyereisen, René; Le Goff, Gaëlle

    2011-01-01

    Methoxyfenozide and methoprene are two insecticides that mimic the action of the main hormones involved in the control of insect growth and development, 20-hydroxyecdysone and juvenile hormone. We investigated their effect on the Spodoptera frugiperda Sf9 cell line. Methoxyfenozide was more toxic than methoprene in cell viability tests and more potent in the inhibition of cellular proliferation. Cell growth arrest occurred in the G2/M phase after a methoprene treatment and more modestly in G1 after methoxyfenozide treatment. Microarray experiments and real-time quantitative PCR to follow the expression of nuclear receptors ultraspiracle and ecdysone receptor were performed to understand the molecular action of these hormone agonists. Twenty-six genes were differentially expressed after methoxyfenozide treatment and 55 genes after methoprene treatment with no gene in common between the two treatments. Our results suggest two different signalling pathways in Sf9 cells.

  18. Effects of hormone agonists on Sf9 cells, proliferation and cell cycle arrest.

    Directory of Open Access Journals (Sweden)

    Maeva Giraudo

    Full Text Available Methoxyfenozide and methoprene are two insecticides that mimic the action of the main hormones involved in the control of insect growth and development, 20-hydroxyecdysone and juvenile hormone. We investigated their effect on the Spodoptera frugiperda Sf9 cell line. Methoxyfenozide was more toxic than methoprene in cell viability tests and more potent in the inhibition of cellular proliferation. Cell growth arrest occurred in the G2/M phase after a methoprene treatment and more modestly in G1 after methoxyfenozide treatment. Microarray experiments and real-time quantitative PCR to follow the expression of nuclear receptors ultraspiracle and ecdysone receptor were performed to understand the molecular action of these hormone agonists. Twenty-six genes were differentially expressed after methoxyfenozide treatment and 55 genes after methoprene treatment with no gene in common between the two treatments. Our results suggest two different signalling pathways in Sf9 cells.

  19. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    DEFF Research Database (Denmark)

    Westhall, Erik; Rossetti, Andrea O; van Rootselaar, Anne-Fleur;

    2016-01-01

    OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists...... patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present...

  20. Delayed hippocampal damage in humans following cardiorespiratory arrest.

    Science.gov (United States)

    Petito, C K; Feldmann, E; Pulsinelli, W A; Plum, F

    1987-08-01

    Transient ischemia in animals produces delayed cell death in vulnerable hippocampal neurons. To see if this occurs in humans, we reexamined brain slides from all patients with anoxic-ischemic encephalopathy and a well-documented cardiorespiratory arrest. Eight patients dying 18 hours or less after cardiac arrest had minimal damage in hippocampus and moderate damage in cerebral cortex and putamen. Six patients living 24 hours or more had severe damage in all four regions. The increase in damage with time postarrest was significant only in the hippocampus. Delayed hippocampal injury now documented in humans provides a target for possible therapy that can be initiated after cardiopulmonary resuscitation.

  1. Optimizing Survival Outcomes For Adult Patients With Nontraumatic Cardiac Arrest.

    Science.gov (United States)

    Jung, Julianna

    2016-10-01

    Patient survival after cardiac arrest can be improved significantly with prompt and effective resuscitative care. This systematic review analyzes the basic life support factors that improve survival outcome, including chest compression technique and rapid defibrillation of shockable rhythms. For patients who are successfully resuscitated, comprehensive postresuscitation care is essential. Targeted temperature management is recommended for all patients who remain comatose, in addition to careful monitoring of oxygenation, hemodynamics, and cardiac rhythm. Management of cardiac arrest in circumstances such as pregnancy, pulmonary embolism, opioid overdose and other toxicologic causes, hypothermia, and coronary ischemia are also reviewed.

  2. Effect of early experience and adaptation period on voluntary intake, digestion, and growth in Barbarine lambs given tannin-containing (Acacia cyanophylla Lindl. foliage) or tannin-free (oaten hay) diets

    Energy Technology Data Exchange (ETDEWEB)

    Ben Salem, H. [Institut National de la Recherche Agronomique de Tunisie, Laboratoire des Productions Animales et Fourrageres, Ariana (Tunisia)]. E-mail: bensalem.hichem@iresa.agrinet.tn; Nefzaouia, A.; Ben Salem, I. [Institut National de la Recherche Agronomique de Tunisie, Laboratoire des Productions Animales et Fourrageres, Ariana (Tunisia); Makkar, H.P.S. [Animal Production and Health Section, Joint FAO/IAEA Division, International Atomic Energy Agency, Vienna (Austria); Hochlef, H. [Institut National de la Recherche Agronomique de Tunisie, Laboratoire des Productions Animales et Fourrageres, Ariana (Tunisia); Ecole Superieure d' Agriculture de Mateur, Mateur (Tunisia); Ben Salem, L. [Office de l' Elevage et des Paturages, Tunis (Tunisia)

    2005-08-19

    Our objective was to determine whether experience early in life and adaptation time (up to 72 days) to tannin-rich diets affect feed intake, digestion, nitrogen balance, and growth in Barbarine lambs given tannin-containing (Acacia cyanophylla Lindl., acacia) or tannin-free (oaten hay) diets later in life. Twelve experienced lambs (live-weight, LW: 13.2 {+-} 2.0 kg) were divided into two equal groups. Each group received air-dried acacia (tannin-containing diet) or oaten hay (hay, tannin free-diet) ad libitum. Twelve other inexperienced lambs (LW 12.3 {+-} 2.5 kg) were also divided into two equal groups. Each group received one of the above two diets. All animals were 4 months old at the start of this experiment and were supplemented with 300 g concentrate. To investigate the carry-over effect of tannins, the acacia-diet was removed on day 73, thus all lambs received thereafter the hay-diet for a further 24 days before starting a 6-day faecal collection period. Irrespective to early experience and adaptation time, the nutritive value of hay-diet was higher than that of acacia-diet and consequently lambs given hay performed better than those receiving acacia (P = 0.0001). Animals exposed to tannins early in life exhibited higher digestible crude protein intake (P = 0.0389), retained more N (P = 0.0963) and excreted more allantoin in urine (P = 0.0248) than the inexperienced lambs. Except plasma urea (P = 0.2923), the adaptation period to experimental diets affected significantly all measured parameters (P 0.0001). Animals adapted to diets for only 6 days exhibited the lowest acacia or hay intake and the highest diet digestibility compared to those adapted to these diets for 24, 48 or 72 days. Weight losses of inexperienced lambs adapted to acacia-diet for 6 days were associated with negative nitrogen balance. Sheep which received the acacia-diet, followed by the hay diet, had similar hay intake, diet digestibility, N balance and growth rate as compared to those

  3. Involvement of p53 in cell death following cell cycle arrest and mitotic catastrophe induced by rotenone.

    Science.gov (United States)

    Gonçalves, António Pedro; Máximo, Valdemar; Lima, Jorge; Singh, Keshav K; Soares, Paula; Videira, Arnaldo

    2011-03-01

    In order to investigate the cell death-inducing effects of rotenone, a plant extract commonly used as a mitochondrial complex I inhibitor, we studied cancer cell lines with different genetic backgrounds. Rotenone inhibits cell growth through the induction of cell death and cell cycle arrest, associated with the development of mitotic catastrophe. The cell death inducer staurosporine potentiates the inhibition of cell growth by rotenone in a dose-dependent synergistic manner. The tumor suppressor p53 is involved in rotenone-induced cell death, since the drug treatment results in increased expression, phosphorylation and nuclear localization of the protein. The evaluation of the effects of rotenone on a p53-deficient cell line revealed that although not required for the promotion of mitotic catastrophe, functional p53 appears to be essential for the extensive cell death that occurs afterwards. Our results suggest that mitotic slippage also occurs subsequently to the rotenone-induced mitotic arrest and cells treated with the drug for a longer period become senescent. Treatment of mtDNA-depleted cells with rotenone induces cell death and cell cycle arrest as in cells containing wild-type mtDNA, but not formation of reactive oxygen species. This suggests that the effects of rotenone are not dependent from the production of reactive oxygen species. This work highlights the multiple effects of rotenone in cancer cells related to its action as an anti-mitotic drug.

  4. Induction of G2/M arrest by pseudolaric acid B is mediated by activation of the ATM signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Ai-guo MENG; Ling-lingJIANG

    2009-01-01

    Aim: The aim of this study was to investigate the mechanism of pseudolaric acid B (PLAB)-induced cell cycle arrest in human melanoma SK-28 cells. Methods: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression was examined by Western blot analysis.Results: PLAB inhibited the growth of human melanoma ceils and induced G2/M arrest in SK-28 cells, accompanied by an up-regulation of Cdc2 phosphorylation and a subsequent down-regulation of Cdc2 expression. Furthermore, PLAB decreased the expression of Cdc25C phosphatase and increased the expression of Wee1 kinase. Meanwhile, a reduction in Cdc2 activity was party due to induction of the expression of p21wsaf1/cip1 in a p53-dependent manner. In addition, PLAB activated the checkpoint kinase, Chk2, and increased the expression of p53, two major targets of ATM kinase. These effects were inhibited by caffeine, an ATM kinase inhibitor. We also found that PLAB significantly enhanced ATM kinase activity. Conclusion: Taken together, these results suggest that PLAB induced G2/M arrest in human melanoma cells via a mechanism involving the activation of ATM, and the effect of PLAB on Cdc2 activity was mediated via interactions with the Chk2-Cdc25C and p53 signalling pathways, two distinct downstream pathways of ATM. PLAB may be a promising chemopreventive agent for treating human melanoma.

