Mechanistic study of DNA damage and radioprotection of small molecule treatment in the irradiated proliferating and quiescent human lung fibroblast cells

International Nuclear Information System (INIS)

Dai, Jiawen; Baskar, Rajamanickam

2014-01-01

Ionizing radiation is an invaluable diagnostic and treatment tool used in various clinical applications and also in cancer control. However, assessing normal tissue injury is of a great interest. Since radiation sensitivity varies with different phases of cell cycle, understanding how these cells differ in their sensitivity will help to prevent or reduce the radiation injury. We have used both proliferating and quiescent human normal lung fibroblast cells and investigated key proteins involved in the cell cycle, DNA damage and death, further the radioprotective role of small molecule after low doses (d ≤1Gy) of radiation exposure. Among the cell cycle/death proteins investigated, p53 and phosphorylation of p53 (Ser-15) were induced in both the proliferating and quiescent phases of cells when studied at different time intervals. In the proliferating cells after irradiation along with p53, cyclin dependent kinase (CDK) inhibitors p21, p27 were induced. However, similarly in the quiescent cells along with the p53, p21 and p27 were also induced. The DNA damage assessed by phosphorylation of histone H2AX expression showed an increase even in the non-dividing quiescent cells after 1 Gy of radiation exposure. Whereas cell cycle proteins Cyclin A and E and cell death proteins Bax and cytochrome-c did not show any increase in the quiescent cells. In conclusion, human normal lung fibroblast cells that are not actively dividing are also showed similar radiation response as of proliferating cells. Furthermore, proliferating and quiescent cells treated with small molecules attenuate p53 and its downstream target protein p21 indicating radioprotection of the cells. The specific activation of p53, phosphorylation of p53 (Ser-15), p21 and phosphorylation of histone H2AX following radiation doses of d ≤ 1 Gy in the quiescent cells demonstrated in this study may give us a better understanding about the radiation response of non-dividing fibroblast cells, which is present in many

Tracking and Finding Slow-Proliferating/Quiescent Cancer Stem Cells with Fluorescent Nanodiamonds.

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Lin, Hsin-Hung; Lee, Hsiao-Wen; Lin, Ruey-Jen; Huang, Chih-Wei; Liao, Yi-Chun; Chen, Yit-Tsong; Fang, Jim-Min; Lee, Te-Chang; Yu, Alice L; Chang, Huan-Cheng

2015-09-09

Quiescent cancer stem cells (CSCs) have long been considered to be a source of tumor initiation. However, identification and isolation of these cells have been hampered by the fact that commonly used fluorescent markers are not sufficiently stable, both chemically and photophysically, to allow tracking over an extended period of time. Here, it is shown that fluorescent nanodiamonds (FNDs) are well suited for this application. Genotoxicity tests of FNDs with comet and micronucleus assays for human fibroblasts and breast cancer cells indicate that the nanoparticles neither cause DNA damage nor impair cell growth. Using AS-B145-1R breast cancer cells as the model cell line for CSC, it is found that the FND labeling outperforms 5-ethynyl-2'-deoxyuridine (EdU) and carboxyfluorescein diacetate succinimidyl ester (CFSE) in regards to its long-term tracking capability (>20 d). Moreover, through a quantification of their stem cell activity by measuring mammosphere-forming efficiencies (MFEs) and self-renewal rates, the FND-positive cells are identified to have an MFE twice as high as that of the FND-negative cells isolated from the same dissociated mammospheres. Thus, the nanoparticle-based labeling technique provides an effective new tool for tracking and finding slow-proliferating/quiescent CSCs in cancer research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distinct cell stress responses induced by ATP restriction in quiescent human fibroblasts

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Nirupama Yalamanchili

2016-10-01

Full Text Available Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly little is known about how quiescent cells respond to energetic and metabolic challenges. To better understand compensatory responses of quiescent cells to metabolic stress, we established, in human primary dermal fibroblasts, an experimental ‘energy restriction’ model. Quiescence was achieved by short-term culture in serum-deprived media and ATP supply restricted using a combination of glucose transport inhibitors and mitochondrial uncouplers. In aggregate, these measures led to markedly reduced intracellular ATP levels while not compromising cell viability over the observation period of 48 h. Analysis of the transcription factor landscape induced by this treatment revealed alterations in several signal transduction nodes beyond the expected biosynthetic adaptations. These included increased abundance of NF-κB regulated transcription factors and altered transcription factor subsets regulated by Akt and p53. The observed changes in gene regulation and corresponding alterations in key signaling nodes are likely to contribute to cell survival at intracellular ATP concentrations substantially below those achieved by growth factor deprivation alone. This experimental model provides a benchmark for the investigation of cell survival pathways and related molecular targets that are associated with restricted energy supply associated with biological aging and metabolic diseases.

The mTOR inhibitor, everolimus (RAD001), overcomes resistance to imatinib in quiescent Ph-positive acute lymphoblastic leukemia cells

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Kuwatsuka, Y; Minami, M; Minami, Y; Sugimoto, K; Hayakawa, F; Miyata, Y; Abe, A; Goff, D J; Kiyoi, H; Naoe, T

2011-01-01

In Ph-positive (Ph + ) leukemia, the quiescent cell state is one of the reasons for resistance to the BCR-ABL-kinase inhibitor, imatinib. In order to examine the mechanisms of resistance due to quiescence and the effect of the mammalian target of rapamycin inhibitor, everolimus, for such a resistant population, we used Ph + acute lymphoblastic leukemia patient cells serially xenotransplanted into NOD/SCID/IL2rγ null (NOG) mice. Spleen cells from leukemic mice showed a higher percentage of slow-cycling G 0 cells in the CD34 + CD38 − population compared with the CD34 + CD38 + and CD34 − populations. After ex vivo imatinib treatment, more residual cells were observed in the CD34 + CD38 − population than in the other populations. Although slow-cycling G 0 cells were insensitive to imatinib in spite of BCR-ABL and CrkL dephosphorylation, combination treatment with everolimus induced substantial cell death, including that of the CD34 + CD38 − population, with p70-S6 K dephosphorylation and decrease of MCL-1 expression. The leukemic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse system with the in vivo combination treatment with imatinib and everolimus showed a decrease of tumor burden including CD34 + cells. These results imply that treatment with everolimus can overcome resistance to imatinib in Ph + leukemia due to quiescence

Identification of quiescent, stem-like cells in the distal female reproductive tract.

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Yongyi Wang

Full Text Available In fertile women, the endometrium undergoes regular cycles of tissue build-up and regression. It is likely that uterine stem cells are involved in this remarkable turn over. The main goal of our current investigations was to identify slow-cycling (quiescent endometrial stem cells by means of a pulse-chase approach to selectively earmark, prospectively isolate, and characterize label-retaining cells (LRCs. To this aim, transgenic mice expressing histone2B-GFP (H2B-GFP in a Tet-inducible fashion were administered doxycycline (pulse which was thereafter withdrawn from the drinking water (chase. Over time, dividing cells progressively loose GFP signal whereas infrequently dividing cells retain H2B-GFP expression. We evaluated H2B-GFP retaining cells at different chase time points and identified long-term (LT; >12 weeks LRCs. The LT-LRCs are negative for estrogen receptor-α and express low levels of progesterone receptors. LRCs sorted by FACS are able to form spheroids capable of self-renewal and differentiation. Upon serum stimulation spheroid cells are induced to differentiate and form glandular structures which express markers of mature műllerian epithelial cells. Overall, the results indicate that quiescent cells located in the distal oviduct have stem-like properties and can differentiate into distinct cell lineages specific of endometrium, proximal and distal oviduct. Future lineage-tracing studies will elucidate the role played by these cells in homeostasis, tissue injury and cancer of the female reproductive tract in the mouse and eventually in man.

The mTOR inhibitor, everolimus (RAD001), overcomes resistance to imatinib in quiescent Ph-positive acute lymphoblastic leukemia cells

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Kuwatsuka, Y; Minami, M; Minami, Y; Sugimoto, K; Hayakawa, F; Miyata, Y; Abe, A [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Goff, D J [Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA (United States); Kiyoi, H [Department of Infectious Diseases, Nagoya University Hospital, Nagoya (Japan); Naoe, T [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan)

2011-05-01

In Ph-positive (Ph{sup +}) leukemia, the quiescent cell state is one of the reasons for resistance to the BCR-ABL-kinase inhibitor, imatinib. In order to examine the mechanisms of resistance due to quiescence and the effect of the mammalian target of rapamycin inhibitor, everolimus, for such a resistant population, we used Ph{sup +} acute lymphoblastic leukemia patient cells serially xenotransplanted into NOD/SCID/IL2rγ{sup null} (NOG) mice. Spleen cells from leukemic mice showed a higher percentage of slow-cycling G{sub 0} cells in the CD34{sup +}CD38{sup −} population compared with the CD34{sup +}CD38{sup +} and CD34{sup −} populations. After ex vivo imatinib treatment, more residual cells were observed in the CD34{sup +}CD38{sup −} population than in the other populations. Although slow-cycling G{sub 0} cells were insensitive to imatinib in spite of BCR-ABL and CrkL dephosphorylation, combination treatment with everolimus induced substantial cell death, including that of the CD34{sup +}CD38{sup −} population, with p70-S6 K dephosphorylation and decrease of MCL-1 expression. The leukemic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse system with the in vivo combination treatment with imatinib and everolimus showed a decrease of tumor burden including CD34{sup +} cells. These results imply that treatment with everolimus can overcome resistance to imatinib in Ph{sup +} leukemia due to quiescence.

The occurrence of recruitment supported from the finding of an increase in radiosensitivity of quiescent cells in solid tumors after fractionated irradiation with X-rays

International Nuclear Information System (INIS)

Masunaga, Shinichiro; Ono, Koji; Kinashi, Yuko; Suzuki, Minoru; Akaboshi, Mitsuhiko

1998-01-01

We examined the behavior of quiescent cells in solid tumors irradiated twice at various intervals with X-rays, using our recently developed method for selectively detecting the response of quiescent cells in solid tumors. To determine the labeling indices of tumors at the second irradiation, each mouse group included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted before the first irradiation. Radiosensitivity of total tumor cells at the second irradiation decreased in proportion to the increase in interval time. However, radiosensitivity of quiescent cells was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings supported the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation. (author)

Bridging the Timescales of Single-Cell and Population Dynamics

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Jafarpour, Farshid; Wright, Charles S.; Gudjonson, Herman; Riebling, Jedidiah; Dawson, Emma; Lo, Klevin; Fiebig, Aretha; Crosson, Sean; Dinner, Aaron R.; Iyer-Biswas, Srividya

2018-04-01

How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to the replication-competent (stalked) stage of the Caulobacter crescentus life cycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For C. crescentus cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time and, thus, yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell-age distribution, and the quiescence timescale.

Massive quiescent galaxies at z > 3 in the Millennium simulation populated by a semi-analytic galaxy formation model

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Rong, Yu; Jing, Yingjie; Gao, Liang; Guo, Qi; Wang, Jie; Sun, Shuangpeng; Wang, Lin; Pan, Jun

2017-10-01

We take advantage of the statistical power of the large-volume dark-matter-only Millennium simulation (MS), combined with a sophisticated semi-analytic galaxy formation model, to explore whether the recently reported z = 3.7 quiescent galaxy ZF-COSMOS-20115 (ZF) can be accommodated in current galaxy formation models. In our model, a population of quiescent galaxies with stellar masses and star formation rates comparable to those of ZF naturally emerges at redshifts z 3.5 massive QGs are rare (about 2 per cent of the galaxies with the similar stellar masses), the existing AGN feedback model implemented in the semi-analytic galaxy formation model can successfully explain the formation of the high-redshift QGs as it does on their lower redshift counterparts.

Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche

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Masahiko Yamaguchi

2015-10-01

Full Text Available Calcitonin receptor (Calcr is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]. To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.

Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

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Driskell, Iwona; Oeztuerk-Winder, Feride; Humphreys, Peter; Frye, Michaela

2015-03-01

Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent. © 2014 AlphaMed Press.

Galaxy And Mass Assembly (GAMA): The mechanisms for quiescent galaxy formation at z < 1

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Rowlands, K.; Wild, V.; Bourne, N.; Bremer, M.; Brough, S.; Driver, S. P.; Hopkins, A. M.; Owers, M. S.; Phillipps, S.; Pimbblet, K.; Sansom, A. E.; Wang, L.; Alpaslan, M.; Bland-Hawthorn, J.; Colless, M.; Holwerda, B. W.; Taylor, E. N.

2018-01-01

One key problem in astrophysics is understanding how and why galaxies switch off their star formation, building the quiescent population that we observe in the local Universe. From the Galaxy And Mass Assembly and VIsible MultiObject Spectrograph Public Extragalactic Redshift surveys, we use spectroscopic indices to select quiescent and candidate transition galaxies. We identify potentially rapidly transitioning post-starburst (PSB) galaxies and slower transitioning green-valley galaxies. Over the last 8 Gyr, the quiescent population has grown more slowly in number density at high masses ({M}_\\ast >10^{11}{M_{⊙}) than at intermediate masses ({M}_\\ast >10^{10.6}{M_{⊙}). There is evolution in both the PSB and green-valley stellar mass functions, consistent with higher mass galaxies quenching at earlier cosmic times. At intermediate masses ({M}_\\ast >10^{10.6}{M_{⊙}), we find a green-valley transition time-scale of 2.6 Gyr. Alternatively, at z ∼ 0.7, the entire growth rate could be explained by fast-quenching PSB galaxies, with a visibility time-scale of 0.5 Gyr. At lower redshift, the number density of PSBs is so low that an unphysically short visibility window would be required for them to contribute significantly to the quiescent population growth. The importance of the fast-quenching route may rapidly diminish at z 10^{11}{M_{⊙}), there is tension between the large number of candidate transition galaxies compared to the slow growth of the quiescent population. This could be resolved if not all high-mass PSB and green-valley galaxies are transitioning from star forming to quiescent, for example if they rejuvenate out of the quiescent population following the accretion of gas and triggering of star formation, or if they fail to completely quench their star formation.

Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.

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Reeve, Rachel L; Yammine, Samantha Z; Morshead, Cindi M; van der Kooy, Derek

2017-09-01

Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP) - Oct4 + cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP + NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4 fl/fl ;Sox1 Cre (Oct4 CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP + dNSCs, in these Oct4 CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine β-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP + dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071-2082. © 2017 AlphaMed Press.

Glucose Regulates Cyclin D2 Expression in Quiescent and Replicating Pancreatic β-Cells Through Glycolysis and Calcium Channels

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Salpeter, Seth J.; Klochendler, Agnes; Weinberg-Corem, Noa; Porat, Shay; Granot, Zvi; Shapiro, A. M. James; Magnuson, Mark A.; Eden, Amir; Grimsby, Joseph; Glaser, Benjamin

2011-01-01

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G2-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication. PMID:21521747

Suppressing star formation in quiescent galaxies with supermassive black hole winds.

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Cheung, Edmond; Bundy, Kevin; Cappellari, Michele; Peirani, Sébastien; Rujopakarn, Wiphu; Westfall, Kyle; Yan, Renbin; Bershady, Matthew; Greene, Jenny E; Heckman, Timothy M; Drory, Niv; Law, David R; Masters, Karen L; Thomas, Daniel; Wake, David A; Weijmans, Anne-Marie; Rubin, Kate; Belfiore, Francesco; Vulcani, Benedetta; Chen, Yan-mei; Zhang, Kai; Gelfand, Joseph D; Bizyaev, Dmitry; Roman-Lopes, A; Schneider, Donald P

2016-05-26

Quiescent galaxies with little or no ongoing star formation dominate the population of galaxies with masses above 2 × 10(10) times that of the Sun; the number of quiescent galaxies has increased by a factor of about 25 over the past ten billion years (refs 1-4). Once star formation has been shut down, perhaps during the quasar phase of rapid accretion onto a supermassive black hole, an unknown mechanism must remove or heat the gas that is subsequently accreted from either stellar mass loss or mergers and that would otherwise cool to form stars. Energy output from a black hole accreting at a low rate has been proposed, but observational evidence for this in the form of expanding hot gas shells is indirect and limited to radio galaxies at the centres of clusters, which are too rare to explain the vast majority of the quiescent population. Here we report bisymmetric emission features co-aligned with strong ionized-gas velocity gradients from which we infer the presence of centrally driven winds in typical quiescent galaxies that host low-luminosity active nuclei. These galaxies are surprisingly common, accounting for as much as ten per cent of the quiescent population with masses around 2 × 10(10) times that of the Sun. In a prototypical example, we calculate that the energy input from the galaxy's low-level active supermassive black hole is capable of driving the observed wind, which contains sufficient mechanical energy to heat ambient, cooler gas (also detected) and thereby suppress star formation.

Cycling G1 CD34+/CD38+ cells potentiate the motility and engraftment of quiescent G0 CD34+/CD38-/low severe combined immunodeficiency repopulating cells.

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Byk, Tamara; Kahn, Joy; Kollet, Orit; Petit, Isabelle; Samira, Sarit; Shivtiel, Shoham; Ben-Hur, Herzl; Peled, Amnon; Piacibello, Wanda; Lapidot, Tsvee

2005-04-01

The mechanism of human stem cell expansion ex vivo is not fully understood. Furthermore, little is known about the mechanisms of human stem cell homing/repopulation and the role that differentiating progenitor cells may play in these processes. We report that 2- to 3-day in vitro cytokine stimulation of human cord blood CD34(+)-enriched cells induces the production of short-term repopulating, cycling G1 CD34(+)/CD38(+) cells with increased matrix metalloproteinase (MMP)-9 secretion as well as increased migration capacity to the chemokine stromal cell-derived factor-1 (SDF-1) and homing to the bone marrow of irradiated nonobese diabetic severe/combined immunodeficiency (NOD/SCID) mice. These cycling G1 cells enhance SDF-1-mediated in vitro migration and in vivo homing of quiescent G0 CD34(+) cells, which is partially abrogated after inhibition of MMP-2/-9 activity. Moreover, the engraftment potential of quiescent G0 SCID repopulating cells (SRCs) is also increased by the cycling G1 CD34(+)/CD38(+) cells. This effect is significantly abrogated after incubation of cycling G1 cells with a neutralizing anti-CXCR4 antibody. Our data suggest synergistic interactions between accessory cycling G1 CD34(+)/CD38(+) committed progenitor cells and quiescent, primitive G0 CD34(+)/CD38(-/low) SRC/stem cells, the former increasing the motility and engraftment potential of the latter, partly via secretion of MMP-9.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

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Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

DNA supercoiling in proliferating and quiescent 67 murine mammary tumor cells

International Nuclear Information System (INIS)

Cochran-Sandhu, L.; Warters, R.L.; Dethlefsen, L.A.

1985-01-01

The nucleoid sedimentation assay, which is a measure of DNA ''compactness'' or supercoiling, was used to evaluate the supercoiling state of proliferating (P) and quiescent (Q) murine mammary tumor cells. Two day old cultures are referred to as P cells, whereas 7 day old cultures maintained without media replenishment are referred to as Q cells (>95% arrested in G/sub 1/). Q nucleoids sedimented significantly less far into neutral sucrose gradients than P nucleoids, suggesting a less compact DNA structure. This was further confirmed by the utilization of two other probes of DNA supercoiling: ionizing radiation and sedimentation through gradients containing the intercalator ethidium bromide (EtBr). Whereas nucleoids from P cells showed a decrease in sedimentation following ionizing radiation and an initial decrease, followed by an increase, in sedimentation through gradients containing increasing concentrations of EtBr, the sedimentation of nucleoids from Q cells did not change following either treatment. These data indicate that the DNA of nucleoids isolated from Q cells is in a ''relaxed'' state. The potential significance of these results is discussed

Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells

International Nuclear Information System (INIS)

Kordes, Claus; Sawitza, Iris; Haeussinger, Dieter

2008-01-01

It is well known that hepatic stellate cells (HSC) develop into cells, which are thought to contribute to liver fibrogenesis. Recent data suggest that HSC are progenitor cells with the capacity to differentiate into cells of endothelial and hepatocyte lineages. The present study shows that β-catenin-dependent canonical Wnt signaling is active in freshly isolated HSC of rats. Mimicking of the canonical Wnt pathway in cultured HSC by TWS119, an inhibitor of the glycogen synthase kinase 3β, led to reduced β-catenin phosphorylation, induced nuclear translocation of β-catenin, elevated glutamine synthetase production, impeded synthesis of α-smooth muscle actin and Wnt5a, but promoted the expression of glial fibrillary acidic protein, Wnt10b, and paired-like homeodomain transcription factor 2c. In addition, canonical Wnt signaling lowered DNA synthesis and hindered HSC from entering the cell cycle. The findings demonstrate that β-catenin-dependent Wnt signaling maintains the quiescent state of HSC and, similar to stem and progenitor cells, influences their developmental fate

Modeling and Analysis of a Nonlinear Age-Structured Model for Tumor Cell Populations with Quiescence

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Liu, Zijian; Chen, Jing; Pang, Jianhua; Bi, Ping; Ruan, Shigui

2018-05-01

We present a nonlinear first-order hyperbolic partial differential equation model to describe age-structured tumor cell populations with proliferating and quiescent phases at the avascular stage in vitro. The division rate of the proliferating cells is assumed to be nonlinear due to the limitation of the nutrient and space. The model includes a proportion of newborn cells that enter directly the quiescent phase with age zero. This proportion can reflect the effect of treatment by drugs such as erlotinib. The existence and uniqueness of solutions are established. The local and global stabilities of the trivial steady state are investigated. The existence and local stability of the positive steady state are also analyzed. Numerical simulations are performed to verify the results and to examine the impacts of parameters on the nonlinear dynamics of the model.

Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis | Office of Cancer Genomics

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The existence of adult pancreatic progenitor cells has been debated. While some favor the concept of facultative progenitors involved in homeostasis and repair, neither a location nor markers for such cells have been defined. Using genetic lineage tracing, we show that Doublecortin-like kinase-1 (Dclk1) labels a rare population of long-lived, quiescent pancreatic cells. In vitro, Dclk1+ cells proliferate readily and sustain pancreatic organoid growth. In vivo, Dclk1+ cells are necessary for pancreatic regeneration following injury and chronic inflammation.

Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential

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Masunaga, S; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kondo, N; Maruhashi, A; Ono, K

2011-01-01

Objectives The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results 3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. Conclusion Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide. PMID:21586505

A SUBSTANTIAL POPULATION OF MASSIVE QUIESCENT GALAXIES AT z ∼ 4 FROM ZFOURGE

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Straatman, Caroline M. S.; Labbé, Ivo [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Spitler, Lee R. [Department of Physics and Astronomy, Faculty of Sciences, Macquarie University, Sydney, NSW 2109 (Australia); Allen, Rebecca; Glazebrook, Karl; Kacprzak, Glenn G. [Centre for Astrophysics and Supercomputing, Swinburne University, Hawthorn, VIC 3122 (Australia); Altieri, Bruno [European Space Astronomy Centre (ESAC)/ESA, Villanueva de la Cañada, 28691, Madrid (Spain); Brammer, Gabriel B. [European Southern Observatory, Alonso de Córdova 3107, Casilla 19001, Vitacura, Santiago (Chile); Dickinson, Mark; Inami, Hanae [National Optical Astronomy Observatory, Tucson, AZ (United States); Van Dokkum, Pieter [Department of Astronomy, Yale University, New Haven, CT 06520 (United States); Kawinwanichakij, Lalit; Mehrtens, Nicola; Papovich, Casey [George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); Kelson, Daniel D.; McCarthy, Patrick J.; Monson, Andy; Murphy, David; Persson, S. Eric; Quadri, Ryan, E-mail: straatman@strw.leidenuniv.nl [Carnegie Observatories, Pasadena, CA 91101 (United States); and others

2014-03-01

We report the likely identification of a substantial population of massive M ∼ 10{sup 11} M {sub ☉} galaxies at z ∼ 4 with suppressed star formation rates (SFRs), selected on rest-frame optical to near-IR colors from the FourStar Galaxy Evolution Survey (ZFOURGE). The observed spectral energy distributions show pronounced breaks, sampled by a set of near-IR medium-bandwidth filters, resulting in tightly constrained photometric redshifts. Fitting stellar population models suggests large Balmer/4000 Å breaks, relatively old stellar populations, large stellar masses, and low SFRs, with a median specific SFR of 2.9 ± 1.8 × 10{sup –11} yr{sup –1}. Ultradeep Herschel/PACS 100 μm, 160 μm and Spitzer/MIPS 24 μm data reveal no dust-obscured SFR activity for 15/19(79%) galaxies. Two far-IR detected galaxies are obscured QSOs. Stacking the far-IR undetected galaxies yields no detection, consistent with the spectral energy distribution fit, indicating independently that the average specific SFR is at least 10 × smaller than that of typical star-forming galaxies at z ∼ 4. Assuming all far-IR undetected galaxies are indeed quiescent, the volume density is 1.8 ± 0.7 × 10{sup –5} Mpc{sup –3} to a limit of log{sub 10} M/M {sub ☉} ≥ 10.6, which is 10 × and 80 × lower than at z = 2 and z = 0.1. They comprise a remarkably high fraction (∼35%) of z ∼ 4 massive galaxies, suggesting that suppression of star formation was efficient even at very high redshift. Given the average stellar age of 0.8 Gyr and stellar mass of 0.8 × 10{sup 11} M {sub ☉}, the galaxies likely started forming stars before z = 5, with SFRs well in excess of 100 M {sub ☉} yr{sup –1}, far exceeding that of similarly abundant UV-bright galaxies at z ≥ 4. This suggests that most of the star formation in the progenitors of quiescent z ∼ 4 galaxies was obscured by dust.

Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas.

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Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

2017-10-01

Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue. Cores with normal human liver served as control. Antibodies directed against adipophilin, α-SMA, CD146, CRBP-1, cytoglobin, desmin, GFAP, nestin, S100A4 and vinculin were examined, with special emphasis on their expression in periacinar cells in the normal human pancreas and perisinusoidal cells in the normal human liver. The immunolabelling capacity was evaluated according to a semiquantitative scoring system. Double-IF of the markers of interest together with markers for other periacinar cells was performed. Moreover, the utility of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin immunohistochemistry was highly dependent on the preanalytical time interval (PATI) from removal of the tissue to formalin fixation. Cytoglobin, S100A4 and vinculin were expressed in periacinar fibroblasts (FBs). The other examined markers were negative in human qPSCs. Our data indicate that cytoglobin and adipophilin are markers of qPSCs in the normal human pancreas. However, the use of adipophilin as a qPSC marker may be limited due to its high dependence on optimal PATI

EVOLUTION OF QUIESCENT AND STAR-FORMING GALAXIES SINCE z ∼ 1.5 AS A FUNCTION OF THEIR VELOCITY DISPERSIONS

International Nuclear Information System (INIS)

Bezanson, Rachel; Van Dokkum, Pieter; Franx, Marijn

2012-01-01

We measure stellar masses and structural parameters for 5500 quiescent and 20,000 star-forming galaxies at 0.3 < z ≤ 1.5 in the Newfirm Medium Band Survey COSMOS and UKIDSS UDS fields. We combine these measurements to infer velocity dispersions and determine how the number density of galaxies at fixed inferred dispersion, or the velocity dispersion function (VDF), evolves with time for each population. We show that the number of galaxies with high velocity dispersions appears to be surprisingly stable with time, regardless of their star formation history. Furthermore, the overall VDF for star-forming galaxies is constant with redshift, extending down to the lowest velocity dispersions probed by this study. The only galaxy population showing strong evolution are quiescent galaxies with low inferred dispersions, whose number density increases by a factor of ∼4 since z = 1.5. This buildup leads to an evolution in the quiescent fraction of galaxies such that the threshold dispersion above which quiescent galaxies dominate the counts moves to lower velocity dispersion with time. We show that our results are qualitatively consistent with a simple model in which star-forming galaxies quench and are added to the quiescent population. In order to compensate for the migration into the quiescent population, the velocity dispersions of star-forming galaxies must increase, with a rate that increases with dispersion.

A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States

Directory of Open Access Journals (Sweden)

Shauna Katz

2016-10-01

Full Text Available Throughout life, adult neural stem cells (NSCs produce new neurons and glia that contribute to crucial brain functions. Quiescence is an essential protective feature of adult NSCs; however, the establishment and maintenance of this state remain poorly understood. We demonstrate that in the adult zebrafish pallium, the brain-enriched miR-9 is expressed exclusively in a subset of quiescent NSCs, highlighting a heterogeneity within these cells, and is necessary to maintain NSC quiescence. Strikingly, miR-9, along with Argonaute proteins (Agos, is localized to the nucleus of quiescent NSCs, and manipulating their nuclear/cytoplasmic ratio impacts quiescence. Mechanistically, miR-9 permits efficient Notch signaling to promote quiescence, and we identify the RISC protein TNRC6 as a mediator of miR-9/Agos nuclear localization in vivo. We propose a conserved non-canonical role for nuclear miR-9/Agos in controlling the balance between NSC quiescence and activation, a key step in maintaining adult germinal pools.

Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao

2001-01-01

Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

Adenovirus type 5 induces progression of quiescent rat cells into S phase without polyamine accumulation.

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Cheetham, B F; Shaw, D C; Bellett, A J

1982-01-01

Adenovirus type 5 induces cellular DNA synthesis and thymidine kinase in quiescent rat cells but does not induce ornithine decarboxylase. We now show that unlike serum, adenovirus type 5 fails to induce S-adenosylmethionine decarboxylase or polyamine accumulation. The inhibition by methylglyoxal bis(guanylhydrazone) of the induction of thymidine kinase by adenovirus type 5 is probably unrelated to its effects on polyamine biosynthesis. Thus, induction of cellular thymidine kinase and DNA replication by adenovirus type 5 is uncoupled from polyamine accumulation. PMID:7177112

Quiescent Galaxies in the 3D-HST Survey: Spectroscopic Confirmation of a Large Number of Galaxies with Relatively Old Stellar Populations at z ~ 2

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Whitaker, Katherine E.; van Dokkum, Pieter G.; Brammer, Gabriel; Momcheva, Ivelina G.; Skelton, Rosalind; Franx, Marijn; Kriek, Mariska; Labbé, Ivo; Fumagalli, Mattia; Lundgren, Britt F.; Nelson, Erica J.; Patel, Shannon G.; Rix, Hans-Walter

2013-06-01

Quiescent galaxies at z ~ 2 have been identified in large numbers based on rest-frame colors, but only a small number of these galaxies have been spectroscopically confirmed to show that their rest-frame optical spectra show either strong Balmer or metal absorption lines. Here, we median stack the rest-frame optical spectra for 171 photometrically quiescent galaxies at 1.4 < z < 2.2 from the 3D-HST grism survey. In addition to Hβ (λ4861 Å), we unambiguously identify metal absorption lines in the stacked spectrum, including the G band (λ4304 Å), Mg I (λ5175 Å), and Na I (λ5894 Å). This finding demonstrates that galaxies with relatively old stellar populations already existed when the universe was ~3 Gyr old, and that rest-frame color selection techniques can efficiently select them. We find an average age of 1.3^{+0.1}_{-0.3} Gyr when fitting a simple stellar population to the entire stack. We confirm our previous result from medium-band photometry that the stellar age varies with the colors of quiescent galaxies: the reddest 80% of galaxies are dominated by metal lines and have a relatively old mean age of 1.6^{+0.5}_{-0.4} Gyr, whereas the bluest (and brightest) galaxies have strong Balmer lines and a spectroscopic age of 0.9^{+0.2}_{-0.1} Gyr. Although the spectrum is dominated by an evolved stellar population, we also find [O III] and Hβ emission. Interestingly, this emission is more centrally concentrated than the continuum with {L_{{O}\\,\\scriptsize{III}}}=1.7+/- 0.3\\times 10^{40} erg s-1, indicating residual central star formation or nuclear activity.

Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

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Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

2014-01-01

Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Suzuki, Minoru

2001-01-01

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. Methods and Materials: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate- 10 B (BSH), or 3 h after oral administration of p-boronophenylalanine- 10 B (BPA), the tumors were irradiated with neutron beams. The tumors without 10 B-compound administration were irradiated with neutron beams or γ-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: Without 10 B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10 B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA

Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb.

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Giachino, Claudio; Taylor, Verdon

2009-07-01

The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreER(T2) allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreER(T2)-expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreER(T2)-expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreER(T2)-targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB.

AN ULTRA-DEEP NEAR-INFRARED SPECTRUM OF A COMPACT QUIESCENT GALAXY AT z = 2.2

International Nuclear Information System (INIS)

Kriek, Mariska; Van Dokkum, Pieter G.; Marchesini, Danilo; Labbe, Ivo; Franx, Marijn; Quadri, Ryan F.; Illingworth, Garth D.

2009-01-01

Several recent studies have shown that about half of the massive galaxies at z ∼ 2 are in a quiescent phase. Moreover, these galaxies are commonly found to be ultra-compact with half-light radii of ∼1 kpc. We have obtained a ∼29 hr spectrum of a typical quiescent, ultra-dense galaxy at z = 2.1865 with the Gemini Near-Infrared Spectrograph. The spectrum exhibits a strong optical break and several absorption features, which have not previously been detected in z > 2 quiescent galaxies. Comparison of the spectral energy distribution with stellar population synthesis models implies a low star formation rate (SFR) of 1-3 M sun yr -1 , an age of 1.3-2.2 Gyr, and a stellar mass of ∼2 x 10 11 M sun . We detect several faint emission lines, with emission-line ratios of [N II]/Hα, [S II]/Hα, and [O II]/[O III] typical of low-ionization nuclear emission-line regions. Thus, neither the stellar continuum nor the nebular emission implies active star formation. The current SFR is <1% of the past average SFR. If this galaxy is representative of compact quiescent galaxies beyond z = 2, it implies that quenching of star formation is extremely efficient and also indicates that low luminosity active galactic nuclei (AGNs) could be common in these objects. Nuclear emission is a potential concern for the size measurement. However, we show that the AGN contributes ∼<8% to the rest-frame optical emission. A possible post-starburst population may affect size measurements more strongly; although a 0.5 Gyr old stellar population can make up ∼<10% of the total stellar mass, it could account for up to ∼40% of the optical light. Nevertheless, this spectrum shows that this compact galaxy is dominated by an evolved stellar population.

BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells

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Lagadinou, Eleni D.; Sach, Alexander; Callahan, Kevin; Rossi, Randall M.; Neering, Sarah J.; Minhajuddin, Mohammad; Ashton, John M.; Pei, Shanshan; Grose, Valerie; O’Dwyer, Kristen M.; Liesveld, Jane L.; Brookes, Paul S.; Becker, Michael W.; Jordan, Craig T.

2013-01-01

Summary Most forms of chemotherapy employ mechanisms involving induction of oxidative stress, a strategy that can be effective due to the elevated oxidative state commonly observed in cancer cells. However, recent studies have shown that relative redox levels in primary tumors can be heterogeneous, suggesting that regimens dependent on differential oxidative state may not be uniformly effective. To investigate this issue in hematological malignancies, we evaluated mechanisms controlling oxidative state in primary specimens derived from acute myelogenous leukemia (AML) patients. Our studies demonstrate three striking findings. First, the majority of functionally-defined leukemia stem cells (LSCs) are characterized by relatively low levels of reactive oxygen species (termed “ROS-low”). Second, ROS-low LSCs aberrantly over-express BCL-2. Third, BCL-2 inhibition reduced oxidative phosphorylation and selectively eradicated quiescent LSCs. Based on these findings, we propose a model wherein the unique physiology of ROS-low LSCs provides an opportunity for selective targeting via disruption of BCL-2-dependent oxidative phosphorylation. PMID:23333149

The assembly histories of quiescent galaxies since z = 0.7 from absorption line spectroscopy

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Choi, Jieun; Conroy, Charlie [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Moustakas, John [Department of Physics and Astronomy, Siena College, Loudonville, NY 12110 (United States); Graves, Genevieve J. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Holden, Bradford P. [UCO/Lick Observatories, University of California, Santa Cruz, CA 95064 (United States); Brodwin, Mark [Department of Physics and Astronomy, University of Missouri, Kansas City, MO 64110 (United States); Brown, Michael J. I. [School of Physics, Monash University, Clayton, Vic 3800 (Australia); Van Dokkum, Pieter G. [Department of Astrophysical Sciences, Yale University, New Haven, CT 06520 (United States)

2014-09-10

We present results from modeling the optical spectra of a large sample of quiescent galaxies between 0.1 < z < 0.7 from the Sloan Digital Sky Survey (SDSS) and the AGN and Galaxy Evolution Survey (AGES). We examine how the stellar ages and abundance patterns of galaxies evolve over time as a function of stellar mass from 10{sup 9.6}-10{sup 11.8} M {sub ☉}. Galaxy spectra are stacked in bins of mass and redshift and modeled over a wavelength range from 4000 Å to 5500 Å. Full spectrum stellar population synthesis modeling provides estimates of the age and the abundances of the elements Fe, Mg, C, N, and Ca. We find negligible evolution in elemental abundances at fixed stellar mass over roughly 7 Gyr of cosmic time. In addition, the increase in stellar ages with time for massive galaxies is consistent with passive evolution since z = 0.7. Taken together, these results favor a scenario in which the inner ∼0.3-3 R {sub e} of massive quiescent galaxies have been passively evolving over the last half of cosmic time. Interestingly, the derived stellar ages are considerably younger than the age of the universe at all epochs, consistent with an equivalent single-burst star formation epoch of z ≲ 1.5. These young stellar population ages coupled with the existence of massive quiescent galaxies at z > 1 indicate the inhomogeneous nature of the z ≲ 0.7 quiescent population. The data also permit the addition of newly quenched galaxies at masses below ∼10{sup 10.5} M {sub ☉} at z < 0.7. Additionally, we analyze very deep Keck DEIMOS spectra of the two brightest quiescent galaxies in a cluster at z = 0.83. There is tentative evidence that these galaxies are older than their counterparts in low-density environments. In the Appendix, we demonstrate that our full spectrum modeling technique allows for accurate and reliable modeling of galaxy spectra to low S/N (∼20 Å{sup –1}) and/or low spectral resolution (R ∼ 500).

Heterogeneity and weak coupling may explain the synchronization characteristics of cells in the arterial wall

DEFF Research Database (Denmark)

Jacobsen, Jens Christian Brings; Aalkjær, Christian; Matchkov, Vladimir

2008-01-01

development of force known as vasomotion. We present experimental data showing a considerable heterogeneity in cellular calcium dynamics in the vascular wall. In stimulated vessels, some SMCs remain quiescent, whereas others display waves of variable frequency. At the onset of vasomotion, all SMCs...... are enrolled into synchronized oscillation.Simulations of coupled SMCs show that the experimentally observed cellular recruitment, the presence of quiescent cells and the variation in oscillation frequency may arise if the cell population is phenotypically heterogeneous. In this case, quiescent cells can...

THE NUMBER DENSITY AND MASS DENSITY OF STAR-FORMING AND QUIESCENT GALAXIES AT 0.4 ≤ z ≤ 2.2

International Nuclear Information System (INIS)

Brammer, Gabriel B.; Whitaker, K. E.; Van Dokkum, P. G.; Lee, K.-S.; Muzzin, A.; Marchesini, D.; Franx, M.; Kriek, M.; Labbe, I.; Quadri, R. F.; Williams, R.; Rudnick, G.

2011-01-01

We study the buildup of the bimodal galaxy population using the NEWFIRM Medium-Band Survey, which provides excellent redshifts and well-sampled spectral energy distributions of ∼27, 000 galaxies with K 3 x 10 10 M sun increases by a factor of ∼10 from z ∼ 2 to the present day, whereas the mass density in star-forming galaxies is flat or decreases over the same time period. Modest mass growth by a factor of ∼2 of individual quiescent galaxies can explain roughly half of the strong density evolution at masses >10 11 M sun , due to the steepness of the exponential tail of the mass function. The rest of the density evolution of massive, quiescent galaxies is likely due to transformation (e.g., quenching) of the massive star-forming population, a conclusion which is consistent with the density evolution we observe for the star-forming galaxies themselves, which is flat or decreasing with cosmic time. Modest mass growth does not explain the evolution of less massive quiescent galaxies (∼10 10.5 M sun ), which show a similarly steep increase in their number densities. The less massive quiescent galaxies are therefore continuously formed by transforming galaxies from the star-forming population.

Structural organization of the quiescent core region in a turbulent channel flow

International Nuclear Information System (INIS)

Yang, Jongmin; Hwang, Jinyul; Sung, Hyung Jin

2016-01-01

Highlights: • The structural organization of the quiescent core region in a turbulent channel flow is explored. • The quiescent core region is the uniform momentum zone located at the center of the channel. • The boundary of the quiescent core region can be identified from the probability density function of the streamwise modal velocity. • The prograde and retrograde vortices form a counter-rotating vortex pair at the boundary of the core region. - Abstract: The structural organization of the quiescent core region in a turbulent channel flow was explored using direct numerical simulation data at Re_τ = 930. The quiescent core region is the uniform momentum zone located at the center of the channel, and contains the highest momentum with a low level of turbulence. The boundary of the quiescent core region can be identified from the probability density function of the streamwise modal velocity. The streamwise velocity changes abruptly near the boundary of the core region. The abrupt jump leads the increase of the velocity gradient, which is similar to the vorticity thickness of the laminar superlayer at the turbulent/non-turbulent interface. The strong shear induced from the abrupt change is originated from the vortical structure lying on the boundary of the core region. The spanwise population densities of the prograde and retrograde vortices have a local maximum near the boundary of the core region. The prograde vortex dominantly contributes to the total mean shear near the core boundary and the contribution to the total mean shear rapidly decreases within the core region. The prograde and retrograde vortices form a counter-rotating vortex pair at the boundary of the core region associated with the nibbling mechanism. The boundary of the core region contains large-scale concave and convex features. The concave (convex) core interface is organized by the negative-u (positive-u) regions which induce the ejections (sweeps) around the core boundary.

The PSA−/lo prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration

Science.gov (United States)

Qin, Jichao; Liu, Xin; Laffin, Brian; Chen, Xin; Choy, Grace; Jeter, Collene; Calhoun-Davis, Tammy; Li, Hangwen; Palapattu, Ganesh S.; Pang, Shen; Lin, Kevin; Huang, Jiaoti; Ivanov, Ivan; Li, Wei; Suraneni, Mahipal V.; Tang, Dean G.

2012-01-01

SUMMARY Prostate cancer (PCa) is heterogeneous and contains both differentiated and undifferentiated tumor cells, but the relative functional contribution of these two cell populations remains unclear. Here we report distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (PSA+) and low (PSA−/lo) levels of the differentiation marker PSA. PSA−/lo PCa cells are quiescent and refractory to stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity. They preferentially express stem cell genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA−/lo PCa cells can initiate robust tumor development and resist androgen ablation in castrated hosts, and harbor highly tumorigenic castration-resistant PCa cells that can be prospectively enriched using ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, undergo symmetric division and are sensitive to castration. Together, our study suggests PSA−/lo cells may represent a critical source of castration-resistant PCa cells. PMID:22560078

Relationship between heart rate and quiescent interval of the cardiac cycle in children using MRI

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Zhang, Wei [Texas Children' s Hospital, E. B. Singleton Department of Pediatric Radiology, Houston, TX (United States); Bogale, Saivivek [Baylor University Medical Center, Department of Radiology, Dallas, TX (United States); Golriz, Farahnaz [Baylor College of Medicine, Department of Radiology, Houston, TX (United States); Krishnamurthy, Rajesh [Nationwide Children' s Hospital, Department of Diagnostic Radiology, Columbus, OH (United States)

2017-11-15

Imaging the heart in children comes with the challenge of constant cardiac motion. A prospective electrocardiography-triggered CT scan allows for scanning during a predetermined phase of the cardiac cycle with least motion. This technique requires knowing the optimal quiescent intervals of cardiac cycles in a pediatric population. To evaluate high-temporal-resolution cine MRI of the heart in children to determine the relationship of heart rate to the optimal quiescent interval within the cardiac cycle. We included a total of 225 consecutive patients ages 0-18 years who had high-temporal-resolution cine steady-state free-precession sequence performed as part of a magnetic resonance imaging (MRI) or magnetic resonance angiography study of the heart. We determined the location and duration of the quiescent interval in systole and diastole for heart rates ranging 40-178 beats per minute (bpm). We performed the Wilcoxon signed rank test to compare the duration of quiescent interval in systole and diastole for each heart rate group. The duration of the quiescent interval at heart rates <80 bpm and >90 bpm was significantly longer in diastole and systole, respectively (P<.0001 for all ranges, except for 90-99 bpm [P=.02]). For heart rates 80-89 bpm, diastolic interval was longer than systolic interval, but the difference was not statistically significant (P=.06). We created a chart depicting optimal quiescent intervals across a range of heart rates that could be applied for prospective electrocardiography-triggered CT imaging of the heart. The optimal quiescent interval at heart rates <80 bpm is in diastole and at heart rates ≥90 bpm is in systole. The period of quiescence at heart rates 80-89 bpm is uniformly short in systole and diastole. (orig.)

Quiescent plasma machine for plasma investigation

International Nuclear Information System (INIS)

Ferreira, J.L.

1993-01-01

A large volume quiescent plasma device is being developed at INPE to study Langmuir waves and turbulence generated by electron beams (E b ≤ 500 e V) interacting with plasma. This new quiescent plasma machine was designed to allow the performance of several experiments specially those related with laboratory space plasma simulation experiments. Current-driven instabilities and related phenomena such as double-layers along magnetic field lines are some of the many experiments planned for this machine. (author)

Growth and decay of runaway electrons above the critical electric field under quiescent conditions

International Nuclear Information System (INIS)

Paz-Soldan, C.; Eidietis, N. W.; Wesley, J. C.; Granetz, R.; Hollmann, E. M.; Moyer, R. A.; Zhang, J.; Crocker, N. A.; Austin, M. E.; Wingen, A.; Zhu, Y.

2014-01-01

Extremely low density operation free of error field penetration supports the excitation of trace-level quiescent runaway electron (RE) populations during the flat-top of DIII-D Ohmic discharges. Operation in the quiescent regime allows accurate measurement of all key parameters important to RE excitation, including the internal broadband magnetic fluctuation level. RE onset is characterized and found to be consistent with primary (Dreicer) generation rates. Impurity-free collisional suppression of the RE population is investigated by stepping the late-time main-ion density, until RE decay is observed. The transition from growth to decay is found to occur 3–5 times above the theoretical critical electric field for avalanche growth and is thus indicative of anomalous RE loss. This suggests that suppression of tokamak RE avalanches can be achieved at lower density than previously expected, though extrapolation requires predictive understanding of the RE loss mechanism and magnitude

The formation of quiescent glomerular endothelial cell monolayer in vitro is strongly dependent on the choice of extracellular matrix coating

International Nuclear Information System (INIS)

Pajęcka, Kamilla; Nielsen, Malik Nygaard; Hansen, Troels Krarup; Williams, Julie M.

2017-01-01

Background and aims: Nephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs). Methods: Primary hGEnCs were seeded on various ECMs. Cell adhesion was monitored by an impedance sensing system. The localization of junctional proteins was assessed by immunofluorescence and the barrier function by passage of fluorescent dextrans and magnitude of VEGF response. Results: All ECM matrices except recombinant human laminin 111 (rhLN111) supported comparable cell proliferation. Culturing hGEnCs on rhLN521, rhLN511 or fibronectin resulted in a physiologically relevant barrier to 70 kDa dextrans which was 82% tighter than that formed on collagen type IV. Furthermore, only hGEnCs cultured on rhLN521 or rhLN511 showed plasma-membrane localized zonula occludens-1 and vascular endothelial cadherin indicative of proper tight and adherens junctions (AJ). Conclusion: We recommend culturing hGEnCs on the mature glomerular basement membrane laminin - rhLN521 – which, as the only commercially available ECM, promotes all of the characteristics of the quiescent hGEnC monolayer: cobblestone morphology, well-defined AJs and physiological perm-selectivity. - Highlights: • rhLN521, rhLN511 and hFN assure physiologically relevant permeability. • rhLN521 and rhLN511 ensure best cell morphology and adherens junction formation. • Collagen IV and I based coating results in disorganized hGEnC monolayer. • Physiologically relevant ECM may lead to down-regulation of self-produced matrices.

The formation of quiescent glomerular endothelial cell monolayer in vitro is strongly dependent on the choice of extracellular matrix coating

Energy Technology Data Exchange (ETDEWEB)

Pajęcka, Kamilla, E-mail: kpaj@novonordisk.com [Global Research, Novo Nordisk A/S, Måløv (Denmark); Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus (Denmark); Nielsen, Malik Nygaard [Global Research, Novo Nordisk A/S, Måløv (Denmark); Hansen, Troels Krarup [Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus (Denmark); Williams, Julie M. [Global Research, Novo Nordisk A/S, Måløv (Denmark)

2017-04-01

Background and aims: Nephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs). Methods: Primary hGEnCs were seeded on various ECMs. Cell adhesion was monitored by an impedance sensing system. The localization of junctional proteins was assessed by immunofluorescence and the barrier function by passage of fluorescent dextrans and magnitude of VEGF response. Results: All ECM matrices except recombinant human laminin 111 (rhLN111) supported comparable cell proliferation. Culturing hGEnCs on rhLN521, rhLN511 or fibronectin resulted in a physiologically relevant barrier to 70 kDa dextrans which was 82% tighter than that formed on collagen type IV. Furthermore, only hGEnCs cultured on rhLN521 or rhLN511 showed plasma-membrane localized zonula occludens-1 and vascular endothelial cadherin indicative of proper tight and adherens junctions (AJ). Conclusion: We recommend culturing hGEnCs on the mature glomerular basement membrane laminin - rhLN521 – which, as the only commercially available ECM, promotes all of the characteristics of the quiescent hGEnC monolayer: cobblestone morphology, well-defined AJs and physiological perm-selectivity. - Highlights: • rhLN521, rhLN511 and hFN assure physiologically relevant permeability. • rhLN521 and rhLN511 ensure best cell morphology and adherens junction formation. • Collagen IV and I based coating results in disorganized hGEnC monolayer. • Physiologically relevant ECM may lead to down-regulation of self-produced matrices.

A Novel View of the Adult Stem Cell Compartment From the Perspective of a Quiescent Population of Very Small Embryonic-Like Stem Cells.

Science.gov (United States)

Ratajczak, Mariusz Z; Ratajczak, Janina; Suszynska, Malwina; Miller, Donald M; Kucia, Magda; Shin, Dong-Myung

2017-01-06

Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed SCs (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs, epiblast SCs, and primordial germ cells suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review, we will critically discuss all these questions and the concept that small dormant SCs related to migratory primordial germ cells, described as very small embryonic-like SCs, are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue-committed SCs and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human very small embryonic-like SC in chemically defined media free from feeder-layer cells open up new and exciting possibilities for their application in regenerative medicine. © 2017 American Heart Association, Inc.

Distinct transcriptional networks in quiescent myoblasts: a role for Wnt signaling in reversible vs. irreversible arrest.

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Sindhu Subramaniam

Full Text Available Most cells in adult mammals are non-dividing: differentiated cells exit the cell cycle permanently, but stem cells exist in a state of reversible arrest called quiescence. In damaged skeletal muscle, quiescent satellite stem cells re-enter the cell cycle, proliferate and subsequently execute divergent programs to regenerate both post-mitotic myofibers and quiescent stem cells. The molecular basis for these alternative programs of arrest is poorly understood. In this study, we used an established myogenic culture model (C2C12 myoblasts to generate cells in alternative states of arrest and investigate their global transcriptional profiles. Using cDNA microarrays, we compared G0 myoblasts with post-mitotic myotubes. Our findings define the transcriptional program of quiescent myoblasts in culture and establish that distinct gene expression profiles, especially of tumour suppressor genes and inhibitors of differentiation characterize reversible arrest, distinguishing this state from irreversibly arrested myotubes. We also reveal the existence of a tissue-specific quiescence program by comparing G0 C2C12 myoblasts to isogenic G0 fibroblasts (10T1/2. Intriguingly, in myoblasts but not fibroblasts, quiescence is associated with a signature of Wnt pathway genes. We provide evidence that different levels of signaling via the canonical Wnt pathway characterize distinct cellular states (proliferation vs. quiescence vs. differentiation. Moderate induction of Wnt signaling in quiescence is associated with critical properties such as clonogenic self-renewal. Exogenous Wnt treatment subverts the quiescence program and negatively affects clonogenicity. Finally, we identify two new quiescence-induced regulators of canonical Wnt signaling, Rgs2 and Dkk3, whose induction in G0 is required for clonogenic self-renewal. These results support the concept that active signal-mediated regulation of quiescence contributes to stem cell properties, and have implications for

Distinct transcriptional networks in quiescent myoblasts: a role for Wnt signaling in reversible vs. irreversible arrest.

Science.gov (United States)

Subramaniam, Sindhu; Sreenivas, Prethish; Cheedipudi, Sirisha; Reddy, Vatrapu Rami; Shashidhara, Lingadahalli Subrahmanya; Chilukoti, Ravi Kumar; Mylavarapu, Madhavi; Dhawan, Jyotsna

2014-01-01

Most cells in adult mammals are non-dividing: differentiated cells exit the cell cycle permanently, but stem cells exist in a state of reversible arrest called quiescence. In damaged skeletal muscle, quiescent satellite stem cells re-enter the cell cycle, proliferate and subsequently execute divergent programs to regenerate both post-mitotic myofibers and quiescent stem cells. The molecular basis for these alternative programs of arrest is poorly understood. In this study, we used an established myogenic culture model (C2C12 myoblasts) to generate cells in alternative states of arrest and investigate their global transcriptional profiles. Using cDNA microarrays, we compared G0 myoblasts with post-mitotic myotubes. Our findings define the transcriptional program of quiescent myoblasts in culture and establish that distinct gene expression profiles, especially of tumour suppressor genes and inhibitors of differentiation characterize reversible arrest, distinguishing this state from irreversibly arrested myotubes. We also reveal the existence of a tissue-specific quiescence program by comparing G0 C2C12 myoblasts to isogenic G0 fibroblasts (10T1/2). Intriguingly, in myoblasts but not fibroblasts, quiescence is associated with a signature of Wnt pathway genes. We provide evidence that different levels of signaling via the canonical Wnt pathway characterize distinct cellular states (proliferation vs. quiescence vs. differentiation). Moderate induction of Wnt signaling in quiescence is associated with critical properties such as clonogenic self-renewal. Exogenous Wnt treatment subverts the quiescence program and negatively affects clonogenicity. Finally, we identify two new quiescence-induced regulators of canonical Wnt signaling, Rgs2 and Dkk3, whose induction in G0 is required for clonogenic self-renewal. These results support the concept that active signal-mediated regulation of quiescence contributes to stem cell properties, and have implications for pathological

The progenitors of local ultra-massive galaxies across cosmic time: from dusty star-bursting to quiescent stellar populations

Energy Technology Data Exchange (ETDEWEB)

Marchesini, Danilo; Marsan, Cemile Z. [Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States); Muzzin, Adam; Franx, Marijn [Leiden Observatory, Leiden University, PO Box 9513, NL-2300 RA Leiden (Netherlands); Stefanon, Mauro [Physics and Astronomy Department, University of Missouri, Columbia, MO 65211 (United States); Brammer, Gabriel G. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Vulcani, Benedetta [Kavli Institute for the Physics and Mathematics of the Universe (WPI), Todai Institutes for Advanced Study, University of Tokyo, Kashiwa 277-8582 (Japan); Fynbo, J. P. U.; Milvang-Jensen, Bo [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark); Dunlop, James S.; Buitrago, Fernando [SUPA, Institute for Astronomy, University of Edinburgh, Royal Observatory, Edinburgh EH9 3HJ (United Kingdom)

2014-10-10

Using the UltraVISTA catalogs, we investigate the evolution in the 11.4 Gyr since z = 3 of the progenitors of local ultra-massive galaxies (log (M {sub star}/M {sub ☉}) ≈ 11.8; UMGs), providing a complete and consistent picture of how the most massive galaxies at z = 0 have assembled. By selecting the progenitors with a semi-empirical approach using abundance matching, we infer a growth in stellar mass of 0.56{sub −0.25}{sup +0.35} dex, 0.45{sub −0.20}{sup +0.16} dex, and 0.27{sub −0.12}{sup +0.08} dex from z = 3, z = 2, and z = 1, respectively, to z = 0. At z < 1, the progenitors of UMGs constitute a homogeneous population of only quiescent galaxies with old stellar populations. At z > 1, the contribution from star-forming galaxies progressively increases, with the progenitors at 2 < z < 3 being dominated by massive (M {sub star} ≈ 2 × 10{sup 11} M {sub ☉}), dusty (A {sub V} ∼ 1-2.2 mag), star-forming (SFR ∼ 100-400 M {sub ☉} yr{sup –1}) galaxies with a large range in stellar ages. At z = 2.75, ∼15% of the progenitors are quiescent, with properties typical of post-starburst galaxies with little dust extinction and strong Balmer break, and showing a large scatter in color. Our findings indicate that at least half of the stellar content of local UMGs was assembled at z > 1, whereas the remaining was assembled via merging from z ∼ 1 to the present. Most of the quenching of the star-forming progenitors happened between z = 2.75 and z = 1.25, in good agreement with the typical formation redshift and scatter in age of z = 0 UMGs as derived from their fossil records. The progenitors of local UMGs, including the star-forming ones, never lived on the blue cloud since z = 3. We propose an alternative path for the formation of local UMGs that refines previously proposed pictures and that is fully consistent with our findings.

Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

International Nuclear Information System (INIS)

Martins-Neves, Sara R; Lopes, Áurio O; Carmo, Anália do; Paiva, Artur A; Simões, Paulo C; Abrunhosa, Antero J; Gomes, Célia MF

2012-01-01

Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma

Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

Directory of Open Access Journals (Sweden)

Martins-Neves Sara R

2012-04-01

Full Text Available Abstract Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.

A massive, quiescent galaxy at a redshift of 3.717

Science.gov (United States)

Glazebrook, Karl; Schreiber, Corentin; Labbé, Ivo; Nanayakkara, Themiya; Kacprzak, Glenn G.; Oesch, Pascal A.; Papovich, Casey; Spitler, Lee R.; Straatman, Caroline M. S.; Tran, Kim-Vy H.; Yuan, Tiantian

2017-04-01

Finding massive galaxies that stopped forming stars in the early Universe presents an observational challenge because their rest-frame ultraviolet emission is negligible and they can only be reliably identified by extremely deep near-infrared surveys. These surveys have revealed the presence of massive, quiescent early-type galaxies appearing as early as redshift z ≈ 2, an epoch three billion years after the Big Bang. Their age and formation processes have now been explained by an improved generation of galaxy-formation models, in which they form rapidly at z ≈ 3-4, consistent with the typical masses and ages derived from their observations. Deeper surveys have reported evidence for populations of massive, quiescent galaxies at even higher redshifts and earlier times, using coarsely sampled photometry. However, these early, massive, quiescent galaxies are not predicted by the latest generation of theoretical models. Here we report the spectroscopic confirmation of one such galaxy at redshift z = 3.717, with a stellar mass of 1.7 × 1011 solar masses. We derive its age to be nearly half the age of the Universe at this redshift and the absorption line spectrum shows no current star formation. These observations demonstrate that the galaxy must have formed the majority of its stars quickly, within the first billion years of cosmic history in a short, extreme starburst. This ancestral starburst appears similar to those being found by submillimetre-wavelength surveys. The early formation of such massive systems implies that our picture of early galaxy assembly requires substantial revision.

Quorum Sensing-Regulated Phenol-Soluble Modulins Limit Persister Cell Populations in Staphylococcus aureus

DEFF Research Database (Denmark)

Bojer, Martin S; Lindemose, Søren; Vestergaard, Martin

2018-01-01

Incomplete killing of bacterial pathogens by antibiotics is an underlying cause of treatment failure and accompanying complications. Among those avoiding chemotherapy are persisters being individual cells in a population that for extended periods of time survive high antibiotic concentrations...... proposedly by being in a quiescent state refractory to antibiotic killing. While investigating the human pathogenStaphylococcus aureusand the influence of growth phase on persister formation, we noted that spent supernatants of stationary phase cultures ofS. aureusorS. epidermidis, but not of distantly...... related bacteria, significantly reduced the persister cell frequency upon ciprofloxacin challenge when added to exponentially growing and stationary phaseS. aureuscells. Curiously, the persister reducing activity ofS. aureussupernatants was also effective against persisters formed by eitherS. carnosusor...

The quiescent and mitogen stimulated peripheral blood mononuclear cells after gamma irradiation and their P53, P21 and H2AX expression

International Nuclear Information System (INIS)

Vilasova, Z.; Vavrova, J.; Sinkorova, Z.; Tichy, A.; Oesterreicher, J.; Rezacova, M.; Zoelzer, F.

2008-01-01

The aim of this study was to compare reaction of quiescent and proliferating PHA (mitogenic lectin phytohemagglutinin)-stimulated human peripheral blood mononuclear cells (PBMCs) to γ-irradiation and analyze changes of proteins related to repair if DNA damage and apoptosis, such as γH2A.X, p53 and its phosphorylations on serine 15 and 392, and p21. Protein changes induced by radiation are different in quiescent and stimulated PBMCs. W e analyzed changes in proteins related to DNA damage repair and apoptosis using the western blot method in quiescent and stimulated PBMCs. Western blot technique can detect γH2A.X increase only at later times, when the phosphorylation of H2A.X is related to the onset of apoptosis (24-72 h after irradiation by the dose of 4 Gy). The level of H2A.X phosphorylation increased after stimulation of PBMC by PHA (72 h, 10 μg/ml) and as shown here it was detectable by western blot analysis. The increase in γH2A.X that we detected by western blot 4 h after irradiation of stimulated lymphocytes was dose dependent. It can be concluded that measurement of γH2A.X during the first hours after the irradiation is a good marker of the received dose of radiation. We compared the dynamics of p53 induction after irradiation by IR in both quiescent and stimulated lymphocytes. p53 increase was observed only in stimulated lymphocytes, as was p53 phosphorylation at serines-392 and -15. The increase in the amount of p53 was not dose-dependent 4 h after the irradiation. On the other hand, phosphorylation of p53 at serine-15 analyzed 4 h after the irradiation is dose-dependent over the studied dose range. Despite the fact that p53 was not detected in quiescent lymphocytes and a reaction to irradiation was not observed either, p21 levels increased after irradiation in both quiescent and stimulated lymphocytes in a dose-dependent manner. IR induces phosphorylation of p53 at both serines-15 and -392 in PHA stimulated human lymphocytes. However

Ionic responses rapidly elicited by activation of protein kinase C in quiescent Swiss 3T3 cells

International Nuclear Information System (INIS)

Vara, F.; Schneider, J.A.; Rozengurt, E.

1985-01-01

Diacylglycerol and phorbol esters activate protein kinase C in intact cells. The authors report here that addition of the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG) to quiescent cultures of Swiss 3T3 cells caused a marked increase in the rate of ouabain-sensitive 86 Rb + uptake, a measure of the activity of the Na + /K + pump. The effect was dose-dependent and could be detected after 1 min of exposure to the diacylglycerol. OAG stimulated Na + influx via an amiloride-sensitive pathway and increased intracellular pH by 0.15 pH unit. Phorbol 12,13-dibutyrate (PBt 2 ) also enhanced ouabain sensitive 86 Rb + uptake and amiloride-sensitive 22 Na + influx. Prolonged treatment (40 hr) of 3T3 cells with PBt 2 at a saturating dose, which reduces the number of PBt 2 binding sites and protein kinase C activity, abolished the ionic response of the cells to a subsequent addition of either OAG or PBt 2 . They suggest that activation of protein kinase C elicits, either directly or indirectly, enhanced Na + /H + antiport activity, which, in turn, leads to Na + influx, intracellular pH modulation, and stimulation of the Na + /K + pump

Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Sakurai, Yoshinori; Kobayashi, Tooru; Takagaki, Masao; Kinashi, Yuko; Akaboshi, Mitsuhiko

2000-01-01

Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays following thermal neutron irradiation with or without 10 B-compound were examined. Methods and Materials: 5-Bromo-2'-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10 B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of γ-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation. Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to γ-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only 10 B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population

On the Evolution of the Central Density of Quiescent Galaxies

International Nuclear Information System (INIS)

Tacchella, Sandro; Carollo, C. Marcella; Woo, Joanna; Faber, S. M.; Koo, David C.; Cibinel, Anna; Dekel, Avishai; Renzini, Alvio

2017-01-01

We investigate the origin of the evolution of the population-averaged central stellar mass density (Σ_1) of quiescent galaxies (QGs) by probing the relation between stellar age and Σ_1 at z ∼ 0. We use the Zurich ENvironmental Study (ZENS), which is a survey of galaxy groups with a large fraction of satellite galaxies. QGs shape a narrow locus in the Σ_1– M _⋆ plane, which we refer to as Σ_1 ridgeline. Colors of ( B − I ) and ( I − J ) are used to divide QGs into three age categories: young ( 4 Gyr). At fixed stellar mass, old QGs on the Σ_1 ridgeline have higher Σ_1 than young QGs. This shows that galaxies landing on the Σ_1 ridgeline at later epochs arrive with lower Σ_1, which drives the zeropoint of the ridgeline down with time. We compare the present-day zeropoint of the oldest population at z = 0 with the zeropoint of the quiescent population 4 Gyr back in time, at z = 0.37. These zeropoints are identical, showing that the intrinsic evolution of individual galaxies after they arrive on the Σ_1 ridgeline must be negligible, or must evolve parallel to the ridgeline during this interval. The observed evolution of the global zeropoint of 0.07 dex over the last 4 Gyr is thus largely due to the continuous addition of newly quenched galaxies with lower Σ_1 at later times (“progenitor bias”). While these results refer to the satellite-rich ZENS sample as a whole, our work suggests a similar age–Σ_1 trend for central galaxies.

THE AGE SPREAD OF QUIESCENT GALAXIES WITH THE NEWFIRM MEDIUM-BAND SURVEY: IDENTIFICATION OF THE OLDEST GALAXIES OUT TO z ∼ 2

International Nuclear Information System (INIS)

Whitaker, Katherine E.; Van Dokkum, Pieter G.; Brammer, Gabriel; Bezanson, Rachel; Lee, Kyoung-Soo; Muzzin, Adam; Wake, David A.; Kriek, Mariska; Franx, Marijn; Quadri, Ryan F.; Labbe, Ivo; Marchesini, Danilo; Illingworth, Garth D.; Rudnick, Gregory

2010-01-01

With a complete, mass-selected sample of quiescent galaxies from the NEWFIRM Medium-Band Survey, we study the stellar populations of the oldest and most massive galaxies (>10 11 M sun ) to high redshift. The sample includes 570 quiescent galaxies selected based on their extinction-corrected U - V colors out to z = 2.2, with accurate photometric redshifts, σ z /(1 + z) ∼ 2%, and rest-frame colors, σ U-V ∼ 0.06 mag. We measure an increase in the intrinsic scatter of the rest-frame U - V colors of quiescent galaxies with redshift. This scatter in color arises from the spread in ages of the quiescent galaxies, where we see both relatively quiescent red, old galaxies and quiescent blue, younger galaxies toward higher redshift. The trends between color and age are consistent with the observed composite rest-frame spectral energy distributions (SEDs) of these galaxies. The composite SEDs of the reddest and bluest quiescent galaxies are fundamentally different, with remarkably well-defined 4000 A and Balmer breaks, respectively. Some of the quiescent galaxies may be up to four times older than the average age and up to the age of the universe, if the assumption of solar metallicity is correct. By matching the scatter predicted by models that include growth of the red sequence by the transformation of blue galaxies to the observed intrinsic scatter, the data indicate that most early-type galaxies formed their stars at high redshift with a burst of star formation prior to migrating to the red sequence. The observed U - V color evolution with redshift is weaker than passive evolution predicts; possible mechanisms to slow the color evolution include increasing amounts of dust in quiescent galaxies toward higher redshift, red mergers at z ∼< 1, and a frosting of relatively young stars from star formation at later times.

On the Evolution of the Central Density of Quiescent Galaxies

Energy Technology Data Exchange (ETDEWEB)

Tacchella, Sandro; Carollo, C. Marcella; Woo, Joanna [Department of Physics, Institute for Astronomy, ETH Zurich, CH-8093 Zurich (Switzerland); Faber, S. M.; Koo, David C. [Department of Astronomy and Astrophysics, University of California Observatories/Lick Observatory, University of California, Santa Cruz, CA (United States); Cibinel, Anna [Astronomy Centre, Department of Physics and Astronomy, University of Sussex, Brighton, BN1 9QH (United Kingdom); Dekel, Avishai [Center for Astrophysics and Planetary Science, Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel); Renzini, Alvio, E-mail: sandro.tacchella@phys.ethz.ch [INAF Osservatorio Astronomico di Padova, vicolo dellOsservatorio 5, I-35122 Padova (Italy)

2017-07-20

We investigate the origin of the evolution of the population-averaged central stellar mass density (Σ{sub 1}) of quiescent galaxies (QGs) by probing the relation between stellar age and Σ{sub 1} at z ∼ 0. We use the Zurich ENvironmental Study (ZENS), which is a survey of galaxy groups with a large fraction of satellite galaxies. QGs shape a narrow locus in the Σ{sub 1}– M {sub ⋆} plane, which we refer to as Σ{sub 1} ridgeline. Colors of ( B − I ) and ( I − J ) are used to divide QGs into three age categories: young (<2 Gyr), intermediate (2–4 Gyr), and old (>4 Gyr). At fixed stellar mass, old QGs on the Σ{sub 1} ridgeline have higher Σ{sub 1} than young QGs. This shows that galaxies landing on the Σ{sub 1} ridgeline at later epochs arrive with lower Σ{sub 1}, which drives the zeropoint of the ridgeline down with time. We compare the present-day zeropoint of the oldest population at z = 0 with the zeropoint of the quiescent population 4 Gyr back in time, at z = 0.37. These zeropoints are identical, showing that the intrinsic evolution of individual galaxies after they arrive on the Σ{sub 1} ridgeline must be negligible, or must evolve parallel to the ridgeline during this interval. The observed evolution of the global zeropoint of 0.07 dex over the last 4 Gyr is thus largely due to the continuous addition of newly quenched galaxies with lower Σ{sub 1} at later times (“progenitor bias”). While these results refer to the satellite-rich ZENS sample as a whole, our work suggests a similar age–Σ{sub 1} trend for central galaxies.

Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.

Science.gov (United States)

Llorens-Bobadilla, Enric; Zhao, Sheng; Baser, Avni; Saiz-Castro, Gonzalo; Zwadlo, Klara; Martin-Villalba, Ana

2015-09-03

Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-wide Gene Expression Analysis of Mucosal Colonic Biopsies and Isolated Colonocytes Suggests a Continuous Inflammatory State in the Lamina Propria of Patients with Quiescent Ulcerative Colitis

DEFF Research Database (Denmark)

Bjerrum, Jacob Tveiten; Hansen, Morten; Olsen, Jørgen

2010-01-01

colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n = 8), quiescent UC (n = 9), and with irritable bowel......Background: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated......-discriminant analysis using the SIMCA-P 11 software (Umetrics, Umea, Sweden). Results: A clear separation between active UC, quiescent UC, and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC...

THE FUNDAMENTAL PLANE OF MASSIVE QUIESCENT GALAXIES OUT TO z ∼ 2

Energy Technology Data Exchange (ETDEWEB)

Van de Sande, Jesse; Franx, Marijn [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Kriek, Mariska [Astronomy Department, University of California at Berkeley, Berkeley, CA 94720 (United States); Bezanson, Rachel [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Van Dokkum, Pieter G. [Department of Astronomy, Yale University, P.O. Box 208101, New Haven, CT 06520-8101 (United States)

2014-10-01

The Fundamental Plane (FP) of early-type galaxies, relating the effective radius, velocity dispersion, and surface brightness, has long been recognized as a unique tool for analyzing galaxy structure and evolution. With the discovery of distant quiescent galaxies and the introduction of high sensitivity near-infrared spectrographs, it is now possible to explore the FP out to z ∼ 2. In this Letter we study the evolution of the FP out to z ∼ 2 using kinematic measurements of massive quiescent galaxies (M {sub *} > 10{sup 11} M {sub ☉}). We find preliminary evidence for the existence of an FP out to z ∼ 2. The scatter of the FP, however, increases from z ∼ 0 to z ∼ 2, even when taking into account the larger measurement uncertainties at higher redshifts. We find a strong evolution of the zero point from z ∼ 2 to z ∼ 0: Δlog{sub 10} M/L{sub g} ∝(– 0.49 ± 0.03)z. In order to assess whether our spectroscopic sample is representative of the early-type galaxy population at all redshifts, we compare their rest-frame g – z colors with those from a larger mass complete sample of quiescent galaxies. At z > 1 we find that the spectroscopic sample is bluer. We use the color offsets to estimate a mass-to-light ratio (M/L) correction. The implied FP zero point evolution after correction is significantly smaller: Δlog{sub 10} M/L{sub g} ∝(– 0.39 ± 0.02)z. This is consistent with an apparent formation redshift of z{sub form}=6.62{sub −1.44}{sup +3.19} for the underlying population, ignoring the effects of progenitor bias. A more complete spectroscopic sample is required at z ∼ 2 to properly measure the M/L evolution from the FP evolution.

Defining a stem cell hierarchy in the intestine: markers, caveats and controversies

Science.gov (United States)

Smith, Nicholas R.; Gallagher, Alexandra C.

2016-01-01

Abstract The past decade has appreciated rapid advance in identifying the once elusive intestinal stem cell (ISC) populations that fuel the continual renewal of the epithelial layer. This advance was largely driven by identification of novel stem cell marker genes, revealing the existence of quiescent, slowly‐ and active‐cycling ISC populations. However, a critical barrier for translating this knowledge to human health and disease remains elucidating the functional interplay between diverse stem cell populations. Currently, the precise hierarchical and regulatory relationships between these ISC populations are under intense scrutiny. The classical theory of a linear hierarchy, where quiescent and slowly‐cycling stem cells self‐renew but replenish an active‐cycling population, is well established in other rapidly renewing tissues such as the haematopoietic system. Efforts to definitively establish a similar stem cell hierarchy within the intestinal epithelium have yielded conflicting results, been difficult to interpret, and suggest non‐conventional alternatives to a linear hierarchy. While these new and potentially paradigm‐shifting discoveries are intriguing, the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system. PMID:26864260

A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation.

Science.gov (United States)

Sun, Jiaqi; Bonaguidi, Michael A; Jun, Heechul; Guo, Junjie U; Sun, Gerald J; Will, Brett; Yang, Zhengang; Jang, Mi-Hyeon; Song, Hongjun; Ming, Guo-li; Christian, Kimberly M

2015-09-04

A converging body of evidence indicates that levels of adult hippocampal neurogenesis vary along the septo-temporal axis of the dentate gyrus, but the molecular mechanisms underlying this regional heterogeneity are not known. We previously identified a niche mechanism regulating proliferation and neuronal development in the adult mouse dentate gyrus resulting from the activity-regulated expression of secreted frizzled-related protein 3 (sfrp3) by mature neurons, which suppresses activation of radial glia-like neural stem cells (RGLs) through inhibition of Wingless/INT (WNT) protein signaling. Here, we show that activation rates within the quiescent RGL population decrease gradually along the septo-temporal axis in the adult mouse dentate gyrus, as defined by MCM2 expression in RGLs. Using in situ hybridization and quantitative real-time PCR, we identified an inverse septal-to-temporal increase in the expression of sfrp3 that emerges during postnatal development. Elimination of sfrp3 and its molecular gradient leads to increased RGL activation, preferentially in the temporal region of the adult dentate gyrus. Our study identifies a niche mechanism that contributes to the graded distribution of neurogenesis in the adult dentate gyrus and has important implications for understanding functional differences associated with adult hippocampal neurogenesis along the septo-temporal axis.

Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

Directory of Open Access Journals (Sweden)

Sara P. Y. Che

2017-11-01

Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

EXPLORING THE z = 3-4 MASSIVE GALAXY POPULATION WITH ZFOURGE: THE PREVALENCE OF DUSTY AND QUIESCENT GALAXIES

Energy Technology Data Exchange (ETDEWEB)

Spitler, Lee R.; Rees, Glen [Department of Physics and Astronomy, Macquarie University, Sydney, NSW 2109 (Australia); Straatman, Caroline M. S.; Labbé, Ivo [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Glazebrook, Karl; Kacprzak, Glenn G.; Nanayakkara, Themiya [Centre for Astrophysics and Supercomputing, Swinburne University, Hawthorn, VIC 3122 (Australia); Tran, Kim-Vy H.; Papovich, Casey; Kawinwanichakij, Lalitwadee; Mehrtens, Nicola; Tilvi, Vithal; Tomczak, Adam R. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); Quadri, Ryan F.; Persson, S. Eric; Kelson, Daniel D.; McCarthy, Patrick J.; Monson, Andrew J. [Carnegie Observatories, Pasadena, CA 91101 (United States); Van Dokkum, Pieter [Department of Astronomy, Yale University, New Haven, CT 06520 (United States); Allen, Rebecca, E-mail: lee.spitler@mq.edu.au [Australian Astronomical Observatory, P.O. Box 296 Epping, NSW 1710 (Australia)

2014-06-01

Our understanding of the redshift z > 3 galaxy population relies largely on samples selected using the popular ''dropout'' technique, typically consisting of UV-bright galaxies with blue colors and prominent Lyman breaks. As it is currently unknown if these galaxies are representative of the massive galaxy population, we here use the FOURSTAR Galaxy Evolution (ZFOURGE) survey to create a stellar mass-limited sample at z = 3-4. Uniquely, ZFOURGE uses deep near-infrared medium-bandwidth filters to derive accurate photometric redshifts and stellar population properties. The mass-complete sample consists of 57 galaxies with log M >10.6, reaching below M {sup *} at z = 3-4. On average, the massive z = 3-4 galaxies are extremely faint in the observed optical with median R{sub tot}{sup AB}=27.48±0.41 (rest-frame M {sub 1700} = –18.05 ± 0.37). They lie far below the UV luminosity-stellar mass relation for Lyman break galaxies and are about ∼100 × fainter at the same mass. The massive galaxies are red (R – K {sub s} {sub AB} = 3.9 ± 0.2; rest-frame UV-slope β = –0.2 ± 0.3) likely from dust or old stellar ages. We classify the galaxy spectral energy distributions by their rest-frame U–V and V–J colors and find a diverse population: 46{sub −6−17}{sup +6+10}% of the massive galaxies are quiescent, 40{sub −6−5}{sup +6+7}% are dusty star-forming galaxies, and only 14{sub −3−4}{sup +3+10}% resemble luminous blue star-forming Lyman break galaxies. This study clearly demonstrates an inherent diversity among massive galaxies at higher redshift than previously known. Furthermore, we uncover a reservoir of dusty star-forming galaxies with 4 × lower specific star-formation rates compared to submillimeter-selected starbursts at z > 3. With 5 × higher numbers, the dusty galaxies may represent a more typical mode of star formation compared to submillimeter-bright starbursts.

Probing the Build-Up of Quiescent Galaxies at z>3

Science.gov (United States)

Finkelstein, Steven

We propose to perform the most robust investigation to date into the evolution of massive quiescent and star-forming galaxies at z > 3, at a time when the universe was less than two billion years old. The build-up of quiescent galaxies in particular is poorly understood, primarily due to large Poisson and cosmic variance issues that have plagued previous studies that probed small volumes, leading to a disagreement on the quiescent fraction by a factor of >3 in the literature. Our proposed work is only now possible due to a new legacy survey led by our team: the Spitzer-HETDEX Exploratory Large Area Survey (SHELA), which is imaging a 23 deg^2 area of the sky at optical, and near, mid and far-infrared, and X-ray wavelengths. In particular, the wide area coverage of the Spitzer/IRAC data allows us to be sensitive to massive galaxies at very high redshifts, the Herschel data allows us to rule out lower-redshift counterparts, and the XMM-Newton data allows us to remove quasar contaminants from our sample. This survey covers a volume >14X that of the largest previous survey for quiescent galaxies at z=3.5, and ~6X larger than that of the largest previous survey for star-forming galaxies at z=4. All of these data exist in the region soon to be observed by the Hobby Eberly Telescope Dark Energy Experiment (HETDEX), which will provide high-precision measures of halo masses and local density at z~3. Using this exquisite multi-wavelength dataset, we will measure the abundance of massive quiescent galaxies at z ~ 3-5, and, combining with measures of the halo masses and environment, compare properties of quiescent galaxies to star-forming galaxies to investigate the physical cause behind the quenching. We will also investigate the onset of quenching in star-forming galaxies in two ways, first by studying the relation between star formation rate and stellar mass, to search for a break in the typically-linear relation at high masses, and second by constraining the feedback

Crypt base columnar stem cells in small intestines of mice are radioresistant

NARCIS (Netherlands)

Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

2012-01-01

BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

THE MID-INFRARED AND NEAR-ULTRAVIOLET EXCESS EMISSIONS OF QUIESCENT GALAXIES ON THE RED SEQUENCE

International Nuclear Information System (INIS)

Ko, Jongwan; Lee, Jong Chul; Hwang, Ho Seong; Sohn, Young-Jong

2013-01-01

We study the mid-infrared (IR) and near-ultraviolet (UV) excess emissions of spectroscopically selected quiescent galaxies on the optical red sequence. We use the Wide-field Infrared Survey Explorer mid-IR and Galaxy Evolution Explorer near-UV data for a spectroscopic sample of galaxies in the Sloan Digital Sky Survey Data Release 7 to study the possible connection between quiescent red-sequence galaxies with and without mid-IR/near-UV excess. Among 648 12 μm detected quiescent red-sequence galaxies without Hα emission, 26% and 55% show near-UV and mid-IR excess emissions, respectively. When we consider only bright (M r n 4000 than those without mid-IR and near-UV excess emissions. We also find that mid-IR weighted mean stellar ages of quiescent red-sequence galaxies with mid-IR excess are larger than those with near-UV excess, and smaller than those without mid-IR and near-UV excess. The environmental dependence of the fraction of quiescent red-sequence galaxies with mid-IR and near-UV excess seems strong even though the trends of quiescent red-sequence galaxies with near-UV excess differ from those with mid-IR excess. These results indicate that the recent star formation traced by near-UV (∼< 1 Gyr) and mid-IR (∼< 2 Gyr) excess is not negligible among nearby, quiescent, red, early-type galaxies. We suggest a possible evolutionary scenario of quiescent red-sequence galaxies from quiescent red-sequence galaxies with near-UV excess to those with mid-IR excess to those without near-UV and mid-IR excess.