  5. Checkpoint adaptation and recovery: back with Polo after the break

    NARCIS (Netherlands)

    Vugt, M.A.T.M. van; Medema, R.H.

    2004-01-01

    S. cerevisiae cells that are unable to repair a double strand break ultimately escape the DNA damage checkpoint arrest and enter mitosis. This process called 'adaptation' depends on functional Cdc5, a Polo-like kinase, and was long thought to be limited to single-cell organisms. However, the recent

  6. Checkpoint adaptation and recovery : back with Polo after the break

    NARCIS (Netherlands)

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

    2004-01-01

    S. cerevisiae cells that are unable to repair a double strand break ultimately escape the DNA damage checkpoint arrest and enter mitosis. This process called 'adaptation' depends on functional Cdc5, a Polo-like kinase, and was long thought to be limited to single-cell organisms. However, the recent

  7. Inhibition of ileal and colonic ornithine decarboxylase activity by alpha-difluoromethylornithine in rats: transient atrophic changes and loss of postresectional adaptive growth.

    Science.gov (United States)

    Kingsnorth, A N; Abu-Khalaf, M; LaMuraglia, G M; McCann, P P; Diekema, K A; Ross, J S; Malt, R A

    1986-06-01

    To determine the role of putrescine synthesis in adaptive hyperplasia of the ileum and colon, DL-alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC), the enzyme controlling putrescine biosynthesis, was fed to rats after excision of the proximal half of the small bowel. A rise in ODC activity (280% in the proximal ileum, 62% in the proximal colon) and a rise in putrescine content (220% in the proximal ileum, 250% in the proximal colon) normally accompanied characteristic cytochemical adaptive increases in the ileum and colon at day 6. Inclusion of 1% DFMO (2.1 gm/kg/day) in drinking water for 12 hours before operation and for 14 days thereafter decreased ODC activity by 85% to 96%, reduced levels of putrescine and spermidine and measurements of the adaptive response by 50% in the ileum, and abolished the adaptive response in the colon. During the first 10 days of DFMO feeding, villous atrophy and other hypoplastic changes occurred in control rats, but by 14 days of DFMO feeding atrophy and hypoplasia were no longer present. Although DFMO inhibits adaptive hyperplasia occurring in the ileum and colon of rats after resection of the proximal half of the small bowel, spontaneous recovery of villous atrophy occurs during further DFMO feeding and may protect the host during chemotherapy.

  8. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Junqiang; Doi, Hiroshi [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Saar, Matthias; Santos, Jennifer [Department of Urology, School of Medicine, Stanford University, Stanford, California (United States); Li, Xuejun; Peehl, Donna M. [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States)

    2013-12-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

  9. Quantitative model of cell cycle arrest and cellular senescence in primary human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Sascha Schäuble

    Full Text Available Primary human fibroblasts in tissue culture undergo a limited number of cell divisions before entering a non-replicative "senescent" state. At early population doublings (PD, fibroblasts are proliferation-competent displaying exponential growth. During further cell passaging, an increasing number of cells become cell cycle arrested and finally senescent. This transition from proliferating to senescent cells is driven by a number of endogenous and exogenous stress factors. Here, we have developed a new quantitative model for the stepwise transition from proliferating human fibroblasts (P via reversibly cell cycle arrested (C to irreversibly arrested senescent cells (S. In this model, the transition from P to C and to S is driven by a stress function γ and a cellular stress response function F which describes the time-delayed cellular response to experimentally induced irradiation stress. The application of this model based on senescence marker quantification at the single-cell level allowed to discriminate between the cellular states P, C, and S and delivers the transition rates between the P, C and S states for different human fibroblast cell types. Model-derived quantification unexpectedly revealed significant differences in the stress response of different fibroblast cell lines. Evaluating marker specificity, we found that SA-β-Gal is a good quantitative marker for cellular senescence in WI-38 and BJ cells, however much less so in MRC-5 cells. Furthermore we found that WI-38 cells are more sensitive to stress than BJ and MRC-5 cells. Thus, the explicit separation of stress induction from the cellular stress response, and the differentiation between three cellular states P, C and S allows for the first time to quantitatively assess the response of primary human fibroblasts towards endogenous and exogenous stress during cellular ageing.

  10. Lysophosphatidate induces chemo-resistance by releasing breast cancer cells from taxol-induced mitotic arrest.

    Directory of Open Access Journals (Sweden)

    Nasser Samadi

    Full Text Available BACKGROUND: Taxol is a microtubule stabilizing agent that arrests cells in mitosis leading to cell death. Taxol is widely used to treat breast cancer, but resistance occurs in 25-69% of patients and it is vital to understand how Taxol resistance develops to improve chemotherapy. The effects of chemotherapeutic agents are overcome by survival signals that cancer cells receive. We focused our studies on autotaxin, which is a secreted protein that increases tumor growth, aggressiveness, angiogenesis and metastasis. We discovered that autotaxin strongly antagonizes the Taxol-induced killing of breast cancer and melanoma cells by converting the abundant extra-cellular lipid, lysophosphatidylcholine, into lysophosphatidate. This lipid stimulates specific G-protein coupled receptors that activate survival signals. METHODOLOGY/PRINCIPAL FINDINGS: In this study we determined the basis of these antagonistic actions of lysophosphatidate towards Taxol-induced G2/M arrest and cell death using cultured breast cancer cells. Lysophosphatidate does not antagonize Taxol action in MCF-7 cells by increasing Taxol metabolism or its expulsion through multi-drug resistance transporters. Lysophosphatidate does not lower the percentage of cells accumulating in G2/M by decreasing exit from S-phase or selective stimulation of cell death in G2/M. Instead, LPA had an unexpected and remarkable action in enabling MCF-7 and MDA-MB-468 cells, which had been arrested in G2/M by Taxol, to normalize spindle structure and divide, thus avoiding cell death. This action involves displacement of Taxol from the tubulin polymer fraction, which based on inhibitor studies, depends on activation of LPA receptors and phosphatidylinositol 3-kinase. CONCLUSIONS/SIGNIFICANCE: This work demonstrates a previously unknown consequence of lysophosphatidate action that explains why autotaxin and lysophosphatidate protect against Taxol-induced cell death and promote resistance to the action of this

  11. Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling.

    Science.gov (United States)

    Song, Wenbin; Dang, Qiang; Xu, Defeng; Chen, Yule; Zhu, Guodong; Wu, Kaijie; Zeng, Jin; Long, Qingzhi; Wang, Xinyang; He, Dalin; Li, Lei

    2014-03-01

    Kaempferol has been shown to inhibit cell growth, induce apoptosis and cell cycle arrest in several tumors, but not in renal cell carcinoma (RCC). In the present study, we investigated the effects of kaempferol and the underlying mechanism(s) on the cell growth of RCC cells. MTT assay and colony formation assay were used to study cell growth, and flow cytometry was used to study apoptosis and cell cycles in different RCC cells treated with various doses of kaempferol. A significant inhibition on cell growth, induction of apoptosis and cell cycle arrest were observed in 786-O and 769-P cells after kaempferol treatment compared with the control group. Moreover, the results clearly showed that kaempferol causes a strong inhibition of the activation of the EGFR/p38 signaling pathways, upregulation of p21 expression and downregulation of cyclin B1 expression in human RCC cells, together with activation of PARP cleavages, induction of apoptotic death and inhibition of cell growth. Collectively, our results suggest that kaempferol may serve as a candidate for chemo-preventive or chemotherapeutic agents for RCC.

  12. Cardiac Arrest after Local Anaesthetic Toxicity in a Paediatric Patient

    Directory of Open Access Journals (Sweden)

    Liana Maria Torres de Araújo Azi

    2016-01-01

    Full Text Available We report a case of a paediatric patient undergoing urological procedure in which a possible inadvertent intravascular or intraosseous injection of bupivacaine with adrenaline in usual doses caused subsequent cardiac arrest, completely reversed after administration of 20% intravenous lipid emulsion. Early diagnosis of local anaesthetics toxicity and adequate cardiovascular resuscitation manoeuvres contribute to the favourable outcome.

  13. Sudden cardiac arrest in sports - need for uniform registration

    DEFF Research Database (Denmark)

    Solberg, E E; Borjesson, M; Sharma, S;

    2016-01-01

    There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities....

  14. Anaphylactic shock and cardiac arrest caused by thiamine infusion

    DEFF Research Database (Denmark)

    Juel, Jacob; Pareek, Manan; Langfrits, Christian Sigvald

    2013-01-01

    intoxication and developed cardiac arrest due to anaphylactic shock following intravenous thiamine infusion. The patient was successfully resuscitated after 15 min and repeated epinephrine administrations. He was discharged in good health after 14 days. This case report emphasises both the importance...

  15. Outcomes After Cardiac Arrest in an Adult Burn Center

    Science.gov (United States)

    2013-12-07

    Outcomes after cardiac arrest in an adult burn center§,§§ Jonathan C. Wilton, Mark O. Hardin , John D. Ritchie, Kevin K. Chung, James K. Aden...PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wilton J. C., Hardin M. O., Ritchie J. D., Chung K. K., Aden J. K., Cancio L. C., Wolf S. E., White C. E., 5d

  16. Parenting and Women Arrested for Intimate Partner Violence

    Science.gov (United States)

    Simmons, Catherine A.; Lehmann, Peter; Dia, David A.