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4+ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

OpenAIRE

Arenaccio, Claudia; Chiozzini, Chiara; Columba-Cabezas, Sandra; Manfredi, Francesco; Affabris, Elisabetta; Baur, Andreas; Federico, Maurizio

2014-01-01

Resting CD4+ T lymphocytes resist human immunodeficiency virus (HIV) infection. Here, we provide evidence that exosomes from HIV-1-infected cells render resting human primary CD4+ T lymphocytes permissive to HIV-1 replication. These results were obtained with transwell cocultures of HIV-1-infected cells with quiescent CD4+ T lymphocytes in the presence of inhibitors of exosome release and were confirmed using exosomes purified from supernatants of HIV-1-infected primary CD4+ T lymphocytes. We...

1-{beta}-D-arabinofuranosylcytosine is cytotoxic in quiescent normal lymphocytes undergoing DNA excision repair

Energy Technology Data Exchange (ETDEWEB)

Yamauchi, Takahiro; Kawai, Yasukazu; Ueda, Takanori [Fukui Medical Univ., Matsuoka (Japan)

2002-12-01

We have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-{beta}-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap-filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay. When normal lymphocytes were treated with ultraviolet C or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the processes of DNA excision repair were promptly initiated and rapidly completed. When the cells were incubated with ara-C prior to irradiation or BCNU treatment, the steps of DNA synthesis and rejoining in the repair processes were both inhibited. The ara-C-mediated inhibition of the repair processes was concentration-dependent, with the effect peaking at 10{mu}M. The combination of ara-C with these DNA repair initiators exerted subsequent cytotoxicity, which was proportional to the extent of the repair inhibition in the presence of ara-C. In conclusion, ara-C was cytotoxic in quiescent cells undergoing DNA repair. This might be attributed to unrepaired DNA damage that remained in the cells, thereby inducing lethal cytotoxicity. Alternatively, ara-C might exert its own cytotoxicity by inhibiting DNA synthesis in the repair processes. Such a strategy may be effective against a dormant subpopulation in acute leukemia that survives chemotherapy. (author)

1-β-D-arabinofuranosylcytosine is cytotoxic in quiescent normal lymphocytes undergoing DNA excision repair

International Nuclear Information System (INIS)

Yamauchi, Takahiro; Kawai, Yasukazu; Ueda, Takanori

2002-01-01

We have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-β-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap-filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay. When normal lymphocytes were treated with ultraviolet C or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the processes of DNA excision repair were promptly initiated and rapidly completed. When the cells were incubated with ara-C prior to irradiation or BCNU treatment, the steps of DNA synthesis and rejoining in the repair processes were both inhibited. The ara-C-mediated inhibition of the repair processes was concentration-dependent, with the effect peaking at 10μM. The combination of ara-C with these DNA repair initiators exerted subsequent cytotoxicity, which was proportional to the extent of the repair inhibition in the presence of ara-C. In conclusion, ara-C was cytotoxic in quiescent cells undergoing DNA repair. This might be attributed to unrepaired DNA damage that remained in the cells, thereby inducing lethal cytotoxicity. Alternatively, ara-C might exert its own cytotoxicity by inhibiting DNA synthesis in the repair processes. Such a strategy may be effective against a dormant subpopulation in acute leukemia that survives chemotherapy. (author)

An EPIC Tale of the Quiescent Particle Background

Science.gov (United States)

Snowden, S.L.; Kuntz, K.D.

2017-01-01

Extended Source Analysis Software Use Based Empirical Investigation: (1) Builds quiescent particle background (QPB) spectra and images for observations of extended sources that fill (or mostly fill) the FOV i.e., annular background subtraction won't work. (2) Uses a combination of Filter Wheel Closed (FWC) and corner data to capture the spectral, spatial, and temporal variation of the quiescent particle background. New Work: (1) Improved understanding of the QPB (aided by adding a whole lot of data since 2008). (2) Significantly improved statistics (did I mention a LOT more data?). (3) Better characterization and identification of anomalous states. (4) Builds backgrounds for some anomalous state. (5) New efficient method for non-anomalous states.

Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1.

Science.gov (United States)

Nguyen, Van Thi; Cancedda, Ranieri; Descalzi, Fiorella

2018-03-01

The idea of rescuing the body self-repair capability lost during evolution is progressively gaining ground in regenerative medicine. In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. Aim of this study was to assess the potential of a platelet lysate (PL) for human articular cartilage repair considering its activity on progenitor cells and differentiated chondrocytes. PL induced the re-entry in the cell cycle of confluent, growth-arrested dedifferentiated/progenitor cartilage cells. In a cartilage permissive culture environment, differentiated cells also resumed proliferation after exposure to PL. These findings correlated with an up-regulation of the proliferation/survival pathways ERKs and Akt and with an induction of cyclin D1. In short- and long-term cultures of articular cartilage explants, we observed a release of proliferating chondroprogenitors able to differentiate and form an "in vitro" tissue with properties of healthy articular cartilage. Moreover, in cultured cartilage cells, PL induced a hypoxia-inducible factor (HIF-1) alpha increase, its nuclear relocation and the binding to HIF-1 responsive elements. These events were possibly related to the cell proliferation because the HIF-1 inhibitor acriflavine inhibited HIF-1 binding to HIF-1 responsive elements and cell proliferation. Our study demonstrates that PL induces quiescent cartilage cell activation and proliferation leading to new cartilage formation, identifies PL activated pathways playing a role in these processes, and provides a rationale to the application of PL for therapeutic treatment of damaged articular cartilage. Copyright © 2017 John Wiley & Sons, Ltd.

Muscle Satellite Cell Protein Teneurin‐4 Regulates Differentiation During Muscle Regeneration

Science.gov (United States)

Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So‐ichiro; Okano, Hideyuki; Takeda, Shin'ichi

2015-01-01

Abstract Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin‐4 (Ten‐4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten‐4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten‐4‐deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten‐4‐deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten‐4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten‐4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. Stem Cells 2015;33:3017–3027 PMID:26013034

Radiosensitization effect by combination with paclitaxel in vivo, including the effect on intratumor quiescent cells

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Nishimura, Yasumasa; Kinashi, Yuko; Takagaki, Masao; Hori, Hitoshi; Nagasawa, Hideko; Uto, Yoshihiro; Tsuchiya, Izumi; Sadahiro, Sotaro; Murayama, Chieko

2001-01-01

Purpose: To evaluate the radiosensitization effect on solid tumors upon combination treatment with paclitaxel (TXL), including the effect on intratumor quiescent (Q) cells. Methods and Materials: Mice bearing SCC VII or EL4 solid tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days to label all proliferating (P) cells. The mice then received γ-irradiation with or without tirapazamine (TPZ) at various time points after TXL administration. Another group of mice received a series of test doses of γ-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors at various time points after TXL administration. Immediately after irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, the tumor cells were isolated from the solid tumors in another group of mice, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN or apoptosis frequency of Q cells was then used to calculate the surviving fraction of Q cells from the regression line for the relationship between the MN or apoptosis frequency and the surviving fraction of total tumor cells. Results: In both SCC VII and EL4 tumors, maximum values of mitotic index (MI) and apoptosis frequency were observed 9 and 24 h after TXL administration, respectively. However, on the whole, the apoptosis frequency for SCC VII was very low. γ-Irradiation 9 h after TXL administration induced significant radiosensitization effects on the total cells of both tumors. Irradiation at 60 h had a more significant effect on total cells of EL4 tumor, but no significant effect on total cells of SCC VII

Exonuclease 1 is a critical mediator of survival during DNA double strand break repair in nonquiescent hematopoietic stem and progenitor cells.

Science.gov (United States)

Desai, Amar; Qing, Yulan; Gerson, Stanton L

2014-02-01

Hematopoietic stem cell (HSC) populations require DNA repair pathways to maintain their long-term survival and reconstitution capabilities, but mediators of these processes are still being elucidated. Exonuclease 1 (Exo1) participates in homologous recombination (HR) and Exo1 loss results in impaired 5' HR end resection. We use cultured Exo1(mut) fibroblasts and bone marrow to demonstrate that loss of Exo1 function results in defective HR in cycling cells. Conversely, in Exo1(mut) mice HR is not required for maintenance of quiescent HSCs at steady state, confirming the steady state HSC reliance on nonhomologous end joining (NHEJ). Exo1(mut) mice sustained serial repopulation, displayed no defect in competitive repopulation or niche occupancy, and exhibited no increased sensitivity to whole body ionizing radiation. However, when Exo1(mut) HSCs were pushed into cell cycle in vivo with 5-fluorouracil or poly IC, the hematopoietic population became hypersensitive to IR, resulting in HSC defects and animal death. We propose Exo1-mediated HR is dispensable for stem cell function in quiescent HSC, whereas it is essential to HSC response to DNA damage processing after cell cycle entry, and its loss is not compensated by intact NHEJ. In HSCs, the maintenance of stem cell function after DNA damage is dependent on the DNA repair capacity, segregated by active versus quiescent points in cell cycle. © AlphaMed Press.

Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis

Energy Technology Data Exchange (ETDEWEB)

Balduino, Alex, E-mail: balduino@uva.edu.br [School of Dentistry, Veiga de Almeida University, Rio de Janeiro, RJ (Brazil); Mello-Coelho, Valeria [Biomedical Science Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ (Brazil); National Institute on Aging, National Institute of Health, Baltimore, MD (United States); Wang, Zhou; Taichman, Russell S.; Krebsbach, Paul H. [Department of Periodontics, Prevention and Geriatrics, University of Michigan School of Dentistry, Ann Arbor, MI (United States); Weeraratna, Ashani T.; Becker, Kevin G. [National Institute on Aging, National Institute of Health, Baltimore, MD (United States); Mello, Wallace de [Instituto Oswaldo Cruz, Rio de Janeiro, RJ (Brazil); Taub, Dennis D. [National Institute on Aging, National Institute of Health, Baltimore, MD (United States); Borojevic, Radovan [Biomedical Science Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ (Brazil)

2012-11-15

In the bone marrow cavity, hematopoietic stem cells (HSC) have been shown to reside in the endosteal and subendosteal perivascular niches, which play specific roles on HSC maintenance. Although cells with long-term ability to reconstitute full hematopoietic system can be isolated from both niches, several data support a heterogenous distribution regarding the cycling behavior of HSC. Whether this distinct behavior depends upon the role played by the stromal populations which distinctly create these two niches is a question that remains open. In the present report, we used our previously described in vivo assay to demonstrate that endosteal and subendosteal stromal populations are very distinct regarding skeletal lineage differentiation potential. This was further supported by a microarray-based analysis, which also demonstrated that these two stromal populations play distinct, albeit complementary, roles in HSC niche. Both stromal populations were preferentially isolated from the trabecular region and behave distinctly in vitro, as previously reported. Even though these two niches are organized in a very close range, in vivo assays and molecular analyses allowed us to identify endosteal stroma (F-OST) cells as fully committed osteoblasts and subendosteal stroma (F-RET) cells as uncommitted mesenchymal cells mainly represented by perivascular reticular cells expressing high levels of chemokine ligand, CXCL12. Interestingly, a number of cytokines and growth factors including interleukin-6 (IL-6), IL-7, IL-15, Hepatocyte growth factor (HGF) and stem cell factor (SCF) matrix metalloproteases (MMPs) were also found to be differentially expressed by F-OST and F-RET cells. Further microarray analyses indicated important mechanisms used by the two stromal compartments in order to create and coordinate the 'quiescent' and 'proliferative' niches in which hematopoietic stem cells and progenitors reside.

Energy Utilization for Survival and Fertilization-Parsimonious Quiescent Sperm Turn Extravagant on Motility Activation in Rat.

Science.gov (United States)

Kumar, Lokesh; Yadav, Santosh K; Kushwaha, Bhavana; Pandey, Aastha; Sharma, Vikas; Verma, Vikas; Maikhuri, Jagdamba P; Rajender, Singh; Sharma, Vishnu L; Gupta, Gopal

2016-04-01

Quiescent sperm survive in cauda epididymis for long periods of time under extreme crowding conditions and with a very limited energy substrate, while after ejaculation, motile sperm live for a much shorter period with an unlimited energy resource and without crowding. Thus, the energy metabolism in relation to the energy requirement of the two may be quite different. A simple physiological technique was evolved to collect viable quiescent sperm from rat cauda epididymis to compare its energy metabolism with motile sperm. Quiescent sperm exhibited 40%-60% higher activities of mitochondrial electron transport chain complexes I-IV and ATP synthase in comparison to motile sperm and accumulated Ca(2+) in the midpiece mitochondria to enhance oxidative phosphorylation (OxPhos). In contrast, motile sperm displayed up to 75% higher activities of key glycolytic enzymes and secreted more than two times the lactate than quiescent sperm. Quiescent sperm phosphorylated AMPK and MAPK-p38, while motile sperm phosphorylated AKT and MAPK/ERK. Glycolytic inhibitor iodoacetamide prevented motility activation of quiescent rat sperm and inhibited conception in rabbits more effectively than OxPhos uncoupler 2,4-dinitrophenol. Apparently, quiescent sperm employ the most energy efficient OxPhos to survive for extended periods of time under extreme conditions of nutrition and crowding. However, on motility initiation, sperm switch predominantly to glycolysis to cater to their high- and quick-energy requirement of much shorter periods. This study also presents a proof of concept for targeting sperm energy metabolism for contraception. © 2016 by the Society for the Study of Reproduction, Inc.

Multi-Wavelength Eclipse Observations of a Quiescent Prominence

Czech Academy of Sciences Publication Activity Database

Jejčič, S.; Heinzel, Petr; Zapiór, M.; Druckmüller, M.; Gunár, Stanislav; Kotrč, Pavel

2014-01-01

Roč. 289, č. 7 (2014), s. 2487-2501 ISSN 0038-0938 R&D Projects: GA ČR GAP209/12/0906 Institutional support: RVO:67985815 Keywords : eclipse observations * prominences * quiescent Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.039, year: 2014

Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation During Muscle Regeneration.

Science.gov (United States)

Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So-Ichiro; Okano, Hideyuki; Takeda, Shin'ichi; Akazawa, Chihiro

2015-10-01

Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin-4 (Ten-4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten-4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten-4-deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten-4-deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten-4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten-4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. © 2015 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

The evolution of the stellar mass functions of star-forming and quiescent galaxies to z = 4 from the COSMOS/ultraVISTA survey

DEFF Research Database (Denmark)

Muzzin, Adam; Marchesini, Danilo; Stefano, Mauro

2013-01-01

We present measurements of the stellar mass functions (SMFs) of star-forming and quiescent galaxies to z = 4 using a sample of 95,675 Ks -selected galaxies in the COSMOS/UltraVISTA field. The SMFs of the combined population are in good agreement with previous measurements and show that the stellar...

Rapid desensitization and resensitization of 5-HT2 receptor mediated phosphatidyl inositol hydrolysis by serotonin agonists in quiescent calf aortic smooth muscle cells

International Nuclear Information System (INIS)

Pauwels, P.J.; Van Gompel, P.; Leysen, J.E.

1990-01-01

Agonist regulation of 5-hydroxytryptamine 2 (5-HT 2 ) receptors was studied in calf aortic smooth muscle cultures incubated in a quiescent, defined synthetic medium that does not stimulate cell proliferation, but that provides cells with supplements that maintain cell viability. In these cells, 5-hydroxytryptamine (5-HT)-induced [ 3 H]inositol phosphates accumulation showed the characteristics of a 5-HT 2 receptor coupled transducing system according to the inhibition of the response by 5-HT 2 antagonists at nanomolar concentrations. The 5-HT 2 receptor coupled response became rapidly desensitized during continued incubation with 5-HT and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM); nearly full desensitization was obtained in two hours with 10 μM 5-HT and DOM pretreatment. The recovery of the response had a half-live of 5 hours after 2 hours pretreatment and of 9.5 to 12.5 hours after 24 to 96 hours agonist pretreatment. The DOM-induced desensitization of the 5-HT 2 receptor coupled response was fully blocked by 0.1 μM cinanserin. Cinanserin alone did not induce desensitization or up-regulation of the 5-HT 2 receptor coupled response at 0.1 μM

Laser scanning cytometry (LCS) allows detailed analysis of the cell cycle in PI stained human fibroblasts (TIG-7).

Science.gov (United States)

Kawasaki, M; Sasaki, K; Satoh, T; Kurose, A; Kamada, T; Furuya, T; Murakami, T; Todoroki, T

1997-01-01

We have demonstrated a method for the in situ determination of the cell cycle phases of TIG-7 fibroblasts using a laser scanning cytometer (LSC) which has not only a function equivalent to flow cytometry (FCM) but also has a capability unique in itself. LSC allows a more detailed analysis of the cell cycle in cells stained with propidium iodide (PI) than FCM. With LSC it is possible to discriminate between mitotic cells and G2 cells, between post-mitotic cells and G1 cells, and between quiescent cells and cycling cells in a PI fluorescence peak (chromatin condensation) vs. fluorescence value (DNA content) cytogram for cells stained with PI. These were amply confirmed by experiments using colcemid and adriamycin. We were able to identify at least six cell subpopulations for PI stained cells using LSC; namely G1, S, G2, M, postmitotic and quiescent cell populations. LSC analysis facilitates the monitoring of effects of drugs on the cell cycle.

The unexpectedly large dust and gas content of quiescent galaxies at z > 1.4

Science.gov (United States)

Gobat, R.; Daddi, E.; Magdis, G.; Bournaud, F.; Sargent, M.; Martig, M.; Jin, S.; Finoguenov, A.; Béthermin, M.; Hwang, H. S.; Renzini, A.; Wilson, G. W.; Aretxaga, I.; Yun, M.; Strazzullo, V.; Valentino, F.

2018-03-01

Early-type galaxies (ETGs) contain most of the stars present in the local Universe and, above a stellar mass content of 5 × 1010 solar masses, vastly outnumber spiral galaxies such as the Milky Way. These massive spheroidal galaxies have, in the present day, very little gas or dust in proportion to their mass1, and their stellar populations have been evolving passively for over 10 billion years. The physical mechanisms that led to the termination of star formation in these galaxies and depletion of their interstellar medium remain largely conjectural. In particular, there are currently no direct measurements of the amount of residual gas that might still be present in newly quiescent spheroidals at high redshift2. Here we show that quiescent ETGs at redshift z 1.8, close to their epoch of quenching, contained at least two orders of magnitude more dust at a fixed stellar mass compared with local ETGs. This implies the presence of substantial amounts of gas (5-10%), which has been consumed less efficiently than in more active galaxies, probably due to their spheroidal morphology, consistent with our simulations. This lower star formation efficiency, combined with an extended hot gas halo possibly maintained by persistent feedback from an active galactic nucleus, keep ETGs mostly passive throughout cosmic time.

Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal

Science.gov (United States)

Chandrakesan, Parthasarathy; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Taylor, Vivian E.; Li, James D.; Ali, Naushad; Sureban, Sripathi M.; Qante, Michael; Wang, Timothy C.; Bronze, Michael S.; Houchen, Courtney W.

2015-01-01

To date, no discrete genetic signature has been defined for isolated Dclk1+ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1+ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1+ cells, we FACS-sorted Dclk1+ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1-CreER;Rosa26-YFP). Analysis of sorted YFP+ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP− cells. Dclk1+ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1+ population. A significant increase in self-renewal capability (14-fold) was observed in in vitro isolated Dclk1+ cells. The unique genetic report presented in this manuscript suggests that Dclk1+ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1+ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells. PMID:26362399

Role of wall-attached structures in the interface of the quiescent core region in turbulent pipe flow

Science.gov (United States)

Yang, Jongmin; Hwang, Jinyul; Sung, Hyung Jin

2017-11-01

The effects of low- and high-speed structures on the interface of the quiescent core region are explored using direct numerical simulation data of turbulent pipe flow. The quiescent core region is a uniform momentum zone located at the center of the pipe flow, which contains the highest streamwise momentum with a low level of turbulence. The interface of the quiescent core region can be identified from the probability density function of the streamwise modal velocity. In the vicinity of the interface of the quiescent core region, the streamwise velocity changes abruptly. The abrupt jump in velocity causes an increase of the velocity gradient. The interface of the quiescent core region is similar to the laminar superlayer in turbulent/non-turbulent interface. The interface of the quiescent core region contains the low- and high-speed structures. They can be classified into wall-attached and detached structures depending on the distance between the structures and the wall. The influence of the detached structures accounted for most of the number of detected structures is negligible due to its small volume. Conversely, the wall-attached structures adjacent to the interface have a huge influence on the statistical amount of the interface, such as entrainment characteristics. This work was supported by the Creative Research Initiatives (No. 2017-013369) program of the National Research Foundation of Korea (MSIP).

Bubble entrapment during sphere impact onto quiescent liquid surfaces

KAUST Repository

Marston, Jeremy; Vakarelski, Ivan Uriev; Thoroddsen, Sigurdur T

2011-01-01

We report observations of air bubble entrapment when a solid sphere impacts a quiescent liquid surface. Using high-speed imaging, we show that a small amount of air is entrapped at the bottom tip of the impacting sphere. This phenomenon is examined

Plant stem cell niches.

Science.gov (United States)

Stahl, Yvonne; Simon, Rüdiger

2005-01-01

Stem cells are required to support the indeterminate growth style of plants. Meristems are a plants stem cell niches that foster stem cell survival and the production of descendants destined for differentiation. In shoot meristems, stem cell fate is decided at the populational level. The size of the stem cell domain at the meristem tip depends on signals that are exchanged with cells of the organizing centre underneath. In root meristems, individual stem cells are controlled by direct interaction with cells of the quiescent centre that lie in the immediate neighbourhood. Analysis of the interactions and signaling processes in the stem cell niches has delivered some insights into the molecules that are involved and revealed that the two major niches for plant stem cells are more similar than anticipated.

Stem Cell Interaction with Somatic Niche May Hold the Key to Fertility Restoration in Cancer Patients

Directory of Open Access Journals (Sweden)

Deepa Bhartiya

2012-01-01

Full Text Available The spontaneous return of fertility after bone marrow transplantation or heterotopic grafting of cryopreserved ovarian cortical tissue has surprised many, and a possible link with stem cells has been proposed. We have reviewed the available literature on ovarian stem cells in adult mammalian ovaries and presented a model that proposes that the ovary harbors two distinct populations of stem cells, namely, pluripotent, quiescent, very small embryonic-like stem cells (VSELs, and slightly larger “progenitor” ovarian germ stem cells (OGSCs. Besides compromising the somatic niche, oncotherapy destroys OGSCs since, like tumor cells, they are actively dividing; however VSELs persist since they are relatively quiescent. BMT or transplanted ovarian cortical tissue may help rejuvenate the ovarian niche, which possibly supports differentiation of persisting VSELs resulting in neo-oogenesis and follicular development responsible for successful pregnancies. Postnatal oogenesis in mammalian ovary from VSELs may be exploited for fertility restoration in cancer survivors including those who were earlier deprived of gametes and/or gonadal tissue cryopreservation options.

Electron densities in quiescent prominences derived from eclipse observations

Czech Academy of Sciences Publication Activity Database

Jejčič, S.; Heinzel, Petr

2009-01-01

Roč. 254, č. 1 (2009), s. 89-100 ISSN 0038-0938 Grant - others:EU(XE) ESA-PECS project No. 98030 Institutional research plan: CEZ:AV0Z10030501 Keywords : prominences quiescent * eclipse observations * visible spectrum Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 3.628, year: 2009

Ordered mesoporous silica prepared by quiescent interfacial growth method - effects of reaction chemistry

Science.gov (United States)

2013-01-01

Acidic interfacial growth can provide a number of industrially important mesoporous silica morphologies including fibers, spheres, and other rich shapes. Studying the reaction chemistry under quiescent (no mixing) conditions is important for understanding and for the production of the desired shapes. The focus of this work is to understand the effect of a number of previously untested conditions: acid type (HCl, HNO3, and H2SO4), acid content, silica precursor type (TBOS and TEOS), and surfactant type (CTAB, Tween 20, and Tween 80) on the shape and structure of products formed under quiescent two-phase interfacial configuration. Results show that the quiescent growth is typically slow due to the absence of mixing. The whole process of product formation and pore structuring becomes limited by the slow interfacial diffusion of silica source. TBOS-CTAB-HCl was the typical combination to produce fibers with high order in the interfacial region. The use of other acids (HNO3 and H2SO4), a less hydrophobic silica source (TEOS), and/or a neutral surfactant (Tweens) facilitate diffusion and homogenous supply of silica source into the bulk phase and give spheres and gyroids with low mesoporous order. The results suggest two distinct regions for silica growth (interfacial region and bulk region) in which the rate of solvent evaporation and local concentration affect the speed and dimension of growth. A combined mechanism for the interfacial bulk growth of mesoporous silica under quiescent conditions is proposed. PMID:24237719

EVIDENCE FOR WIDESPREAD ACTIVE GALACTIC NUCLEUS ACTIVITY AMONG MASSIVE QUIESCENT GALAXIES AT z ∼ 2

International Nuclear Information System (INIS)

Olsen, Karen P.; Rasmussen, Jesper; Toft, Sune; Zirm, Andrew W.

2013-01-01

We quantify the presence of active galactic nuclei (AGNs) in a mass-complete (M * > 5 × 10 10 M ☉ ) sample of 123 star-forming and quiescent galaxies at 1.5 ≤ z ≤ 2.5, using X-ray data from the 4 Ms Chandra Deep Field-South (CDF-S) survey. 41% ± 7% of the galaxies are detected directly in X-rays, 22% ± 5% with rest-frame 0.5-8 keV luminosities consistent with hosting luminous AGNs (L 0.5-8keV > 3 × 10 42 erg s –1 ). The latter fraction is similar for star-forming and quiescent galaxies, and does not depend on galaxy stellar mass, suggesting that perhaps luminous AGNs are triggered by external effects such as mergers. We detect significant mean X-ray signals in stacked images for both the individually non-detected star-forming and quiescent galaxies, with spectra consistent with star formation only and/or a low-luminosity AGN in both cases. Comparing star formation rates inferred from the 2-10 keV luminosities to those from rest-frame IR+UV emission, we find evidence for an X-ray excess indicative of low-luminosity AGNs. Among the quiescent galaxies, the excess suggests that as many as 70%-100% of these contain low- or high-luminosity AGNs, while the corresponding fraction is lower among star-forming galaxies (43%-65%). Our discovery of the ubiquity of AGNs in massive, quiescent z ∼ 2 galaxies provides observational support for the importance of AGNs in impeding star formation during galaxy evolution.

Early events elicited by bombesin and structurally related peptides in quiescent Swiss 3T3 cells. II. Changes in Na+ and Ca2+ fluxes, Na+/K+ pump activity, and intracellular pH

International Nuclear Information System (INIS)

Mendoza, S.A.; Schneider, J.A.; Lopez-Rivas, A.; Sinnett-Smith, J.W.; Rozengurt, E.

1986-01-01

The amphibian tetradecapeptide, bombesin, and structurally related peptides caused a marked increase in ouabain-sensitive 86 Rb + uptake (a measure of Na + /K + pump activity) in quiescent Swiss 3T3 cells. This effect occurred within seconds after the addition of the peptide and appeared to be mediated by an increase in Na + entry into the cells. The effect of bombesin on Na + entry and Na + /K + pump activity was concentration dependent with half-maximal stimulation occurring at 0.3-0.4 nM. The structurally related peptides litorin, gastrin-releasing peptide, and neuromedin B also stimulated ouabain-sensitive 86 Rb + uptake; the relative potencies of these peptides in stimulating the Na + /K + pump were comparable to their potencies in increasing DNA synthesis. Bombesin increased Na + influx, at least in part, through an Na + /H + antiport. The peptide augmented intracellular pH and this effect was abolished in the absence of extracellular Na + . In addition to monovalent ion transport, bombesin and the structurally related peptides rapidly increased the efflux of 45 Ca 2+ from quiescent Swiss 3T3 cells. This Ca 2+ came from an intracellular pool and the efflux was associated with a 50% decrease in total intracellular Ca 2+ . The peptides also caused a rapid increase in cytosolic free calcium concentration. Prolonged pretreatment of Swiss 3T3 cells with phorbol dibutyrate, which causes a loss of protein kinase C activity, greatly decreased the stimulation of 86 Rb + uptake and Na + entry by bombesin implicating this phosphotransferase system in the mediation of part of these responses to bombesin. Since some activation of monovalent ion transport by bombesin was seen in phorbol dibutyrate-pretreated cells, it is likely that the peptide also stimulates monovalent ion transport by a second mechanism

Muscle Stem Cell Fate Is Controlled by the Cell-Polarity Protein Scrib

Directory of Open Access Journals (Sweden)

Yusuke Ono

2015-02-01

Full Text Available Satellite cells are resident skeletal muscle stem cells that supply myonuclei for homeostasis, hypertrophy, and repair in adult muscle. Scrib is one of the major cell-polarity proteins, acting as a potent tumor suppressor in epithelial cells. Here, we show that Scrib also controls satellite-cell-fate decisions in adult mice. Scrib is undetectable in quiescent cells but becomes expressed during activation. Scrib is asymmetrically distributed in dividing daughter cells, with robust accumulation in cells committed to myogenic differentiation. Low Scrib expression is associated with the proliferative state and preventing self-renewal, whereas high Scrib levels reduce satellite cell proliferation. Satellite-cell-specific knockout of Scrib in mice causes a drastic and insurmountable defect in muscle regeneration. Thus, Scrib is a regulator of tissue stem cells, controlling population expansion and self-renewal with Scrib expression dynamics directing satellite cell fate.

Spectral Energy Distribution of Markarian 501: Quiescent State Versus Extreme Outburst

Science.gov (United States)

Acciari, V. A.; Arlen, T.; Aune, T.; Beilicke, M.; Benbow, W.; Böttcher, M.; Boltuch, D.; Bradbury, S. M.; Buckley, J. H.; Bugaev, V.; Cannon, A.; Cesarini, A.; Ciupik, L.; Cui, W.; Dickherber, R.; Duke, C.; Errando, M.; Falcone, A.; Finley, J. P.; Finnegan, G.; Fortson, L.; Furniss, A.; Galante, N.; Gall, D.; Godambe, S.; Grube, J.; Guenette, R.; Gyuk, G.; Hanna, D.; Holder, J.; Huang, D.; Hui, C. M.; Humensky, T. B.; Imran, A.; Kaaret, P.; Karlsson, N.; Kertzman, M.; Kieda, D.; Konopelko, A.; Krawczynski, H.; Krennrich, F.; Madhavan, A. S.; Maier, G.; McArthur, S.; McCann, A.; Moriarty, P.; Ong, R. A.; Otte, A. N.; Pandel, D.; Perkins, J. S.; Pichel, A.; Pohl, M.; Quinn, J.; Ragan, K.; Reyes, L. C.; Reynolds, P. T.; Roache, E.; Rose, H. J.; Schroedter, M.; Sembroski, G. H.; Steele, D.; Swordy, S. P.; Theiling, M.; Thibadeau, S.; Varlotta, A.; Vassiliev, V. V.; Vincent, S.; Wakely, S. P.; Ward, J. E.; Weekes, T. C.; Weinstein, A.; Weisgarber, T.; Williams, D. A.; Wood, M.; Zitzer, B.; VERITAS Collaboration; Aleksić, J.; Antonelli, L. A.; Antoranz, P.; Backes, M.; Barrio, J. A.; Bastieri, D.; Becerra González, J.; Bednarek, W.; Berdyugin, A.; Berger, K.; Bernardini, E.; Biland, A.; Blanch, O.; Bock, R. K.; Boller, A.; Bonnoli, G.; Bordas, P.; Borla Tridon, D.; Bosch-Ramon, V.; Bose, D.; Braun, I.; Bretz, T.; Camara, M.; Carmona, E.; Carosi, A.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; Dazzi, F.; De Angelis, A.; De Cea del Pozo, E.; De Lotto, B.; De Maria, M.; De Sabata, F.; Delgado Mendez, C.; Diago Ortega, A.; Doert, M.; Domínguez, A.; Dominis Prester, D.; Dorner, D.; Doro, M.; Elsaesser, D.; Errando, M.; Ferenc, D.; Fonseca, M. V.; Font, L.; García López, R. J.; Garczarczyk, M.; Gaug, M.; Giavitto, G.; Godinović, N.; Hadasch, D.; Herrero, A.; Hildebrand, D.; Höhne-Mönch, D.; Hose, J.; Hrupec, D.; Jogler, T.; Klepser, S.; Krähenbühl, T.; Kranich, D.; Krause, J.; La Barbera, A.; Leonardo, E.; Lindfors, E.; Lombardi, S.; Longo, F.; López, M.; Lorenz, E.; Majumdar, P.; Makariev, M.; Maneva, G.; Mankuzhiyil, N.; Mannheim, K.; Maraschi, L.; Mariotti, M.; Martínez, M.; Mazin, D.; Meucci, M.; Miranda, J. M.; Mirzoyan, R.; Miyamoto, H.; Moldón, J.; Moralejo, A.; Nieto, D.; Nilsson, K.; Orito, R.; Oya, I.; Paoletti, R.; Paredes, J. M.; Partini, S.; Pasanen, M.; Pauss, F.; Pegna, R. G.; Perez-Torres, M. A.; Persic, M.; Peruzzo, L.; Pochon, J.; Prada, F.; Prada Moroni, P. G.; Prandini, E.; Puchades, N.; Puljak, I.; Reichardt, I.; Reinthal, R.; Rhode, W.; Ribó, M.; Rico, J.; Rissi, M.; Rügamer, S.; Saggion, A.; Saito, K.; Saito, T. Y.; Salvati, M.; Sánchez-Conde, M.; Satalecka, K.; Scalzotto, V.; Scapin, V.; Schultz, C.; Schweizer, T.; Shayduk, M.; Shore, S. N.; Sierpowska-Bartosik, A.; Sillanpää, A.; Sitarek, J.; Sobczynska, D.; Spanier, F.; Spiro, S.; Stamerra, A.; Steinke, B.; Storz, J.; Strah, N.; Struebig, J. C.; Suric, T.; Takalo, L.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Torres, D. F.; Vankov, H.; Wagner, R. M.; Weitzel, Q.; Zabalza, V.; Zandanel, F.; Zanin, R.; MAGIC Collaboration; Paneque, D.; Hayashida, M.

2011-03-01

The very high energy (VHE; E > 100 GeV) blazar Markarian 501 (Mrk 501) has a well-studied history of extreme spectral variability and is an excellent laboratory for studying the physical processes within the jets of active galactic nuclei. However, there are few detailed multiwavelength studies of Mrk 501 during its quiescent state, due to its low luminosity. A short-term multiwavelength study of Mrk 501 was coordinated in 2009 March, focusing around a multi-day observation with the Suzaku X-ray satellite and including γ-ray data from VERITAS, MAGIC, and the Fermi Gamma-ray Space Telescope with the goal of providing a well-sampled multiwavelength baseline measurement of Mrk 501 in the quiescent state. The results of these quiescent-state observations are compared to the historically extreme outburst of 1997 April 16, with the goal of examining variability of the spectral energy distribution (SED) between the two states. The derived broadband SED shows the characteristic double-peaked profile. We find that the X-ray peak shifts by over two orders of magnitude in photon energy between the two flux states while the VHE peak varies little. The limited shift in the VHE peak can be explained by the transition to the Klein-Nishina (KN) regime. Synchrotron self-Compton models are matched to the data and the implied KN effects are explored.

SPECTRAL ENERGY DISTRIBUTION OF MARKARIAN 501: QUIESCENT STATE VERSUS EXTREME OUTBURST

International Nuclear Information System (INIS)

Acciari, V. A.; Benbow, W.; Arlen, T.; Aune, T.; Beilicke, M.; Buckley, J. H.; Bugaev, V.; Dickherber, R.; Boettcher, M.; Boltuch, D.; Bradbury, S. M.; Cannon, A.; Cesarini, A.; Ciupik, L.; Cui, W.; Finley, J. P.; Duke, C.; Errando, M.; Falcone, A.; Finnegan, G.

2011-01-01

The very high energy (VHE; E > 100 GeV) blazar Markarian 501 (Mrk 501) has a well-studied history of extreme spectral variability and is an excellent laboratory for studying the physical processes within the jets of active galactic nuclei. However, there are few detailed multiwavelength studies of Mrk 501 during its quiescent state, due to its low luminosity. A short-term multiwavelength study of Mrk 501 was coordinated in 2009 March, focusing around a multi-day observation with the Suzaku X-ray satellite and including γ-ray data from VERITAS, MAGIC, and the Fermi Gamma-ray Space Telescope with the goal of providing a well-sampled multiwavelength baseline measurement of Mrk 501 in the quiescent state. The results of these quiescent-state observations are compared to the historically extreme outburst of 1997 April 16, with the goal of examining variability of the spectral energy distribution (SED) between the two states. The derived broadband SED shows the characteristic double-peaked profile. We find that the X-ray peak shifts by over two orders of magnitude in photon energy between the two flux states while the VHE peak varies little. The limited shift in the VHE peak can be explained by the transition to the Klein-Nishina (KN) regime. Synchrotron self-Compton models are matched to the data and the implied KN effects are explored.

WHAT TURNS GALAXIES OFF? THE DIFFERENT MORPHOLOGIES OF STAR-FORMING AND QUIESCENT GALAXIES SINCE z ∼ 2 FROM CANDELS

International Nuclear Information System (INIS)

Bell, Eric F.; Herrington, Jessica; Van der Wel, Arjen; Papovich, Casey; Kocevski, Dale; Faber, S. M.; Cheung, Edmond; Koo, David C.; McGrath, Elizabeth J.; Lotz, Jennifer; Ferguson, Harry; Koekemoer, Anton; Grogin, Norman; McIntosh, Daniel H.; Kartaltepe, Jeyhan; Wuyts, Stijn; Conselice, Christopher J.; Dekel, Avishai; Dunlop, James S.; Giavalisco, Mauro

2012-01-01

We use HST/WFC3 imaging from the CANDELS Multi-Cycle Treasury Survey, in conjunction with the Sloan Digital Sky Survey, to explore the evolution of galactic structure for galaxies with stellar masses >3 × 10 10 M ☉ from z = 2.2 to the present epoch, a time span of 10 Gyr. We explore the relationship between rest-frame optical color, stellar mass, star formation activity, and galaxy structure. We confirm the dramatic increase from z = 2.2 to the present day in the number density of non-star-forming galaxies above 3 × 10 10 M ☉ reported by others. We further find that the vast majority of these quiescent systems have concentrated light profiles, as parameterized by the Sérsic index, and the population of concentrated galaxies grows similarly rapidly. We examine the joint distribution of star formation activity, Sérsic index, stellar mass, inferred velocity dispersion, and stellar surface density. Quiescence correlates poorly with stellar mass at all z 1.3, and somewhat less well at lower redshifts. Yet, there is significant scatter between quiescence and galaxy structure: while the vast majority of quiescent galaxies have prominent bulges, many of them have significant disks, and a number of bulge-dominated galaxies have significant star formation. Noting the rarity of quiescent galaxies without prominent bulges, we argue that a prominent bulge (and perhaps, by association, a supermassive black hole) is an important condition for quenching star formation on galactic scales over the last 10 Gyr, in qualitative agreement with the active galactic nucleus feedback paradigm.

How dead are dead galaxies? Mid-infrared fluxes of quiescent galaxies at redshift 0.3 < z < 2.5: implications for star formation rates and dust heating

International Nuclear Information System (INIS)

Fumagalli, Mattia; Labbé, Ivo; Patel, Shannon G.; Franx, Marijn; Van Dokkum, Pieter; Momcheva, Ivelina; Nelson, Erica; Brammer, Gabriel; Da Cunha, Elisabete; Rix, Hans-Walter; Maseda, Michael; Schreiber, Natascha M. Förster; Kriek, Mariska; Quadri, Ryan; Wake, David; Lundgren, Britt; Whitaker, Katherine E.; Marchesini, Danilo; Pacifici, Camilla; Skelton, Rosalind E.