    2010-01-01

    Exploring the relationship between parenting and women's use of violence the current study surveyed 106 mothers arrested for intimate partner violence (IPV) related crimes on parenting styles and attitudes toward when using violence against their partner is justified. Findings indicate parenting styles indicative of low belief in using physical…

  17. 19 CFR 162.63 - Arrests and seizures.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Arrests and seizures. 162.63 Section 162.63 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Controlled Substances, Narcotics, and Marihuana §...

  18. Cdc20 control of cell fate during prolonged mitotic arrest

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2011-01-01

    The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations...

  19. Design of Lightning Arresters for Electrical Power Systems Protection

    Directory of Open Access Journals (Sweden)

    Shehab Abdulwadood

    2013-01-01

    Full Text Available This paper presents an overview of how the lightning strikes and their effects on power distribution systems can be modeled, where the results give a clear picture of how to eliminate the devastating impact, caused by lightning, by using lightning arresters. The program ATP-Draw (Alternative Transient Program was used to simulate the problem and was applied on a part of a power network.The simulation was done once when the lightning strikes a transmission line and a substation with no lightning arresters in use and once more with their use. The source of the lightning was represented by the ATP models (Type-15 surge function and Type-13 ramp function and the surge arrester was represented by the MOV-Type 92 component. The voltage was recorded at the substation 110/22 kV and at all loads in the electric network, and was drawn by the PlotXWin program. The results obtained indicate that the voltages induced by the lightning can reach values of the order of millions over insulation flashover levels for 22 kV equipment, where is clearly seen in Fig. 12 to 16 and Tab.10, which requires the installation of lightning arresters.

  20. Chemical Society Reinstates Iranian Chemists; Iranian-American Scholar Arrested

    Science.gov (United States)

    Bollag, Burton

    2007-01-01

    The frosty relationship between the United States and Iran has created a chill in many areas of scholarly endeavor. One resulting battle, over whether Iranian scholars can belong to the American Chemical Society, has been largely resolved. But a new imbroglio looms with the arrest of a prominent U.S.-Iranian scholar who was visiting Tehran. The…

  1. Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Søholm, Helle;

    2014-01-01

    AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopres...

  2. 多重外部因素下珠三角外贸企业适应性成长机制%Adaptive Growth Mechanism of Foreign Trade Enterprises in the Pearl River Delta with Multiple External Factors

    Institute of Scientific and Technical Information of China (English)

    袁裕辉

    2012-01-01

    Multiple factors such as global social responsibility campaign, financial crisis, digital manufacturing, and virtual communities will change the ecological environment of the foreign trade enterprises in the Pearl River Delta. Through the a-nalysis on growth factors of foreign trade enterprises in the Pearl River Delta, its adaptive growth mechanism model has been constructed from the perspective of complex adaptive theory. Studies show that adaptive growth enterprises must be able to respond quickly to external environment' s change and reconstruct "internal model". Finally, in view of the multiple external factor, the paper puts forward the corresponding rapid response mechanisms consisting of technology innovation, system innovation, marketing innovation, and consciousness innovation.%全球社会责任运动、金融危机、制造业数字化、虚拟社区等多重因素将改变珠三角外贸企业的生态环境.基于复杂自适应理论的视角分析了影响珠三角外贸企业成长的因素,并构建了其适应性成长机制模型.研究结果表明:企业只有快速响应外部生态环境变化而重构“内部模型”,才能适应性成长.最后,针对目前多重外部因素的影响,提出了由技术创新、制度创新、营销创新、意识创新等构建的快速响应机制.

  3. The arresting phase determines the total healing time of

    Directory of Open Access Journals (Sweden)

    LI Ping

    2012-04-01

    Full Text Available 【Abstract】Objective: Radiation is an important cause of delayed wound healing, and there still exist many questions regarding the patterns and mechanisms of wound healing. This study investigated the characteristics of wound healing after varying doses of local radiation and explored possible causes of the delay in healing caused by radiation. Methods: A full-thickness dorsal longitudinal skin tissue, 2 cm in diameter, was excised after local irradiation on one side of the back of swine, and the other side was wounded as a control. The size of the wound area was re-corded every two days after injury. Pathological changes, proliferating cell nuclear antigen (PCNA, immunohisto-chemistry and apoptosis levels (TUNEL assay were mea-sured at different time points after wounding. Results: The course of wound healing can be divided into four phases, namely: the arresting phase, the healing priming phase, the fast healing phase, and the healed phase. Although the total wound healing time was closely corre-lated to the dose of irradiation (R 2 = 0.9758, it was more dependent on the length of the arresting phase (R 2 =0.9903 because once the arresting phase ended, the wound healed at a similar speed regardless of radiation doses. Pathologi-cal analysis showed that compared with the control side there were more necrotic tissues, slower epithelial crawling, as well as fewer blood vessels and cellular components in the irradiated side at the arresting phase, while other phases revealed no significant difference concerning these measurements. Immunohistochemistry showed that the ir-radiated wounds had significantly less PCNA-positive and more TUNEL-positive labeling of cells in the arresting phase than in other phases. Moreover, the changes were posi-tively related to the radiation doses, but there was no obvi-ous difference in cell proliferation or apoptosis among the healing priming phase, fast healing phase or healed phase, whether on the control side

  4. Selection of Variants Utilizing Heparin Sulphate For Cell Entry When South African Territories Foot-and-Mouth Disease Virus is Adapted for Growth on Cell Culture

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) attains entry to epithelial cells by affinity for at least four members of the integrin family of receptors. Adaptation of field isolates to grow in cultured cells is an essential step towards development of vaccines against new outbreak strains. This is made poss...

  5. Adaptation of in vivo amino acid kinetics facilitates increased amino acid availability for fetal growth in adolescent and adult pregnancies alike

    Science.gov (United States)

    During pregnancy, adult women with a normal BMI synthesize extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and ...

  6. 10 CFR 1047.5 - Exercise of arrest authority-general guidelines.

    Science.gov (United States)

    2010-01-01

    .... (c) After the arrest is effected, the arrested person shall be advised of his or her constitutional right against self-incrimination (Miranda warnings). If the circumstances are such that making...

  7. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu

    2007-01-01

    AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells.Possible molecular mechanisms were explored.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT)assay,plasmid transfection,reporter assay,FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS:C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest.During the process,the expression of p21 protein increased,while that of cyclinD1,phospho-ERK1/2 and c-myc decreased.Furthermore,the level of CDK7 was downregulated,while the transcriptional activity of PPARγ was upregulated.Addition of GW9662,which is a PPARγ specific antagonist,could reserve the modulation action on CDK7.CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7,at least partly,through PPARγ activation.The ERK signaling pathway was involved in this process.

  8. Tea pigments induce cell-cycle arrest and apoptosis in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Jia; Chi Han; Jun-Shi Chen

    2005-01-01

    AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis.METHODS: HepG2 cells were seeded at a density of 5×105/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21WAF1 proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells.RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21WAF1 protein and downregulation of Bcl-2 protein.CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.

  9. Organizational Adaptation and Strategic Choice: The Dual Theme of Business Growth%组织适应力与战略选择:企业成长的双重主题

    Institute of Scientific and Technical Information of China (English)

    吕子剑; 黄洋

    2011-01-01

    市场环境和组织内部环境变化日益加快,企业的成长是否具有可持续性愈来愈成为战略管理的理论与实践所关注的内容.分析了战略选择与组织适应能力互补互动对企业的可持续成长的重要影响.%With the accelerating change of market environment and internal environment, whether the growth of the enterprise is sustained has increasingly become the interested topic in the domain of strategic management theory and its practice. The significant effect of the interaction between strategic choice and organizational adaptation to the sustained growth of an enterprise is analyzed.

  10. 30 CFR 77.508-1 - Lightning arresters; wires entering buildings.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Lightning arresters; wires entering buildings... OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508-1 Lightning arresters; wires entering buildings. Lightning arresters protecting exposed telephone wires entering buildings shall be provided...

  11. Mechanical cardiopulmonary resuscitation in in-hospital cardiac arrest : a systematic review

    NARCIS (Netherlands)

    Lameijer, Heleen; Immink, Rosa S.; Broekema, Josien J.; Ter Maaten, Jan C.

    2015-01-01

    With increasing rates of in-hospital cardiac arrest, improving resuscitation outcomes is essential. Mechanical chest compressors seem to be related to improved outcome in out-of hospital cardiac arrest; however, the literature on its use in in-hospital cardiac arrest is scarce. We used the Medline p

  12. U.S. Juvenile Arrests: Gang Membership, Social Class, and Labeling Effects

    Science.gov (United States)

    Tapia, Mike

    2011-01-01

    This study addresses the link between gang membership and arrest frequency, exploring the Gang x Socioeconomic status interaction on those arrests. Notoriously poor, delinquent, and often well-known to police, America's gang youth should have very high odds of arrest. Yet it is unclear whether mere membership in a gang increases the risk of arrest…

  13. Modes of induced cardiac arrest: hyperkalemia and hypocalcemia--literature review.

    Science.gov (United States)

    Oliveira, Marcos Aurélio Barboza de; Brandi, Antônio Carlos; Santos, Carlos Alberto dos; Botelho, Paulo Henrique Husseini; Cortez, José Luis Lasso; Braile, Domingo Marcolino

    2014-01-01

    The entry of sodium and calcium play a key effect on myocyte subjected to cardiac arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused by hypocalcemia maintains intracellular adenosine triphosphate levels, improves diastolic performance and reduces oxygen consumption, which can be translated into better protection to myocyte injury induced by cardiac arrest.