2014-01-01

We investigate star formation rates (SFRs) of quiescent galaxies at high redshift (0.3 < z < 2.5) using 3D-HST WFC3 grism spectroscopy and Spitzer mid-infrared data. We select quiescent galaxies on the basis of the widely used UVJ color-color criteria. Spectral energy distribution (SED) fitting (rest-frame optical and near-IR) indicates very low SFRs for quiescent galaxies (sSFR ∼ 10 –12 yr –1 ). However, SED fitting can miss star formation if it is hidden behind high dust obscuration and ionizing radiation is re-emitted in the mid-infrared. It is therefore fundamental to measure the dust-obscured SFRs with a mid-IR indicator. We stack the MIPS 24 μm images of quiescent objects in five redshift bins centered on z = 0.5, 0.9, 1.2, 1.7, 2.2 and perform aperture photometry. Including direct 24 μm detections, we find sSFR ∼ 10 –11.9 × (1 + z) 4 yr –1 . These values are higher than those indicated by SED fitting, but at each redshift they are 20-40 times lower than those of typical star-forming galaxies. The true SFRs of quiescent galaxies might be even lower, as we show that the mid-IR fluxes can be due to processes unrelated to ongoing star formation, such as cirrus dust heated by old stellar populations and circumstellar dust. Our measurements show that star formation quenching is very efficient at every redshift. The measured SFR values are at z > 1.5 marginally consistent with the ones expected from gas recycling (assuming that mass loss from evolved stars refuels star formation) and well below that at lower redshifts.

How dead are dead galaxies? Mid-infrared fluxes of quiescent galaxies at redshift 0.3 < z < 2.5: implications for star formation rates and dust heating

Energy Technology Data Exchange (ETDEWEB)

Fumagalli, Mattia; Labbé, Ivo; Patel, Shannon G.; Franx, Marijn [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Van Dokkum, Pieter; Momcheva, Ivelina; Nelson, Erica [Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Brammer, Gabriel [European Southern Observatory, Alonso de Cordova 3107, Casilla 19001, Vitacura, Santiago (Chile); Da Cunha, Elisabete; Rix, Hans-Walter; Maseda, Michael [Max Planck Institute for Astronomy (MPIA), Konigstuhl 17, D-69117 Heidelberg (Germany); Schreiber, Natascha M. Förster [Max-Planck-Institut für Extraterrestrische Physik, Giessenbachstrasse, D-85748 Garching (Germany); Kriek, Mariska [Department of Astronomy, University of California, Berkeley, CA 94720 (United States); Quadri, Ryan [Observatories of the Carnegie Institution of Washington, Pasadena, CA 91101 (United States); Wake, David; Lundgren, Britt [Department of Astronomy, University of Wisconsin, Madison, WI 53706 (United States); Whitaker, Katherine E. [Astrophysics Science Division, Goddard Space Flight Center, Code 665, Greenbelt, MD 20771 (United States); Marchesini, Danilo [Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States); Pacifici, Camilla [Yonsei University Observatory, Yonsei University, Seoul 120-749 (Korea, Republic of); Skelton, Rosalind E. [South African Astronomical Observatory, Observatory Road, Cape Town (South Africa)

2014-11-20

We investigate star formation rates (SFRs) of quiescent galaxies at high redshift (0.3 < z < 2.5) using 3D-HST WFC3 grism spectroscopy and Spitzer mid-infrared data. We select quiescent galaxies on the basis of the widely used UVJ color-color criteria. Spectral energy distribution (SED) fitting (rest-frame optical and near-IR) indicates very low SFRs for quiescent galaxies (sSFR ∼ 10{sup –12} yr{sup –1}). However, SED fitting can miss star formation if it is hidden behind high dust obscuration and ionizing radiation is re-emitted in the mid-infrared. It is therefore fundamental to measure the dust-obscured SFRs with a mid-IR indicator. We stack the MIPS 24 μm images of quiescent objects in five redshift bins centered on z = 0.5, 0.9, 1.2, 1.7, 2.2 and perform aperture photometry. Including direct 24 μm detections, we find sSFR ∼ 10{sup –11.9} × (1 + z){sup 4} yr{sup –1}. These values are higher than those indicated by SED fitting, but at each redshift they are 20-40 times lower than those of typical star-forming galaxies. The true SFRs of quiescent galaxies might be even lower, as we show that the mid-IR fluxes can be due to processes unrelated to ongoing star formation, such as cirrus dust heated by old stellar populations and circumstellar dust. Our measurements show that star formation quenching is very efficient at every redshift. The measured SFR values are at z > 1.5 marginally consistent with the ones expected from gas recycling (assuming that mass loss from evolved stars refuels star formation) and well below that at lower redshifts.

Production of a large, quiescent, magnetized plasma

Science.gov (United States)

Landt, D. L.; Ajmera, R. C.

1976-01-01

An experimental device is described which produces a large homogeneous quiescent magnetized plasma. In this device, the plasma is created in an evacuated brass cylinder by ionizing collisions between electrons emitted from a large-diameter electron gun and argon atoms in the chamber. Typical experimentally measured values of the electron temperature and density are presented which were obtained with a glass-insulated planar Langmuir probe. It is noted that the present device facilitates the study of phenomena such as waves and diffusion in magnetized plasmas.

Cytomatrix synthesis in MDCK epithelial cells

International Nuclear Information System (INIS)

Mitchell, J.J.; Low, R.B.; Woodcock-Mitchell, J.L.

1990-01-01

Detailed information regarding the synthesis rates of individual protein components is important in understanding the assembly and dynamics of the cytoskeletal matrix of eukaryotic cells. As an approach to this topic, the dual isotope technique of Clark and Zak, was employed to measure fractional synthesis rates (FSRs) in growing and quiescent cultures of MDCK epithelial cells. Cell protein was labeled to equilibrium with [14C]leucine over several days and then pulse-labeled for 4 hours with [3H]leucine. FSRs (as percent per hour) were calculated from the 3H/14C ratio of cell extracts or individual proteins separated by two-dimensional polyacrylamide gel electrophoresis and the 3H/14C ratio of free leucine in the medium. Synthesis of total cell protein rose from approximately 1.4%/hour in quiescent cells to 3.5%/hour in the growing cultures. The latter rate was sufficient to account for the rate of protein accumulation and a low level of turnover in the growing cultures. The FSR of the buffered-Triton soluble extract was higher and the cytoskeletal FSR significantly lower than that for total protein in quiescent monolayers. This difference, however, was not observed in growing cultures. A distinct pattern of differences was seen in the FSRs of individual cytoskeletal proteins in the quiescent cultures. Vimentin synthesis was significantly lower than that of the keratins and the keratin FSRs were not obviously matched in pairwise fashion. Unexpectedly, the FSRs of alpha- and beta-tubulin diverged in quiescent cells with alpha-tubulin turnover exceeding beta-tubulin. Likewise, components of the microfilament lattice showed unequal fractional synthesis rates, myosin and alpha-actinin being faster than actin. In addition, the FSR for globular actin exceeded that of the cytoskeletal associated form

ICES IN THE QUIESCENT IC 5146 DENSE CLOUD

International Nuclear Information System (INIS)

Chiar, J. E.; Pendleton, Y. J.; Allamandola, L. J.; Ennico, K.; Greene, T. P.; Roellig, T. L.; Sandford, S. A.; Boogert, A. C. A.; Geballe, T. R.; Mason, R. E.; Keane, J. V.; Lada, C. J.; Tielens, A. G. G. M.; Werner, M. W.; Whittet, D. C. B.; Decin, L.; Eriksson, K.

2011-01-01

This paper presents spectra in the 2 to 20 μm range of quiescent cloud material located in the IC 5146 cloud complex. The spectra were obtained with NASA's Infrared Telescope Facility SpeX instrument and the Spitzer Space Telescope's Infrared Spectrometer. We use these spectra to investigate dust and ice absorption features in pristine regions of the cloud that are unaltered by embedded stars. We find that the H 2 O-ice threshold extinction is 4.03 ± 0.05 mag. Once foreground extinction is taken into account, however, the threshold drops to 3.2 mag, equivalent to that found for the Taurus dark cloud, generally assumed to be the touchstone quiescent cloud against which all other dense cloud and embedded young stellar object observations are compared. Substructure in the trough of the silicate band for two sources is attributed to CH 3 OH and NH 3 in the ices, present at the ∼2% and ∼5% levels, respectively, relative to H 2 O-ice. The correlation of the silicate feature with the E(J - K) color excess is found to follow a much shallower slope relative to lines of sight that probe diffuse clouds, supporting the previous results by Chiar et al.

Incidencia de infecciones quiescentes de Botrytis cinerea en flores y

Directory of Open Access Journals (Sweden)

MolinaG. Gilma Sandra

2004-12-01

Full Text Available

Se aisló Botrytis cinerea de flores y frutos asintomáticos de mora de castilla ( Rubus glaucus Benth. en  seis estados fenológicos desde botón cerrado hasta fruto maduro. Estas infecciones quiescentes ocurrieron raramente en botones florales cerrados, pero cuando éstos abren las estructuras florales aparecen colonizadas. La alta frecuencia de infecciones quiescentes en frutos en desarrollo y frutos maduros es atribuible a infecciones tempranas en estructuras florales. Inoculaciones hechas con conidias de B. cinerea marcadas con calcofluor produjeron infecciones en todos los estados fenológicos; la germinación de conidias en los seis estados fenológicos se inició a las 10 horas después de

The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.

Science.gov (United States)

Isern, Joan; García-García, Andrés; Martín, Ana M; Arranz, Lorena; Martín-Pérez, Daniel; Torroja, Carlos; Sánchez-Cabo, Fátima; Méndez-Ferrer, Simón

2014-09-25

Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

Edge stability and performance of the ELM-free quiescent H-mode and the quiescent double barrier mode on DIII-D

International Nuclear Information System (INIS)

West, W.P.; Burrell, K.H.; Snyder, P.B.; Gohil, P.; Lao, L.L.; Leonard, A.W.; Osborne, T.H.; Thomas, D.M.; Casper, T.A.; Lasnier, C.J.; Doyle, E.J.; Wang, G.; Zeng, L.; Nave, M.F.F.

2005-01-01

The quiescent H (QH) mode, an edge localized mode (ELM)-free, high-confinement mode, combines well with an internal transport barrier to form quiescent double barrier (QDB) stationary state, high performance plasmas. The QH-mode edge pedestal pressure is similar to that seen in ELMing phases of the same discharge, with similar global energy confinement. The pedestal density in early ELMing phases of strongly pumped counter injection discharges drops and a transition to QH-mode occurs, leading to lower calculated edge bootstrap current. Plasmas current ramp experiment and ELITE code modeling of edge stability suggest that QHmodes lie near an edge current stabilty boundary. At high triangularity, QH-mode discharges operate at higher pedestal density and pressure, and have achieved ITER level values of β PED and ν*. The QDB achieves performance of β N H 89 ∼ 7 in quasi-stationary conditions for a duration of 10 τ E , limited by hardware. Recently we demonstrated stationary state QDB discharges with little change in kinetic and q profiles (q 0 > 1) for 2 s, comparable to ELMing 'hybrid scenarios', yet without the debilitating effects of ELMs. Plasma profile control tools, including electron cyclotron heating and current drive and neutral beam heating, have been demonstrated to control simultaneously the q profile development, the density peaking, impurity accumulation and plasma beta. (author)

THE UVJ SELECTION OF QUIESCENT AND STAR-FORMING GALAXIES: SEPARATING EARLY- AND LATE-TYPE GALAXIES AND ISOLATING EDGE-ON SPIRALS

International Nuclear Information System (INIS)

Patel, Shannon G.; Franx, Marijn; Holden, Bradford P.; Illingworth, Garth D.; Kelson, Daniel D.; Van der Wel, Arjen

2012-01-01

We utilize for the first time Hubble Space Telescope Advanced Camera for Surveys imaging to examine the structural properties of galaxies in the rest-frame U – V versus V – J diagram (i.e., the UVJ diagram) using a sample at 0.6 ☉ >10.25). The use of the UVJ diagram as a tool to distinguish quiescent galaxies from star-forming galaxies (SFGs) is becoming more common due to its ability to separate red quiescent galaxies from reddened SFGs. Quiescent galaxies occupy a small and distinct region of UVJ color space and we find most of them to have concentrated profiles with high Sérsic indices (n > 2.5) and smooth structure characteristic of early-type systems. SFGs populate a broad but well-defined sequence of UVJ colors and are comprised of objects with a mix of Sérsic indices. Interestingly, most UVJ-selected SFGs with high Sérsic indices also display structure due to dust and star formation typical of the n < 2.5 SFGs and late-type systems. Finally, we find that the position of an SFG on the sequence of UVJ colors is determined to a large degree by the mass of the galaxy and its inclination. Systems that are closer to edge-on generally display redder colors and lower [O II]λ3727 luminosity per unit mass as a consequence of the reddening due to dust within the disks. We conclude that the two main features seen in UVJ color space correspond closely to the traditional morphological classes of early- and late-type galaxies.

Skin stem cell hypotheses and long term clone survival--explored using agent-based modelling.

Science.gov (United States)

Li, X; Upadhyay, A K; Bullock, A J; Dicolandrea, T; Xu, J; Binder, R L; Robinson, M K; Finlay, D R; Mills, K J; Bascom, C C; Kelling, C K; Isfort, R J; Haycock, J W; MacNeil, S; Smallwood, R H

2013-01-01

Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.

Cell cycle-dependent regulation of kainate-induced inward currents in microglia

International Nuclear Information System (INIS)

Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

2006-01-01

Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

Jet meandering by a foil pitching in quiescent fluid

Science.gov (United States)

Shinde, Sachin Y.; Arakeri, Jaywant H.

2013-04-01

The flow produced by a rigid symmetric NACA0015 airfoil purely pitching at a fixed location in quiescent fluid (the limiting case of infinite Strouhal number) is studied using visualizations and particle image velocimetry. A weak jet is generated whose inclination changes continually with time. This meandering is observed to be random and independent of the initial conditions, over a wide range of pitching parameters.

Skin Stem Cell Hypotheses and Long Term Clone Survival – Explored Using Agent-based Modelling

Science.gov (United States)

Li, X.; Upadhyay, A. K.; Bullock, A. J.; Dicolandrea, T.; Xu, J.; Binder, R. L.; Robinson, M. K.; Finlay, D. R.; Mills, K. J.; Bascom, C. C.; Kelling, C. K.; Isfort, R. J.; Haycock, J. W.; MacNeil, S.; Smallwood, R. H.

2013-01-01

Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation. PMID:23712735

Quiescent plasma machine for beam-plasma interaction and wave studies

International Nuclear Information System (INIS)

Ferreira, J.L.

1994-01-01

A quiescent double plasma machine for beam-plasma interaction wave studies is described. A detailed description of several plasma diagnostics used for plasma and wave excitation detection is given. A beam-plasma wave dispersion relation is used to compare theoretical values with the experimentally measured Langmuir wave frequencies and wavelengths. (author). 14 refs, 10 figs

The fraction of quiescent massive galaxies in the early Universe

Science.gov (United States)

Fontana, A.; Santini, P.; Grazian, A.; Pentericci, L.; Fiore, F.; Castellano, M.; Giallongo, E.; Menci, N.; Salimbeni, S.; Cristiani, S.; Nonino, M.; Vanzella, E.

2009-07-01

Aims: We attempt to compile a complete, mass-selected sample of galaxies with low specific star-formation rates, and compare their properties with theoretical model predictions. Methods: We use the f(24 μ m})/f(K) flux ratio and the SED fitting to the 0.35-8.0 μm spectral distribution, to select quiescent galaxies from z≃ 0.4 to z≃ 4 in the GOODS-MUSIC sample. Our observational selection can be translated into thresholds in specific star-formation rate dot{M}/M_*, which can be compared with theoretical predictions. Results: In the framework of the well-known global decline in quiescent galaxy fraction with redshift, we find that a non-negligible fraction {≃ 15-20% of massive galaxies with low specific star-formation rate exists up to z≃ 4, including a tail of “red and dead” galaxies with dot{M}/M_*<10-11 yr-1. Theoretical models vary to a large extent in their predictions for the fraction of galaxies with low specific star-formation rates, but are unable to provide a global match to our data.

Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

International Nuclear Information System (INIS)

Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean; Larsen, Annette K.; Escargueil, Alexandre

2016-01-01

We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

Energy Technology Data Exchange (ETDEWEB)

Lorenzi, Tommaso [Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan 94230 Cedex, France & INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Chisholm, Rebecca H. [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052 (Australia); Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean [Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Larsen, Annette K.; Escargueil, Alexandre [Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris (France); INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris (France)

2016-06-08

We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy.

Science.gov (United States)

Sanada, Fumihiro; Kim, Junghyun; Czarna, Anna; Chan, Noel Yan-Ki; Signore, Sergio; Ogórek, Barbara; Isobe, Kazuya; Wybieralska, Ewa; Borghetti, Giulia; Pesapane, Ada; Sorrentino, Andrea; Mangano, Emily; Cappetta, Donato; Mangiaracina, Chiara; Ricciardi, Mario; Cimini, Maria; Ifedigbo, Emeka; Perrella, Mark A; Goichberg, Polina; Choi, Augustine M; Kajstura, Jan; Hosoda, Toru; Rota, Marcello; Anversa, Piero; Leri, Annarosa

2014-01-03

Hypoxia favors stem cell quiescence, whereas normoxia is required for stem cell activation, but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal. Here, we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot re-enter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy. Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggest that a pool of functionally competent CSCs persists in the senescent heart and that this stem cell compartment can promote myocyte regeneration effectively, partly correcting the aging myopathy.

The Pan-STARRS1 medium-deep survey: The role of galaxy group environment in the star formation rate versus stellar mass relation and quiescent fraction out to z ∼ 0.8

Energy Technology Data Exchange (ETDEWEB)

Lin, Lihwai; Chen, Chin-Wei; Coupon, Jean; Hsieh, Bau-Ching [Institute of Astronomy and Astrophysics, Academia Sinica, Taipei 106, Taiwan, R.O.C. (China); Jian, Hung-Yu [Department of Physics, National Taiwan University, Taipei 106, Taiwan, R.O.C. (China); Foucaud, Sebastien [Department of Earth Sciences, National Taiwan Normal University, N°88, Tingzhou Road, Sec. 4, Taipei 11677, Taiwan, R.O.C. (China); Norberg, Peder; Bower, R. G.; Cole, Shaun; Arnalte-Mur, Pablo; Draper, P. [Institute for Computational Cosmology, Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Heinis, Sebastien [Department of Astronomy, University of Maryland, MD 20742 (United States); Phleps, Stefanie [Max-Planck-Institut für Extraterrestrische Physik, Giessenbachstraße, D-85748 Garching (Germany); Chen, Wen-Ping [Graduate Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan, R.O.C. (China); Lee, Chien-Hsiu [University Observatory Munich, Scheinerstrasse 1, D-81679 Munich (Germany); Burgett, William; Chambers, K. C.; Denneau, L.; Flewelling, H.; Hodapp, K. W., E-mail: lihwailin@asiaa.sinica.edu.tw [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); and others

2014-02-10

Using a large optically selected sample of field and group galaxies drawn from the Pan-STARRS1 Medium-Deep Survey (PS1/MDS), we present a detailed analysis of the specific star formation rate (SSFR)—stellar mass (M {sub *}) relation, as well as the quiescent fraction versus M {sub *} relation in different environments. While both the SSFR and the quiescent fraction depend strongly on stellar mass, the environment also plays an important role. Using this large galaxy sample, we confirm that the fraction of quiescent galaxies is strongly dependent on environment at a fixed stellar mass, but that the amplitude and the slope of the star-forming sequence is similar between the field and groups: in other words, the SSFR-density relation at a fixed stellar mass is primarily driven by the change in the star-forming and quiescent fractions between different environments rather than a global suppression in the star formation rate for the star-forming population. However, when we restrict our sample to the cluster-scale environments (M > 10{sup 14} M {sub ☉}), we find a global reduction in the SSFR of the star-forming sequence of 17% at 4σ confidence as opposed to its field counterpart. After removing the stellar mass dependence of the quiescent fraction seen in field galaxies, the excess in the quiescent fraction due to the environment quenching in groups and clusters is found to increase with stellar mass, although deeper and larger data from the full PS1/MDS will be required to draw firm conclusions. We argue that these results are in favor of galaxy mergers to be the primary environment quenching mechanism operating in galaxy groups whereas strangulation is able to reproduce the observed trend in the environment quenching efficiency and stellar mass relation seen in clusters. Our results also suggest that the relative importance between mass quenching and environment quenching depends on stellar mass—the mass quenching plays a dominant role in producing quiescent

The Pan-STARRS1 medium-deep survey: The role of galaxy group environment in the star formation rate versus stellar mass relation and quiescent fraction out to z ∼ 0.8

International Nuclear Information System (INIS)

Lin, Lihwai; Chen, Chin-Wei; Coupon, Jean; Hsieh, Bau-Ching; Jian, Hung-Yu; Foucaud, Sebastien; Norberg, Peder; Bower, R. G.; Cole, Shaun; Arnalte-Mur, Pablo; Draper, P.; Heinis, Sebastien; Phleps, Stefanie; Chen, Wen-Ping; Lee, Chien-Hsiu; Burgett, William; Chambers, K. C.; Denneau, L.; Flewelling, H.; Hodapp, K. W.

2014-01-01

Using a large optically selected sample of field and group galaxies drawn from the Pan-STARRS1 Medium-Deep Survey (PS1/MDS), we present a detailed analysis of the specific star formation rate (SSFR)—stellar mass (M * ) relation, as well as the quiescent fraction versus M * relation in different environments. While both the SSFR and the quiescent fraction depend strongly on stellar mass, the environment also plays an important role. Using this large galaxy sample, we confirm that the fraction of quiescent galaxies is strongly dependent on environment at a fixed stellar mass, but that the amplitude and the slope of the star-forming sequence is similar between the field and groups: in other words, the SSFR-density relation at a fixed stellar mass is primarily driven by the change in the star-forming and quiescent fractions between different environments rather than a global suppression in the star formation rate for the star-forming population. However, when we restrict our sample to the cluster-scale environments (M > 10 14 M ☉ ), we find a global reduction in the SSFR of the star-forming sequence of 17% at 4σ confidence as opposed to its field counterpart. After removing the stellar mass dependence of the quiescent fraction seen in field galaxies, the excess in the quiescent fraction due to the environment quenching in groups and clusters is found to increase with stellar mass, although deeper and larger data from the full PS1/MDS will be required to draw firm conclusions. We argue that these results are in favor of galaxy mergers to be the primary environment quenching mechanism operating in galaxy groups whereas strangulation is able to reproduce the observed trend in the environment quenching efficiency and stellar mass relation seen in clusters. Our results also suggest that the relative importance between mass quenching and environment quenching depends on stellar mass—the mass quenching plays a dominant role in producing quiescent galaxies for more

WHAT TURNS GALAXIES OFF? THE DIFFERENT MORPHOLOGIES OF STAR-FORMING AND QUIESCENT GALAXIES SINCE z {approx} 2 FROM CANDELS

Energy Technology Data Exchange (ETDEWEB)

Bell, Eric F.; Herrington, Jessica [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Van der Wel, Arjen [Max-Planck Institut fuer Astronomie, Koenigstuhl 17, D-69117 Heidelberg (Germany); Papovich, Casey [George P. and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy, and Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843-4242 (United States); Kocevski, Dale; Faber, S. M.; Cheung, Edmond; Koo, David C.; McGrath, Elizabeth J. [UCO/Lick Observatory, Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Lotz, Jennifer; Ferguson, Harry; Koekemoer, Anton; Grogin, Norman [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); McIntosh, Daniel H. [Department of Physics, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Kartaltepe, Jeyhan [NOAO-Tucson, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Wuyts, Stijn [Max-Planck-Institut fuer Extraterrestrische Physik, Giessenbachstrasse, D-85748 Garching (Germany); Conselice, Christopher J. [University of Nottingham, School of Physics and Astronomy, Nottingham NG7 2RD (United Kingdom); Dekel, Avishai [Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel); Dunlop, James S. [Institute for Astronomy, University of Edinburgh, Royal Observatory, Blackford Hill, Edinburgh EH9 3HJ (United Kingdom); Giavalisco, Mauro, E-mail: ericbell@umich.edu [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); and others

2012-07-10

We use HST/WFC3 imaging from the CANDELS Multi-Cycle Treasury Survey, in conjunction with the Sloan Digital Sky Survey, to explore the evolution of galactic structure for galaxies with stellar masses >3 Multiplication-Sign 10{sup 10} M{sub Sun} from z = 2.2 to the present epoch, a time span of 10 Gyr. We explore the relationship between rest-frame optical color, stellar mass, star formation activity, and galaxy structure. We confirm the dramatic increase from z = 2.2 to the present day in the number density of non-star-forming galaxies above 3 Multiplication-Sign 10{sup 10} M{sub Sun} reported by others. We further find that the vast majority of these quiescent systems have concentrated light profiles, as parameterized by the Sersic index, and the population of concentrated galaxies grows similarly rapidly. We examine the joint distribution of star formation activity, Sersic index, stellar mass, inferred velocity dispersion, and stellar surface density. Quiescence correlates poorly with stellar mass at all z < 2.2. Quiescence correlates well with Sersic index at all redshifts. Quiescence correlates well with 'velocity dispersion' and stellar surface density at z > 1.3, and somewhat less well at lower redshifts. Yet, there is significant scatter between quiescence and galaxy structure: while the vast majority of quiescent galaxies have prominent bulges, many of them have significant disks, and a number of bulge-dominated galaxies have significant star formation. Noting the rarity of quiescent galaxies without prominent bulges, we argue that a prominent bulge (and perhaps, by association, a supermassive black hole) is an important condition for quenching star formation on galactic scales over the last 10 Gyr, in qualitative agreement with the active galactic nucleus feedback paradigm.

Muscle satellite cell heterogeneity and self-renewal

Science.gov (United States)

Motohashi, Norio; Asakura, Atsushi

2014-01-01

Adult skeletal muscle possesses extraordinary regeneration capacities. After muscle injury or exercise, large numbers of newly formed muscle fibers are generated within a week as a result of expansion and differentiation of a self-renewing pool of muscle stem cells termed muscle satellite cells. Normally, satellite cells are mitotically quiescent and reside beneath the basal lamina of muscle fibers. Upon regeneration, satellite cells are activated, and give rise to daughter myogenic precursor cells. After several rounds of proliferation, these myogenic precursor cells contribute to the formation of new muscle fibers. During cell division, a minor population of myogenic precursor cells returns to quiescent satellite cells as a self-renewal process. Currently, accumulating evidence has revealed the essential roles of satellite cells in muscle regeneration and the regulatory mechanisms, while it still remains to be elucidated how satellite cell self-renewal is molecularly regulated and how satellite cells are important in aging and diseased muscle. The number of satellite cells is decreased due to the changing niche during ageing, resulting in attenuation of muscle regeneration capacity. Additionally, in Duchenne muscular dystrophy (DMD) patients, the loss of satellite cell regenerative capacity and decreased satellite cell number due to continuous needs for satellite cells lead to progressive muscle weakness with chronic degeneration. Thus, it is necessary to replenish muscle satellite cells continuously. This review outlines recent findings regarding satellite cell heterogeneity, asymmetric division and molecular mechanisms in satellite cell self-renewal which is crucial for maintenance of satellite cells as a muscle stem cell pool throughout life. In addition, we discuss roles in the stem cell niche for satellite cell maintenance, as well as related cell therapies for approaching treatment of DMD. PMID:25364710

Muscle Satellite Cell Heterogeneity and Self-Renewal

Directory of Open Access Journals (Sweden)

Norio eMotohashi

2014-01-01

Full Text Available Adult skeletal muscle possesses extraordinary regeneration capacities. After muscle injury or exercise, large numbers of newly formed muscle fibers are generated within a week as a result of expansion and differentiation of a self-renewing pool of muscle stem cells termed muscle satellite cells. Normally, satellite cells are mitotically quiescent and reside beneath the basal lamina of muscle fibers. Upon regeneration, satellite cells are activated, and give rise to daughter myogenic precursor cells. After several rounds of proliferation, these myogenic precursor cells contribute to the formation of new muscle fibers. During cell division, a minor population of myogenic precursor cells returns to quiescent satellite cells as a self-renewal process. Currently, accumulating evidence has revealed the essential roles of satellite cells in muscle regeneration and the regulatory mechanisms, while it still remains to be elucidated how satellite cell self-renewal is molecularly regulated and how satellite cells are important in aging and diseased muscle. The number of satellite cells is decreased due to the changing niche during ageing, resulting in attenuation of muscle regeneration capacity. Additionally, in Duchenne muscular dystrophy (DMD patients, the loss of satellite cell regenerative capacity and decreased satellite cell number due to continuous needs for satellite cells lead to progressive muscle weakness with chronic degeneration. Thus, it is necessary to replenish muscle satellite cells continuously. This review outlines recent findings regarding satellite cell heterogeneity, asymmetric division and molecular mechanisms in satellite cell self-renewal which is crucial for maintenance of satellite cells as a muscle stem cell pool throughout life. In addition, we discuss roles in the stem cell niche for satellite cell maintenance, as well as related cell therapies for approaching treatment of DMD.

Bacillus subtilis Swarmer Cells Lead the Swarm, Multiply, and Generate a Trail of Quiescent Descendants

Directory of Open Access Journals (Sweden)

Lina Hamouche

2017-02-01

Full Text Available Bacteria adopt social behavior to expand into new territory, led by specialized swarmers, before forming a biofilm. Such mass migration of Bacillus subtilis on a synthetic medium produces hyperbranching dendrites that transiently (equivalent to 4 to 5 generations of growth maintain a cellular monolayer over long distances, greatly facilitating single-cell gene expression analysis. Paradoxically, while cells in the dendrites (nonswarmers might be expected to grow exponentially, the rate of swarm expansion is constant, suggesting that some cells are not multiplying. Little attention has been paid to which cells in a swarm are actually multiplying and contributing to the overall biomass. Here, we show in situ that DNA replication, protein translation and peptidoglycan synthesis are primarily restricted to the swarmer cells at dendrite tips. Thus, these specialized cells not only lead the population forward but are apparently the source of all cells in the stems of early dendrites. We developed a simple mathematical model that supports this conclusion.

Deep absorption line studies of quiescent galaxies at z similar z ~ 2

DEFF Research Database (Denmark)

Toft, Sune; Gallazzi, Anna Rita; Zirm, Andrew Wasmuth

2012-01-01

the majority of its stars at z > 3 and currently has little or no ongoing star formation. We compile a sample of three other z similar to 2 quiescent galaxies with measured velocity dispersions, two of which are also post-starburst like. Their dynamical-mass-size relation is offset significantly less than...... the stellar-mass-size relation from the local early-type relations, which we attribute to a lower central dark matter fraction. Recent cosmological merger simulations agree qualitatively with the data, but cannot fully account for the evolution in the dark matter fraction. The z similar to 2 FP requires......We present dynamical and structural scaling relations of quiescent galaxies at z = 2, including the dynamical-mass-size relation and the first constraints on the fundamental plane (FP). The backbone of the analysis is a new, very deep Very Large Telescope/X-shooter spectrum of a massive, compact...

Stem cell targets and dosimetry for radiation-induced leukaemia and bone cancer

International Nuclear Information System (INIS)

Richardson, R.B.

2007-01-01

The ICRP are proposing changes to the assumed targets for the induction of bone cancer and leukaemias as described by Harrison et al in an accompanying article. This study of radiation targets in the skeleton finds that the endosteum of the long bone medullary cavities is not an important target, especially in the adult, as it supports a very low stem cell population associated with high adiposity, whereas the periosteum has a strong mesenchymal stem cell population throughout lifetime. Quiescent stem cells are found to be preferentially located close to the trabecular bone surface in the osteoblastic niche, whereas progenitors of stem cells prefer to reside in perivascular niches. Evidence is given in support of the suggestion that the absence of excess bone-cancer in atomic bomb survivors may be related to the extremely low prevalence of Paget's disease in Japan. The hypoxic conditions of the endosteum adjacent to quiescent bone surfaces provide a radioprotective stem cell microenvironment by a factor of 2-3 fold, whereas greater radiosensitivity is prevalent in the young and individuals with benign diseases of bone. Increasing the volume of the bone cancer target from a 10 μm thick endosteum to a 50 μm peripheral marrow layer will result in an approximately three-fold decline in the mean dose from alpha-emitters in bone. These new observations are shown to go some way in explaining the low incidences for leukaemia and especially bone cancer in radium dial painters, Thorotrast patients and Mayak nuclear workers. (author)

A CREB-MPP7-AMOT Regulatory Axis Controls Muscle Stem Cell Expansion and Self-Renewal Competence

Directory of Open Access Journals (Sweden)

Lydia Li

2017-10-01

Full Text Available Summary: Skeletal muscle regeneration requires resident muscle stem cells, termed satellite cells (SCs. SCs are largely quiescent during homeostasis yet become activated upon injury to supply myonuclei and self-renewed SCs. Molecular mechanisms underlying the competence of SCs to proliferate and self-renew in response to injury remain unclear. Here, we show that CREB activity establishes proliferative potential during SC quiescence. SCs with inhibited CREB activity remain quiescent and positioned in their niche, but upon injury, they cannot enter or maintain a proliferative state for expansion and self-renewal. We demonstrate mechanistically that Mpp7 is a CREB target and its functional mediator. MPP7 loss affects the level and sub-cellular localization of AMOT and YAP1 in quiescent SCs. Furthermore, MPP7 and AMOT are required for YAP1 nuclear accumulation, and the three are individually required for a proliferative state in myoblasts. We propose that the CREB-MPP7-AMOT-YAP1 axis establishes the competence of quiescent SCs to expand and self-renew, thereby preserving stem cell function. : Satellite cells are quiescent muscle stem cells that have the ability to regenerate muscles after injury. Li and Fan reveal an MPP7-AMOT-YAP1 regulatory axis that acts downstream of CREB to instill satellite cell competence. They also show how this regulatory axis prepares satellite cells for robust muscle regeneration after injury.

THE IMPACT OF SURFACE TEMPERATURE INHOMOGENEITIES ON QUIESCENT NEUTRON STAR RADIUS MEASUREMENTS

Energy Technology Data Exchange (ETDEWEB)

Elshamouty, K. G.; Heinke, C. O.; Morsink, S. M.; Stevens, A. L. [Department of Physics, University of Alberta, CCIS 4-181, Edmonton, AB T6G 2E1 (Canada); Bogdanov, S., E-mail: alshamou@ualberta.ca [Columbia Astrophysics Laboratory, Columbia University, 550 West 120th Street, NY 10027 (United States)

2016-08-01

Fitting the thermal X-ray spectra of neutron stars (NSs) in quiescent X-ray binaries can constrain the masses and radii of NSs. The effect of undetected hot spots on the spectrum, and thus on the inferred NS mass and radius, has not yet been explored for appropriate atmospheres and spectra. A hot spot would harden the observed spectrum, so that spectral modeling tends to infer radii that are too small. However, a hot spot may also produce detectable pulsations. We simulated the effects of a hot spot on the pulsed fraction and spectrum of the quiescent NSs X5 and X7 in the globular cluster 47 Tucanae, using appropriate spectra and beaming for hydrogen atmosphere models, incorporating special and general relativistic effects, and sampling a range of system angles. We searched for pulsations in archival Chandra HRC-S observations of X5 and X7, placing 90% confidence upper limits on their pulsed fractions below 16%. We use these pulsation limits to constrain the temperature differential of any hot spots, and to then constrain the effects of possible hot spots on the X-ray spectrum and the inferred radius from spectral fitting. We find that hot spots below our pulsation limit could bias the spectroscopically inferred radius downward by up to 28%. For Cen X-4 (which has deeper published pulsation searches), an undetected hot spot could bias its inferred radius downward by up to 10%. Improving constraints on pulsations from quiescent LMXBs may be essential for progress in constraining their radii.

THE IMPACT OF SURFACE TEMPERATURE INHOMOGENEITIES ON QUIESCENT NEUTRON STAR RADIUS MEASUREMENTS

International Nuclear Information System (INIS)

Elshamouty, K. G.; Heinke, C. O.; Morsink, S. M.; Stevens, A. L.; Bogdanov, S.

2016-01-01

Fitting the thermal X-ray spectra of neutron stars (NSs) in quiescent X-ray binaries can constrain the masses and radii of NSs. The effect of undetected hot spots on the spectrum, and thus on the inferred NS mass and radius, has not yet been explored for appropriate atmospheres and spectra. A hot spot would harden the observed spectrum, so that spectral modeling tends to infer radii that are too small. However, a hot spot may also produce detectable pulsations. We simulated the effects of a hot spot on the pulsed fraction and spectrum of the quiescent NSs X5 and X7 in the globular cluster 47 Tucanae, using appropriate spectra and beaming for hydrogen atmosphere models, incorporating special and general relativistic effects, and sampling a range of system angles. We searched for pulsations in archival Chandra HRC-S observations of X5 and X7, placing 90% confidence upper limits on their pulsed fractions below 16%. We use these pulsation limits to constrain the temperature differential of any hot spots, and to then constrain the effects of possible hot spots on the X-ray spectrum and the inferred radius from spectral fitting. We find that hot spots below our pulsation limit could bias the spectroscopically inferred radius downward by up to 28%. For Cen X-4 (which has deeper published pulsation searches), an undetected hot spot could bias its inferred radius downward by up to 10%. Improving constraints on pulsations from quiescent LMXBs may be essential for progress in constraining their radii.

Study of discharge in quiescent plasma machine of the INPE

International Nuclear Information System (INIS)

Ferreira, J.G.; Ferreira, J.L.; Ludwig, G.O.; Maciel, H.S.

1988-12-01

Measurements of principal plasma parameters produced by quiescent plasma machine of the Instituto de Pesquisas Espaciais (INPE) for current of 500 mA and several values of pressure and discharge power are presented. A qualitative interpretation for obtained results is done and a simple model for plasma density is compared with experimental values. The conditions of cathode operation are also investigated. (M.C.K.)

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

Science.gov (United States)

Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

Modeling quiescent phase transport of air bubbles induced by breaking waves

Science.gov (United States)

Shi, Fengyan; Kirby, James T.; Ma, Gangfeng

Simultaneous modeling of both the acoustic phase and quiescent phase of breaking wave-induced air bubbles involves a large range of length scales from microns to meters and time scales from milliseconds to seconds, and thus is computational unaffordable in a surfzone-scale computational domain. In this study, we use an air bubble entrainment formula in a two-fluid model to predict air bubble evolution in the quiescent phase in a breaking wave event. The breaking wave-induced air bubble entrainment is formulated by connecting the shear production at the air-water interface and the bubble number intensity with a certain bubble size spectra observed in laboratory experiments. A two-fluid model is developed based on the partial differential equations of the gas-liquid mixture phase and the continuum bubble phase, which has multiple size bubble groups representing a polydisperse bubble population. An enhanced 2-DV VOF (Volume of Fluid) model with a k - ɛ turbulence closure is used to model the mixture phase. The bubble phase is governed by the advection-diffusion equations of the gas molar concentration and bubble intensity for groups of bubbles with different sizes. The model is used to simulate air bubble plumes measured in laboratory experiments. Numerical results indicate that, with an appropriate parameter in the air entrainment formula, the model is able to predict the main features of bubbly flows as evidenced by reasonable agreement with measured void fraction. Bubbles larger than an intermediate radius of O(1 mm) make a major contribution to void fraction in the near-crest region. Smaller bubbles tend to penetrate deeper and stay longer in the water column, resulting in significant contribution to the cross-sectional area of the bubble cloud. An underprediction of void fraction is found at the beginning of wave breaking when large air pockets take place. The core region of high void fraction predicted by the model is dislocated due to use of the shear

Controlling the diversity of cell populations in a stem cell culture

NARCIS (Netherlands)

Heo, Inha; Clevers, Hans

2015-01-01

Culturing intestinal stem cells into 3D organoids results in heterogeneous cell populations, reflecting the in vivo cell type diversity. In a recent paper published in Nature, Wang et al. established a culture condition for a highly homogeneous population of intestinal stem cells.

Radiobiological properties of spermatogonial stem cells in C3H/101 hybrid mice and evaluation of the model for induction of genetic damage in spermatogonial stem cells

International Nuclear Information System (INIS)

De Rooij, V.

1993-01-01

C3H/101 (3H1) hybrid mice are studied, in order to find answers to the following questions: What are the D 0 values for killing of proliferating and quiescent stem cells by X-irradiation in 3H1 mice; How many stem cells are present per 3H1 testis and what is the density of these cells during the epithelial cycle; What are the approximate numbers of proliferating and quiescent stem cells in a 3H1 mouse testis. (R.P.) 5 figs

Observations of current flow to a positively polarized electrode in a quiescent magnetoplasma

International Nuclear Information System (INIS)

Ferreira, J.L.; Urrutia, J.M.; Stenzel, R.L.

1988-05-01

This work reports experimental studies on the current flow to an electrode immersed in a quiescent magnetized plasma. The observed intense current driven instabilities during the current flow were found to be related with an anomalous current transport. (author)

Serum-induced G0/G1 transition in chemically transformed 3T3 cells

International Nuclear Information System (INIS)

Gray, H.E.; Buchou, T.; Mester, J.

1987-01-01

Quiescent, chemically transformed (benzo-a-pyrene) BALB/c 3T3 cells (BP A31) enter the cell division cycle when exposed to complete medium containing 10% fetal calf serum (FCS); the number of cells recruited is a function of the duration of serum exposure. The recruitment of cells by short (<4 h) serum pulses is not inhibited by simultaneous exposure to cycloheximide (CH), and therefore the initial commitment does not require protein synthesis. The cells enter S phase with a constant delay following the removal of CH, even if CH exposure has been continued for as long as 20 h after the end of the serum pulse. The cell recruitment by serum pulses was inhibited by 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of cytoplasmic mRNA accumulation. These data suggest that serum exposure produces a stable memory that is necessary and sufficient for the eventual progression through G1 to S phase that occurs when protein synthesis is resumed after the removal of CH; this memory probably consists of mRNA species that are induced by serum and that are stable in the absence of protein synthesis. Unexpectedly, pretreatment of quiescent BP A31 cells with CH (8-24 h) dramatically increased the fraction of the total cell population that is recruited by a serum pulse of fixed duration

Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing.

Science.gov (United States)

Kurashima, Yosuke; Kiyono, Hiroshi

2017-04-26

The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses. The bacterial population within gut-associated lymphoid tissues creates the intratissue cohabitations for harmonized mucosal immunity. Intermolecular and intercellular communication among epithelial, immune, and mesenchymal cells creates an environment conducive for epithelial regeneration and mucosal healing. This review summarizes the so-called intestinal mucosal ecological network-the complex but vital molecular and cellular interactions of epithelial mesenchymal cells, immune cells, and commensal microbiota that achieve intestinal homeostasis, regeneration, and healing.

Template DNA-strand co-segregation and asymmetric cell division in skeletal muscle stem cells.

Science.gov (United States)

Shinin, Vasily; Gayraud-Morel, Barbara; Tajbakhsh, Shahragim

2009-01-01

Stem cells are present in all tissues and organs, and are crucial for normal regulated growth. How the pool size of stem cells and their progeny is regulated to establish the tissue prenatally, then maintain it throughout life, is a key question in biology and medicine. The ability to precisely locate stem and progenitors requires defining lineage progression from stem to differentiated cells, assessing the mode of cell expansion and self-renewal and identifying markers to assess the different cell states within the lineage. We have shown that during lineage progression from a quiescent adult muscle satellite cell to a differentiated myofibre, both symmetric and asymmetric divisions take place. Furthermore, we provide evidence that a sub-population of label retaining satellite cells co-segregate template DNA strands to one daughter cell. These findings provide a means of identifying presumed stem and progenitor cells within the lineage. In addition, asymmetric segregation of template DNA and the cytoplasmic protein Numb provides a landmark to define cell behaviour as self-renewal and differentiation decisions are being executed.

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

Directory of Open Access Journals (Sweden)

Alexander Lorz

2017-08-01

Full Text Available Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug’s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large �

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

Science.gov (United States)

Lorz, Alexander; Botesteanu, Dana-Adriana; Levy, Doron

2017-01-01

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug’s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/switch-off” increase in the average

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

KAUST Repository

Lorz, Alexander; Botesteanu, Dana-Adriana; Levy, Doron

2017-01-01

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug's effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/ switch-off” increase in the average

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

KAUST Repository

Lorz, Alexander

2017-08-30

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug\\'s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/ switch-off” increase in the average

The quiescent state of the neutron-star X-ray transient GRS 1747-312 in the globular cluster Terzan 6

Science.gov (United States)

Vats, Smriti; Wijnands, Rudy; Parikh, Aastha S.; Ootes, Laura; Degenaar, Nathalie; Page, Dany

2018-04-01

We studied the transient neutron-star low-mass X-ray binary GRS 1747-312, located in the globular cluster Terzan 6, in its quiescent state after its outburst in August 2004, using an archival XMM-Newton observation. A source was detected in this cluster and its X-ray spectrum can be fitted with the combination of a soft, neutron-star atmosphere model and a hard, power-law model. Both contributed roughly equally to the observed 0.5-10 keV luminosity (˜4.8 × 1033 erg s-1). This type of X-ray spectrum is typically observed for quiescent neutron-star X-ray transients that are perhaps accreting in quiescence at very low rates. Therefore, if this X-ray source is the quiescent counterpart of GRS 1747-312, then this source is also accreting at low levels in-between outbursts. Since source confusion a likely problem in globular clusters, it is quite possible that part, if not all, of the emission we observed is not related to GRS 1747-312, and is instead associated with another source or conglomeration of sources in the cluster. Currently, it is not possible to determine exactly which part of the emission truly originates from GRS1747-312, and a Chandra observation (when no source is in outburst in Terzan 6) is needed to be conclusive. Assuming that the detected emission is due to GRS 1747-312, we discuss the observed results in the context of what is known about other quiescent systems. We also investigated the thermal evolution of the neutron-star in GRS 1747-312, and inferred that GRS 1747-312 can be considered a typical quiescent system under our assumptions.

KMOS"3"D Reveals Low-level Star Formation Activity in Massive Quiescent Galaxies at 0.7 < z < 2.7

International Nuclear Information System (INIS)

Belli, Sirio; Genzel, Reinhard; Förster Schreiber, Natascha M.; Wisnioski, Emily; Wilman, David J.; Mendel, J. Trevor; Beifiori, Alessandra; Bender, Ralf; Burkert, Andreas; Chan, Jeffrey; Davies, Rebecca L.; Davies, Ric; Fabricius, Maximilian; Fossati, Matteo; Galametz, Audrey; Lang, Philipp; Lutz, Dieter; Wuyts, Stijn; Brammer, Gabriel B.; Momcheva, Ivelina G.

2017-01-01

We explore the H α emission in the massive quiescent galaxies observed by the KMOS"3"D survey at 0.7 < z < 2.7. The H α line is robustly detected in 20 out of 120 UVJ -selected quiescent galaxies, and we classify the emission mechanism using the H α line width and the [N ii]/H α line ratio. We find that AGNs are likely to be responsible for the line emission in more than half of the cases. We also find robust evidence for star formation activity in nine quiescent galaxies, which we explore in detail. The H α kinematics reveal rotating disks in five of the nine galaxies. The dust-corrected H α star formation rates are low (0.2–7 M _⊙ yr"−"1), and place these systems significantly below the main sequence. The 24 μ m-based, infrared luminosities, instead, overestimate the star formation rates. These galaxies present a lower gas-phase metallicity compared to star-forming objects with similar stellar mass, and many of them have close companions. We therefore conclude that the low-level star formation activity in these nine quiescent galaxies is likely to be fueled by inflowing gas or minor mergers, and could be a sign of rejuvenation events.

Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

Science.gov (United States)

Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

2016-01-01

The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

What Turns Galaxies Off? the Different Morphologies of Star-Forming and Quiescent Galaxies Since z Approximates 2 from CANDELS

Science.gov (United States)

Bell, Eric F.; VanDerWel, Arjen; Papovich, Casey; Kocevski, Dale; Lotz, Jennifer; McIntosh, Daniel H.; Kartaltepe, Jeyhan; Faber, S. M.; Ferguson, Harry; Koekemoer, Anton;

Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing.

Science.gov (United States)

Hochgerner, Hannah; Zeisel, Amit; Lönnerberg, Peter; Linnarsson, Sten

2018-02-01

The dentate gyrus of the hippocampus is a brain region in which neurogenesis persists into adulthood; however, the relationship between developmental and adult dentate gyrus neurogenesis has not been examined in detail. Here we used single-cell RNA sequencing to reveal the molecular dynamics and diversity of dentate gyrus cell types in perinatal, juvenile, and adult mice. We found distinct quiescent and proliferating progenitor cell types, linked by transient intermediate states to neuroblast stages and fully mature granule cells. We observed shifts in the molecular identity of quiescent and proliferating radial glia and granule cells during the postnatal period that were then maintained through adult stages. In contrast, intermediate progenitor cells, neuroblasts, and immature granule cells were nearly indistinguishable at all ages. These findings demonstrate the fundamental similarity of postnatal and adult neurogenesis in the hippocampus and pinpoint the early postnatal transformation of radial glia from embryonic progenitors to adult quiescent stem cells.

Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

Directory of Open Access Journals (Sweden)

Kazuyo Yasuda

Full Text Available Cancer stem-like cells (CSCs/cancer-initiaiting cells (CICs are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br cells from ovarian cancer cells. Both SP cells and ALDH(Br cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2, than those of main population (MP cells and ALDH(Low cells, respectively. We analyzed an SP and ALDH(Br overlapping population (SP/ALDH(Br, and the SP/ALDH(Br population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br cells, enabling initiation of tumor with as few as 10(2 cells. Furthermore, SP/ADLH(Br population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low, MP/ALDH(Br and MP/ALDH(Low cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

Gene expression changes in diapause or quiescent potato cyst nematode, Globodera pallida, eggs after hydration or exposure to tomato root diffusate.

Science.gov (United States)

Palomares-Rius, Juan Emilio; Hedley, Pete; Cock, Peter J A; Morris, Jenny A; Jones, John T; Blok, Vivian C

2016-01-01

Plant-parasitic nematodes (PPN) need to be adapted to survive in the absence of a suitable host or in hostile environmental conditions. Various forms of developmental arrest including hatching inhibition and dauer stages are used by PPN in order to survive these conditions and spread to other areas. Potato cyst nematodes (PCN) (Globodera pallida and G. rostochiensis) are frequently in an anhydrobiotic state, with unhatched nematode persisting for extended periods of time inside the cyst in the absence of the host. This paper shows fundamental changes in the response of quiescent and diapaused eggs of G. pallida to hydration and following exposure to tomato root diffusate (RD) using microarray gene expression analysis encompassing a broad set of genes. For the quiescent eggs, 547 genes showed differential expression following hydration vs. hydratation and RD (H-RD) treatment whereas 708 genes showed differential regulation for the diapaused eggs following these treatments. The comparison between hydrated quiescent and diapaused eggs showed marked differences, with 2,380 genes that were differentially regulated compared with 987 genes following H-RD. Hydrated quiescent and diapaused eggs were markedly different indicating differences in adaptation for long-term survival. Transport activity is highly up-regulated following H-RD and few genes were coincident between both kinds of eggs. With the quiescent eggs, the majority of genes were related to ion transport (mainly sodium), while the diapaused eggs showed a major diversity of transporters (amino acid transport, ion transport, acetylcholine or other molecules).

Gene expression changes in diapause or quiescent potato cyst nematode, Globodera pallida, eggs after hydration or exposure to tomato root diffusate

Directory of Open Access Journals (Sweden)

Juan Emilio Palomares-Rius

2016-02-01

Full Text Available Plant-parasitic nematodes (PPN need to be adapted to survive in the absence of a suitable host or in hostile environmental conditions. Various forms of developmental arrest including hatching inhibition and dauer stages are used by PPN in order to survive these conditions and spread to other areas. Potato cyst nematodes (PCN (Globodera pallida and G. rostochiensis are frequently in an anhydrobiotic state, with unhatched nematode persisting for extended periods of time inside the cyst in the absence of the host. This paper shows fundamental changes in the response of quiescent and diapaused eggs of G. pallida to hydration and following exposure to tomato root diffusate (RD using microarray gene expression analysis encompassing a broad set of genes. For the quiescent eggs, 547 genes showed differential expression following hydration vs. hydratation and RD (H-RD treatment whereas 708 genes showed differential regulation for the diapaused eggs following these treatments. The comparison between hydrated quiescent and diapaused eggs showed marked differences, with 2,380 genes that were differentially regulated compared with 987 genes following H-RD. Hydrated quiescent and diapaused eggs were markedly different indicating differences in adaptation for long-term survival. Transport activity is highly up-regulated following H-RD and few genes were coincident between both kinds of eggs. With the quiescent eggs, the majority of genes were related to ion transport (mainly sodium, while the diapaused eggs showed a major diversity of transporters (amino acid transport, ion transport, acetylcholine or other molecules.

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

International Nuclear Information System (INIS)

Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xueshun; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

2013-01-01

Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma

Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

Science.gov (United States)

Ito, Kyoko; Ito, Keisuke

2016-01-01

Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

Satellite Cell Self-Renewal.

Science.gov (United States)

Giordani, Lorenzo; Parisi, Alice; Le Grand, Fabien

2018-01-01

Adult skeletal muscle is endowed with regenerative potential through partially recapitulating the embryonic developmental program. Upon acute injury or in pathological conditions, quiescent muscle-resident stem cells, called satellite cells, become activated and give rise to myogenic progenitors that massively proliferate, differentiate, and fuse to form new myofibers and restore tissue functionality. In addition, a proportion of activated cells returns back to quiescence and replenish the pool of satellite cells in order to maintain the ability of skeletal muscle tissue to repair. Self-renewal is the process by which stem cells divide to make more stem cells to maintain the stem cell population throughout life. This process is controlled by cell-intrinsic transcription factors regulated by cell-extrinsic signals from the niche and the microenvironment. This chapter provides an overview about the general aspects of satellite cell biology and focuses on the cellular and molecular aspects of satellite cell self-renewal. To date, we are still far from understanding how a very small proportion of the satellite cell progeny maintain their stem cell identity when most of their siblings progress through the myogenic program to construct myofibers. © 2018 Elsevier Inc. All rights reserved.

The quiescent state of the neutron-star X-ray transient GRS 1747-312 in the globular cluster Terzan 6

Science.gov (United States)

Vats, Smriti; Wijnands, Rudy; Parikh, Aastha S.; Ootes, Laura; Degenaar, Nathalie; Page, Dany

2018-06-01

We studied the transient neutron-star low-mass X-ray binary GRS 1747-312, located in the globular cluster Terzan 6, in its quiescent state after its outburst in August 2004, using an archival XMM-Newton observation. A source was detected in this cluster and its X-ray spectrum can be fitted with the combination of a soft, neutron-star atmosphere model and a hard, power-law model. Both contributed roughly equally to the observed 0.5-10 keV luminosity (˜4.8 × 1033 erg s-1). This type of X-ray spectrum is typically observed for quiescent neutron-star X-ray transients that are perhaps accreting in quiescence at very low rates. Therefore, if this X-ray source is the quiescent counterpart of GRS 1747-312, then this source is also accreting at low levels in-between outbursts. Since source confusion is a likely problem in globular clusters, it is quite possible that part, if not all, of the emission we observed is not related to GRS 1747-312, and is instead associated with another source or conglomeration of sources in the cluster. Currently, it is not possible to determine exactly which part of the emission truly originates from GRS 1747-312, and a Chandra observation (when no source is in outburst in Terzan 6) is needed to be conclusive. Assuming that the detected emission is due to GRS 1747-312, we discuss the observed results in the context of what is known about other quiescent systems. We also investigated the thermal evolution of the neutron star in GRS 1747-312, and inferred that GRS 1747-312 can be considered a typical quiescent system under our assumptions.

WFC3 GRISM CONFIRMATION OF THE DISTANT CLUSTER Cl J1449+0856 AT (z) = 2.00: QUIESCENT AND STAR-FORMING GALAXY POPULATIONS

Energy Technology Data Exchange (ETDEWEB)

Gobat, R.; Strazzullo, V.; Daddi, E. [Laboratoire AIM-Paris-Saclay, CEA/DSM-CNRS-Université Paris Diderot, Irfu/Service d' Astrophysique, CEA Saclay, Orme des Merisiers, F-91191 Gif sur Yvette (France); Onodera, M.; Carollo, M. [Institute for Astronomy, ETH Zürich Wolfgang-Pauli-strasse 27, 8093 Zürich (Switzerland); Renzini, A. [INAF-Osservatorio Astronomico di Padova Vicolo dell' Osservatorio 5, I-35122 Padova (Italy); Finoguenov, A. [University of Helsinki, P.O. Box 33 (Yliopistonkatu 4), FI-00014 Helsinki (Finland); Cimatti, A. [Università di Bologna, Dipartimento di Astronomia Via Ranzani 1, I-40127 Bologna (Italy); Scarlata, C. [School of Physics and Astronomy, University of Minnesota 116 Church Street Southeast, Minneapolis, MN 55455 (United States); Arimoto, N. [Subaru Telescope, National Astronomical Observatory of Japan 650 North A' ohoku Place, Hilo, HI 96720 (United States)

2013-10-10

We present deep Hubble Space Telescope Wide Field Camera 3 (HST/WFC3) slitless spectroscopic observations of the distant cluster Cl J1449+0856. These cover a single pointing with 18 orbits of G141 spectroscopy and F140W imaging, allowing us to derive secure redshifts down to M{sub 140} ∼ 25.5 AB and 3σ line fluxes of ∼5 × 10{sup –18} erg s{sup –1} cm{sup –2}. In particular, we were able to spectroscopically confirm 12 early-type galaxies (ETGs) in the field up to z ∼ 3, 6 of which are in the cluster core, which represents the first direct spectroscopic confirmation of quiescent galaxies in a z = 2 cluster environment. With 140 redshifts in a ∼6 arcmin{sup 2} field, we can trace the spatial and redshift galaxy distribution in the cluster core and background field. We find two strong peaks at z = 2.00 and z = 2.07, where only one was seen in our previously published ground-based data. Due to the spectroscopic confirmation of the cluster ETGs, we can now reevaluate the redshift of Cl J1449+0856 at z = 2.00, rather than z = 2.07, with the background overdensity being revealed to be sparse and {sup s}heet{sup -}like. This presents an interesting case of chance alignment of two close yet unrelated structures, each one preferentially selected by different observing strategies. With 6 quiescent or early-type spectroscopic members and 20 star-forming ones, Cl J1449+0856 is now reliably confirmed to be at z = 2.00. The identified members can now allow for a detailed study of galaxy properties in the densest environment at z = 2.

Slow-cycling stem cells in hydra contribute to head regeneration

Directory of Open Access Journals (Sweden)

Niraimathi Govindasamy

2014-11-01

Full Text Available Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8–10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals.

Phenotype heterogeneity in cancer cell populations

International Nuclear Information System (INIS)

Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

2016-01-01

Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

Phenotype heterogeneity in cancer cell populations

Energy Technology Data Exchange (ETDEWEB)

Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

2016-06-08

Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

Phenotype heterogeneity in cancer cell populations

Science.gov (United States)

Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

2016-06-01

Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

KMOS{sup 3D} Reveals Low-level Star Formation Activity in Massive Quiescent Galaxies at 0.7 < z < 2.7

Energy Technology Data Exchange (ETDEWEB)

Belli, Sirio; Genzel, Reinhard; Förster Schreiber, Natascha M.; Wisnioski, Emily; Wilman, David J.; Mendel, J. Trevor; Beifiori, Alessandra; Bender, Ralf; Burkert, Andreas; Chan, Jeffrey; Davies, Rebecca L.; Davies, Ric; Fabricius, Maximilian; Fossati, Matteo; Galametz, Audrey; Lang, Philipp; Lutz, Dieter [Max-Planck-Institut für Extraterrestrische Physik (MPE), Giessenbachstr. 1, D-85748 Garching (Germany); Wuyts, Stijn [Department of Physics, University of Bath, Claverton Down, Bath, BA2 7AY (United Kingdom); Brammer, Gabriel B.; Momcheva, Ivelina G. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); and others

2017-05-20

We explore the H α emission in the massive quiescent galaxies observed by the KMOS{sup 3D} survey at 0.7 < z < 2.7. The H α line is robustly detected in 20 out of 120 UVJ -selected quiescent galaxies, and we classify the emission mechanism using the H α line width and the [N ii]/H α line ratio. We find that AGNs are likely to be responsible for the line emission in more than half of the cases. We also find robust evidence for star formation activity in nine quiescent galaxies, which we explore in detail. The H α kinematics reveal rotating disks in five of the nine galaxies. The dust-corrected H α star formation rates are low (0.2–7 M {sub ⊙} yr{sup −1}), and place these systems significantly below the main sequence. The 24 μ m-based, infrared luminosities, instead, overestimate the star formation rates. These galaxies present a lower gas-phase metallicity compared to star-forming objects with similar stellar mass, and many of them have close companions. We therefore conclude that the low-level star formation activity in these nine quiescent galaxies is likely to be fueled by inflowing gas or minor mergers, and could be a sign of rejuvenation events.

Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.

Science.gov (United States)

Yano, Shuya; Miwa, Shinji; Mii, Sumiyuki; Hiroshima, Yukihiko; Uehara, Fuminaru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Zhao, Ming; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

2015-01-01

The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.

Starburst to Quiescent from HST/ALMA

DEFF Research Database (Denmark)

Gómez-Guijarro, C.; Toft, S.; Karim, A.

2018-01-01

Dust-enshrouded, starbursting, submillimeter galaxies (SMGs) at z ≥ 3 have been proposed as progenitors of z ≥ 2 compact quiescent galaxies (cQGs). To test this connection, we present a detailed spatially resolved study of the stars, dust, and stellar mass in a sample of six submillimeter...... (β) maps with the FIR dust continuum to study the infrared excess (IRX = L IR/L UV)–β relation. The SMGs display systematically higher IRX values than expected from the nominal trend, demonstrating that the FIR and UV emissions are spatially disconnected. Finally, we show that the SMGs fall...... on the mass–size plane at smaller stellar masses and sizes than the cQGs at z = 2. Taking into account the expected evolution in stellar mass and size between z = 4.5 and z = 2 due to the ongoing starburst and mergers with minor companions, this is in agreement with a direct evolutionary connection between...

Gene expression heterogeneities in embryonic stem cell populations

DEFF Research Database (Denmark)

Martinez Arias, Alfonso; Brickman, Joshua M

2011-01-01

Stem and progenitor cells are populations of cells that retain the capacity to populate specific lineages and to transit this capacity through cell division. However, attempts to define markers for stem cells have met with limited success. Here we consider whether this limited success reflects...... an intrinsic requirement for heterogeneity with stem cell populations. We focus on Embryonic Stem (ES) cells, in vitro derived cell lines from the early embryo that are considered both pluripotent (able to generate all the lineages of the future embryo) and indefinitely self renewing. We examine the relevance...... of recently reported heterogeneities in ES cells and whether these heterogeneities themselves are inherent requirements of functional potency and self renewal....

CANDELS+3D-HST: Compact SFGs at z ∼ 2-3, the progenitors of the first quiescent galaxies

Energy Technology Data Exchange (ETDEWEB)

Barro, G.; Faber, S. M.; Koo, D. C.; Guo, Y. [UCO/Lick Observatory and Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Pérez-González, P. G. [Universidad Complutense de Madrid, F. CC. Físicas, 28040 Madrid (Spain); Pacifici, C. [Yonsei University Observatory, Yonsei University, Seoul 120-749 (Korea, Republic of); Trump, J. R. [Pennsylvania State University, University Park, PA 16802 (United States); Wuyts, S.; Hsu, L. [Max-Planck-Institut für extraterrestrische Physik, Postfach 1312, Giessenbachstr., D-85741 Garching (Germany); Bell, E. [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Dekel, A. [Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel); Porter, L.; Primack, J. [Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, CA 95064 (United States); Ferguson, H. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Ashby, M. L. N.; Fazio, G. G. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Caputi, K. [Kapteyn Astronomical Institute, University of Groningen, P.O. Box 800, 9700 AV Groningen (Netherlands); Ceverino, D. [Departamento de Física Teórica, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Croton, D. [Centre for Astrophysics and Supercomputing, Swinburne University of Technology, PO Box 218, Hawthorn, VIC 3122 (Australia); Giavalisco, M. [Astronomy Department, University of Massachusetts, 710 North Pleasant Street, Amherst, MA 01003 (United States); and others

2014-08-10

We analyze the star-forming and structural properties of 45 massive (log(M/M{sub ☉}) >10) compact star-forming galaxies (SFGs) at 2 < z < 3 to explore whether they are progenitors of compact quiescent galaxies at z ∼ 2. The optical/NIR and far-IR Spitzer/Herschel colors indicate that most compact SFGs are heavily obscured. Nearly half (47%) host an X-ray-bright active galactic nucleus (AGN). In contrast, only about 10% of other massive galaxies at that time host AGNs. Compact SFGs have centrally concentrated light profiles and spheroidal morphologies similar to quiescent galaxies and are thus strikingly different from other SFGs, which typically are disk-like and sometimes clumpy or irregular. Most compact SFGs lie either within the star formation rate (SFR)-mass main sequence (65%) or below it (30%), on the expected evolutionary path toward quiescent galaxies. These results show conclusively that galaxies become more compact before they lose their gas and dust, quenching star formation. Using extensive HST photometry from CANDELS and grism spectroscopy from the 3D-HST survey, we model their stellar populations with either exponentially declining (τ) star formation histories (SFHs) or physically motivated SFHs drawn from semianalytic models (SAMs). SAMs predict longer formation timescales and older ages ∼2 Gyr, which are nearly twice as old as the estimates of the τ models. Both models yield good spectral energy distribution fits, indicating that the systematic uncertainty in the age due to degeneracies in the SFH is of that order of magnitude. However, SAM SFHs better match the observed slope and zero point of the SFR-mass main sequence. Contrary to expectations, some low-mass compact SFGs (log(M/M{sub ☉}) =10-10.6) have younger ages but lower specific SFRs than that of more massive galaxies, suggesting that the low-mass galaxies reach the red sequence faster. If the progenitors of compact SFGs are extended SFGs, state-of-the-art SAMs show that mergers

CANDELS+3D-HST: Compact SFGs at z ∼ 2-3, the progenitors of the first quiescent galaxies

International Nuclear Information System (INIS)

Barro, G.; Faber, S. M.; Koo, D. C.; Guo, Y.; Pérez-González, P. G.; Pacifici, C.; Trump, J. R.; Wuyts, S.; Hsu, L.; Bell, E.; Dekel, A.; Porter, L.; Primack, J.; Ferguson, H.; Ashby, M. L. N.; Fazio, G. G.; Caputi, K.; Ceverino, D.; Croton, D.; Giavalisco, M.

2014-01-01

We analyze the star-forming and structural properties of 45 massive (log(M/M ☉ ) >10) compact star-forming galaxies (SFGs) at 2 < z < 3 to explore whether they are progenitors of compact quiescent galaxies at z ∼ 2. The optical/NIR and far-IR Spitzer/Herschel colors indicate that most compact SFGs are heavily obscured. Nearly half (47%) host an X-ray-bright active galactic nucleus (AGN). In contrast, only about 10% of other massive galaxies at that time host AGNs. Compact SFGs have centrally concentrated light profiles and spheroidal morphologies similar to quiescent galaxies and are thus strikingly different from other SFGs, which typically are disk-like and sometimes clumpy or irregular. Most compact SFGs lie either within the star formation rate (SFR)-mass main sequence (65%) or below it (30%), on the expected evolutionary path toward quiescent galaxies. These results show conclusively that galaxies become more compact before they lose their gas and dust, quenching star formation. Using extensive HST photometry from CANDELS and grism spectroscopy from the 3D-HST survey, we model their stellar populations with either exponentially declining (τ) star formation histories (SFHs) or physically motivated SFHs drawn from semianalytic models (SAMs). SAMs predict longer formation timescales and older ages ∼2 Gyr, which are nearly twice as old as the estimates of the τ models. Both models yield good spectral energy distribution fits, indicating that the systematic uncertainty in the age due to degeneracies in the SFH is of that order of magnitude. However, SAM SFHs better match the observed slope and zero point of the SFR-mass main sequence. Contrary to expectations, some low-mass compact SFGs (log(M/M ☉ ) =10-10.6) have younger ages but lower specific SFRs than that of more massive galaxies, suggesting that the low-mass galaxies reach the red sequence faster. If the progenitors of compact SFGs are extended SFGs, state-of-the-art SAMs show that mergers and disk

Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

Science.gov (United States)

Strand, Marie; Micchelli, Craig A

2013-01-01

Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P) axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs) of the acidic copper cell region (CCR), which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

Directory of Open Access Journals (Sweden)

Marie Strand

Full Text Available Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs of the acidic copper cell region (CCR, which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration

Directory of Open Access Journals (Sweden)

Dingxiao Zhang

2018-01-01

Full Text Available The existence of slow-cycling luminal cells in the prostate has been suggested, but their identity and functional properties remain unknown. Using a bigenic mouse model to earmark, isolate, and characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC population in the luminal cell layer as luminal progenitors. Molecular and biological characterizations show that these luminal LRCs are significantly enriched in the mouse proximal prostate, exhibit relative dormancy, display bipotency in both in vitro and in vivo assays, and express a stem/progenitor gene signature with resemblance to aggressive prostate cancer. Importantly, these LRCs, compared with bulk luminal cells, maintain a lower level of androgen receptor (AR expression and are less androgen dependent and also castration resistant in vivo. Finally, analysis of phenotypic markers reveals heterogeneity within the luminal progenitor cell pool. Our study establishes luminal LRCs as progenitors that may serve as a cellular origin for castration-resistant prostate cancer.

Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches

NARCIS (Netherlands)

Hira, Vashendriya V. V.; van Noorden, Cornelis J. F.; Carraway, Hetty E.; Maciejewski, Jaroslaw P.; Molenaar, Remco J.

2017-01-01

Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are

Excess of mutational jackpot events in expanding populations revealed by spatial Luria–Delbrück experiments

Science.gov (United States)

Fusco, Diana; Gralka, Matti; Kayser, Jona; Anderson, Alex; Hallatschek, Oskar

2016-01-01

The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance. PMID:27694797

Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbrück experiments.

Science.gov (United States)

Fusco, Diana; Gralka, Matti; Kayser, Jona; Anderson, Alex; Hallatschek, Oskar

2016-10-03

The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance.

On interfaces between cell populations with different mobilities

KAUST Repository

Lorenzi, Tommaso

2016-11-18

Partial differential equations describing the dynamics of cell population densities from a fluid mechanical perspective can model the growth of avascular tumours. In this framework, we consider a system of equations that describes the interaction between a population of dividing cells and a population of non-dividing cells. The two cell populations are characterised by different mobilities. We present the results of numerical simulations displaying two-dimensional spherical waves with sharp interfaces between dividing and non-dividing cells. Furthermore, we numerically observe how different ratios between the mobilities change the morphology of the interfaces, and lead to the emergence of finger-like patterns of invasion above a threshold. Motivated by these simulations, we study the existence of one-dimensional travelling wave solutions.

Stellar Velocity Dispersion: Linking Quiescent Galaxies to their Dark Matter Halos

OpenAIRE

Zahid, H. Jabran; Sohn, Jubee; Geller, Margaret J.

2018-01-01

We analyze the Illustris-1 hydrodynamical cosmological simulation to explore the stellar velocity dispersion of quiescent galaxies as an observational probe of dark matter halo velocity dispersion and mass. Stellar velocity dispersion is proportional to dark matter halo velocity dispersion for both central and satellite galaxies. The dark matter halos of central galaxies are in virial equilibrium and thus the stellar velocity dispersion is also proportional to dark matter halo mass. This prop...

Premalignant quiescent melanocytic nevi do not express the MHC class I chain-related protein A

Directory of Open Access Journals (Sweden)

Mercedes B. Fuertes

2011-08-01

Full Text Available The MHC class I chain-related protein A (MICA is an inducible molecule almost not expressed by normal cells but strongly up-regulated in tumor cells. MICA-expressing cells are recognized by natural killer (NK cells, CD8+ aßTCR and ?dTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA triggers IFN-? secretion and cytotoxicity against malignant cells. Although most solid tumors express MICA and this molecule is a target during immune surveillance against tumors, it has been observed that high grade tumors from different histotypes express low amounts of cell surface MICA due to a metalloprotease- induced shedding. Also, melanomas develop after a complex process of neotransformation of normal melanocytes. However, the expression of MICA in premalignant stages (primary human quiescent melanocytic nevi remains unknown. Here, we assessed expression of MICA by flow cytometry using cell suspensions from 15 primary nevi isolated from 11 patients. When collected material was abundant, cell lysates were prepared and MICA expression was also analyzed by Western blot. We observed that MICA was undetectable in the 15 primary nevi (intradermic, junction, mixed, lentigo and congenital samples as well as in normal skin, benign lesions (seborrheic keratosis, premalignant lesions (actinic keratosis and benign basocellular cancer. Conversely, a primary recently diagnosed melanoma showed intense cell surface MICA. We conclude that the onset of MICA expression is a tightly regulated process that occurs after melanocytes trespass the stage of malignant transformation. Thus, analysis of MICA expression in tissue sections of skin samples may constitute a useful marker to differentiate between benign and malignant nevi.

The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

Science.gov (United States)

Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

2012-01-01

Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. PMID:22662253

Bacterial viruses enable their host to acquire antibiotic resistance genes from neighbouring cells

DEFF Research Database (Denmark)

Haaber, Jakob Krause; Leisner, Jørgen; Cohn, Marianne Thorup

2016-01-01

Prophages are quiescent viruses located in the chromosomes of bacteria. In the human pathogen, Staphylococcus aureus, prophages are omnipresent and are believed to be responsible for the spread of some antibiotic resistance genes. Here we demonstrate that release of phages from a subpopulation of S....... aureus cells enables the intact, prophage-containing population to acquire beneficial genes from competing, phage-susceptible strains present in the same environment. Phage infection kills competitor cells and bits of their DNA are occasionally captured in viral transducing particles. Return...... of such particles to the prophage-containing population can drive the transfer of genes encoding potentially useful traits such as antibiotic resistance. This process, which can be viewed as ‘auto-transduction’, allows S. aureus to efficiently acquire antibiotic resistance both in vitro and in an in vivo virulence...

Early events elicited by Bombesin and structurally related peptides in quiescent Swiss 3T3 cells. I. Activation of protein kinase C and inhibition of epidermal growth factor binding

International Nuclear Information System (INIS)

Zachary, I.; Sinnett-Smith, J.W.; Rozengurt, E.

1986-01-01

Addition of bombesin to quiescent cultures of Swiss 3T3 cells caused a rapid increase in the phosphorylation of an M/sub r/ 80,000 cellular protein (designated 80k). The effect was both concentration and time dependent. The 80k phosphoproteins generated in response to bombesin and to phorbol 12,13-dibutyrate were identical as judged by one- and two-dimensional PAGE and by peptide mapping after partial proteolysis with Staphylococcus aureus V8 protease. In addition, prolonged pretreatment of 3T3 cells with phorbol 12,13-dibutyrate, which leads to the disappearance of protein kinase C activity, blocked the ability of bombesin to stimulate 80k. Bombesin also caused a rapid (1 min) inhibition of 125 I-labeled epidermal growth factor ( 125 I-EGF) binding to Swiss 3T3 cells. The inhibition was both concentration and temperature dependent and resulted from a marked decrease in the affinity of the EGF receptor for its ligand. These results strongly suggest that these responses are mediated by specific high-affinity receptors that recognize the peptides of the bombesin family in Swiss 3T3 cells. While an increase in cytosolic Ca 2+ concentration does not mediate the bombesin inhibition of 125 I-EGF binding, the activation of protein kinase C in intact Swiss 3T3 cells by peptides of the bombesin family may lead to rapid inhibition of the binding of 125 I-EGF to its cellular receptor

A STATISTICAL STUDY OF TRANSVERSE OSCILLATIONS IN A QUIESCENT PROMINENCE

Energy Technology Data Exchange (ETDEWEB)

Hillier, A. [Kwasan and Hida Observatories, Kyoto University, Kyoto 607-8471 (Japan); Morton, R. J. [Mathematics and Information Science, Northumbria University, Pandon Building, Camden Street, Newcastle upon Tyne NE1 8ST (United Kingdom); Erdélyi, R., E-mail: andrew@kwasan.kyoto-u.ac.jp [Solar Physics and Space Plasma Research Centre (SP2RC), University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom)

2013-12-20

The launch of the Hinode satellite has allowed for seeing-free observations at high-resolution and high-cadence making it well suited to study the dynamics of quiescent prominences. In recent years it has become clear that quiescent prominences support small-amplitude transverse oscillations, however, sample sizes are usually too small for general conclusions to be drawn. We remedy this by providing a statistical study of transverse oscillations in vertical prominence threads. Over a 4 hr period of observations it was possible to measure the properties of 3436 waves, finding periods from 50 to 6000 s with typical velocity amplitudes ranging between 0.2 and 23 km s{sup –1}. The large number of observed waves allows the determination of the frequency dependence of the wave properties and derivation of the velocity power spectrum for the transverse waves. For frequencies less than 7 mHz, the frequency dependence of the velocity power is consistent with the velocity power spectra generated from observations of the horizontal motions of magnetic elements in the photosphere, suggesting that the prominence transverse waves are driven by photospheric motions. However, at higher frequencies the two distributions significantly diverge, with relatively more power found at higher frequencies in the prominence oscillations. These results highlight that waves over a large frequency range are ubiquitous in prominences, and that a significant amount of the wave energy is found at higher frequency.

A STATISTICAL STUDY OF TRANSVERSE OSCILLATIONS IN A QUIESCENT PROMINENCE

International Nuclear Information System (INIS)

Hillier, A.; Morton, R. J.; Erdélyi, R.

2013-01-01

The launch of the Hinode satellite has allowed for seeing-free observations at high-resolution and high-cadence making it well suited to study the dynamics of quiescent prominences. In recent years it has become clear that quiescent prominences support small-amplitude transverse oscillations, however, sample sizes are usually too small for general conclusions to be drawn. We remedy this by providing a statistical study of transverse oscillations in vertical prominence threads. Over a 4 hr period of observations it was possible to measure the properties of 3436 waves, finding periods from 50 to 6000 s with typical velocity amplitudes ranging between 0.2 and 23 km s –1 . The large number of observed waves allows the determination of the frequency dependence of the wave properties and derivation of the velocity power spectrum for the transverse waves. For frequencies less than 7 mHz, the frequency dependence of the velocity power is consistent with the velocity power spectra generated from observations of the horizontal motions of magnetic elements in the photosphere, suggesting that the prominence transverse waves are driven by photospheric motions. However, at higher frequencies the two distributions significantly diverge, with relatively more power found at higher frequencies in the prominence oscillations. These results highlight that waves over a large frequency range are ubiquitous in prominences, and that a significant amount of the wave energy is found at higher frequency

Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells.

Science.gov (United States)

Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

2015-09-08

B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process.

Programmed cell death of tobacco BY-2 cells induced by still culture conditions is affected by the age of the culture under agitation.

Science.gov (United States)

Hiraga, Asahi; Kaneta, Tsuyoshi; Sato, Yasushi; Sato, Seiichi

2010-01-25

Evans Blue staining indicated that actively growing tobacco BY-2 cells in the exponential phase died more rapidly than quiescent cells in the stationary phase when the cells cultured under agitation were placed under still conditions. Fifty percent cell death was induced at about 18, 26, 80 and 140 h for early, mid, late exponential- and stationary-phase cells, respectively. Actively growing cells became TUNEL (transferase-mediated dUTP nick end labelling)-positive more rapidly than quiescent cells, suggesting that the cell death evaluated by Evans Blue is accompanied by DNA cleavages. Electrophoresis of genomic DNA showed a typical 'DNA laddering' pattern formed by multiples of about 200 bp internucleosomal units. Chromatin condensation was first detected at least within 24 h by light microscopy, and then cell shrinkage followed. These findings suggest that the death of BY-2 cells induced by still conditions is PCD (programmed cell death).

A plant U-box protein, PUB4, regulates asymmetric cell division and cell proliferation in the root meristem

NARCIS (Netherlands)

Kinoshita, A.; Hove, ten C.A.; Tabata, R.; Yamada, M.; Shimizu, N.; Ishida, T.; Yamaguchi, K.; Shigenobu, S.; Takebayashi, Y.; Luchies, J.; Kobayashi, M.; Kurata, T.; Wada, T.; Seo, M.; Hasebe, M.; Blilou, I.; Fukuda, H.; Scheres, B.; Heidstra, R.; Kamiya, Y.; Sawa, S.