  14. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  15. The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green

    2011-01-01

    The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here......, we show that SSX2 is involved in regulation of cancer cell growth. We found that ectopic expression of SSX2 in melanoma and colon cancer cells strongly reduced cell growth and induced apoptosis in vitro. Importantly, in a xenograft mouse model, the growth of tumors derived from SSX2 overexpressing...... an increase in the number of gamma-H2AX ‘DNA damage foci’, indicating replicative stress, which may lead to genomic instability. As the p53 tumor suppressor is an inducer of G1 arrest after DNA damage and often deregulated in cancer cells, we investigated if the growth reduction due to SSX2 expression was p53...

  16. The impact of emotional disturbances on the arrest trajectories of youth as they transition into young adulthood.

    Science.gov (United States)

    Constantine, Robert J; Andel, Ross; Robst, John; Givens, Eugenia M

    2013-08-01

    This article identifies the arrest trajectories of youth from ages 12 through 24 years old and tests hypotheses derived from Moffitt's developmental taxonomic theory of crime concerning the impact of various emotional disturbances on the specific trajectories of the youth involved. The study uses exclusively administrative data sets and includes a gender and racially diverse sample of 10,360 youth (30.7% females) who were arrested at least once between ages 12 and 24 in the early 2000s. Latent class growth analysis was employed in order to identify distinct arrest trajectories of youth in the sample. Multinomial logistic regression was used to identify diagnostic and other characteristics associated with membership in the specific trajectories predicted by Moffitt's theory. Five trajectory classes were identified, 3 of which were consistent with taxonomic theory including high and classic adolescence limited trajectory classes and a "snared adolescence limited class" described more recently by Moffitt. The distribution of youth among the 5 classes was very different for those with and without emotional disturbances. Youth with emotional disturbances in their late adolescent years were more likely to fall into the high arrest trajectory class and much less likely to fall into the low arrest trajectory class. Compared to youth without an emotional disturbance, youth with psychotic disorders were more than twice as likely to fall into the high as into the low arrest trajectory class. Youth with disruptive behavior disorders were more than twice as likely to fall into the high and intermediate classes as into the low trajectory class. Anxiety and depressive disorders were not associated with significantly greater likelihood of falling into any one of the trajectory classes. Youth in the snared adolescence limited class were more likely than those in the classic adolescence limited class to be male, black versus white and in the foster care enrollment category lending

  17. MiR-92a mediates AZD6244 induced apoptosis and G1-phase arrest of lymphoma cells by targeting Bim.

    Science.gov (United States)

    Lv, Xiao-Bin; Zhang, Xing; Deng, Lan; Jiang, Ling; Meng, Wei; Lu, Zhigang; Wang, Xiuju

    2014-04-01

    AZD6244, an ATP-uncompetitive inhibitor of mitogen-activated protein kinase 1/2 (MEK1/2), has shown activity in several malignant tumours. However, whether AZD6244 has a function in lymphoma cells is not known. We report that AZD6244 treatment represses the growth of Raji and MOLT4 cells by inducing apoptosis and G1-phase arrest. Using miRNAs array and quantitative RT-PCR, miR-92a was downregulated byAZD6244 treatment through the ERK1/2-AP1 signalling pathway. Overexpression of miR-92a abrogated AZD6244-induced apoptosis and G1-phase arrest, indicating that it is involved in the cytotoxicity of AZD6244 in lymphoma cells. A luciferase reporter assay showed that miR-92a directly targetsthe 3'-UTRs of Bim. Overexpression of miR-92a mimics downregulated Bim mRNA and protein expression level, indicating that miR-92a negatively regulates its expression at both levels. Silencing Bim decreases AZD6244-induced apoptosis and G1-phase arrest, suggesting that Bim contributes to the growth arrest. Thus, miR-92a mediates AZD6244-induced cytotoxicity of lymphoma cells by targeting Bim. Downregulation of miR-92a by AZD6244 is mediated by the ERK1/2-AP1 signalling pathway.

  18. Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells.

    Science.gov (United States)

    Ma, Li-Li; Wang, Da-Wei; Yu, Xu-Dong; Zhou, Yan-Ling

    2016-07-01

    Tangeretin (TANG), present in peel of citrus fruits, has been shown to various medicinal properties such as chemopreventive and neuroprotective. However, the chemopreventive effect of TANG on glioblastoma cells has not been examined. The present study was designed to explore the anticancer potential of TANG in glioblastoma cells and to investigate the related mechanism. Human glioblastoma U-87MG and LN-18 cells were treated with 45μM concentration of TANG and cell growth was measured by MTT assay. The cell cycle distribution and cell death were measured by flow cytometry. The expression of cell cycle and apoptosis related genes were analyzed by quantitative RT-PCR and western blot. The cells treated with TANG were significantly increased cell growth suppression and cell death effects than vehicle treated cells. Further, TANG treatment increases G2/M arrest and apoptosis by modulating PTEN and cell-cycle regulated genes such as cyclin-D and cdc-2 mRNA and protein expressions. Moreover, the ability of TANG to decrease cell growth and to induce cell death was compromised when PTEN was knockdown by siRNA. Taken together, the chemopreventive effect of TANG is associated with regulation of cell-cycle and apoptosis in glioblastoma, thereby attenuating glioblastoma cell growth. Hence, the present findings suggest that TANG may be a therapeutic agent for glioblastoma treatment.

  19. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase.

    Science.gov (United States)

    Inoue, Minoru; Yoshimura, Michio; Kobayashi, Minoru; Morinibu, Akiyo; Itasaka, Satoshi; Hiraoka, Masahiro; Harada, Hiroshi

    2015-10-27

    The cytotoxicity of ionizing radiation depends on the cell cycle phase; therefore, its pharmacological manipulation, especially the induction of cell cycle arrest at the radiosensitive mitotic-phase (M-phase), has been attempted for effective radiation therapy. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that functions in mitotic progression, and is now recognized as a potential target for radiosensitization. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating cell cycle phases of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. The TAK-960 treatment exhibited radiosensitizing effects in vitro, especially when it increased the proportion of M-phase cells. TAK-960 did not sensitize cancer cells to radiation when an insufficient amount of time was provided to induce mitotic arrest. The overexpression of a PLK1 mutant, PLK1-R136G&T210D, which was confirmed to cancel the TAK-960-mediated increase in the proportion of mitotic cells, abrogated the radiosensitizing effects of TAK-960. A tumor growth delay assay also demonstrated that the radiosensitizing effects of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis for targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatments.

  20. Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/m cell cycle arrest and apoptosis.

    Directory of Open Access Journals (Sweden)

    Hefen Sun

    Full Text Available The treatment of human hepatocellular carcinoma (HCC cell lines with (+-isocorydine, which was isolated and purified from Papaveraceae sp. plants, resulted in a growth inhibitory effect caused by the induction of G2/M phase cell cycle arrest and apoptosis. We report that isocorydine induces G2/M phase arrest by increasing cyclin B1 and p-CDK1 expression levels, which was caused by decreasing the expression and inhibiting the activation of Cdc25C. The phosphorylation levels of Chk1 and Chk2 were increased after ICD treatment. Furthermore, G2/M arrest induced by ICD can be disrupted by Chk1 siRNA but not by Chk2 siRNA. In addition, isocorydine treatment led to a decrease in the percentage of CD133(+ PLC/PRF/5 cells. Interestingly, isocorydine treatment dramatically decreased the tumorigenicity of SMMC-7721 and Huh7 cells. These findings indicate that isocorydine might be a potential therapeutic drug for the chemotherapeutic treatment of HCC.

  1. RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

    Science.gov (United States)

    Russo, P; Ottoboni, C; Crippa, A; Riou, J F; O'Connor, P M

    2001-04-01

    A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

  2. Tributyltin induces G2/M cell cycle arrest via NAD(+)-dependent isocitrate dehydrogenase in human embryonic carcinoma cells.

    Science.gov (United States)

    Asanagi, Miki; Yamada, Shigeru; Hirata, Naoya; Itagaki, Hiroshi; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

    2016-04-01

    Organotin compounds, such as tributyltin (TBT), are well-known endocrine-disrupting chemicals (EDCs). We have recently reported that TBT induces growth arrest in the human embryonic carcinoma cell line NT2/D1 at nanomolar levels by inhibiting NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the irreversible conversion of isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we examined whether TBT at nanomolar levels affects cell cycle progression in NT2/D1 cells. Propidium iodide staining revealed that TBT reduced the ratio of cells in the G1 phase and increased the ratio of cells in the G2/M phase. TBT also reduced cell division cycle 25C (cdc25C) and cyclin B1, which are key regulators of G2/M progression. Furthermore, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. The G2/M arrest induced by TBT was abolished by NAD-IDHα knockdown. Treatment with a cell-permeable α-ketoglutarate analogue recovered the effect of TBT, suggesting the involvement of NAD-IDH. Taken together, our data suggest that TBT at nanomolar levels induced G2/M cell cycle arrest via NAD-IDH in NT2/D1 cells. Thus, cell cycle analysis in embryonic cells could be used to assess cytotoxicity associated with nanomolar level exposure of EDCs.

  3. The use of COD and plastic instability in crack propagation and arrest in shells

    Science.gov (United States)

    Erdogan, F.; Ratwani, M.