2015-01-01

The root meristem (RM) is a fundamental structure that is responsible for postembryonic root growth. The RM contains the quiescent center (QC), stem cells and frequently dividing meristematic cells, in which the timing and the frequency of cell division are tightly regulated. In Arabidopsis

A population of Pax7-expressing muscle progenitor cells show differential responses to muscle injury dependent on developmental stage and injury extent

Directory of Open Access Journals (Sweden)

Stefanie eKnappe

2015-08-01

Full Text Available Muscle regeneration in vertebrates occurs by the activation of quiescent progenitor cells that express pax7 and replace and repair damaged fibers. We have developed a mechanical injury paradigm in zebrafish to determine whether developmental stage and injury size affect the regeneration dynamics of damaged muscle. We found that both small, focal injuries and large injuries affecting the entire myotome lead to the expression of myf5 and myogenin. Their expression was prolonged in older larvae, indicating a slower process of regeneration. We characterized the endogenous behavior of a population of muscle-resident Pax7-expressing cells using a pax7a:eGFP transgenic line and found that GFP+ cell migration in the myotome dramatically declined between 5 and 7 days post fertilization (dpf. Following a small injury, we observed that GFP+ cells responded by extending processes, before migrating to the injured fibers. Furthermore, these cells responded more rapidly to injury in 4dpf larvae compared to 7dpf. Interestingly, we did not see GFP+ fibers after repair of small injuries, indicating that pax7a-expressing cells did not contribute to fiber formation in this injury context. On the contrary, numerous GFP+ fibers could be observed after a large single myotome injury. Both injury models were accompanied by an increased number of proliferating GFP+ cells, which was more pronounced in larvae injured at 4dpf than 7dpf, This indicates intriguing developmental differences, even at these relatively early ages. Our data also suggests an interesting disparity in the role that pax7a-expressing muscle progenitor cells play during muscle regeneration, which may reflect the extent of muscle damage.

Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells.

Directory of Open Access Journals (Sweden)

Souheil-Antoine Younes

2011-10-01

Full Text Available Memory phenotype (CD44(bright, CD25(negative CD4 spleen and lymph node T cells (MP cells proliferate rapidly in normal or germ-free donors, with BrdU uptake rates of 6% to 10% per day and Ki-67 positivity of 18% to 35%. The rapid proliferation of MP cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (LCMV-specific memory cells that divide at rates ranging from <1% to 2% per day over the period from 15 to 60 days after LCMV infection. Anti-MHC class II antibodies fail to inhibit the in situ proliferation of MP cells, implying a non-T-cell receptor (TCR-driven proliferation. Such proliferation is partially inhibited by anti-IL-7Rα antibody. The sequence diversity of TCRβ CDR3 gene segments is comparable among the proliferating and quiescent MP cells from conventional and germ-free mice, implying that the majority of proliferating MP cells have not recently derived from a small cohort of cells that expand through multiple continuous rounds of cell division. We propose that MP cells constitute a diverse cell population, containing a subpopulation of slowly dividing authentic antigen-primed memory cells and a majority population of rapidly proliferating cells that did not arise from naïve cells through conventional antigen-driven clonal expansion.

Fibroblast spheroids as a model to study sustained fibroblast quiescence and their crosstalk with tumor cells

Energy Technology Data Exchange (ETDEWEB)

Salmenperä, Pertteli, E-mail: pertteli.salmenpera@helsinki.fi [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Karhemo, Piia-Riitta [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Räsänen, Kati [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Laakkonen, Pirjo [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Vaheri, Antti [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland)

2016-07-01

Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i. e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similar secretory phenotype as seen in senescence and they expressed senescence-associated-β-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in soft-agarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescence-associated-β-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. - Highlights: • Fibroblasts acquire a sustained quiescence when grown as multicellular spheroids. • This quiescence is associated with drastic change in gene expression. • Fibroblasts spheroids secrete various inflammation-linked cytokines and chemokines. • Fibroblasts spheroids reduced growth of RT3 SCC cells in xenograft model.

Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

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Wu, Jincheng; Tzanakakis, Emmanuel S.

2014-01-01

Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming

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Li Guo

2017-12-01

Full Text Available Summary: A suitable source of progenitor cells is required to attenuate disease or affect cure. We present an “interrupted reprogramming” strategy to generate “induced progenitor-like (iPL cells” using carefully timed expression of induced pluripotent stem cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc; OSKM from non-proliferative Club cells. Interrupted reprogramming allowed controlled expansion yet preservation of lineage commitment. Under clonogenic conditions, iPL cells expanded and functioned as a bronchiolar progenitor-like population to generate mature Club cells, mucin-producing goblet cells, and cystic fibrosis transmembrane conductance regulator (CFTR-expressing ciliated epithelium. In vivo, iPL cells can repopulate CFTR-deficient epithelium. This interrupted reprogramming process could be metronomically applied to achieve controlled progenitor-like proliferation. By carefully controlling the duration of expression of OSKM, iPL cells do not become pluripotent, and they maintain their memory of origin and retain their ability to efficiently return to their original phenotype. A generic technique to produce highly specified populations may have significant implications for regenerative medicine. : In this article Waddell, Nagy, and colleagues present an “interrupted reprogramming” strategy to produce highly specified functional “induced progenitor-like cells” from mature quiescent cells. They propose that careful control of the duration of transient expression of iPSC reprogramming factors (OSKM allows controlled expansion yet preservation of parental lineage without traversing the pluripotent state. Keywords: generation of induced progenitor-like cells

Pneumococcal Competence Coordination Relies on a Cell-Contact Sensing Mechanism.

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Marc Prudhomme

2016-06-01

Full Text Available Bacteria have evolved various inducible genetic programs to face many types of stress that challenge their growth and survival. Competence is one such program. It enables genetic transformation, a major horizontal gene transfer process. Competence development in liquid cultures of Streptococcus pneumoniae is synchronized within the whole cell population. This collective behavior is known to depend on an exported signaling Competence Stimulating Peptide (CSP, whose action generates a positive feedback loop. However, it is unclear how this CSP-dependent population switch is coordinated. By monitoring spontaneous competence development in real time during growth of four distinct pneumococcal lineages, we have found that competence shift in the population relies on a self-activated cell fraction that arises via a growth time-dependent mechanism. We demonstrate that CSP remains bound to cells during this event, and conclude that the rate of competence development corresponds to the propagation of competence by contact between activated and quiescent cells. We validated this two-step cell-contact sensing mechanism by measuring competence development during co-cultivation of strains with altered capacity to produce or respond to CSP. Finally, we found that the membrane protein ComD retains the CSP, limiting its free diffusion in the medium. We propose that competence initiator cells originate stochastically in response to stress, to form a distinct subpopulation that then transmits the CSP by cell-cell contact.

EUV observations of quiescent prominences from Skylab

International Nuclear Information System (INIS)

Moe, O.K.

1979-01-01

The authors report measurements of line intensities and line widths for three quiescent prominences observed with the Naval Research Laboratory slit spectrograph on ATM/Skylab. The wavelengths of the observed lines cover the range 1175 A to 1960 A. The measured intensities have been calibrated to within approximately a factor 2 and are average intensities over a 2 arc sec by 60 arc set slit. Nonthermal velocities are derived from the measured line widths. The nonthermal velocity is found to increase with temperature in the prominence transition zone. Electron densities and pressures are derived from density sensitive line ratios. Electron pressures for two of the prominences are found to lie in the range 0.04-0.08 dyn cm -2 , while values for the third and most intense and active of the three prominences are in the range 0.07-0.22 dyn cm -2 . (Auth.)

Low-n magnetohydrodynamic edge instabilities in quiescent H-mode plasmas with a safety-factor plateau

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Zheng, L.J.; Kotschenreuther, M.T.; Valanju, P.

2013-01-01

Low-n magnetohydrodynamic (MHD) modes in the quiescent high confinement mode (H-mode) pedestal are investigated in this paper. Here, n is the toroidal mode number. The low collisionality regime is considered, so that a safety-factor plateau arises in the pedestal region because of the strong bootstrap current. The JET-like (Joint European Torus) equilibria of quiescent H-mode discharges are generated numerically using the VMEC code. The stability of this type of equilibria is analysed using the AEGIS code, with subsonic rotation effects taken into account. The current investigation extends the previous studies of n = 1 modes to n = 2 and 3 modes. The numerical results show that the MHD instabilities in this type of equilibria have characteristic features of the infernal mode. We find that this type of mode tends to prevail when the safety-factor value in the shear-free region is slightly larger than an integer. In this case the frequencies (ω n ) of modes with toroidal mode number n roughly follow the rule ω n ∼ −nΩ p , where Ω p is the local rotation frequency where the infernal harmonic prevails. Since the infernal mode tends to develop near the pedestal top, where pressure driving is strong but magnetic shear stabilization is weak, this local rotation frequency tends to be close to the pedestal top value. These typical mode features bear close resemblance to the edge harmonic oscillations (or outer modes) at the quiescent H-mode discharges observed experimentally. (paper)

PRE-ERUPTION OSCILLATIONS IN THIN AND LONG FEATURES IN A QUIESCENT FILAMENT

International Nuclear Information System (INIS)

Joshi, Anand D.; Hanaoka, Yoichiro; Suematsu, Yoshinori; Morita, Satoshi; Yurchyshyn, Vasyl; Cho, Kyung-Suk

2016-01-01

We investigate the eruption of a quiescent filament located close to an active region. Large-scale activation was observed in only half of the filament in the form of pre-eruption oscillations. Consequently only this half erupted nearly 30 hr after the oscillations commenced. Time-slice diagrams of 171 Å images from the Atmospheric Imaging Assembly were used to study the oscillations. These were observed in several thin and long features connecting the filament spine to the chromosphere below. This study traces the origin of such features and proposes their possible interpretation. Small-scale magnetic flux cancellation accompanied by a brightening was observed at the footpoint of the features shortly before their appearance, in images recorded by the Helioseismic and Magnetic Imager. A slow rise of the filament was detected in addition to the oscillations, indicating a gradual loss of equilibrium. Our analysis indicates that a change in magnetic field connectivity between two neighbouring active regions and the quiescent filament resulted in a weakening of the overlying arcade of the filament, leading to its eruption. It is also suggested that the oscillating features are filament barbs, and the oscillations are a manifestation during the pre-eruption phase of the filaments.

PRE-ERUPTION OSCILLATIONS IN THIN AND LONG FEATURES IN A QUIESCENT FILAMENT

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Joshi, Anand D.; Hanaoka, Yoichiro; Suematsu, Yoshinori; Morita, Satoshi [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan); Yurchyshyn, Vasyl; Cho, Kyung-Suk, E-mail: anand.joshi@nao.ac.jp [Korea Astronomy and Space Science Institute, Daejeon 34055 (Korea, Republic of)

2016-12-20

We investigate the eruption of a quiescent filament located close to an active region. Large-scale activation was observed in only half of the filament in the form of pre-eruption oscillations. Consequently only this half erupted nearly 30 hr after the oscillations commenced. Time-slice diagrams of 171 Å images from the Atmospheric Imaging Assembly were used to study the oscillations. These were observed in several thin and long features connecting the filament spine to the chromosphere below. This study traces the origin of such features and proposes their possible interpretation. Small-scale magnetic flux cancellation accompanied by a brightening was observed at the footpoint of the features shortly before their appearance, in images recorded by the Helioseismic and Magnetic Imager. A slow rise of the filament was detected in addition to the oscillations, indicating a gradual loss of equilibrium. Our analysis indicates that a change in magnetic field connectivity between two neighbouring active regions and the quiescent filament resulted in a weakening of the overlying arcade of the filament, leading to its eruption. It is also suggested that the oscillating features are filament barbs, and the oscillations are a manifestation during the pre-eruption phase of the filaments.

Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent.

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Lévy, Camille; Amirache, Fouzia; Girard-Gagnepain, Anais; Frecha, Cecilia; Roman-Rodríguez, Francisco J; Bernadin, Ornellie; Costa, Caroline; Nègre, Didier; Gutierrez-Guerrero, Alejandra; Vranckx, Lenard S; Clerc, Isabelle; Taylor, Naomi; Thielecke, Lars; Cornils, Kerstin; Bueren, Juan A; Rio, Paula; Gijsbers, Rik; Cosset, François-Loïc; Verhoeyen, Els

2017-10-24

Hematopoietic stem cell (HSC)-based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein-displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34 + (hCD34 + ) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34 + cells, whereas conventional vesicular stomatitis virus G (VSV-G)-LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor. Importantly, reconstitution of NOD/SCIDγc -/- (NSG) mice with H/F-LV transduced prestimulated or resting hCD34 + cells confirmed these high transduction levels in all myeloid and lymphoid lineages. Remarkably, for resting CD34 + cells, secondary recipients exhibited increasing transduction levels of up to 100%, emphasizing that H/F-LVs efficiently gene-marked HSCs in the resting state. Because H/F-LVs promoted ex vivo gene modification of minimally manipulated CD34 + progenitors that maintained stemness, we assessed their applicability in Fanconi anemia, a bone marrow (BM) failure with chromosomal fragility. Notably, only H/F-LVs efficiently gene-corrected minimally stimulated hCD34 + cells in unfractionated BM from these patients. These H/F-LVs improved HSC gene delivery in the absence of cytokine stimulation while maintaining their stem cell potential. Thus, H/F-LVs will facilitate future clinical applications requiring HSC gene modification, including BM failure syndromes, for which treatment has been very challenging up to now.

The radius of the quiescent neutron star in the globular cluster M13

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Shaw, A. W.; Heinke, C. O.; Steiner, A. W.; Campana, S.; Cohn, H. N.; Ho, W. C. G.; Lugger, P. M.; Servillat, M.

2018-06-01

X-ray spectra of quiescent low-mass X-ray binaries containing neutron stars can be fit with atmosphere models to constrain the mass and the radius. Mass-radius constraints can be used to place limits on the equation of state of dense matter. We perform fits to the X-ray spectrum of a quiescent neutron star in the globular cluster M13, utilizing data from ROSAT, Chandra, and XMM-Newton, and constrain the mass-radius relation. Assuming an atmosphere composed of hydrogen and a 1.4 M⊙ neutron star, we find the radius to be R_NS=12.2^{+1.5}_{-1.1} km, a significant improvement in precision over previous measurements. Incorporating an uncertainty on the distance to M13 relaxes the radius constraints slightly and we find R_NS=12.3^{+1.9}_{-1.7} km (for a 1.4M⊙ neutron star with a hydrogen atmosphere), which is still an improvement in precision over previous measurements, some of which do not consider distance uncertainty. We also discuss how the composition of the atmosphere affects the derived radius, finding that a helium atmosphere implies a significantly larger radius.

Regulation of DNA repair processes in mammalian cell

International Nuclear Information System (INIS)

Bil'din, V.N.; Sergina, T.B.; Zhestyanikov, V.D.

1992-01-01

A study was made of the repair of ionizing radiation-induced DNA single-strand breaks (SSB) in proliferating and quiescent mouse Swiss 3T6 cells and in those stimulated from the quiet status by epidermal growth factor in combination with insulin, in the presence of specific inhibitors of DNA polymerase α and β (aphidicolin) and DNA polymerase β (2', 3'-dideoxythjymidine-5'-triphosphate). The repair of DNA SSB induced by X-ray-irradiation (10 Gy) or by γ-ray irradiation (150 Gy) is more sensitive to aphidicolin and mitogen-simulated cells three times stronger than in proliferating cells. The influence of 2', 3'-dideoxythymidine-5'-triphosphate on the rate of DNA SSB repair in cells of all the three types does not differ. Thus, the decrease in DNA repair efficiency in quiescent cells is connected with a decrease in the activity of aphidicolin-sensitive DNA polymerase, apparently DNA polymerase α

Tracking Traction Force Changes of Single Cells on the Liquid Crystal Surface

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Chin Fhong Soon

2015-01-01

Full Text Available Cell migration is a key contributor to wound repair. This study presents findings indicating that the liquid crystal based cell traction force transducer (LCTFT system can be used in conjunction with a bespoke cell traction force mapping (CTFM software to monitor cell/surface traction forces from quiescent state in real time. In this study, time-lapse photo microscopy allowed cell induced deformations in liquid crystal coated substrates to be monitored and analyzed. The results indicated that the system could be used to monitor the generation of cell/surface forces in an initially quiescent cell, as it migrated over the culture substrate, via multiple points of contact between the cell and the surface. Future application of this system is the real-time assaying of the pharmacological effects of cytokines on the mechanics of cell migration.

Delay equations modeling the effects of phase-specific drugs and immunotherapy on proliferating tumor cells.

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Barbarossa, Maria Vittoria; Kuttler, Christina; Zinsl, Jonathan

2012-04-01

In this work we present a mathematical model for tumor growth based on the biology of the cell cycle. For an appropriate description of the effects of phase-specific drugs, it is necessary to look at the cell cycle and its phases. Our model reproduces the dynamics of three different tumor cell populations: quiescent cells, cells during the interphase and mitotic cells. Starting from a partial differential equations (PDEs) setting, a delay differential equations (DDE) model is derived for an easier and more realistic approach. Our equations also include interactions of tumor cells with immune system effectors. We investigate the model both from the analytical and the numerical point of view, give conditions for positivity of solutions and focus on the stability of the cancer-free equilibrium. Different immunotherapeutic strategies and their effects on the tumor growth are considered, as well.

Live cell imaging reveals marked variability in myoblast proliferation and fate

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2013-01-01

Background During the process of muscle regeneration, activated stem cells termed satellite cells proliferate, and then differentiate to form new myofibers that restore the injured area. Yet not all satellite cells contribute to muscle repair. Some continue to proliferate, others die, and others become quiescent and are available for regeneration following subsequent injury. The mechanisms that regulate the adoption of different cell fates in a muscle cell precursor population remain unclear. Methods We have used live cell imaging and lineage tracing to study cell fate in the C2 myoblast line. Results Analyzing the behavior of individual myoblasts revealed marked variability in both cell cycle duration and viability, but similarities between cells derived from the same parental lineage. As a consequence, lineage sizes and outcomes differed dramatically, and individual lineages made uneven contributions toward the terminally differentiated population. Thus, the cohort of myoblasts undergoing differentiation at the end of an experiment differed dramatically from the lineages present at the beginning. Treatment with IGF-I increased myoblast number by maintaining viability and by stimulating a fraction of cells to complete one additional cell cycle in differentiation medium, and as a consequence reduced the variability of the terminal population compared with controls. Conclusion Our results reveal that heterogeneity of responses to external cues is an intrinsic property of cultured myoblasts that may be explained in part by parental lineage, and demonstrate the power of live cell imaging for understanding how muscle differentiation is regulated. PMID:23638706

Making sense of snapshot data: ergodic principle for clonal cell populations.

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Thomas, Philipp

2017-11-01

Population growth is often ignored when quantifying gene expression levels across clonal cell populations. We develop a framework for obtaining the molecule number distributions in an exponentially growing cell population taking into account its age structure. In the presence of generation time variability, the average acquired across a population snapshot does not obey the average of a dividing cell over time, apparently contradicting ergodicity between single cells and the population. Instead, we show that the variation observed across snapshots with known cell age is captured by cell histories, a single-cell measure obtained from tracking an arbitrary cell of the population back to the ancestor from which it originated. The correspondence between cells of known age in a population with their histories represents an ergodic principle that provides a new interpretation of population snapshot data. We illustrate the principle using analytical solutions of stochastic gene expression models in cell populations with arbitrary generation time distributions. We further elucidate that the principle breaks down for biochemical reactions that are under selection, such as the expression of genes conveying antibiotic resistance, which gives rise to an experimental criterion with which to probe selection on gene expression fluctuations. © 2017 The Author(s).

Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus

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Kahlia Wong

2014-08-01

Full Text Available Thymic epithelial cells (TECs are critical for T cell development and self-tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration.

Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis.

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MacLean, Adam L; Lo Celso, Cristina; Stumpf, Michael P H

2017-01-01

Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe. The application of population dynamics to biology is amongst the oldest applications of mathematics to biology, and the population dynamics perspective continues to offer much today. Here we describe the impact that such a perspective has made in the field of stem cell biology. Using hematopoietic stem cells as our model system, we discuss the approaches that have been used to study their key properties, such as capacity for self-renewal, differentiation, and cell fate lineage choice. We will also discuss the relevance of population dynamics in models of stem cells and cancer, where competition naturally emerges as an influential factor on the temporal evolution of cell populations. Stem Cells 2017;35:80-88. © 2016 AlphaMed Press.

STAR FORMATION SIGNATURES IN OPTICALLY QUIESCENT EARLY-TYPE GALAXIES

International Nuclear Information System (INIS)

Salim, Samir; Rich, R. Michael

2010-01-01

In recent years, an argument has been made that a high fraction of early-type galaxies (ETGs) in the local universe experience low levels (∼ sun yr -1 ) of star formation (SF) that causes strong excess in UV flux, yet leaves the optical colors red. Many of these studies were based on Galaxy Evolution Explorer imaging of Sloan Digital Sky Survey (SDSS) galaxies (z ∼ 0.1), and were thus limited by its 5'' FWHM. Poor UV resolution left other possibilities for UV excess open, such as the old populations or an active galactic nucleus (AGN). Here, we study high-resolution far-ultraviolet HST/ACS images of optically quiescent early-type galaxies with strong UV excess. The new images show that three-quarters of these moderately massive (∼5 x 10 10 M sun ) ETGs shows clear evidence of extended SF, usually in form of wide or concentric UV rings, and in some cases, striking spiral arms. SDSS spectra probably miss these features due to small fiber size. UV-excess ETGs have on average less dust and larger UV sizes (D > 40 kpc) than other green-valley galaxies, which argues for an external origin for the gas that is driving the SF. Thus, most of these galaxies appear 'rejuvenated' (e.g., through minor gas-rich mergers or intergalactic medium accretion). For a smaller subset of the sample, the declining SF (from the original internal gas) cannot be ruled out. SF is rare in very massive early-types (M * > 10 11 M sun ), a possible consequence of AGN feedback. In addition to extended UV emission, many galaxies show a compact central source, which may be a weak, optically inconspicuous AGN.

Chapter 22. Cell population kinetics

International Nuclear Information System (INIS)

Tubiana, M.

1975-01-01

The main contribution of radioisotopes to the development of a new discipline, cell population kinetics, was shown. The aim of this science is to establish, for each tissue of the organism, the life span of its component cells and the mechanisms governing its growth, its differentiation and its homeostasis with respect to outside attacks. Labelling techniques have been used to follow the cells during these various processes. The case of non-dividing cells was considered first, taking as example, the red blood cells of which the lifetime was studied, after which the case of proliferating cells was examined using 14 C- or tritium-labelled thymidine. The methods used to measure the cell cycle parameters were described: labelled-mitosis curve method, double-labelling and continuous labelling methods, proliferation coefficient measurement. Cell kinetics were shown to allow an interpretation of radiobiological data. Finally the practical value of cell kinetics research was shown [fr

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

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Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

2013-10-14

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

Activation of different neural precursor populations in the adult hippocampus: does this lead to new neurons with discrete functions?

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Jhaveri, Dhanisha J; Taylor, Chanel J; Bartlett, Perry F

2012-07-01

Resident populations of stem and precursor cells drive the production of new neurons in the adult hippocampus. Recent discoveries have highlighted that a large proportion of these precursor cells are in fact quiescent and can be activated by distinct neuronal activity under both normal physiological and pathological conditions. As growing evidence indicates that newborn neurons play a critical role in cognitive functions such as learning and memory and in mood regulation, it is paramount that we obtain a better understanding of how the reservoirs of stem and precursor cells are maintained and activated. In this review, we critically examine the roles of key molecular mechanisms that have been shown to regulate hippocampal precursor cells, especially their activation. We believe that understanding the mechanistic details of the activity-driven regulation of precursor cells will equip us with the ability to develop tailored strategies to trigger the generation of new neurons, thereby improving the functional outcomes in various neurological and psychiatric conditions. Copyright © 2012 Wiley Periodicals, Inc.

Multiple dendritic cell populations activate CD4+ T cells after viral stimulation.

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Adele M Mount

2008-02-01

Full Text Available Dendritic cells (DC are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8alpha DC play a prominent, and sometimes exclusive, role in driving amplification of CD8(+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4(+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4(+ and CD8(+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8alpha DC populations in the amplification of CD8(+ and CD4(+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8(+ T cells are dominated by presentation of antigen by CD8alpha DC but can involve non-CD8alpha DC. In contrast, CD4(+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4(+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity.

A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii.

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Shima P Damodaran

Full Text Available To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers and a significant subpopulation of slowly dividing cells (slow-growers. These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes.

Waves and turbulences studies in plasmas: ten years of research on quiescent plasmas at the Brazilian Space Research National Institute

International Nuclear Information System (INIS)

Ferreira, J.L.

1991-01-01

Quiescent plasmas generated by thermionic discharges and surface confined by multipole magnetic fields have been used in basic plasma research since 1973. The first machine was developed at UCLA (USA) to produce an uniform plasma for beam and waves studies in large cross section plasmas. A double quiescent plasma machine was constructed at the plasma laboratory of INPE in 1981, it began its operation producing linear ion-acoustic waves in an Argon plasma. Later on non linear ion acoustic waves and solitons were studied in plasma containing several species of negative and positive ions. The anomalous particle transport across multipole magnetic fields were also investigated. An anomalous resistivity associated with an ion acoustic turbulence is responsible for the formation of a small amplitude double-layer. The existence of a bootstrap mechanism is shown experimentally. Today, the main interest is toward the generation of Langmuir waves in non uniform plasmas. An experimental study on Langmuir wave generation using a grid system is been carried on. A magnetized quiescent plasma device for studies of whistle wave generation is been constructed. This machine will make possible future studies on several wave modes of magnetized plasmas. (author). 31 refs, 16 figs

Stellar Velocity Dispersion: Linking Quiescent Galaxies to Their Dark Matter Halos

Science.gov (United States)

Zahid, H. Jabran; Sohn, Jubee; Geller, Margaret J.

2018-06-01

We analyze the Illustris-1 hydrodynamical cosmological simulation to explore the stellar velocity dispersion of quiescent galaxies as an observational probe of dark matter halo velocity dispersion and mass. Stellar velocity dispersion is proportional to dark matter halo velocity dispersion for both central and satellite galaxies. The dark matter halos of central galaxies are in virial equilibrium and thus the stellar velocity dispersion is also proportional to dark matter halo mass. This proportionality holds even when a line-of-sight aperture dispersion is calculated in analogy to observations. In contrast, at a given stellar velocity dispersion, the dark matter halo mass of satellite galaxies is smaller than virial equilibrium expectations. This deviation from virial equilibrium probably results from tidal stripping of the outer dark matter halo. Stellar velocity dispersion appears insensitive to tidal effects and thus reflects the correlation between stellar velocity dispersion and dark matter halo mass prior to infall. There is a tight relation (≲0.2 dex scatter) between line-of-sight aperture stellar velocity dispersion and dark matter halo mass suggesting that the dark matter halo mass may be estimated from the measured stellar velocity dispersion for both central and satellite galaxies. We evaluate the impact of treating all objects as central galaxies if the relation we derive is applied to a statistical ensemble. A large fraction (≳2/3) of massive quiescent galaxies are central galaxies and systematic uncertainty in the inferred dark matter halo mass is ≲0.1 dex thus simplifying application of the simulation results to currently available observations.

Self-propelled heaving and pitching flexible fin in a quiescent flow

International Nuclear Information System (INIS)

Kim, Boyoung; Park, Sung Goon; Huang, Weixi; Sung, Hyung Jin

2016-01-01

Highlights: • A self-propelled flexible fin with heaving and pitching motions in a quiescent flow has been simulated by using the penalty immersed boundary method. • The cruising speed and the swimming efficiency of the self-propelled fin were determined as functions of the bending coefficient (γ), the heaving amplitude (A_h). • We optimized the cruising speed and the swimming efficiency with respect to γ, f, A_h, A_p, and Δϕ. - Abstract: A self-propelled flexible fin with heaving and pitching motions in a quiescent flow has been simulated by using the penalty immersed boundary method. The flexible fin can move freely in the horizontal direction and the body of the flexible fin moves passively along with the active head motion. The position of the head of the fin was described as a harmonic heaving oscillation in the vertical direction, while the inclination angle of the head was prescribed as a harmonic oscillation with a moving clamped condition for the heaving and pitching fin. The cruising speed and the swimming efficiency of the self-propelled fin were determined as functions of the bending stiffness (γ), the heaving amplitude (A_h), the pitching amplitude (A_p), the flapping frequency (f) and the phase difference (Δϕ) between A_h and A_p. We optimized the cruising speed and the swimming efficiency with respect to γ, f, A_h, A_p and Δϕ. For a certain range of A_p, the swimming efficiency of the heaving and pitching fin is larger than that of a heaving-only fin.

Quiescent and Eruptive Prominences at Solar Minimum: A Statistical Study via an Automated Tracking System

Science.gov (United States)

Loboda, I. P.; Bogachev, S. A.

2015-07-01

We employ an automated detection algorithm to perform a global study of solar prominence characteristics. We process four months of TESIS observations in the He II 304Å line taken close to the solar minimum of 2008-2009 and mainly focus on quiescent and quiescent-eruptive prominences. We detect a total of 389 individual features ranging from 25×25 to 150×500 Mm2 in size and obtain distributions of many of their spatial characteristics, such as latitudinal position, height, size, and shape. To study their dynamics, we classify prominences as either stable or eruptive and calculate their average centroid velocities, which are found to rarely exceed 3 km/s. In addition, we give rough estimates of mass and gravitational energy for every detected prominence and use these values to estimate the total mass and gravitational energy of all simultaneously existing prominences (1012 - 1014 kg and 1029 - 1031 erg). Finally, we investigate the form of the gravitational energy spectrum of prominences and derive it to be a power-law of index -1.1 ± 0.2.

Trail networks formed by populations of immune cells

International Nuclear Information System (INIS)

Yang, Taeseok Daniel; Kwon, Tae Goo; Park, Jin-sung; Lee, Kyoung J

2014-01-01

Populations of biological cells that communicate with each other can organize themselves to generate large-scale patterns. Examples can be found in diverse systems, ranging from developing embryos, cardiac tissues, chemotaxing ameba and swirling bacteria. The similarity, often shared by the patterns, suggests the existence of some general governing principle. On the other hand, rich diversity and system-specific properties are exhibited, depending on the type of involved cells and the nature of their interactions. The study on the similarity and the diversity constitutes a rapidly growing field of research. Here, we introduce a new class of self-organized patterns of cell populations that we term as ‘cellular trail networks’. They were observed with populations of rat microglia, the immune cells of the brain and the experimental evidence suggested that haptotaxis is the key element responsible for them. The essential features of the observed patterns are well captured by the mathematical model cells that actively crawl and interact with each other through a decomposing but non-diffusing chemical attractant laid down by the cells. Our finding suggests an unusual mechanism of socially cooperative long-range signaling for the crawling immune cells. (paper)

Endothelial Progenitor Cell Fraction Contained in Bone Marrow-Derived Mesenchymal Stem Cell Populations Impairs Osteogenic Differentiation

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Fabian Duttenhoefer

2015-01-01

Full Text Available In bone tissue engineering (TE endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs are a rich source of mesenchymal stem cells (MSCs able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+ and CD133+ were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+ or medium containing platelet lysate (PL. MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+ medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.

Coordination between chromosome replication, segregation, and cell division in Caulobacter crescentus

DEFF Research Database (Denmark)

Jensen, Rasmus Bugge

2006-01-01

Progression through the Caulobacter crescentus cell cycle is coupled to a cellular differentiation program. The swarmer cell is replicationally quiescent, and DNA replication initiates at the swarmer-to-stalked cell transition. There is a very short delay between initiation of DNA replication...

A microarray analysis of two distinct lymphatic endothelial cell populations

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Bernhard Schweighofer

2015-06-01

Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

Science.gov (United States)

Kosan, Christian; Godmann, Maren

2016-01-01

All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

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Christian Kosan

2016-01-01

Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

Influence of physiological environment on the expression of thermotolerance in proliferating (P) and quiescent (Q) tumor cells

International Nuclear Information System (INIS)

Wallen, C.A.; Gutierrez, R.H.

1987-01-01

Alteration of the physiological environment of Q 66 and 67 mouse mammary tumor cells by placing them in either fresh, complete medium or a balanced salt solution supplemented with 24 mM glucose resulted in a significant increase in the time at 45 0 C necessary to measure cytotoxicity. The degree of increased resistance was dependent on the solution used to change the environment and the length of time the cells were allowed to equilibrate in this new environment. The aim of the present study is to determine if alterations in the Q cell environment has significant effects on the expression of thermotolerance. Pure P and Q cell populations of both 66 and 67 cell lines are exposed continuously to either 42 or 43 0 C and assayed for colony formation at various times for the development of thermotolerance. The comparison of thermotolerance development both in terms of time course and extent are measured in Q cells under 5 conditions: 1) normal, depleted medium (pH 6.8), 2) fresh, complete medium (pH 7.2), 3) balanced salt solution with 24 mM glucose (pH 7.2), 4) balanced salt solution with no glucose (pH 7.2), and 5) depleted medium supplemented with fresh serum (pH 6.8). These data have implications for the importance of Q cells in determining the outcome of clinical hyperthermia and the role of other stressors on the expression of thermotolerance

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

Science.gov (United States)

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

2015-04-01

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Quiescent H-mode plasmas with strong edge rotation in the cocurrent direction.

Science.gov (United States)

Burrell, K H; Osborne, T H; Snyder, P B; West, W P; Fenstermacher, M E; Groebner, R J; Gohil, P; Leonard, A W; Solomon, W M

2009-04-17

For the first time in any tokamak, quiescent H-mode (QH-mode) plasmas have been created with strong edge rotation in the direction of the plasma current. This confirms the theoretical prediction that the QH mode should exist with either sign of the edge rotation provided the magnitude of the shear in the edge rotation is sufficiently large and demonstrates that counterinjection and counteredge rotation are not essential for the QH mode. Accordingly, the present work demonstrates a substantial broadening of the QH-mode operating space and represents a significant confirmation of the theory.

Emergence of cytotoxic resistance in cancer cell populations*

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Lorenzi Tommaso

2015-01-01

Full Text Available We formulate an individual-based model and an integro-differential model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

Shaping bacterial population behavior through computer-interfaced control of individual cells.

Science.gov (United States)

Chait, Remy; Ruess, Jakob; Bergmiller, Tobias; Tkačik, Gašper; Guet, Călin C

2017-11-16

Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.

Cell mass and cell cycle dynamics of an asynchronous budding yeast population

DEFF Research Database (Denmark)

Lencastre Fernandes, Rita; Carlquist, Magnus; Lundin, Luisa

2013-01-01

of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate...

Progenitor cell populations in the periodontal ligament of mice

International Nuclear Information System (INIS)

McCulloch, C.A.

1985-01-01

Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation. The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3 H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells

A Search for Millisecond-pulsar Radio Emission from the Faint Quiescent Soft X-Ray Transient 1H 1905+000

Energy Technology Data Exchange (ETDEWEB)

Mikhailov, K.; Van Leeuwen, J. [Anton Pannekoek Institute for Astronomy, University of Amsterdam, Science Park 904, P.O. Box 94249, 1090 GE Amsterdam (Netherlands); Jonker, P. G., E-mail: K.Mikhailov@uva.nl [SRON, the Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA, Utrecht (Netherlands)

2017-05-01

Transitional millisecond pulsars (tMSPs) switch between an accretion-powered state without radio pulsations and a rotation-powered state with radio pulsations. In the former state, tMSPs are X-ray bright, while in the latter state, they are X-ray dim. Soft X-ray transients (SXTs) undergo similar switches in X-ray, between “high” states with bright X-ray outbursts and “low” states of quiescence. The upper limit on the quiescent X-ray luminosity of SXT 1H 1905+000 suggests that its luminosity might be similar to that of the known tMSPs. A detection of radio pulsations would link SXTs more strongly with tMSPs; and thus, e.g., put stricter constraints on tMSP transitional timescales through the connection with the well-known SXT periods of quiescence. A nondetection allows us, based on the telescope sensitivity, to estimate how likely these sources are to pulsate in radio. Over a 10-year span, 2006–2015, we carried out targeted radio observations at 400/800 MHz with Arecibo, and searched for radio pulsations from the quiescent SXT 1H 1905+000. None of the observations have revealed radio pulsations from the targeted SXT. For a 1 ms pulsar, our flux density upper limit is 10.3 μ Jy. At an assumed distance of 10 kpc this translates to a pseudo-luminosity upper limit of 1.0 mJy kpc{sup 2}, which makes our search complete to ∼85% of the known MSP population. Given the high sensitivity, and the generally large beaming fraction of millisecond pulsars, we conclude that SXT 1H 1905+000 is unlikely to emit in radio as a tMSP.

CURRENT DRIVE AND PRESSURE PROFILE MODIFICATION WITH ELECTRON CYCLOTRON POWER IN DIII-D QUIESCENT DOUBLE BARRIER EXPERIMENTS

International Nuclear Information System (INIS)

CASPER, TA; BURRELL, KH; DOYLE, EJ; GOHIL, P; GREENFIELD, CM; GROEBNER, RJ; JAYAKUMAR, RJ; MAKOWSKI, MA; RHODES, TL; WEST, WP

2003-01-01

OAK-B135 High confinement mode (H-mode) operation is a leading scenario for burning plasma devices due to its inherently high energy-confinement characteristics. The quiescent H-mode (QH-mode) offers these same advantages with the additional attraction of more steady edge conditions where the highly transient power loads due to edge localized mode (ELM) activity is replaced by the steadier power and particle losses associated with an edge harmonic oscillation (EHO). With the addition of an internal transport barrier (ITB), the capability is introduced for independent control of both the edge conditions and the core confinement region giving potential control of fusion power production for an advanced tokamak configuration. The quiescent double barrier (QDB) conditions explored in DIII-D experiments exhibit these characteristics and have resulted in steady plasma conditions for several confinement times (∼ 26 τ E ) with moderately high stored energy, β N H 89 ∼ 7 for 10 τ E

A robust low quiescent current power receiver for inductive power transmission in bio implants

Science.gov (United States)

Helalian, Hamid; Pasandi, Ghasem; Jafarabadi Ashtiani, Shahin

2017-05-01

In this paper, a robust low quiescent current complementary metal-oxide semiconductor (CMOS) power receiver for wireless power transmission is presented. This power receiver consists of three main parts including rectifier, switch capacitor DC-DC converter and low-dropout regulator (LDO) without output capacitor. The switch capacitor DC-DC converter has variable conversion ratios and synchronous controller that lets the DC-DC converter to switch among five different conversion ratios to prevent output voltage drop and LDO regulator efficiency reduction. For all ranges of output current (0-10 mA), the voltage regulator is compensated and is stable. Voltage regulator stabilisation does not need the off-chip capacitor. In addition, a novel adaptive biasing frequency compensation method for low dropout voltage regulator is proposed in this paper. This method provides essential minimum current for compensation and reduces the quiescent current more effectively. The power receiver was designed in a 180-nm industrial CMOS technology, and the voltage range of the input is from 0.8 to 2 V, while the voltage range of the output is from 1.2 to 1.75 V, with a maximum load current of 10 mA, the unregulated efficiency of 79.2%, and the regulated efficiency of 64.4%.

Lgr5 marks cycling, yet long-lived, hair follicle stem cells.

NARCIS (Netherlands)

Jaks, V.; Barker, N.; Kasper, M.; van Es, J.H.; Snippert, H.J.G.; Clevers, H.; Toftgard, R.

2008-01-01

In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair follicles and in the lower outer root sheath of anagen hair

Multistage carcinogenesis in cell culture.

Science.gov (United States)

Rubin, H

2001-01-01

Rodent fibroblasts explanted from embryos to culture undergo a period of declining growth rate in serial passages leading to crisis, followed by the appearance of variants which can multiply indefinitely. If the "immortal" cell line was established by low density passage, i.e., 3T3 cells, it has a low saturation density and is non-tumorigenic. If it was established by high density passage, it has a high saturation density and is tumorigenic. The establishment of cells goes through successive stages, including increased capacity to multiply in low serum concentration, growth to high saturation density, growth in suspension, assisted tumour formation in susceptible hosts and unassisted tumour formation. Chromosome aberrations and aneuploidy occur long before the capacity to produce tumours appears. Contrary to conventional belief, human fibroblast populations also undergo a continuous loss of capacity to multiply from the time of explantation, with only the longest surviving clone reaching the Hayflick limit. Neoplastic transformation of rodent cells is strongly favoured by maintaining them in a quiescent state at confluence for prolonged periods, which results in genetic damage to the cells. It also produces a large variety of chromosomal aberrations in human cells and extends their replicative lifespan. Individual clones are more susceptible to spontaneous transformation than their heterogeneous parental cultures. The implications of these results for tumour development in vivo are that oncogenic genetic changes may be common under stressful conditions which restrict replication, and that such changes are maximized when a rogue clone reaches a critical size that reduces stabilizing interactions with neighbouring clones. An alternative explanation, described in the Addendum, which we retrospectively favor is that the easily transformed clones are a minority in the uncloned parental population. The reason they transform before the parental population is that when

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

Science.gov (United States)

Stampfer, Martha R; Garbe, James C

2015-02-24

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

DNA Damage: A Sensible Mediator of the Differentiation Decision in Hematopoietic Stem Cells and in Leukemia

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Cary N. Weiss

2015-03-01

Full Text Available In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to self-renew, in order to maintain the stem cell population for the lifetime of the organism, and to differentiate, in order to give rise to the multiple lineages of the hematopoietic system. In recent years, increasing evidence has suggested a role for the accumulation of reactive oxygen species and DNA damage in the decision for hematopoietic stem cells to exit quiescence and to differentiate. In this review, we will examine recent work supporting the idea that detection of cell stressors, such as oxidative and genetic damage, is an important mediator of cell fate decisions in hematopoietic stem cells. We will explore the benefits of such a system in avoiding the development and progression of malignancies, and in avoiding tissue exhaustion and failure. Additionally, we will discuss new work that examines the accumulation of DNA damage and replication stress in aging hematopoietic stem cells and causes us to rethink ideas of genoprotection in the bone marrow niche.

Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

Science.gov (United States)

Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

2012-01-01

TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

AUTOMATICALLY DETECTING AND TRACKING CORONAL MASS EJECTIONS. I. SEPARATION OF DYNAMIC AND QUIESCENT COMPONENTS IN CORONAGRAPH IMAGES

International Nuclear Information System (INIS)

Morgan, Huw; Byrne, Jason P.; Habbal, Shadia Rifai

2012-01-01

Automated techniques for detecting and tracking coronal mass ejections (CMEs) in coronagraph data are of ever increasing importance for space weather monitoring and forecasting. They serve to remove the biases and tedium of human interpretation, and provide the robust analysis necessary for statistical studies across large numbers of observations. An important requirement in their operation is that they satisfactorily distinguish the CME structure from the background quiescent coronal structure (streamers, coronal holes). Many studies resort to some form of time differencing to achieve this, despite the errors inherent in such an approach—notably spatiotemporal crosstalk. This article describes a new deconvolution technique that separates coronagraph images into quiescent and dynamic components. A set of synthetic observations made from a sophisticated model corona and CME demonstrates the validity and effectiveness of the technique in isolating the CME signal. Applied to observations by the LASCO C2 and C3 coronagraphs, the structure of a faint CME is revealed in detail despite the presence of background streamers that are several times brighter than the CME. The technique is also demonstrated to work on SECCHI/COR2 data, and new possibilities for estimating the three-dimensional structure of CMEs using the multiple viewing angles are discussed. Although quiescent coronal structures and CMEs are intrinsically linked, and although their interaction is an unavoidable source of error in any separation process, we show in a companion paper that the deconvolution approach outlined here is a robust and accurate method for rigorous CME analysis. Such an approach is a prerequisite to the higher-level detection and classification of CME structure and kinematics.

Influence of Cell-Cell Interactions on the Population Growth Rate in a Tumor

Science.gov (United States)

Chen, Yong

2017-12-01

The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems. Supported by the National Natural Science Foundation of China under Grant Nos. 11675008 and 21434001

Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors.

Science.gov (United States)

Podsakoff, G; Wong, K K; Chatterjee, S

1994-09-01

Gene transfer vectors based on adeno-associated virus (AAV) are emerging as highly promising for use in human gene therapy by virtue of their characteristics of wide host range, high transduction efficiencies, and lack of cytopathogenicity. To better define the biology of AAV-mediated gene transfer, we tested the ability of an AAV vector to efficiently introduce transgenes into nonproliferating cell populations. Cells were induced into a nonproliferative state by treatment with the DNA synthesis inhibitors fluorodeoxyuridine and aphidicolin or by contact inhibition induced by confluence and serum starvation. Cells in logarithmic growth or DNA synthesis arrest were transduced with vCWR:beta gal, an AAV-based vector encoding beta-galactosidase under Rous sarcoma virus long terminal repeat promoter control. Under each condition tested, vCWR:beta Gal expression in nondividing cells was at least equivalent to that in actively proliferating cells, suggesting that mechanisms for virus attachment, nuclear transport, virion uncoating, and perhaps some limited second-strand synthesis of AAV vectors were present in nondividing cells. Southern hybridization analysis of vector sequences from cells transduced while in DNA synthetic arrest and expanded after release of the block confirmed ultimate integration of the vector genome into cellular chromosomal DNA. These findings may provide the basis for the use of AAV-based vectors for gene transfer into quiescent cell populations such as totipotent hematopoietic stem cells.

The Two Populations of Kisspeptin Neurons Are Involved in the Ram-Induced LH Pulsatile Secretion and LH Surge in Anestrous Ewes.

Science.gov (United States)

Fabre-Nys, Claude; Cognié, Juliette; Dufourny, Laurence; Ghenim, Meriem; Martinet, Stephanie; Lasserre, Olivier; Lomet, Didier; Millar, Robert P; Ohkura, Satoshi; Suetomi, Yuta

2017-11-01

Exposure to a ram during spring stimulates luteinizing hormone (LH) secretion and can induce ovulation in sexually quiescent ewes ("ram effect"). Kisspeptin (Kiss) present in the arcuate nucleus (ARC) and the preoptic area (POA) is a potent stimulators of LH secretion. Our aim was to investigate whether Kiss neurons mediate the increase in LH secretion during the ram effect. With double immunofluorescent detection, we identified Kiss neurons (Kiss IR) activated (Fos IR) by exposure to a ram for 2 hours (M2) or 12 hours (M12) or to ewes for 2 hours (C). The density of cells Kiss + Fos IR and the proportion of Kiss IR cells that were also Fos IR cells were higher in M2 and M12 than in C in ARC (P populations of Kiss neurons are involved in the ram-induced pulsatile LH secretion and in the LH surge. Copyright © 2017 Endocrine Society.

Giant quiescent solar filament observed with high-resolution spectroscopy

Science.gov (United States)

Kuckein, C.; Verma, M.; Denker, C.

2016-05-01

Aims: An extremely large filament was studied in various layers of the solar atmosphere. The inferred physical parameters and the morphological aspects are compared with smaller quiescent filaments. Methods: A giant quiet-Sun filament was observed with the high-resolution Echelle spectrograph at the Vacuum Tower Telescope at Observatorio del Teide, Tenerife, Spain, on 2011 November 15. A mosaic of spectra (ten maps of 100″ × 182″) was recorded simultaneously in the chromospheric absorption lines Hα and Na I D2. Physical parameters of the filament plasma were derived using cloud model (CM) inversions and line core fits. The spectra were complemented with full-disk filtergrams (He I λ10830 Å, Hα, and Ca II K) of the Chromospheric Telescope (ChroTel) and full-disk magnetograms of the Helioseismic and Magnetic Imager (HMI). Results: The filament had extremely large linear dimensions (~817 arcsec), which corresponds to about 658 Mm along a great circle on the solar surface. A total amount of 175119 Hα contrast profiles were inverted using the CM approach. The inferred mean line-of-sight (LOS) velocity, Doppler width, and source function were similar to previous works of smaller quiescent filaments. However, the derived optical thickness was higher. LOS velocity trends inferred from the Hα line core fits were in accord but weaker than those obtained with CM inversions. Signatures of counter-streaming flows were detected in the filament. The largest brightening conglomerates in the line core of Na I D2 coincided well with small-scale magnetic fields as seen by HMI. Mixed magnetic polarities were detected close to the ends of barbs. The computation of photospheric horizontal flows based on HMI magnetograms revealed flow kernels with a size of 5-8 Mm and velocities of 0.30-0.45 km s-1 at the ends of the filament. Conclusions: The physical properties of extremely large filaments are similar to their smaller counterparts, except for the optical thickness, which in

Functional heterogeneity and heritability in CHO cell populations.

Science.gov (United States)

Davies, Sarah L; Lovelady, Clare S; Grainger, Rhian K; Racher, Andrew J; Young, Robert J; James, David C

2013-01-01

In this study, we address the hypothesis that it is possible to exploit genetic/functional variation in parental Chinese hamster ovary (CHO) cell populations to isolate clonal derivatives that exhibit superior, heritable attributes for biomanufacturing--new parental cell lines which are inherently more "fit for purpose." One-hundred and ninety-nine CHOK1SV clones were isolated from a donor CHOK1SV parental population by limiting dilution cloning and microplate image analysis, followed by primary analysis of variation in cell-specific proliferation rate during extended deep-well microplate suspension culture of individual clones to accelerate genetic drift in isolated cultures. A subset of 100 clones were comparatively evaluated for transient production of a recombinant monoclonal antibody (Mab) and green fluorescent protein following transfection of a plasmid vector encoding both genes. The heritability of both cell-specific proliferation rate and Mab production was further assessed using a subset of 23 clones varying in functional capability that were subjected to cell culture regimes involving both cryopreservation and extended sub-culture. These data showed that whilst differences in transient Mab production capability were not heritable per se, clones exhibiting heritable variation in specific proliferation rate, endocytotic transfectability and N-glycan processing were identified. Finally, for clonal populations most "evolved" by extended sub-culture in vitro we investigated the relationship between cellular protein biomass content, specific proliferation rate and cell surface N-glycosylation. Rapid-specific proliferation rate was inversely correlated to CHO cell size and protein content, and positively correlated to cell surface glycan content, although substantial clone-specific variation in ability to accumulate cell biomass was evident. Taken together, our data reveal the dynamic nature of the CHO cell functional genome and the potential to evolve and

CANDELS: THE PROGENITORS OF COMPACT QUIESCENT GALAXIES AT z ∼ 2

International Nuclear Information System (INIS)

Barro, Guillermo; Faber, S. M.; Koo, David C.; Kocevski, Dale D.; Trump, Jonathan R.; Mozena, Mark; McGrath, Elizabeth; Cheung, Edmond; Fang, Jerome; Pérez-González, Pablo G.; Williams, Christina C.; Van der Wel, Arjen; Wuyts, Stijn; Bell, Eric F.; Croton, Darren J.; Ceverino, Daniel; Dekel, Avishai; Ashby, M. L. N.; Ferguson, Henry C.; Fontana, Adriano

2013-01-01

We combine high-resolution Hubble Space Telescope/WFC3 images with multi-wavelength photometry to track the evolution of structure and activity of massive (M * > 10 10 M ☉ ) galaxies at redshifts z = 1.4-3 in two fields of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey. We detect compact, star-forming galaxies (cSFGs) whose number densities, masses, sizes, and star formation rates (SFRs) qualify them as likely progenitors of compact, quiescent, massive galaxies (cQGs) at z = 1.5-3. At z ∼> 2, cSFGs present SFR = 100-200 M ☉ yr –1 , yet their specific star formation rates (sSFR ∼ 10 –9 yr –1 ) are typically half that of other massive SFGs at the same epoch, and host X-ray luminous active galactic nuclei (AGNs) 30 times (∼30%) more frequently. These properties suggest that cSFGs are formed by gas-rich processes (mergers or disk-instabilities) that induce a compact starburst and feed an AGN, which, in turn, quench the star formation on dynamical timescales (few 10 8 yr). The cSFGs are continuously being formed at z = 2-3 and fade to cQGs down to z ∼ 1.5. After this epoch, cSFGs are rare, thereby truncating the formation of new cQGs. Meanwhile, down to z = 1, existing cQGs continue to enlarge to match local QGs in size, while less-gas-rich mergers and other secular mechanisms shepherd (larger) SFGs as later arrivals to the red sequence. In summary, we propose two evolutionary tracks of QG formation: an early (z ∼> 2), formation path of rapidly quenched cSFGs fading into cQGs that later enlarge within the quiescent phase, and a late-arrival (z ∼< 2) path in which larger SFGs form extended QGs without passing through a compact state.

Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells

Science.gov (United States)

Bhattacharya, Sujoy; Ray, Ramesh M.; Johnson, Leonard R.

2014-01-01

Homeostasis of the gastrointestinal epithelium is dependent upon a balance between cell proliferation and apoptosis. Cyclin-dependent kinases (Cdks) are well known for their role in cell proliferation. Previous studies from our group have shown that polyamine-depletion of intestinal epithelial cells (IEC-6) decreases cyclin-dependent kinase 2 (Cdk2) activity, increases p53 and p21Cip1 protein levels, induces G1 arrest, and protects cells from camptothecin (CPT)-induced apoptosis. Although emerging evidence suggests that members of the Cdk family are involved in the regulation of apoptosis, their roles directing apoptosis of IEC-6 cells are not known. In this study, we report that inhibition of Cdk1, 2, and 9 (with the broad range Cdk inhibitor, AZD5438) in proliferating IEC-6 cells triggered DNA damage, activated p53 signaling, inhibited proliferation, and induced apoptosis. By contrast, inhibition of Cdk2 (with NU6140) increased p53 protein and activity, inhibited proliferation, but had no effect on apoptosis. Notably, AZD5438 sensitized, whereas, NU6140 rescued proliferating IEC-6 cells from CPT-induced apoptosis. However, in colon carcinoma (Caco2) cells with mutant p53, treatment with either AZD5438 or NU6140 blocked proliferation, albeit more robustly with AZD5438. Both Cdk inhibitors induced apoptosis in Caco2 cells in a p53-independent manner. In serum starved quiescent IEC-6 cells, both AZD5438 and NU6140 decreased TNF- /CPT-induced activation of p53 and, consequently, rescued cells from apoptosis, indicating that sustained Cdk activity is required for apoptosis of quiescent cells. Furthermore, AZD5438 partially reversed the protective effect of polyamine depletion whereas NU6140 had no effect. Together, these results demonstrate that Cdks possess opposing roles in the control of apoptosis in quiescent and proliferating cells. In addition, Cdk inhibitors uncouple proliferation from apoptosis in a p53-dependent manner. PMID:24242917

Harmonic oscillations of a circular cylinder moving with constant velocity in a quiescent fluid

OpenAIRE

Jan Novaes Recica; Luiz Antonio Alcântara Pereira; Miguel Hiroo Hirata

2008-01-01

The flow around an oscillating circular cylinder which moves with constant velocity in a quiescent Newtonian fluid with constant properties is analyzed. The influences of the frequency and amplitude oscillation on the aerodynamic loads and on the Strouhal number are presented. For the numerical simulation, a cloud of discrete Lamb vortices are utilized. For each time step of the simulation, a number of discrete vortices are placed close to the body surface; the intensity of theirs is determin...

Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells.

Science.gov (United States)

Sánchez, Mario; Ceci, Maria Laura; Gutiérrez, Daniela; Anguita-Salinas, Consuelo; Allende, Miguel L

2016-04-07

Regenerating damaged tissue is a complex process, requiring progenitor cells that must be stimulated to undergo proliferation, differentiation and, often, migratory behaviors and morphological changes. Multiple cell types, both resident within the damaged tissue and recruited to the lesion site, have been shown to participate. However, the cellular and molecular mechanisms involved in the activation of progenitor cell proliferation and differentiation after injury, and their regulation by different cells types, are not fully understood. The zebrafish lateral line is a suitable system to study regeneration because most of its components are fully restored after damage. The posterior lateral line (PLL) is a mechanosensory system that develops embryonically and is initially composed of seven to eight neuromasts distributed along the trunk and tail, connected by a continuous stripe of interneuromastic cells (INCs). The INCs remain in a quiescent state owing to the presence of underlying Schwann cells. They become activated during development to form intercalary neuromasts. However, no studies have described if INCs can participate in a regenerative event, for example, after the total loss of a neuromast. We used electroablation in transgenic larvae expressing fluorescent proteins in PLL components to completely ablate single neuromasts in larvae and adult fish. This injury results in discontinuity of the INCs, Schwann cells, and the PLL nerve. In vivo imaging showed that the INCs fill the gap left after the injury and can regenerate a new neuromast in the injury zone. Further, a single INC is able to divide and form all cell types in a regenerated neuromast and, during this process, it transiently expresses the sox2 gene, a neural progenitor cell marker. We demonstrate a critical role for Schwann cells as negative regulators of INC proliferation and neuromast regeneration, and that this inhibitory property is completely dependent on active ErbB signaling. The potential

CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

DEFF Research Database (Denmark)

Abdallah, Basem M; Al-Shammary, Asma; Skagen, Peter

2015-01-01

Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and pro...

Experimental studies on the surface confined quiescent plasma at INPE

International Nuclear Information System (INIS)

Ferreira, J.L.; Ferreira, J.G.; Sandonato, G.M.; Alves, M.V.; Ludwig, G.O.; Montes, A.

1988-01-01

The quiescent plasma machines used in several experiments at the Associated Plasma Laboratory in INPE are presented. The research activities comprise particle simulation studies on ion acoustic double layers, and studies on the plasma production and loss in surface confined magnetic multidipole thermionic discharges. Recent results from these studies have shown a non-maxwellian plasma formed in most of the discharge conditions. The plasma leakage through the multidipole fields shows an anomalous diffusion process driven by ion acoustic turbulence in the magnetic sheath. The information derived from these studies are being used in the construction and characterization of ion sources for shallow ion implantation in semiconductors, in ion thruster for space propulsion and in the development of powerful ion sources for future use in neutral beam injection systems. (author) [pt

Experimental studies on the surface confined quiescent plasma at INPE

International Nuclear Information System (INIS)

Ferreira, J.L.; Ferreira, J.G.; Sandonato, G.M.; Alves, M.V.; Ludwig, G.O.; Montes, A.

1988-06-01

Quiescent plasma machines are being used in several experiments at the Associated Plasma Laboratory in INPE. The research activities comprises particle simulation studies on ion acoustic double Layers, and studies on the plasma production and loss in surface confined magnetic multidipole thermionic discharges. Recent results from these studies have shown a non-maxwellian plasma formed in most of the discharge conditions. The plasma leakage through the multidipole fields shows an anomalous diffusion process driven by ion acoustic turbulence in the magnetic sheath. The information derived from these studies are being used in the construction and characterization of ion sources for shallow ion implantation in semiconductors, in ion thruster for space propulsion and in the development of powerful ion sources for future use in neutral beam injection systems. (author) [pt

Evidence for quiescent synchrotron emission in the black hole X-ray transient Swift J1357.2–0933

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Shahbaz T.

2013-12-01

Full Text Available We present high time-resolution optical and infrared observations of the edge-on black hole X-ray transient Swift J1357.2-0933. Our data taken in 2012 shows the system to be at its pre-outburst magnitude and so the system is in quiescence. In contrast to other X-ray transients, the quiescent light curves of Swift J1357.2-0933 do not show the secondary star’s ellipsoidal modulation. The optical and infrared light curves is dominated by variability with an optical fractional rms of about 20 per cent, much larger than what is observed in other systems. The quiescent ultraviolet to mid-IR spectral energy distribution in quiescence is dominated by a nonthermal component with a power–law index of −1.4, (the broad-band rms SED has a similar index which arises from optically thin synchrotron emission from a jet; the lack of a peak in the spectral energy distribution rules out advection-dominated models (based on [19].

What Population Reveals about Individual Cell Identity: Single-Cell Parameter Estimation of Models of Gene Expression in Yeast.

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Artémis Llamosi

2016-02-01

Full Text Available Significant cell-to-cell heterogeneity is ubiquitously observed in isogenic cell populations. Consequently, parameters of models of intracellular processes, usually fitted to population-averaged data, should rather be fitted to individual cells to obtain a population of models of similar but non-identical individuals. Here, we propose a quantitative modeling framework that attributes specific parameter values to single cells for a standard model of gene expression. We combine high quality single-cell measurements of the response of yeast cells to repeated hyperosmotic shocks and state-of-the-art statistical inference approaches for mixed-effects models to infer multidimensional parameter distributions describing the population, and then derive specific parameters for individual cells. The analysis of single-cell parameters shows that single-cell identity (e.g. gene expression dynamics, cell size, growth rate, mother-daughter relationships is, at least partially, captured by the parameter values of gene expression models (e.g. rates of transcription, translation and degradation. Our approach shows how to use the rich information contained into longitudinal single-cell data to infer parameters that can faithfully represent single-cell identity.

Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells.

Science.gov (United States)

Bargaje, Rhishikesh; Trachana, Kalliopi; Shelton, Martin N; McGinnis, Christopher S; Zhou, Joseph X; Chadick, Cora; Cook, Savannah; Cavanaugh, Christopher; Huang, Sui; Hood, Leroy

2017-02-28

Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.

Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

International Nuclear Information System (INIS)

Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui

2014-01-01

Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1 + or nestin + stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU + cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU + cells, very few are mash1 + or nestin + stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1 + microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

Activation of intracellular angiotensin AT2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

DEFF Research Database (Denmark)

Zhao, Yi; Lützen, Ulf; Fritsch, Jürgen

2015-01-01

The presence of AT2 receptors in mitochondria and their role in NO generation and cell aging were recently demonstrated in various human and mouse non-tumour cells. We investigated the intracellular distribution of AT2 receptors including their presence in mitochondria and the role in the induction...... agonist, Compound 21 (C21) penetrates the cell membrane of quiescent SK-UT-1 cells, activates intracellular AT2 receptors and induces rapid cell death; approximately 70% of cells died within 24 h. The cells, which escaped from the cell death, displayed activation of the mitochondrial apoptotic pathway, i...

Distinct types of glial cells populate the Drosophila antenna

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Jhaveri Dhanisha

2005-11-01

Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population

Science.gov (United States)

WATANABE, YUSAKU; YOSHIMURA, KIYOSHI; YOSHIKAWA, KOICHI; TSUNEDOMI, RYOICHI; SHINDO, YOSHITARO; MATSUKUMA, SOU; MAEDA, NORIKO; KANEKIYO, SHINSUKE; SUZUKI, NOBUAKI; KURAMASU, ATSUO; SONODA, KOUHEI; TAMADA, KOJI; KOBAYASHI, SEI; SAYA, HIDEYUKI; HAZAMA, SHOICHI; OKA, MASAAKI

2014-01-01

Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLCenriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy. PMID:25118635

The Circadian Molecular Clock Regulates Adult Hippocampal Neurogenesis by Controlling the Timing of Cell-Cycle Entry and Exit

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Pascale Bouchard-Cannon

2013-11-01

Full Text Available The subgranular zone (SGZ of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body.

Population dynamics in vasopressin cells.

Science.gov (United States)

Leng, Gareth; Brown, Colin; Sabatier, Nancy; Scott, Victoria

2008-01-01

Most neurons sense and code change, and when presented with a constant stimulus they adapt, so as to be able to detect a fresh change. However, for some things it is important to know their absolute level; to encode such information, neurons must sustain their response to an unchanging stimulus while remaining able to respond to a change in that stimulus. One system that encodes the absolute level of a stimulus is the vasopressin system, which generates a hormonal signal that is proportional to plasma osmolality. Vasopressin cells sense plasma osmolality and secrete appropriate levels of vasopressin from the neurohypophysis as needed to control water excretion; this requires sustained secretion under basal conditions and the ability to increase (or decrease) secretion should plasma osmolality change. Here we explore the mechanisms that enable vasopressin cells to fulfill this function, and consider how coordination between the cells might distribute the secretory load across the population of vasopressin cells. 2008 S. Karger AG, Basel.

Modelling cell cycle synchronisation in networks of coupled radial glial cells.

Science.gov (United States)

Barrack, Duncan S; Thul, Rüdiger; Owen, Markus R

2015-07-21

Radial glial cells play a crucial role in the embryonic mammalian brain. Their proliferation is thought to be controlled, in part, by ATP mediated calcium signals. It has been hypothesised that these signals act to locally synchronise cell cycles, so that clusters of cells proliferate together, shedding daughter cells in uniform sheets. In this paper we investigate this cell cycle synchronisation by taking an ordinary differential equation model that couples the dynamics of intracellular calcium and the cell cycle and extend it to populations of cells coupled via extracellular ATP signals. Through bifurcation analysis we show that although ATP mediated calcium release can lead to cell cycle synchronisation, a number of other asynchronous oscillatory solutions including torus solutions dominate the parameter space and cell cycle synchronisation is far from guaranteed. Despite this, numerical results indicate that the transient and not the asymptotic behaviour of the system is important in accounting for cell cycle synchronisation. In particular, quiescent cells can be entrained on to the cell cycle via ATP mediated calcium signals initiated by a driving cell and crucially will cycle in near synchrony with the driving cell for the duration of neurogenesis. This behaviour is highly sensitive to the timing of ATP release, with release at the G1/S phase transition of the cell cycle far more likely to lead to near synchrony than release during mid G1 phase. This result, which suggests that ATP release timing is critical to radial glia cell cycle synchronisation, may help us to understand normal and pathological brain development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transport of gaseous pollutants around a human body in quiescent indoor environment

DEFF Research Database (Denmark)

Licina, Dusan; Melikov, Arsen Krikor; Mioduszewski, Pawel

2014-01-01

(CBL) to transport the pollution in quiescent indoor environment. A human body is resembled by a thermal manikin with a body shape and surface temperature distribution of a real person. The objective of the study is to examine the impact of the pollutant location around the human body on the pollution...... concentration levels in the breathing zone. The results show that the location of the pollution source has a considerable influence of the breathing zone concentrations. This is contributed to the human CBL, as it pulls the pollution emitted close to the human body and transports it to the breathing zone...... the human body should be recognized in ventilation design practice....

The effect of ultraviolet light on arrested human diploid cell populations

International Nuclear Information System (INIS)

Kantor, G.J.; Warner, C.; Hull, D.R.

1977-01-01

The results of the experiments to determine an effect of UV (254 nm) on human diploid fibroblasts (HDF) arrested with respect to division by using 0.5% fetal calf serum in the culture medium are reported. A fraction of cells from irradiated arrested populations, maintained in the arrested state post-irradiation, was lost from the populations. The extent of cell loss was fluence-dependent and cell strain specific. A Xeroderma pigmentosum cell strain was more sensitive to UV than were normal HDF. No difference in sensitivity were observed when arrested populations established from normal HDF populations of various in vitro ages were used. The length of the pre-irradiation arrested period affected the sensitivity of normal HDF, which appeared more resistant at longer arrested periods, but not the sensitivity of arrested Xeroderma populations. These results suggest that DNA repair processes play a role in maintaining irradiated cells in the arrested state. The suggestion is made that the lethal event caused by UV is an effect on transcription leading to an inhibition of required protein synthesis. (author)

Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat

Directory of Open Access Journals (Sweden)

Boudreaux Crystal E

2012-05-01

Full Text Available Abstract Background An appropriate balance in placental regulatory T cells (Tregs, an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation. Methods We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6. Results FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals. Conclusion Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

OpenAIRE

Kosan, Christian; Godmann, Maren

2015-01-01

All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several trans...

Primary cilium - antenna-like structure on the surface of most mammalian cell types

International Nuclear Information System (INIS)

Dvorak, J; Kasaova, L; Filip, S; Petera, J; Sitorova, V; Nikolov, D Hadzi; Ryska, A; Mokry, J; Richter, I

2011-01-01

The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G 1 (G 0 ) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

Primary cilium - antenna-like structure on the surface of most mammalian cell types

Science.gov (United States)

Dvorak, J.; Sitorova, V.; Hadzi Nikolov, D.; Mokry, J.; Richter, I.; Kasaova, L.; Filip, S.; Ryska, A.; Petera, J.

2011-12-01

The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G1(G0) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

Late post-irradiation phenomena in mammalain cell populations. Pt. 2. Intraclonal recovery in sublines isolated from X-irradiated L5178Y-S cell populations

International Nuclear Information System (INIS)

Beer, J.Z.

1975-01-01

Clonal analysis of L5178Y-S cell populations irradiated with 300 rads of X-rays indicates occurence of cell sublines with considerably prolonged mean doubling times up to 22 h as compared to 10-11 h for control. Subsequent observations of growth of the handicapped sublines derived from single cells showed capability of all more than 100 studied sublines to recover normal proliferative activity. This process of intraclonal recovery required in many cases longer periods of time, corresponding to many tens, sometimes more than 200, generations. Late intraclonal recovery was further analysed by subcloning. It was found that although cytochemically assayed viability of the handicapped sublines was normal, cloning efficiency strongly depended on the stage of the recovery process. The recovery processes occuring in clones isolated from irradiated cell populations were compared with analogous processes occuring in slowly growing sublines isolated from non-irradiated cell cultures. Marked differences in kinetics of these processes show that either they are different in sublines derived from irradiated and non-irradiated cell populations or that the mechanisms of the late intraclonal recovery are affected by radiation. The results presented allow to conclude that gradual post-irradiation recovery of growth depends primarily on formation, in the developing populations, of cells with higher proliferative activities. Possible nature of the recovery processes is discussed in the light of available information on mammalian somatic cell variants with altered drug or temperature sensitivity, or with nutritional requirements. A sequence is proposed of changes leading from radiation-induced disturbance of the normably existing equilibrium between three basic cell subpopulations to ultimate restoration of this equilibrium. (author)

Reduced satellite cell number in situ in muscular contractures from children with cerebral palsy.

Science.gov (United States)

Dayanidhi, Sudarshan; Dykstra, Peter B; Lyubasyuk, Vera; McKay, Bryon R; Chambers, Henry G; Lieber, Richard L

2015-07-01

Satellite cells (SC) are quiescent adult muscle stem cells critical for postnatal development. Children with cerebral palsy have impaired muscular growth and develop contractures. While flow cytometry previously demonstrated a reduced SC population, extracellular matrix abnormalities may influence the cell isolation methods used, systematically isolating fewer cells from CP muscle and creating a biased result. Consequently, the purpose of this study was to use immunohistochemistry on serial muscle sections to quantify SC in situ. Serial cross-sections from human gracilis muscle biopsies (n = 11) were labeled with fluorescent antibodies for Pax7 (SC transcriptional marker), laminin (basal lamina), and 4',6-diamidino-2-phenylindole (nuclei). Fluorescence microscopy under high magnification was used to identify SC based on labeling and location. Mean SC/100 myofibers was reduced by ∼70% (p muscle growth and apparent decreased responsiveness of CP muscle to exercise. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

MASSIVE BLACK HOLES IN STELLAR SYSTEMS: 'QUIESCENT' ACCRETION AND LUMINOSITY

International Nuclear Information System (INIS)

Volonteri, M.; Campbell, D.; Mateo, M.; Dotti, M.

2011-01-01

Only a small fraction of local galaxies harbor an accreting black hole, classified as an active galactic nucleus. However, many stellar systems are plausibly expected to host black holes, from globular clusters to nuclear star clusters, to massive galaxies. The mere presence of stars in the vicinity of a black hole provides a source of fuel via mass loss of evolved stars. In this paper, we assess the expected luminosities of black holes embedded in stellar systems of different sizes and properties, spanning a large range of masses. We model the distribution of stars and derive the amount of gas available to a central black hole through a geometrical model. We estimate the luminosity of the black holes under simple, but physically grounded, assumptions on the accretion flow. Finally, we discuss the detectability of 'quiescent' black holes in the local universe.

Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

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Shengxiu Li

Full Text Available TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

Energy Technology Data Exchange (ETDEWEB)

Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

2014-08-01

Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

International Nuclear Information System (INIS)

Nagata, Yosuke; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

2014-01-01

Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

Radiation dose to trabecular bone marrow stem cells from 3H, 14C and selected α-emitters incorporated in a bone remodeling compartment

International Nuclear Information System (INIS)

Nie Huiling; Richardson, Richard B

2009-01-01

A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for 3 H, 14 C and a set of α-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 μm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 μm endosteum for 3 H, 14 C and α-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal α-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

Experimental depletion of different renal interstitial cell populations

International Nuclear Information System (INIS)

Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

1988-01-01

To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

Nonequilibrium population dynamics of phenotype conversion of cancer cells.

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Joseph Xu Zhou

Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

THE RELATION BETWEEN DYNAMICAL MASS-TO-LIGHT RATIO AND COLOR FOR MASSIVE QUIESCENT GALAXIES OUT TO z ∼ 2 AND COMPARISON WITH STELLAR POPULATION SYNTHESIS MODELS

International Nuclear Information System (INIS)

Van de Sande, Jesse; Franx, Marijn; Kriek, Mariska; Bezanson, Rachel; Van Dokkum, Pieter G.

2015-01-01

We explore the relation between the dynamical mass-to-light ratio (M/L) and rest-frame color of massive quiescent galaxies out to z ∼ 2. We use a galaxy sample with measured stellar velocity dispersions in combination with Hubble Space Telescope and ground-based multi-band photometry. Our sample spans a large range in log M dyn /L g (of 1.6 dex) and log M dyn /L K (of 1.3 dex). There is a strong, approximately linear correlation between the M/L for different wavebands and rest-frame color. The root-mean-square scatter in log M dyn /L residuals implies that it is possible to estimate the M/L with an accuracy of ∼0.25 dex from a single rest-frame optical color. Stellar population synthesis (SPS) models with a Salpeter stellar initial mass function (IMF) cannot simultaneously match M dyn /L g versus (g – z) rest-frame and M dyn /L K versus (g – K) rest-frame . By changing the slope of the IMF we are still unable to explain the M/L of the bluest and reddest galaxies. We find that an IMF with a slope between α = 2.35 and α = 1.35 provides the best match. We also explore a broken IMF with a Salpeter slope at M < 1 M ☉ and M > 4 M ☉ and a slope α in the intermediate region. The data favor a slope of α = 1.35 over α = 2.35. Nonetheless, our results show that variations between different SPS models are comparable to the IMF variations. In our analysis we assume that the variation in M/L and color is driven by differences in age, and that other contributions (e.g., metallicity evolution, dark matter) are small. These assumptions may be an important source of uncertainty as galaxies evolve in more complex ways

Modeling population dynamics of mitochondria in mammalian cells

Science.gov (United States)

Kornick, Kellianne; Das, Moumita

Mitochondria are organelles located inside eukaryotic cells and are essential for several key cellular processes such as energy (ATP) production, cell signaling, differentiation, and apoptosis. All organisms are believed to have low levels of variation in mitochondrial DNA (mtDNA), and alterations in mtDNA are connected to a range of human health conditions, including epilepsy, heart failure, Parkinsons disease, diabetes, and multiple sclerosis. Therefore, understanding how changes in mtDNA accumulate over time and are correlated to changes in mitochondrial function and cell properties can have a profound impact on our understanding of cell physiology and the origins of some diseases. Motivated by this, we develop and study a mathematical model to determine which cellular parameters have the largest impact on mtDNA population dynamics. The model consists of coupled ODEs to describe subpopulations of healthy and dysfunctional mitochondria subject to mitochondrial fission, fusion, autophagy, and mutation. We study the time evolution and stability of each sub-population under specific selection biases and pressures by tuning specific terms in our model. Our results may provide insights into how sub-populations of mitochondria survive and evolve under different selection pressures. This work was supported by a Grant from the Moore Foundation.

A probabilistic model for cell population phenotyping using HCS data.

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Edouard Pauwels

Full Text Available High Content Screening (HCS platforms allow screening living cells under a wide range of experimental conditions and give access to a whole panel of cellular responses to a specific treatment. The outcome is a series of cell population images. Within these images, the heterogeneity of cellular response to the same treatment leads to a whole range of observed values for the recorded cellular features. Consequently, it is difficult to compare and interpret experiments. Moreover, the definition of phenotypic classes at a cell population level remains an open question, although this would ease experiments analyses. In the present work, we tackle these two questions. The input of the method is a series of cell population images for which segmentation and cellular phenotype classification has already been performed. We propose a probabilistic model to represent and later compare cell populations. The model is able to fully exploit the HCS-specific information: "dependence structure of population descriptors" and "within-population variability". The experiments we carried out illustrate how our model accounts for this specific information, as well as the fact that the model benefits from considering them. We underline that these features allow richer HCS data analysis than simpler methods based on single cellular feature values averaged over each well. We validate an HCS data analysis method based on control experiments. It accounts for HCS specificities that were not taken into account by previous methods but have a sound biological meaning. Biological validation of previously unknown outputs of the method constitutes a future line of work.

FREQUENCY OF QUIESCENT FUNGI AND POST-HARVEST ALTERNATIVE MANAGEMENT OF STEM END ROT IN PAPAYA

OpenAIRE

DANIELA DAMBROS AMARAL; ANA LETICIA ROCHA MONTEIRO; ELIAS INÁCIO DA SILVA; SEVERINA RODRIGUES DE OLIVEIRA LINS; SONIA MARIA ALVES DE OLIVEIRA

2017-01-01

The aim of this study was to evaluate the frequency of quiescent fungi and the effect of phosphites under modified atmosphere on Lasiodiplodia theobromae in papaya. The fruits were treated with a range of doses of phosphites and their actions evaluated under conditions of ambient and modified atmosphere. Of the eight fungal genera found, Lasiodiplodia was the most common. No interaction was observed between the evaluated factors and only atmosphere and dose were independently significant. The...

FREQUENCY OF QUIESCENT FUNGI AND POST-HARVEST ALTERNATIVE MANAGEMENT OF STEM END ROT IN PAPAYA

OpenAIRE

AMARAL, DANIELA DAMBROS; MONTEIRO, ANA LETICIA ROCHA; SILVA, ELIAS INÁCIO DA; LINS, SEVERINA RODRIGUES DE OLIVEIRA; OLIVEIRA, SONIA MARIA ALVES DE

2017-01-01

ABSTRACT The aim of this study was to evaluate the frequency of quiescent fungi and the effect of phosphites under modified atmosphere on Lasiodiplodia theobromae in papaya. The fruits were treated with a range of doses of phosphites and their actions evaluated under conditions of ambient and modified atmosphere. Of the eight fungal genera found, Lasiodiplodia was the most common. No interaction was observed between the evaluated factors and only atmosphere and dose were independently signifi...

Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

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Jinah Han

2015-02-01

Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

Reciprocal control of cell proliferation and migration

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De Donatis Alina

2010-09-01

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

A transgenic mouse marking live replicating cells reveals in vivo transcriptional program of proliferation

DEFF Research Database (Denmark)

Klochendler, Agnes; Weinberg-Corem, Noa; Moran, Maya

2012-01-01

Most adult mammalian tissues are quiescent, with rare cell divisions serving to maintain homeostasis. At present, the isolation and study of replicating cells from their in vivo niche typically involves immunostaining for intracellular markers of proliferation, causing the loss of sensitive biolo...

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

Science.gov (United States)

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

2005-05-01

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

Melatonin suppresses activation of hepatic stellate cells through ROR alpha-mediated inhibition of 5-lipoxygenase

NARCIS (Netherlands)

Shajari, Shiva; Laliena, Almudena; Heegsma, Janette; Jesus Tunon, Maria; Moshage, Han; Faber, Klaas Nico

2015-01-01

Liver fibrosis is scar tissue resulting from an uncontrolled wound-healing process in response to chronic liver injury. Liver damage generates an inflammatory reaction that activates hepatic stellate cells (HSC) that transdifferentiate from quiescent cells that control retinol metabolism to

Harmonic oscillations of a circular cylinder moving with constant velocity in a quiescent fluid

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Jan Novaes Recica

2008-01-01

Full Text Available The flow around an oscillating circular cylinder which moves with constant velocity in a quiescent Newtonian fluid with constant properties is analyzed. The influences of the frequency and amplitude oscillation on the aerodynamic loads and on the Strouhal number are presented. For the numerical simulation, a cloud of discrete Lamb vortices are utilized. For each time step of the simulation, a number of discrete vortices are placed close to the body surface; the intensity of theirs is determined such as to satisfy the no-slip boundary condition.

Microenvironmental regulation of hematopoietic stem cells and its implications in leukemogenesis.

Science.gov (United States)

Seshadri, Madhav; Qu, Cheng-Kui

2016-07-01

Hematopoietic stem cells (HSCs) are a population of cells in the bone marrow which can self-renew, differentiate into late lineage progenitors, or remain quiescent. HSCs exist alongside several cell types in the bone marrow microenvironment that comprise the stem cell niche. These cells regulate HSC function and can contribute to leukemogenesis. In this review we will discuss recent advances in this field. In the vascular niche, arteriolar and sinusoidal zones appear to play distinct roles in HSC function. Endothelial cells modulate HSC function via Notch and other signaling pathways. In the endosteal niche multiple cell types regulate HSCs. Osteoblasts promote HSC quiescence via secreted factors and possibly physical interactions, whereas adipocytes may oppose HSC quiescence. The balance of these opposing factors depends on metabolic cues. Feedback from HSC-derived cells, including macrophages and megakaryocytes also appears to regulate HSC quiescence. Dysfunction of the bone marrow microenvironment, including mesenchymal stem cell-derived stromal cells and the sympathetic nervous system can induce or alter the progression of hematologic malignancies. Many cell types in the bone marrow microenvironment affect HSC function and contribute to malignancy. Further understanding how HSCs are regulated by the microenvironment has clinical implications for stem cell transplantation and other therapies for hematologic malignancies.

Identification of Proliferative and Apoptotic Sertoli Cells Using Fluorescence and Confocal Microscopy.

Science.gov (United States)

Martínez-Hernández, Jesús; Seco-Rovira, Vicente; Beltrán-Frutos, Ester; Quesada-Cubo, Victor; Ferrer, Concepción; Pastor, Luis Miguel

2018-01-01

Sertoli cells, the testicular somatic cells of the seminiferous epithelium, are vital for the survival of the epithelium. They undergo proliferation and apoptosis during fetal, neonatal, and prepubertal development. Apoptosis is increased in certain situations such as exposure to many substances, for example, toxics, or short photoperiod in the non-breeding season of some mammals. Therefore, it has always been considered that Sertoli cells that reach adulthood are quiescent cells, that is to say, nonproliferative, do not die, are terminally differentiated, and whose numbers remain constant. Recently, a degree of both proliferation and apoptosis has been observed in normal adult conditions, suggesting that consideration of this cell as quiescent may be subject to change. All this make it necessary to use histochemical techniques to demonstrate whether Sertoli cells are undergoing proliferation or apoptosis in histological sections and to allow the qualitative and quantitative study of these. In this chapter, we present two double-staining techniques that can be used for identifying Sertoli cells in proliferation or apoptosis by fluorescence microscopy. In both, the Sertoli cells are identified by an immunohistochemistry for vimentin followed by an immunohistochemistry for PCNA or a TUNEL histochemistry.