    1974-01-01

    The initiation, growth, and possible arrest of fracture in cylindrical shells containing initial defects are dealt with. For those defects which may be approximated by a part-through semi-elliptic surface crack which is sufficiently shallow so that part of the net ligament in the plane of the crack is still elastic, the existing flat plate solution is modified to take into account the shell curvature effect as well as the effect of the thickness and the small scale plastic deformations. The problem of large defects is then considered under the assumptions that the defect may be approximated by a relatively deep meridional part-through surface crack and the net ligament through the shell wall is fully yielded. The results given are based on an 8th order bending theory of shallow shells using a conventional plastic strip model to account for the plastic deformations around the crack border.

  4. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  5. A Case of Morgagni Hernia Resulting with Respiratory Arrest

    Directory of Open Access Journals (Sweden)

    Cavit Çöl

    2011-05-01

    Full Text Available Morgagni’s hernia is seen at a rate of 3-4% among all diaphragmatic hernias. It develops from a defect in the pleuroperitoneal membrane. Herniation of the omentum is seen most commonly, that of the colon frequently, and herniation of small bowel and stomach is seen rarely. When being examined due to anemia and dyspnea, a 53-year-old male patient suffered from a respiratory arrest and was hence intubated and placed under treatment at the intensive care unit. On radiological examination, a giant diaphragmatic hernia was observed bilaterally, more marked on the right side. On laparotomy, especially on the right side, the caecum, the ascending colon, the transverse colon, the appendix, the omentum and part of the small bowel was seen to be herniated. Primary diaphragmatic repair + right hemicolectomy + end-to-end ileo-transversostomy was performed. We have reported this case because it was a giant hernia which caused respiratory arrest.

  6. Cardiac Arrest in a Pregnant Patient Diagnosed with Bochdalek Hernia

    Directory of Open Access Journals (Sweden)

    Pinar Karabacak

    2016-09-01

    Full Text Available Bochdalek hernia is thought to be the result of a defect of the pleuroperitoneal fold and the septum transversum fusion in the 8th week of gestation. The majority of these patients present with respiratory distress after delivery; asymptomatic progress until adulthood is an extremely rare clinical occurrence. The adult form of a Bochdalek hernia accompanying pregnancy is a rare entity. A 39-year-old, 24-week pregnant patient applied to Emergency service with epigastric pain and vomiting. Abdominal ultrasonography was planned due to the abdominal pain; sudden cardiopulmonary arrest occurred during the procedure. In this case report, congenital diaphragmatic hernia in a young pregnant woman who underwent cardiac arrest is presented.

  7. Arrested of coalescence of emulsion droplets of arbitrary size

    Science.gov (United States)

    Mbanga, Badel L.; Burke, Christopher; Blair, Donald W.; Atherton, Timothy J.

    2013-03-01

    With applications ranging from food products to cosmetics via targeted drug delivery systems, structured anisotropic colloids provide an efficient way to control the structure, properties and functions of emulsions. When two fluid emulsion droplets are brought in contact, a reduction of the interfacial tension drives their coalescence into a larger droplet of the same total volume and reduced exposed area. This coalescence can be partially or totally hindered by the presence of nano or micron-size particles that coat the interface as in Pickering emulsions. We investigate numerically the dependance of the mechanical stability of these arrested shapes on the particles size, their shape anisotropy, their polydispersity, their interaction with the solvent, and the particle-particle interactions. We discuss structural shape changes that can be induced by tuning the particles interactions after arrest occurs, and provide design parameters for the relevant experiments.

  8. Thermal Arrest Memory Effect in Ni-Mn-Ga Alloys

    Directory of Open Access Journals (Sweden)

    A. Rudajevova

    2008-01-01

    Full Text Available Dilatation characteristics were measured to investigate the thermal arrest memory effect in Ni53.6Mn27.1Ga19.3 and Ni54.2Mn29.4Ga16.4 alloys. Interruption of the martensite-austenite phase transformation is connected with the reduction of the sample length after thermal cycle. If a total phase transformation took place in the complete thermal cycle following the interruption, then the sample length would return to its original length. Analysis of these results has shown that the thermal arrest memory effect is a consequence of a stress-focusing effect and shape memory effect. The stress-focusing effect occurs when the phase transformation propagates radially in a cylindrical sample from the surface, inward to the center. Evolution and release of the thermoelastic deformations in both alloys during heating and cooling are analyzed.

  9. Anaphylaxis with Latrodectus Antivenin Resulting in Cardiac Arrest

    OpenAIRE

    Murphy, Christine M.; Hong, Jeannie J.; Beuhler, Michael C.

    2011-01-01

    Latrodectus mactans antivenin is a safe and effective therapy for severe black widow spider envenomations when given to most patients. We report a case of a 37-year-old male with a history of asthma that was given L. mactans antivenin for symptoms related to a black widow envenomation and developed a severe anaphylactic reaction resulting in cardiac arrest. When traditional therapies failed, the patient was given methylene blue for anaphylactic shock resulting in a 30-h period of hemodynamic ...

  10. Luminescence from Tube-Arrest Bubbles in Pure Glycerin

    Institute of Scientific and Technical Information of China (English)

    陈岐岱; 王龙

    2004-01-01

    Single transient cavitation bubble with luminescence has been generated in pure glycerin by using the ‘tube arrest'method. The analyses of high-speed photograph and light emission data suggest that the light emission would be a single bubble sonoluminescence. The luminescence pulse width is observed to wry from sub-nanosecond to about 30 ns. The width and intensity of luminescence pulses increases with the height of the liquid column height and decreases with the liquid temperature.

  11. Comments on metal oxide surge arresters surges energy absorption capacity

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, M.L.B. [Escola Federal de Engenharia de Itajuba, Minas Gerais (Brazil); Zanetta, L.C. Jr. [E. Politecnica Univ. de Sao Paulo, Sao Paulo (Brazil)

    1996-12-31

    This paper presents an approach to determine the energy absorption capacity of metal oxide surge arrester resistors. The proposed approach deals with the discharge current peak versus discharge current time relation. A testing method and a statistical evaluation are proposed. After determining the discharge current withstanding limit of the tested metal oxide resistors, the prospective energy absorption capacity limit is computed. Finally, comments on the obtained results are presented.

  12. Prognostic Value of Brain Diffusion Weighted Imaging After Cardiac Arrest

    Science.gov (United States)

    Wijman, Christine A.C.; Mlynash, Michael; Caulfield, Anna Finley; Hsia, Amie W.; Eyngorn, Irina; Bammer, Roland; Fischbein, Nancy; Albers, Gregory W.; Moseley, Michael

    2009-01-01

    Objective Outcome prediction is challenging in comatose post-cardiac arrest survivors. We assessed the feasibility and prognostic utility of brain diffusion-weighted MRI (DWI) during the first week. Methods Consecutive comatose post-cardiac arrest patients were prospectively enrolled. MRI data of patients who met predefined specific prognostic criteria were used to determine distinguishing ADC thresholds. Group 1: death at 6 months and absent motor response or absent pupillary reflexes or bilateral absent cortical responses at 72 hours, or vegetative at 1 month. Group 2A: Glasgow outcome scale (GOS) score of 4 or 5 at 6 months. Group 2B: GOS of 3 at 6 months. The percentage of voxels below different apparent diffusion coefficient (ADC) thresholds was calculated at 50 × 10−6 mm2/sec intervals. Results Overall, 86% of patients underwent MR imaging. Fifty-one patients with 62 brain MRIs were included in the analyses. Forty patients met the specific prognostic criteria. The percentage of brain volume with an ADC value below 650–700 × 10−6 mm2/sec best differentiated between group 1 and groups 2A and 2B combined (p<0.001), while the 400–450 × 10−6 mm2/sec threshold best differentiated between groups 2A and 2B (p=0.003). The ideal time window for prognostication using DWI was between 49 to 108 hours after the arrest. When comparing MRI in this time window with the 72 hour neurological examination MRI improved the sensitivity for predicting poor outcome by 38% while maintaining 100% specificity (p=0.021). Interpretation Quantitative DWI in comatose post-cardiac arrest survivors holds great promise as a prognostic adjunct. PMID:19399889

  13. Arresting Strategy Based on Dynamic Criminal Networks Changing over Time

    Directory of Open Access Journals (Sweden)

    Junqing Yuan

    2013-01-01

    Full Text Available We investigate a sequence of dynamic criminal networks on a time series based on the dynamic network analysis (DNA. According to the change of networks’ structure, networks’ variation trend is analyzed to forecast its future structure. Finally, an optimal arresting time and priority list are designed based on our analysis. Better results can be expected than that based on social network analysis (SNA.

  14. Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice.

    Science.gov (United States)

    Burkhardt, Sabrina; Borsos, Máté; Szydlowska, Anna; Godwin, Jonathan; Williams, Suzannah A; Cohen, Paula E; Hirota, Takayuki; Saitou, Mitinori; Tachibana-Konwalski, Kikuë

    2016-03-07

    Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation in mitosis and meiosis [1]. Rec8-containing cohesin, bound to Smc3/Smc1α or Smc3/Smc1β, maintains bivalent cohesion in mammalian meiosis [2-6]. In females, meiotic DNA replication and recombination occur in fetal oocytes. After birth, oocytes arrest at the prolonged dictyate stage until recruited to grow into mature oocytes that divide at ovulation. How cohesion is maintained in arrested oocytes remains a pivotal question relevant to maternal age-related aneuploidy. Hypothetically, cohesin turnover regenerates cohesion in oocytes. Evidence for post-replicative cohesion establishment mechanism exists, in yeast and invertebrates [7, 8]. In mouse fetal oocytes, cohesin loading factor Nipbl/Scc2 localizes to chromosome axes during recombination [9, 10]. Alternatively, cohesion is maintained without turnover. Consistent with this, cohesion maintenance does not require Smc1β transcription, but unlike Rec8, Smc1β is not required for establishing bivalent cohesion [11, 12]. Rec8 maintains cohesion without turnover during weeks of oocyte growth [3]. Whether the same applies to months or decades of arrest is unknown. Here, we test whether Rec8 activated in arrested mouse oocytes builds cohesion revealed by TEV cleavage and live-cell imaging. Rec8 establishes cohesion when activated during DNA replication in fetal oocytes using tamoxifen-inducible Cre. In contrast, no new cohesion is detected when Rec8 is activated in arrested oocytes by tamoxifen despite cohesin synthesis. We conclude that cohesion established in fetal oocytes is maintained for months without detectable turnover in dictyate-arrested oocytes. This implies that women's fertility depends on the longevity of cohesin proteins that established cohesion in utero.

  15. Effect of walking stress on growth, physiological adaptability and endocrine responses in Malpura ewes in a semi-arid tropical environment

    Science.gov (United States)

    Sejian, Veerasamy; Maurya, Vijai P.; Naqvi, Syed M. K.

    2012-03-01

    Sheep in hot semi-arid environments are mostly reared using extensive systems. In addition to thermal stress and feed scarcity, the animals need to walk long distances for grazing in this ecological zone. A study was conducted to assess the effect of long-distance walking on adaptive capability in terms of physiological, biochemical and endocrine responses in Malpura ewes. Fourteen adult Malpura non-pregnant ewes weighing between 33 and 35 kg were used in the study. The ewes were randomly allocated into two groups of seven animals each: GI ( n = 7; Control), and GII ( n = 7; walking stress). The animals were stall-fed with a diet consisting of 70% roughage and 30% concentrate. Both GI and GII ewes had uniform access to feed and water. The walking stress group (GII) ewes were made to walk 14 km in two spans between 0900 and 1500 hours with 1 h 30 min for each span (7 km) of walking. The ewes subjected to walking stress (GII) were prevented from grazing by applying a face mask made of cotton thread. The study was conducted for a period of two estrous cycles (35 days) during the autumn season (October-November). Physiological responses were recorded twice daily at 0800 and 1400 hours at weekly intervals. Blood samples were collected from the jugular vein at weekly intervals to study the effects of walking stress on blood biochemical and endocrine parameters. The results indicate that walking stress had significant ( P stress did not influence the reproductive hormone levels. The significant changes in RR, RT, plasma cortisol, T3 and T4 show that Malpura ewes have the capability to adapt to long-distance walking, and that adrenal and thyroid gland hormones play a significant role in such adaptation.

  16. Resource allocation among sexual, clonal reproduction and vegetative growth of two Potamogeton species and their hybrid:Adaptability of the hybrid in relation to its parents

    Institute of Scientific and Technical Information of China (English)

    Fan LIU; Xiao-Lin ZHANG; Qing-Feng WANG; Hui LIU; Guang-Xi WANG; Wei LI

    2013-01-01

    Resource allocation,as well as the tradeoffs among different reproductive components,plays an important role in the adaptability of plants to different environments.The hybrid may exhibit a higher adaptability in life history in heterogeneous environments because of the genetic variation derived from its parents.In this study,we exploited three levels of water depths and two types of sediments to investigate the resource allocation pattern of the first generation of the natural hybrid Potamogeton × intortifolius compared to its parents P.wrightii and P.perfoliatus.We also measured the ramet survivorship and the seed set of the hybrid P.× intortifolius.Our results showed that P.×intortifolius had higher ramet survival than its parents at 1.5-m water depth on clay sediment.The possible tradeoffs showed that in P.×intortifolius the tradeoff pattern between sexual and clonal reproduction was more pronounced in limiting environments.The individuals allocated more resources to sexual reproduction when the environment was limiting,which might confer a higher ability to utilize resources,to produce offspring and to found new populations.Although the seed set of P.×intortifolius was lower than its parents,it had a higher ability to increase its seed set when the environment was limiting (sandy sediment) than its parents,which might benefit its future survival.These results indicated that the F1 hybrid P.×intortifolius was more able to adapt to limiting environments than one or both of its two parental taxa.

  17. Use of Adaptive Laboratory Evolution To Discover Key Mutations Enabling Rapid Growth of Escherichia coli K-12 MG1655 on Glucose Minimal Medium

    DEFF Research Database (Denmark)

    LaCroix, Ryan A.; Sandberg, Troy E.; O'Brien, Edward J.;

    2015-01-01

    using a gene classification system alone. The methods described here represent a powerful combination of technologies to increase the speed and efficiency of ALE studies. The identified mutations can be examined as genetic parts for increasing growth rate in a desired strain and for understanding rapid...

  18. A large specific deterrent effect of arrest for patronizing a prostitute.

    Directory of Open Access Journals (Sweden)

    Devon D Brewer

    Full Text Available BACKGROUND: Prior research suggests that arrest, compared with no police detection, of some types of offenders does not decrease the chances they will reoffend. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the specific deterrent effect of arrest for patronizing a street prostitute in Colorado Springs by comparing the incidence of arrest for clients of prostitutes first detected through public health surveillance with the incidence of rearrest for clients first detected by police arrest. Although these sets of clients were demographically and behaviorally similar, arrest reduced the likelihood of a subsequent arrest by approximately 70%. In other areas of the United States, arrest did not appear to displace a client's patronizing. CONCLUSIONS/SIGNIFICANCE: Our results suggest that apprehending clients decreases their patronizing behavior substantially.

  19. The European integration in criminal field the European arrest warrant

    Directory of Open Access Journals (Sweden)

    Palmieri Marco

    2005-01-01

    Full Text Available The author deals with some thesis in connection with the European arrest warrant experience, what will be an interesting test for many EU countries. It affects prerogatives always reserved to state-power and main expression of national sovereignty. Anyway, bringing up to the theoretical elaboration of the so-called "third pillar", it needs to set them in action, and verify if European states are really willing to create a common juridical space putting apart claims and prejudices. Most of appraisals addressed to European arrest warrant seem to repudiate just the principle of mutual confidence in respective judiciary systems, principle the new form of cooperation is based on. Briefly, they assert a decision issued by another Member State wouldn't assure all guarantees as own juridical system. Reform would surely have been more effective and consistent if, before creating a common procedure substantial rules were set. European arrest warrant was born in order to replace the long and complex extradition system with a quick and effective tool, fit for contrasting new forms of criminality, that are able to profit boundary openings in order to escape justice.

  20. Out-of-hospital therapeutic hypothermia in cardiac arrest victims

    Directory of Open Access Journals (Sweden)

    Holzer Michael

    2009-10-01

    Full Text Available Abstract Despite many years of research, outcome after cardiac arrest is dismal. Since 2005, the European Resuscitation Council recommends in its guidelines the use of mild therapeutic hypothermia (32-34° for 12 to 24 hours in patients successfully resuscitated from cardiac arrest. The benefit of resuscitative mild hypothermia (induced after resuscitation is well established, while the benefit of preservative mild to moderate hypothermia (induced during cardiac arrest needs further investigation before recommending it for clinical routine. Animal data and limited human data suggest that early and fast cooling might be essential for the beneficial effect of resuscitative mild hypothermia. Out-of-hospital cooling has been shown to be feasible and safe by means of intravenous infusion with cold fluids or non-invasively with cooling pads. A combination of these cooling methods might further improve cooling efficacy. If out-of-hospital cooling will further improve functional outcome as compared with in-hospital cooling needs to be determined in a prospective, randomised, sufficiently powered clinical trial.

  1. ADAPT Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Diagnostics and Prognostics Testbed (ADAPT) Project Lead: Scott Poll Subject Fault diagnosis in electrical power systems Description The Advanced...

  2. The pRB-related protein p107 contains two growth suppression domains : independent interactions with E2F and cyclin/cdk complexes

    NARCIS (Netherlands)

    Zhu, L.; Enders, G.; Lees, J.A.; Beijersbergen, R.L.; Bernards, R.A.; Harlow, E.

    1995-01-01

    Unregulated expression of either the retinoblastoma protein (pRB) or the related protein p107 can cause growth arrest of sensitive cells in the G1 phase of the cell cycle. However, growth arrests mediated by p107 and pRB are not identical. Through structure-function and co-expression analyses we hav

  3. Critical Role Played by Cyclin D3 in the MyoD-Mediated Arrest of Cell Cycle during Myoblast Differentiation

    OpenAIRE

    1999-01-01

    During the terminal differentiation of skeletal myoblasts, the activities of myogenic factors regulate not only tissue-specific gene expressions but also the exit from the cell cycle. The induction of cell cycle inhibitors such as p21 and pRb has been shown to play a prominent role in the growth arrest of differentiating myoblasts. Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and wit...

  4. Arrest of Avalanche Propagation by Discontinuities on Snow Cover

    Science.gov (United States)

    Frigo, B.; Chiaia, B.

    2009-04-01

    Considering the spatial variability of the snow cover, the paper analyses, in the framework of Fracture Mechanics, the Mode II fracture propagation on snow cover that leads to large dry slab avalanches. Under the hypothesis of a perfectly brittle phenomenon, avalanche triggering is usually investigated numerically by means of Linear Elastic Fracture Mechanics (McClung, 1979; Chiaia et al., 2008). Since, however, the real phenomenon is intrinsically dynamical, another aspect to investigate is represented by dynamic fracture propagation. In this paper, we model dynamic crack propagation into a dry snow slab, to assess the possibility of crack arrest due to the presence of weak zones distributed along the snow slope. As a consequence of the first triggering mechanism (the Mode II fracture propagation on the weak plane), the secondary Mode I crack propagation in the crown is studied by means of numerical simulations based on Dynamic Elastic Fracture Mechanics and on the theory of crack arresters. By taking into account kinetic energy and using the FEM software FRANC 2D (Wawrzynek and Ingraffea, 1993), several paths of crown fracture propagation and their stability have been investigated. The snowpack is considered as a linear-elastic plate (2D problem), whose physical and mechanical parameters are chosen according to classical literature values. To investigate the possible arrest of crown fracture, we apply the theory of crack arresters, usually adopted for pipelines and perforated steel sheets fracture problems. To study crack arrest, different crack paths are simulated, in discontinuous (equipped with different shapes and geometries of artificial voids) snowpacks. The simulations show the effectiveness of these weak zones, to reduce substantially the crack driving force of the propagating fracture. This means that, increasing spatial variability tends to stabilize the snow slope, eventually splitting a major avalanche event into smaller, independent avalanches. Our

  5. Correction of severe wrist deformity following physeal arrest of the distal radius with the aid of a three-dimensional computer simulation.

    Science.gov (United States)

    Murase, Tsuyoshi; Oka, Kunihiro; Moritomo, Hisao; Goto, Akira; Sugamoto, Kazuomi; Yoshikawa, Hideki

    2009-11-01

    Growth arrest following physeal injury may result in severe limb deformity. We report a case of complex wrist deformity caused by injury to the distal radial physis resulting in radial shortening and abnormal inclination of the radial articular surface, which was successfully treated by gradual correction after computer simulation. The simulation enabled us to develop an appropriate operative plan by accurately calculating the axis of the three-dimensional (3D) deformity using computer bone models. In the simulative surgery with a full-size stereolithography bone model, an Ilizarov external fixator was applied to the radius such that its two hinges were located on the virtual axis of the deformity, which was reproduced in the actual surgery. This technique of 3D computer simulation is a useful alternative to plan accurate correction of complex limb deformities following growth arrest.

  6. Cardiac arrests in patients undergoing gastrointestinal endoscopy: A retrospective analysis of 73,029 procedures

    Directory of Open Access Journals (Sweden)

    Basavana Goudra

    2015-01-01

    Full Text Available Background/Aims: Airway difficulties leading to cardiac arrest are frequently encountered during propofol sedation in patients undergoing gastrointestinal (GI endoscopy. With a noticeable increase in the use of propofol for endoscopic sedation, we decided to examine the incidence and outcome of cardiac arrests in patients undergoing gastrointestinal (GI endoscopy with sedation. Patients and Methods: In this retrospective study, cardiac arrest data obtained from the clinical quality improvement and local registry over 5 years was analyzed. The information of patients who sustained cardiac arrest attributable to sedation was studied in detail. Analysis included comparison of cardiac arrests due to all causes until discharge (or death versus the cardiac arrests and death occurring during the procedure and in the recovery area. Results: The incidence of cardiac arrest and death (all causes, until discharge was 6.07 and 4.28 per 10,000 in patients sedated with propofol, compared with non–propofol-based sedation (0.67 and 0.44. The incidence of cardiac arrest during and immediately after the procedure (recovery area for all endoscopies was 3.92 per 10,000; of which, 72% were airway management related. About 90.0% of all peri-procedural cardiac arrests occurred in patients who received propofol. Conclusions: The incidence of cardiac arrest and death is about 10 times higher in patients receiving propofol-based sedation compared with those receiving midazolam–fentanyl sedation. More than two thirds of these events occur during EGD and ERCP.

  7. Adaptive, growth-oriented, and positive perceptions of mother-daughter elder caregiving relationships: a path-analytic investigation of predictors.

    Science.gov (United States)

    Hollis-Sawyer, L A

    2001-01-01

    One hundred twenty-two pairs (n = 244) of filial caregivers (daughters) and care recipients (mothers) were interviewed separately, to investigate the factors underlying positive, growth-oriented caregiving relationships. The outcome variable examined was the type of caregiving pair (positive, negative, mixed, and neutral), as determined by "blind" raters. Based on existing research, factors examined as being significant predictors of this outcome variable were perceived roles (role changes, role relations) and individual-difference characteristics (personality dimensions, fluid intellectual ability). The results of the path model tested support the importance of individual-difference factors in understanding positive mother-daughter elder caregiving relationships.

  8. The effect of the siliceous composites of rice husk and green tea on growth and development of Fragaria × ananassa Duch. regenerants during the adaptation to ex vitro conditions

    Directory of Open Access Journals (Sweden)

    E. V. Ambros

    2015-10-01

    Full Text Available The effect of the composites of rice husk and green tea derived by mechanochemical method on growth and development of 6 cultivars of F. × ananassa Duch. during the adaptation to ex vitro conditions has been studied for the first time. The stimulating action of composite on both increment of the above-ground mass, and formation of the root system was revealed. The height of the rosette relative to the control was reliably increased by 1.3–4.1 times, the length of the root system – 1.1–2.0 times, the number of roots – 1.3–1.8 depending on the genotype.DOI: 10.14258/turczaninowia.18.3.5

  9. Cell cycle arrest by prostaglandin A1 at the G1/S phase interface with up-regulation of oncogenes in S-49 cyc- cells

    Science.gov (United States)

    Hughes-Fulford, M.

    1994-01-01

    Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the -49 lymphoma variant (cyc-) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc- cells. DNA synthesis is inhibited 42% by dmPGA1 (50 microM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the alpha, beta unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc- cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30-50 microns) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc- cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block.(ABSTRACT TRUNCATED AT 250 WORDS).

  10. Mutations in the Arabidopsis homolog of LST8/GβL, a partner of the target of Rapamycin kinase, impair plant growth, flowering, and metabolic adaptation to long days.

    Science.gov (United States)

    Moreau, Manon; Azzopardi, Marianne; Clément, Gilles; Dobrenel, Thomas; Marchive, Chloé; Renne, Charlotte; Martin-Magniette, Marie-Laure; Taconnat, Ludivine; Renou, Jean-Pierre; Robaglia, Christophe; Meyer, Christian

    2012-02-01

    The conserved Target of Rapamycin (TOR) kinase forms high molecular mass complexes and is a major regulator of cellular adaptations to environmental cues. The Lethal with Sec Thirteen 8/G protein β subunit-like (LST8/GβL) protein is a member of the TOR complexes, and two putative LST8 genes are present in Arabidopsis thaliana, of which only one (LST8-1) is significantly expressed. The Arabidopsis LST8-1 protein is able to complement yeast lst8 mutations and interacts with the TOR kinase. Mutations in the LST8-1 gene resulted in reduced vegetative growth and apical dominance with abnormal development of flowers. Mutant plants were also highly sensitive to long days and accumulated, like TOR RNA interference lines, higher amounts of starch and amino acids, including proline and glutamine, while showing reduced concentrations of inositol and raffinose. Accordingly, transcriptomic and enzymatic analyses revealed a higher expression of genes involved in nitrate assimilation when lst8-1 mutants were shifted to long days. The transcriptome of lst8-1 mutants in long days was found to share similarities with that of a myo-inositol 1 phosphate synthase mutant that is also sensitive to the extension of the light period. It thus appears that the LST8-1 protein has an important role in regulating amino acid accumulation and the synthesis of myo-inositol and raffinose during plant adaptation to long days.

  11. Sulforaphane, a Dietary Isothiocyanate, Induces G2/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association

    Science.gov (United States)

    Cheng, Ya-Min; Tsai, Ching-Chou; Hsu, Yi-Chiang

    2016-01-01

    Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN) is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G2/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa). We found that cytotoxicity is associated with an accumulation of cells in the G2/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G2/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins. PMID:27626412

  12. Sulforaphane, a Dietary Isothiocyanate, Induces G2/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association

    Directory of Open Access Journals (Sweden)

    Ya-Min Cheng

    2016-09-01

    Full Text Available Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G2/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa. We found that cytotoxicity is associated with an accumulation of cells in the G2/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G2/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins.

  13. Analyses of Adaptation, Growth and Ornamental Value of 9 Eucalyptus Species%9种观赏性桉树引种试验分析

    Institute of Scientific and Technical Information of China (English)

    王楚彪; 刘丽婷; 武海霞; 莫晓勇

    2013-01-01

    Seedlings from 20 families representing 9 species of ornamental Eucalyptus were established at 3 experimental field sites .At age two -year these trials were analyzed for growth and survival - including caus-es of mortality -and this provided the basis for evaluating families and species on their ornamental value . The species with acceptable survival and growth were then further investigated in a second assessment , with traits being analyzed , in order to provide a scientific basis for introduction of ornamental Eucalyptus in future .%  通过育苗与栽种,对9种20个家系的观赏性桉树在3个试验地进行引种试验,经过调查,分析栽种2年来的生长情况,总结引种桉树成活率不高的原因,初步筛选出具观赏价值的树种,进行第2次调查,分析其性状,为今后观赏桉树的继续引种提供依据。

  14. Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer.

    Science.gov (United States)

    Milagre, Carla S; Gopinathan, Ganga; Everitt, Gemma; Thompson, Richard G; Kulbe, Hagen; Zhong, Haihong; Hollingsworth, Robert E; Grose, Richard; Bowtell, David D L; Hochhauser, Daniel; Balkwill, Frances R

    2015-04-01

    Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer.

  15. Haemophilus ducreyi Seeks Alternative Carbon Sources and Adapts to Nutrient Stress and Anaerobiosis during Experimental Infection of Human Volunteers.

    Science.gov (United States)

    Gangaiah, Dharanesh; Zhang, Xinjun; Baker, Beth; Fortney, Kate R; Gao, Hongyu; Holley, Concerta L; Munson, Robert S; Liu, Yunlong; Spinola, Stanley M

    2016-05-01

    Haemophilus ducreyi causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans, H. ducreyi resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014, http://dx.doi.org/10.1128/mBio.01081-13) suggested that H. ducreyi encounters growth conditions in human lesions resembling those found in stationary phase. However, how H. ducreyi transcriptionally responds to stress during human infection is unknown. Here, we determined the H. ducreyi transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the in vivo transcriptome is distinct from those of in vitro growth. Compared to the inoculum (mid-log-phase bacteria), H. ducreyi harvested from pustules differentially expressed ∼93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (l-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis. H. ducreyi upregulated few genes (hgbA, flp-tad, and lspB-lspA2) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed in vivo, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans.

  16. Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells.

    Science.gov (United States)

    Park, Cheol; Choi, Young-Whan; Hyun, Sook Kyung; Kwon, Hyun Ju; Hwang, Hye Jin; Kim, Gi-Young; Choi, Byung Tae; Kim, Byung-Woo; Choi, Il-Whan; Moon, Sung-Kwon; Kim, Wun-Jae; Choi, Yung Hyun

    2009-10-01

    We isolated two phytochemical lignans, schisandrin and schisandrin C, from Schizandra chinensis Baill and investigated their anti-cancer effects in human leukemia U937 cells. Schisandrin C inhibited cell growth in a dose-dependent manner, which was associated with the induction of G1 arrest of the cell cycle and apoptosis; schisandrin did not inhibit growth. Schisandrin C induced G1 arrest was correlated with down-regulation of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk) 4 and E2Fs expression, inhibition of phosphorylation of retinoblastoma protein (pRB), and up-regulation of the Cdk inhibitor p21(WAF1/CIP1). In addition, schisandrin C-induced apoptosis was associated with down-regulation of expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, proteolytic activation of caspase-3 and -9, and a concomitant degradation of poly(ADP-ribose) polymerase (PARP). Furthermore, schisandrin C-induced apoptosis was significantly inhibited by a caspase-3 specific inhibitor z-DEVD-fmk, indicating an important role for caspase-3 in the schisandrin C mechanism. In summary, growth inhibition by schisandrin C is related to cell cycle arrest at G1 and induction of caspase-3-dependent apoptosis in U937 cells; these findings suggest that schisandrin C may be a useful chemotherapeutic agent.

  17. Induction of G1 Cell Cycle Arrest in Human Glioma Cells by Salinomycin Through Triggering ROS-Mediated DNA Damage In Vitro and In Vivo.

    Science.gov (United States)

    Zhao, Shi-Jun; Wang, Xian-Jun; Wu, Qing-Jian; Liu, Chao; Li, Da-Wei; Fu, Xiao-Ting; Zhang, Hui-Fang; Shao, Lu-Rong; Sun, Jing-Yi; Sun, Bao-Liang; Zhai, Jing; Fan, Cun-Dong

    2016-12-19

    Chemotherapy has always been one of the most effective ways in combating human glioma. However, the high metastatic potential and resistance toward standard chemotherapy severely hindered the chemotherapy outcomes. Hence, searching effective chemotherapy drugs and clarifying its mechanism are of great significance. Salinomycin an antibiotic shows novel anticancer potential against several human tumors, including human glioma, but its mechanism against human glioma cells has not been fully elucidated. In the present study, we demonstrated that salinomycin treatment time- and dose-dependently inhibited U251 and U87 cells growth. Mechanically, salinomycin-induced cell growth inhibition against human glioma was mainly achieved by induction of G1-phase arrest via triggering reactive oxide species (ROS)-mediated DNA damage, as convinced by the activation of histone, p53, p21 and p27. Furthermore, inhibition of ROS accumulation effectively attenuated salinomycin-induced DNA damage and G1 cell cycle arrest, and eventually reversed salinomycin-induced cytotoxicity. Importantly, salinomycin treatment also significantly inhibited the U251 tumor xenograft growth in vivo through triggering DNA damage-mediated cell cycle arrest with involvement of inhibiting cell proliferation and angiogenesis. The results above validated the potential of salinomycin-based chemotherapy against human glioma.

  18. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2014-01-01

    growing planktonic cells, voriconazole had limited antifungal activity, flucytosine was fungistatic, caspofungin and amphotericin B were fungicidal. In growth-arrested cells, only amphotericin B had antifungal activity. Confocal microscopy and colony count viability assays revealed that the response...

  19. Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line

    Institute of Scientific and Technical Information of China (English)

    Jing-Pin Lin; Jai-Sing Yang; Jau-Hong Lee; Wen-Tsong Hsieh; Jing-Gung Chung

    2006-01-01

    AIM: To investigate the relationship between the inhibited growth (cytotoxic activity) of berberine and apoptotic pathway with its molecular mechanism of action.METHODS: The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group (apoptosis) were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting.RESULTS: For SNU-5 cell line, the IC (50) was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis.CONCLUSION: Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

  20. Toothbrush Adaptations.

    Science.gov (United States)

    Exceptional Parent, 1987

    1987-01-01

    Suggestions are presented for helping disabled individuals learn to use or adapt toothbrushes for proper dental care. A directory lists dental health instructional materials available from various organizations. (CB)

  1. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    We investigate why some exchange relationships terminate prematurely. We argue that investments in informal governance structures induce premature termination in relationships already governed by formal contracts. The formalized adaptive behavior of formal governance structures and the flexible a...

  2. Case study: flame arresters and exploding gasoline containers.

    Science.gov (United States)

    Hasselbring, Lori C

    2006-03-17

    This paper describes the case study of a portable plastic gasoline container explosion and fire. While working at home on a science project to determine the burn rates of different types of wood fuel, a 14-year-old boy was severely burned after flames traveled back up into the portable gasoline container and exploded. A witness heard the explosion and reports that the flames went perhaps 10 ft in the air. It is shown by experimentation that a flame arrester installed in the pour opening of the portable gasoline container would have prevented an explosion inside the gasoline container.

  3. The inflammatory marker suPAR after cardiac arrest

    DEFF Research Database (Denmark)

    Rundgren, Malin; Lyngbaek, Stig; Fisker, Helle;

    2015-01-01

    BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is released in response to inflammatory stimuli, and plasma levels are associated with long-term outcomes. The ischemia/reperfusion injury caused by cardiac arrest (CA) and resuscitation triggers an inflammatory response...... analysis shoved an AUC of 0.76 at 6 hours. In the subgroup of CA of cardiac cause, the AUC was 0.84. CONCLUSION: suPAR levels at 6 and 36 hours after CA were significantly higher in nonsurviving patients compared with survivors; however, the overlap in suPAR levels between the outcome groups...

  4. Adulthood animal abuse among men arrested for domestic violence.

    Science.gov (United States)

    Febres, Jeniimarie; Brasfield, Hope; Shorey, Ryan C; Elmquist, Joanna; Ninnemann, Andrew; Schonbrun, Yael C; Temple, Jeff R; Recupero, Patricia R; Stuart, Gregory L

    2014-09-01

    Learning more about intimate partner violence (IPV), perpetrators could aid the development of more effective treatments. The prevalence of adulthood animal abuse (AAA) perpetration and its association with IPV perpetration, antisociality, and alcohol use in 307 men arrested for domestic violence were examined. Forty-one percent (n = 125) of the men committed at least one act of animal abuse since the age of 18, in contrast to the 1.5% prevalence rate reported by men in the general population. Controlling for antisociality and alcohol use, AAA showed a trend toward a significant association with physical and severe psychological IPV perpetration.

  5. [Cardiac arrest in newborn of mother treated with labetalol].

    Science.gov (United States)

    Sala, X; Monsalve, C; Comas, C; Botet, F; Nalda, M A

    1993-01-01

    The use of beta-adrenergic antagonists for the control of high blood pressure associated to pregnancy is frequent. Their use is related with the appearance of undesirable effects of the fetus. The case of neonatal cardiac arrest attributed, to the administration of labetalol to the mother is presented. The high transplacentary passage, the different pharmacokinetics of the drug in the newborn and the clinical evolution of the patient suggests its involvement. It is concluded that labetalol may cause severe undesirable effects in newborns and fetal heart rate of the mother and neonate should be monitored upon use of this drug.

  6. Hedonic "adaptation"

    OpenAIRE

    2008-01-01

    People live in a world in which they are surrounded by potential disgust elicitors such as ``used'' chairs, air, silverware, and money as well as excretory activities. People function in this world by ignoring most of these, by active avoidance, reframing, or adaptation. The issue is particularly striking for professions, such as morticians, surgeons, or sanitation workers, in which there is frequent contact with major disgust elicitors. In this study, we study the ``adaptation'' process to d...

  7. Strategic Adaptation

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related...... concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation...

  8. Effectiveness of installing two pairs of distribution surge arresters in parallel

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, Hitoshi; Asakawa, Akira; Yokoyama, Shigeru [Central Research Institute of Electric Power Industry (Japan); Nakada, Kazuo [Hokurika Electric Power Co. (Japan)

    1999-07-01

    Lightning strokes with a l