The Role of Integrin α6 (CD49f) in Stem Cells: More than a Conserved Biomarker.

Science.gov (United States)

Krebsbach, Paul H; Villa-Diaz, Luis G

2017-08-01

Stem cells have the capacity for self-renewal and differentiation into specialized cells that form and repopulated all tissues and organs, from conception to adult life. Depending on their capacity for differentiation, stem cells are classified as totipotent (ie, zygote), pluripotent (ie, embryonic stem cells), multipotent (ie, neuronal stem cells, hematopoietic stem cells, epithelial stem cells, etc.), and unipotent (ie, spermatogonial stem cells). Adult or tissue-specific stem cells reside in specific niches located in, or nearby, their organ or tissue of origin. There, they have microenvironmental support to remain quiescent, to proliferate as undifferentiated cells (self-renewal), and to differentiate into progenitors or terminally differentiated cells that migrate from the niche to perform specialized functions. The presence of proteins at the cell surface is often used to identify, classify, and isolate stem cells. Among the diverse groups of cell surface proteins used for these purposes, integrin α6, also known as CD49f, may be the only biomarker commonly found in more than 30 different populations of stem cells, including some cancer stem cells. This broad expression among stem cell populations indicates that integrin α6 may play an important and conserved role in stem cell biology, which is reaffirmed by recent demonstrations of its role maintaining self-renewal of pluripotent stem cells and breast and glioblastoma cancer stem cells. Therefore, this review intends to highlight and synthesize new findings on the importance of integrin α6 in stem cell biology.

Comparison between various biomarkers of senescence in bone marrow-derived stromal cells in vitro and ex-vivo

DEFF Research Database (Denmark)

Nehlin, Jan; Kassem, Moustapha; Frary, Charles

Senescent stem cells are classified as non-quiescent, irreversibly growth-arrested, non-terminally differentiated, apoptosis resistant multipotent stem cells that maintain an altered gene expression from their juvenescent precursors. Established markers of senescence such as senescent-associated ...

Effect of radiotherapy on stem cells in head and neck region

International Nuclear Information System (INIS)

Sharma, Anu; Krishnan, Manu

2014-01-01

Head and neck cancers form a major group of dreaded diseases in India. Radiation therapy is one important treatment modality for this type of cancer. However, inadvertent radiation to normal tissue leads to depletion of its critical stem cells due to genotoxic damage. Cells mostly affected by radiation are rapidly dividing bone marrow and epidermal skin stem cells. The erythroid and myeloid progenitor cells of bone marrow bear the brunt of it causing leucopenia/thrombocytopenia/anemia. Alopecia and pigmentation mark the changes on skin. In brain, two stem cell populations; subgranular and subventricular zones, where neurogenesis occurs throughout life are affected. However, terminally differentiating neurons with low proliferative capacity are spared. In oral tissues, xerostomia is a prominent feature, while dental pulp stem cells undergo senescence. Enamel calcification and tooth root formation are also impaired. Eye shows changes in the limbal stem cells that replace corneal epithelium. All these imply a varied response of stem cells to radiation therapy based on their proliferation capacity; quiescent stem cells being more resistant whereas actively dividing cells, less resistant to radiotherapy. This paper evaluates the differential response of stem cells to radiation therapy in the head and neck area and thereby aims to predict their therapeutic potential. (author)

DYRK1A is a regulator of S phase entry in hepatic progenitor cells

NARCIS (Netherlands)

Kruitwagen, Hedwig Suzanne; Westendorp, Bart; Viebahn, Cornelia S; Post, Krista; van Wolferen, Monique E; Oosterhoff, Loes A; Egan, David A; Delabar, Jean-Maurice; Toussaint, Mathilda Jm; Schotanus, Baukje A; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Spee, Bart

Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second line of defense in liver regeneration. They are normally quiescent, but in case of severe liver damage HPC proliferation is triggered by external activation mechanisms from their niche. Although several important

Use of Multicolor Flow Cytometry for Isolation of Specific Cell Populations Deriving from Differentiated Human Embryonic Stem Cells

NARCIS (Netherlands)

Mengarelli, Isabella; Fryga, Andrew; Barberi, Tiziano

2016-01-01

Flow Cytometry-Sorting (FCM-Sorting) is a technique commonly used to identify and isolate specific types of cells from a heterogeneous population of live cells. Here we describe a multicolor flow cytometry technique that uses five distinct cell surface antigens to isolate four live populations with

Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

Science.gov (United States)

de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

2017-03-01

An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

Targeting population heterogeneity for optimal cell factories

DEFF Research Database (Denmark)

Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.

the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were constructed which enabled us to perform single cell level...... analysis, and thereby created the possibility to map population heterogeneity. A factorial design with pH, glucose concentration and oxygen level was performed in batch cultivations using the growth reporter strains to evaluate the effect of those environmental factors on heterogeneity level and amount......To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

Emergence of a super-synchronized mobbing state in a large population of coupled chemical oscillators

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Ghoshal, Gourab; Muñuzuri, Alberto P.; Pérez-Mercader, Juan

2016-01-01

Oscillatory phenomena are ubiquitous in Nature. The ability of a large population of coupled oscillators to synchronize constitutes an important mechanism to express information and establish communication among members. To understand such phenomena, models and experimental realizations of globally coupled oscillators have proven to be invaluable in settings as varied as chemical, biological and physical systems. A variety of rich dynamical behavior has been uncovered, although usually in the context of a single state of synchronization or lack thereof. Through the experimental and numerical study of a large population of discrete chemical oscillators, here we report on the unexpected discovery of a new phenomenon revealing the existence of dynamically distinct synchronized states reflecting different degrees of communication. Specifically, we discover a novel large-amplitude super-synchronized state separated from the conventionally reported synchronized and quiescent states through an unusual sharp jump transition when sampling the strong coupling limit. Our results assume significance for further elucidating globally coherent phenomena, such as in neuropathologies, bacterial cell colonies, social systems and semiconductor lasers.

The Lifespan and Turnover of Microglia in the Human Brain

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Pedro Réu

2017-07-01

Full Text Available The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.

Analysing the Influence of the Spontaneous Aneuploidy Frequency on the Cell Population System Cultivation

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G. A. Nefedov

2015-01-01

Full Text Available The paper provides a qualitative analysis of M.S. Vinogradova's nonlinear model for dynamics of the cell population system. This system describes the stem cells cultivation in vitro under resource constraints. The system consists of two populations, namely: population of normal cells and population of abnormal cells. Resource constraints are considered as linear dependences of mitosis parameters on the normalized densities of each population.One of the key parameters that effects on the realization of the system evolution scenarios is a parameter that determines a share of the normal cells, which pass, when dividing, into population of the abnormal cells. The paper analyses both the existence conditions of the rest points and the changes of the evolution scenarios of population system with changing abovementioned parameter and other system parameters held fixed. It is shown that there is a saddle-node bifurcation in the system; the bifurcation value of the parameter is found. The paper shows the interval of parameter values in which the favorable scenarios of population system evolution are implemented. It also presents results of mathematical modeling.

A sub-population of circulating porcine gammadelta T cells can act as professional antigen presenting cells.

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Takamatsu, H-H; Denyer, M S; Wileman, T E

2002-09-10

A sub-population of circulating porcine gammadelta T cells express cell surface antigens associated with antigen presenting cells (APCs), and are able to take up soluble antigen very effectively. Functional antigen presentation by gammadelta T cells to memory helper T cells was studied by inbred pig lymphocytes immunised with ovalbumin (OVA). After removing all conventional APCs from the peripheral blood of immunised pigs, the remaining lymphocytes still proliferated when stimulated with OVA. When gammadelta T cells were further depleted, OVA specific proliferation was abolished, but reconstitution with gammadelta T cells restored proliferation. The proliferation was blocked by monoclonal antibodies (mAb) against MHC class II or CD4, and by pre-treatment of gammadelta T cells with chloroquine. These results indicate that a sub-population of circulating porcine gammadelta T cells act as APCs and present antigen via MHC class II.

Quantitation of DNA repair in brain cell cultures: implications for autoradiographic analysis of mixed cell populations

International Nuclear Information System (INIS)

Dambergs, R.; Kidson, C.

1979-01-01

Quantitation of DNA repair in the mixed cell population of mouse embryo brain cultures has been assessed by autoradiographic analysis of unscheduled DNA synthesis following UV-irradiation. The proportion of labelled neurons and the grain density over neuronal nuclei were both less than the corresponding values for glial cells. The nuclear geometries of these two classes of cell are very different. Partial correction for the different geometries by relating grain density to nuclear area brought estimates of neuronal and glial DNA repair synthesis more closely in line. These findings have general implications for autoradiographic measurement of DNA repair in mixed cell populations and in differentiated versus dividing cells. (author)

Microwave structure of quiescent solar filaments at high resolution

International Nuclear Information System (INIS)

Gary, D.E.

1986-01-01

High resolution very low altitude maps of a quiescent filament at three frequencies are presented. The spatial resolution (approx. 15'' at 1.45 GHz, approx. 6'' at 4.9 GHz, and approx. 2'' at 15 GHz) is several times better than previously attained. At each frequency, the filament appears as a depression in the quiet Sun background. The depression is measurably wider and longer in extent than the corresponding H alpha filament at 1.45 GHz and 4.9 GHz, indicating that the depression is due in large part to a deficit in coronal density associated with the filament channel. In contrast, the shape of the radio depression at 15 CHz closely matches that of the H alpha filament. In addition, the 15 GHz map shows enhanced emission along both sides of the radio depression. A similar enhancement is seen in an observation of a second filament 4 days later, which suggests that the enhancement is a general feature of filaments. Possible causes of the enhanced emission are explored

Targeting of beta-arrestin2 to the centrosome and primary cilium: role in cell proliferation control.

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Anahi Molla-Herman

Full Text Available The primary cilium is a sensory organelle generated from the centrosome in quiescent cells and found at the surface of most cell types, from where it controls important physiological processes. Specific sets of membrane proteins involved in sensing the extracellular milieu are concentrated within cilia, including G protein coupled receptors (GPCRs. Most GPCRs are regulated by beta-arrestins, betaarr1 and betaarr2, which control both their signalling and endocytosis, suggesting that betaarrs may also function at primary cilium.In cycling cells, betaarr2 was observed at the centrosome, at the proximal region of the centrioles, in a microtubule independent manner. However, betaarr2 did not appear to be involved in classical centrosome-associated functions. In quiescent cells, both in vitro and in vivo, betaarr2 was found at the basal body and axoneme of primary cilia. Interestingly, betaarr2 was found to interact and colocalize with 14-3-3 proteins and Kif3A, two proteins known to be involved in ciliogenesis and intraciliary transport. In addition, as suggested for other centrosome or cilia-associated proteins, betaarrs appear to control cell cycle progression. Indeed, cells lacking betaarr2 were unable to properly respond to serum starvation and formed less primary cilia in these conditions.Our results show that betaarr2 is localized to the centrosome in cycling cells and to the primary cilium in quiescent cells, a feature shared with other proteins known to be involved in ciliogenesis or primary cilium function. Within cilia, betaarr2 may participate in the signaling of cilia-associated GPCRs and, therefore, in the sensory functions of this cell "antenna".

Binding, internalization and fate of Huntingtin Exon1 fibrillar assemblies in mitotic and nonmitotic neuroblastoma cells.

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Ruiz-Arlandis, G; Pieri, L; Bousset, L; Melki, R

2016-02-01

The aggregation of Huntingtin (HTT) protein and of its moiety encoded by its Exon1 (HTTExon1) into fibrillar structures inside neurons is the molecular hallmark of Huntington's disease. Prion-like transmission of these aggregates between cells has been demonstrated. The cell-to-cell transmission mechanisms of these protein aggregates and the susceptibility of different kinds of neuronal cells to these toxic assemblies still need assessment. Here, we documented the binding to and internalization by differentiated and undifferentiated neuroblastoma cells of exogenous fibrillar HTTExon1 and polyglutamine (polyQ) polypeptides containing the same number of glutamines. We assessed the contribution of endocytosis to fibrillar HTTExon1 uptake, their intracellular localization and fate. We observed that undifferentiated neuroblastoma cells were more susceptible to fibrillar HTTExon1 and polyQ than their differentiated counterparts. Furthermore, we demonstrated that exogenous HTTExon1 aggregates are mainly taken up by endocytosis and directed to lysosomal compartments in both mitotic and quiescent cells. These data suggest that the rates of endocytic processes that differ in mitotic and quiescent cells strongly impact the uptake of exogenous HTTExon1 and polyQ fibrils. This may be either the consequence of distinct metabolisms or distributions of specific protein partners for amyloid-like assemblies at the surface of highly dividing versus quiescent cells. Our results highlight the importance of endocytic processes in the internalization of exogenous HTTExon1 fibrils and suggest that a proportion of those assemblies reach the cytosol where they can amplify by recruiting the endogenous protein after escaping, by yet an unknown process, from the endo-lysosomal compartments. © 2015 British Neuropathological Society.

Analysis of in vitro secretion profiles from adipose-derived cell populations

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Blaber Sinead P

2012-08-01

Full Text Available Abstract Background Adipose tissue is an attractive source of cells for therapeutic purposes because of the ease of harvest and the high frequency of mesenchymal stem cells (MSCs. Whilst it is clear that MSCs have significant therapeutic potential via their ability to secrete immuno-modulatory and trophic cytokines, the therapeutic use of mixed cell populations from the adipose stromal vascular fraction (SVF is becoming increasingly common. Methods In this study we have measured a panel of 27 cytokines and growth factors secreted by various combinations of human adipose-derived cell populations. These were 1. co-culture of freshly isolated SVF with adipocytes, 2. freshly isolated SVF cultured alone, 3. freshly isolated adipocytes alone and 4. adherent adipose-derived mesenchymal stem cells (ADSCs at passage 2. In addition, we produced an ‘in silico’ dataset by combining the individual secretion profiles obtained from culturing the SVF with that of the adipocytes. This was compared to the secretion profile of co-cultured SVF and adipocytes. Two-tailed t-tests were performed on the secretion profiles obtained from the SVF, adipocytes, ADSCs and the ‘in silico’ dataset and compared to the secretion profiles obtained from the co-culture of the SVF with adipocytes. A p-value of  Results A co-culture of SVF and adipocytes results in a distinct secretion profile when compared to all other adipose-derived cell populations studied. This illustrates that cellular crosstalk during co-culture of the SVF with adipocytes modulates the production of cytokines by one or more cell types. No biologically relevant differences were detected in the proteomes of SVF cultured alone or co-cultured with adipocytes. Conclusions The use of mixed adipose cell populations does not appear to induce cellular stress and results in enhanced secretion profiles. Given the importance of secreted cytokines in cell therapy, the use of a mixed cell population such as the

A STRONGLY LENSED MASSIVE ULTRACOMPACT QUIESCENT GALAXY AT z ∼ 2.4 IN THE COSMOS/UltraVISTA FIELD

International Nuclear Information System (INIS)

Muzzin, Adam; Labbé, Ivo; Franx, Marijn; Holt, J.; Szomoru, Daniel; Van de Sande, Jesse; Van Dokkum, Pieter; Brammer, Gabriel; Marchesini, Danilo; Stefanon, Mauro; Buitrago, F.; Dunlop, James; Caputi, K. I.; Fynbo, J. P. U.; Milvang-Jensen, Bo; Le Févre, Olivier; McCracken, Henry J.

2012-01-01

We report the discovery of a massive ultracompact quiescent galaxy that has been strongly lensed into multiple images by a foreground galaxy at z 0.960. This system was serendipitously discovered as a set of extremely K s -bright high-redshift galaxies with red J – K s colors using new data from the UltraVISTA YJHK s near-infrared survey. The system was also previously identified as an optically faint lens/source system using the COSMOS Advanced Camera for Surveys (ACS) imaging by Faure et al. Photometric redshifts for the three brightest images of the source galaxy determined from 27-band photometry place the source at z = 2.4 ± 0.1. We provide an updated lens model for the system that is a good fit to the positions and morphologies of the galaxies in the ACS image. The lens model implies that the magnification of the three brightest images is a factor of 4-5. We use the lens model, combined with the K s -band image, to constrain the size and Sérsic profile of the galaxy. The best-fit model is an ultracompact galaxy (R e = 0.64 +0.08 –0.18 kpc, lensing-corrected), with a Sérsic profile that is intermediate between a disk and a bulge profile (n 2.2 +2.3 – 0 .9 ), albeit with considerable uncertainties on the Sérsic profile. We present aperture photometry for the source galaxy images that have been corrected for flux contamination from the central lens. The best-fit stellar population model is a massive galaxy (log(M star /M ☉ ) = 10.8 +0.1 –0.1 , lensing-corrected) with an age of 1.0 +1.0 –0.4 Gyr, moderate dust extinction (A v = 0.8 +0.5 –0.6 ), and a low specific star formation rate (log(SSFR) –1 ). This is typical of massive ''red-and-dead'' galaxies at this redshift and confirms that this source is the first bona fide strongly lensed massive ultracompact quiescent galaxy to be discovered. We conclude with a discussion of the prospects of finding a larger sample of these galaxies.

Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression.

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Collins, Steven J; Tumpach, Carolin; Groveman, Bradley R; Drew, Simon C; Haigh, Cathryn L

2018-03-24

Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life.

The first X-ray imaging spectroscopy of quiescent solar active regions with NuSTAR

DEFF Research Database (Denmark)

Hannah, Iain G.; Grefenstette, Brian W.; Smith, David M.

2016-01-01

We present the first observations of quiescent active regions (ARs) using the Nuclear Spectroscopic Telescope Array (NuSTAR), a focusing hard X-ray telescope capable of studying faint solar emission from high-temperature and non-thermal sources. We analyze the first directly imaged and spectrally...... resolved X-rays above 2 keV from non-flaring ARs, observed near the west limb on 2014 November 1. The NuSTAR X-ray images match bright features seen in extreme ultraviolet and soft X-rays. The NuSTAR imaging spectroscopy is consistent with isothermal emission of temperatures 3.1-4.4 MK and emission...

A density cusp of quiescent X-ray binaries in the central parsec of the Galaxy

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Hailey, Charles J.; Mori, Kaya; Bauer, Franz E.; Berkowitz, Michael E.; Hong, Jaesub; Hord, Benjamin J.

2018-04-01

The existence of a ‘density cusp’—a localized increase in number—of stellar-mass black holes near a supermassive black hole is a fundamental prediction of galactic stellar dynamics. The best place to detect such a cusp is in the Galactic Centre, where the nearest supermassive black hole, Sagittarius A*, resides. As many as 20,000 black holes are predicted to settle into the central parsec of the Galaxy as a result of dynamical friction; however, so far no density cusp of black holes has been detected. Low-mass X-ray binary systems that contain a stellar-mass black hole are natural tracers of isolated black holes. Here we report observations of a dozen quiescent X-ray binaries in a density cusp within one parsec of Sagittarius A*. The lower-energy emission spectra that we observed in these binaries is distinct from the higher-energy spectra associated with the population of accreting white dwarfs that dominates the central eight parsecs of the Galaxy. The properties of these X-ray binaries, in particular their spatial distribution and luminosity function, suggest the existence of hundreds of binary systems in the central parsec of the Galaxy and many more isolated black holes. We cannot rule out a contribution to the observed emission from a population (of up to about one-half the number of X-ray binaries) of rotationally powered, millisecond pulsars. The spatial distribution of the binary systems is a relic of their formation history, either in the stellar disk around Sagittarius A* (ref. 7) or through in-fall from globular clusters, and constrains the number density of sources in the modelling of gravitational waves from massive stellar remnants, such as neutron stars and black holes.

Nutrient acquisition strategies of mammalian cells.

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Palm, Wilhelm; Thompson, Craig B

2017-06-07

Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. We also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

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Kaoru Miyazaki

Full Text Available Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay.ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells.We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue reconstitution. Using this assay, we demonstrated that ESP

Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells

DEFF Research Database (Denmark)

Hald, Bjørn Olav; Hendriksen, Morten; Sørensen, Preben Graae

2013-01-01

Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredict...

The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit.

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Bouchard-Cannon, Pascale; Mendoza-Viveros, Lucia; Yuen, Andrew; Kærn, Mads; Cheng, Hai-Ying M

2013-11-27

The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells.

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Hashimoto, Takashi; He, Zhiwei; Ma, Wei-Ya; Schmid, Patricia C; Bode, Ann M; Yang, Chung S; Dong, Zigang

2004-05-01

Caffeine is a major biologically active constituent in coffee and tea. Because caffeine has been reported to inhibit carcinogenesis in UVB-exposed mice, the cancer-preventing effect of caffeine has attracted considerable attention. In the present study, the effect of caffeine in quiescent (G0 phase) cells was investigated. Pretreatment with caffeine suppressed cell proliferation in a dose-dependent manner 36 h after addition of fetal bovine serum as a cell growth stimulator. Analysis by flow cytometry showed that caffeine suppressed cell cycle progression at the G0/G1 phase, i.e., 18 h after addition of fetal bovine serum, the percentages of cells in G0/G1 phase in 1 mM caffeine-treated cells and in caffeine-untreated cells were 61.7 and 29.0, respectively. The percentage of cells in G0/G1 phase at 0 h was 75.5. Caffeine inhibited phosphorylation of retinoblastoma protein at Ser780 and Ser807/Ser811, the sites where retinoblastoma protein has been reported to be phosphorylated by cyclin-dependent kinase 4 (cdk4). Furthermore, caffeine inhibited the activation of the cyclin D1-cdk4 complex in a dose-dependent manner. However this compound did not directly inhibit the activity of this complex. In addition, caffeine did not affect p16INK4 or p27Kip1 protein levels, but inhibited the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3beta. Our results showed that caffeine suppressed the progression of quiescent cells into the cell cycle. The inhibitory mechanism may be due to the inhibition of cell growth signal-induced activation of cdk4, which may be involved in the inhibition of carcinogenesis in vivo.

Concise Review: Quiescence in Adult Stem Cells

DEFF Research Database (Denmark)

Rumman, M; Dhawan, J; Kassem, Moustapha

2015-01-01

Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve...... stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim...

Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

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Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

2004-01-01

In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

Self-synchronization of populations of nonlinear oscillators in the thermodynamic limit

International Nuclear Information System (INIS)

Bonilla, L.L.; Casado, J.M.; Morillo, M.

1987-01-01

A population of identical nonlinear oscillators, subject to random forces and coupled via a mean-field interaction, is studied in the thermodynamic limit. The model presents a nonequilibrium phase transition from a stationary to a time-periodic probability density. Below the transition line, the population of oscillators is in a quiescent state with order parameter equal to zero. Above the transition line, there is a state of collective rhythmicity characterized by a time-periodic behavior of the order parameter and all moments of the probability distribution. The information entropy of the ensemble is a constant both below and above the critical line. Analytical and numerical analyses of the model are provided

Constraining the Dense Matter Equation of State with ATHENA-WFI observations of Neutron Stars in Quiescent LMXBs

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Guillot, Sebastien; Oezel, F.

2015-09-01

The study of neutron star quiescent low-mass X-ray binaries (qLMXBs) will address one of the main science goals of the Athena x-ray observatory. The study of the soft X-ray thermal emission from the neutron star surface in qLMXBs is a crucial tool to place constrains on the dense matter equation of state. I will briefly review this method, its strength and current weaknesses and limitations, as well as the current constraints on the equation of state from qLMXBs. The superior sensitivity of Athena will permit the acquisition of unprecedentedly high signal-to-noise spectra from these sources. It has been demonstrated that a single qLMXB, even with high S/N, will not place useful constraints on the EoS. However, a combination of qLMXBs spectra has shown promises of obtaining tight constraints on the equation of state. I will discuss the expected prospects for observations of qLMXBs inside globular clusters -- those that Athena will be able to resolve. I will also present the constraints on the equation of state that Athena will be able to obtain from these qLMXBs and from a population of qLMXBs in the field of the Galaxy, with distance measurements provided by Gaia.

Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

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Siebler Mario

2009-08-01

Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

TCR tuning of T cell subsets.

Science.gov (United States)

Cho, Jae-Ho; Sprent, Jonathan

2018-05-01

After selection in the thymus, the post-thymic T cell compartments comprise heterogenous subsets of naive and memory T cells that make continuous T cell receptor (TCR) contact with self-ligands bound to major histocompatibility complex (MHC) molecules. T cell recognition of self-MHC ligands elicits covert TCR signaling and is particularly important for controlling survival of naive T cells. Such tonic TCR signaling is tightly controlled and maintains the cells in a quiescent state to avoid autoimmunity. Here, we review how naive and memory T cells are differentially tuned and wired for TCR sensitivity to self and foreign ligands. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Establishment of reference CD4+ T cell values for adult Indian population

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Ray Krishnangshu

2011-10-01

Full Text Available Abstract Background CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. Methods A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre healthy participants were enrolled in the study. The ratio of male (N = 645 to female (N = 561 of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS, version 15 and Prism software version 5. Results The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population. Conclusion The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

OpenAIRE

Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch...

Cellular population dynamics control the robustness of the stem cell niche

Directory of Open Access Journals (Sweden)

Adam L. MacLean

2015-11-01

Full Text Available Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain ‘stemness’ through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell–niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell–cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche – and hence of the stem cell pool in the niche – depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.

Insulin resistance in vascular endothelial cells promotes intestinal tumour formation

DEFF Research Database (Denmark)

Wang, X; Häring, M-F; Rathjen, Thomas

2017-01-01

in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte...... adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules...

Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail: mishima-k@dent.showa-u.ac.jp

2013-05-01

Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K.

2013-01-01

Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities

The link between negative affect, vagal tone, and visceral sensitivity in quiescent Crohn's disease.

Science.gov (United States)

Rubio, A; Pellissier, S; Picot, A; Dantzer, C; Bonaz, B

2014-08-01

Autonomic dysfunction and mood disorders are frequently described in Crohn's disease (CD) and are known to influence visceral sensitivity. We addressed the link between vagal tone, negative affect, and visceral sensitivity in CD patients without concomitant features of irritable bowel syndrome (IBS). Rectal distensions to a discomfort threshold of 70% and onset of pain were performed in nine CD patients in remission and eight healthy controls. Autonomic parameters were evaluated with heart rate variability and electrodermal reactivity. We showed that CD patients had (i) higher scores of depressive symptomatology (12 ± 3 in patients vs 4 ± 1 in controls on the Center for Epidemiologic Studies-Depression Scale; p = 0.038), (ii) reduced vagal tone (HF 257 ± 84 ms(2) vs 1607 ± 1032 ms(2) , p = 0.043; LF 455 ± 153 ms(2) vs 1629 ± 585 ms(2) , p = 0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and (iv) higher tolerance to rectal distension pressures (43 ± 3 mmHg vs 30 ± 2 mmHg, p = 0.002) and low sensitivity index scores. In conclusion, our results provide preliminary evidence that patients with quiescent CD, in the absence of IBS, are hyposensate to experimental rectal distension. These data provide further evidence that anxiety and depressive symptomatology in addition to autonomic dysfunction modulate visceral pain perception in quiescent CD patients in the absence of IBS. © 2014 John Wiley & Sons Ltd.

CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

DEFF Research Database (Denmark)

Harkness, Linda; Zaher, Walid; Ditzel, Nicholas

2016-01-01

BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous hMSC...... population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high...... and adipocytes on the basis of gene expression and protein production of lineage-specific markers. In vivo, hMSC-CD146(+) and hMSC-CD146(-) cells formed bone and bone marrow organ when implanted subcutaneously in immune-deficient mice. Bone was enriched in hMSC-CD146(-) cells (12.6 % versus 8.1 %) and bone...

HOX and TALE signatures specify human stromal stem cell populations from different sources.

Science.gov (United States)

Picchi, Jacopo; Trombi, Luisa; Spugnesi, Laura; Barachini, Serena; Maroni, Giorgia; Brodano, Giovanni Barbanti; Boriani, Stefano; Valtieri, Mauro; Petrini, Mario; Magli, Maria Cristina

2013-04-01

Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues. Copyright © 2012 Wiley Periodicals, Inc.

Disappearance of statin following serum-stimulated cell cycle entry

International Nuclear Information System (INIS)

Wang, E.; Lin, S.L.

1986-01-01

Statin, a protein of 57,000 D, is present in the nuclei of quiescent of senescent fibroblasts, but is absent in their young replicating counterparts. Immunohistochemical survey of a variety of tissues demonstrates that the presence of statin is a marker for cells that are no longer involved in proliferation, i.e. those cells that are terminally differentiated. Statin expression was examined by immunofluorescence microscopy in serum-starved cultures whose replication had been reinitiated by raising the serum concentration from 0.5 to 10%. Prior to serum addition, more than 85% of the cells stained positively for statin. After stimulation with serum, the expression of statin disappeared rapidly within the first 12-14 h. On the other hand, and increase in the level of DNA synthesis, signifying entry into S phase, was observed initially at 18 h after serum stimulation, and reached maximal levels 6h later. Immunoprecipitation of statin derived from cells harvested at different intervals after serum stimulation revealed that the level of statin synthesis was reduced by 4 h and was hardly detectable at 8 h. These results demonstrate that (1) the synthesis of statin occurs primarily when cells are in a quiescent state, and declines rapidly when cells are induced to proliferate; (2) this decline precedes the transition from G1 to S phase

Multiband Observations of the Quasar PKS 2326–502 during Active and Quiescent Gamma-Ray States in 2010–2012

Energy Technology Data Exchange (ETDEWEB)

Dutka, Michael S. [The Catholic University of America, 620 Michigan Avenue, NE, Washington, DC 20064 (United States); Carpenter, Bryce D.; Gehrels, Neil [NASA Goddard Space Flight Center, Astrophysics Science Division, Code 661, Greenbelt, MD 20771 (United States); Ojha, Roopesh [UMBC/NASA Goddard Space Flight Center, Astrophysics Science Division, Code 661, Greenbelt, MD 20771 (United States); Finke, Justin D. [Naval Research Laboratory, Space Science Division, Code 7653, 4555 Overlook Avenue, SW, Washington, DC 20375 (United States); D’Ammando, Filippo [Università di Bologna Dipartimento di Fisica e Astronomia, INAF-IRA, Bologna (Italy); Kadler, Matthias [Lehrstuhl für Astronomie, Universität Würzburg, Emil -Fischer-Straße 31, D-97074 Würzburg (Germany); Edwards, Philip G. [CSIRO Astronomy and Space Science, P.O. Box 76, Epping NSW 1710 (Australia); Stevens, Jamie [CSIRO Astronomy and Space Science, 1828 Yarrie Lake Road, Narrabri NSW 2390 (Australia); Torresi, Eleonora; Grandi, Paola [Istituto Nazionale di Astrofisica, (National Institute of Astrophysics) INAF-IASFBO, via Gobetti 101, I-40129 Bologna (Italy); Nesci, Roberto [Istituto Nazionale di Astrofisica, (National Institute of Astrophysics) INAF-IAPS, via Fosso del Cavaliere 100, I-00133 Roma (Italy); Krauß, Felicia [GRAPPA and Anton Pannekoek Institute for Astronomy, University of Amsterdam, Science Park 904, 1098 XH Amsterdam (Netherlands); Müller, Cornelia [Department of Astrophysics/IMAPP, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen (Netherlands); Wilms, Joern, E-mail: ditko86@gmail.com, E-mail: carpbr01@gmail.com [Remeis Observatory and ECAP, Sternwartstr. 7, D-96049 Bamberg (Germany)

2017-02-01

Quasi-simultaneous observations of the Flat Spectrum Radio Quasar PKS 2326−502 were carried out in the γ -ray, X-ray, UV, optical, near-infrared, and radio bands. Using these observations, we are able to characterize the spectral energy distribution (SED) of the source during two flaring and one quiescent γ -ray states. These data were used to constrain one-zone leptonic models of the SEDs of each flare and investigate the physical conditions giving rise to them. While modeling one flare required only changes in the electron spectrum compared to the quiescent state, modeling the other flare required changes in both the electron spectrum and the size of the emitting region. These results are consistent with an emerging pattern of two broad classes of flaring states seen in blazars. Type 1 flares are explained by changes solely in the electron distribution, whereas type 2 flares require a change in an additional parameter. This suggests that different flares, even in the same source, may result from different physical conditions or different regions in the jet.

Cell growth state determines susceptibility of repair DNA synthesis to inhibition by hydroxyurea and 1-beta-D-arabinofuranosylcytosine

International Nuclear Information System (INIS)

Mullinger, A.M.; Collins, A.R.; Johnson, R.T.

1983-01-01

The effects of inhibitors of replicative DNA synthesis on repair DNA synthesis have been examined by autoradiography in several different cell types and in cells in different growth states. Hydroxyurea (HU) and 1-beta-D-arabinofuranosylcytosine (ara C), administered together, influence unscheduled DNA synthesis (UDS) in a manner which is independent of the status of the cell culture (normal or transformed) and of the species, but which is strongly affected by whether the cells are proliferating or quiescent. In proliferating human, Chinese hamster and Microtus cell cultures, UDS is not inhibited by HU and ara C, and may even appear to be stimulated. In quiescent cultures of these cells UDS is reduced by HU and ara C. In cells reseeded from a confluent culture and followed during proliferation and back to quiescence the effect of inhibitors parallels the growth pattern. The results are interpreted in terms of changes in the sizes of endogenous DNA precursor pools; they underline the potential problems associated with quantitating UDS in the presence of inhibitors

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

International Nuclear Information System (INIS)

Duverger, James Elber; Boudreau-Béland, Jonathan; Le, Minh Duc; Comtois, Philippe

2014-01-01

Self-organization of pacemaker (PM) activity of interconnected elements is important to the general theory of reaction–diffusion systems as well as for applications such as PM activity in cardiac tissue to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes (NRVMs) are often used as experimental models in studies on cardiac electrophysiology. These monolayers exhibit automaticity (spontaneous activation) of their electrical activity. At low plated density, cells usually show a heterogeneous population consisting of PM and quiescent excitable cells (QECs). It is therefore highly probable that monolayers of NRVMs consist of a heterogeneous network of the two cell types. However, the effects of density and spatial distribution of the PM cells on spontaneous activity of monolayers remain unknown. Thus, a simple stochastic pattern formation algorithm was implemented to distribute PM and QECs in a binary-like 2D network. A FitzHugh–Nagumo excitable medium was used to simulate electrical spontaneous and propagating activity. Simulations showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of PM cells. In most simulations, the first initiation sites were found to be located near the substrate boundaries. Comparison with experimental data obtained from cardiomyocyte monolayers shows important similarities in the position of initiation site activity. However, limitations in the model that do not reflect the complex beat-to-beat variation found in experiments indicate the need for a more realistic cardiomyocyte representation. (paper)

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

Science.gov (United States)

Elber Duverger, James; Boudreau-Béland, Jonathan; Le, Minh Duc; Comtois, Philippe

2014-11-01

Self-organization of pacemaker (PM) activity of interconnected elements is important to the general theory of reaction-diffusion systems as well as for applications such as PM activity in cardiac tissue to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes (NRVMs) are often used as experimental models in studies on cardiac electrophysiology. These monolayers exhibit automaticity (spontaneous activation) of their electrical activity. At low plated density, cells usually show a heterogeneous population consisting of PM and quiescent excitable cells (QECs). It is therefore highly probable that monolayers of NRVMs consist of a heterogeneous network of the two cell types. However, the effects of density and spatial distribution of the PM cells on spontaneous activity of monolayers remain unknown. Thus, a simple stochastic pattern formation algorithm was implemented to distribute PM and QECs in a binary-like 2D network. A FitzHugh-Nagumo excitable medium was used to simulate electrical spontaneous and propagating activity. Simulations showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of PM cells. In most simulations, the first initiation sites were found to be located near the substrate boundaries. Comparison with experimental data obtained from cardiomyocyte monolayers shows important similarities in the position of initiation site activity. However, limitations in the model that do not reflect the complex beat-to-beat variation found in experiments indicate the need for a more realistic cardiomyocyte representation.

On interfaces between cell populations with different mobilities

KAUST Repository

Lorenzi, Tommaso; Lorz, Alexander; Perthame, Benoit

2016-01-01

Partial differential equations describing the dynamics of cell population densities from a fluid mechanical perspective can model the growth of avascular tumours. In this framework, we consider a system of equations that describes the interaction

A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates.

Science.gov (United States)

Radtke, Stefan; Adair, Jennifer E; Giese, Morgan A; Chan, Yan-Yi; Norgaard, Zachary K; Enstrom, Mark; Haworth, Kevin G; Schefter, Lauren E; Kiem, Hans-Peter

2017-11-01

Hematopoietic reconstitution after bone marrow transplantation is thought to be driven by committed multipotent progenitor cells followed by long-term engrafting hematopoietic stem cells (HSCs). We observed a population of early-engrafting cells displaying HSC-like behavior, which persisted long-term in vivo in an autologous myeloablative transplant model in nonhuman primates. To identify this population, we characterized the phenotype and function of defined nonhuman primate hematopoietic stem and progenitor cell (HSPC) subsets and compared these to human HSPCs. We demonstrated that the CD34 + CD45RA - CD90 + cell phenotype is highly enriched for HSCs. This population fully supported rapid short-term recovery and robust multilineage hematopoiesis in the nonhuman primate transplant model and quantitatively predicted transplant success and time to neutrophil and platelet recovery. Application of this cell population has potential in the setting of HSC transplantation and gene therapy/editing approaches. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Novel microchip-based tools facilitating live cell imaging and assessment of functional heterogeneity within NK cell populations

Directory of Open Access Journals (Sweden)

Elin eForslund

2012-10-01

Full Text Available Each individual has a heterogeneous pool of NK cells consisting of cells that may be specialized towards specific functional responses such as secretion of cytokines or killing of tumor cells. Many conventional methods are not fit to characterize heterogeneous populations as they measure the average response of all cells. Thus, there is a need for experimental platforms that provide single cell resolution. In addition, there are also transient and stochastic variations in functional responses at the single cell level, calling for methods that allow studies of many events over extended times. This paper presents a versatile microchip platform enabling long-term microscopic studies of individual NK cells interacting with target cells. Each microchip contains an array of microwells, optimized for medium or high-resolution time-lapse imaging of single or multiple NK and target cells, or for screening of thousands of isolated NK-target cell interactions. Individual NK cells confined with target cells in small microwells is a suitable setup for high-content screening and rapid assessment of heterogeneity within populations, while microwells of larger dimensions are appropriate for studies of NK cell migration and sequential interactions with multiple target cells. By combining the chip technology with ultrasonic manipulation, NK and target cells can be forced to interact and positioned with high spatial accuracy within individual microwells. This setup effectively and synchronously creates NK-target conjugates at hundreds of parallel positions in the microchip. Thus, this facilitates assessment of temporal aspects of NK-target cell interactions, e.g. conjugation, immune synapse formation and cytotoxic events. The microchip platform presented here can be used to effectively address questions related to fundamental functions of NK cells that can lead to better understanding of how the behavior of individual cells add up to give a functional response at

Reduced satellite cell population may lead to contractures in children with cerebral palsy.

Science.gov (United States)

Smith, Lucas R; Chambers, Henry G; Lieber, Richard L

2013-03-01

Satellite cells are the stem cells residing in muscle responsible for skeletal muscle growth and repair. Skeletal muscle in cerebral palsy (CP) has impaired longitudinal growth that results in muscle contractures. We hypothesized that the satellite cell population would be reduced in contractured muscle. We compared the satellite cell populations in hamstring muscles from participants with CP contracture (n=8; six males, two females; age range 6-15y; Gross Motor Function Classification System [GMFCS] levels II-V; 4 with hemiplegia, 4 with diplegia) and from typically developing participants (n=8; six males, two females, age range 15-18y). Muscle biopsies were extracted from the gracilis and semitendinosus muscles and mononuclear cells were isolated. Cell surface markers were stained with fluorescently conjugated antibodies to label satellite cells (neural cell adhesion molecule) and inflammatory and endothelial cells (CD34 and CD4 respectively). Cells were analyzed using flow cytometry to determine cell populations. After gating for intact cells a mean of 12.8% (SD 2.8%) were determined to be satellite cells in typically developing children, but only 5.3% (SD 2.3%; p0.05) suggesting the isolation procedure was valid. A reduced satellite cell population may account for the decreased longitudinal growth of muscles in CP that develop into fixed contractures or the decreased ability to strengthen muscle in CP. This suggests a unique musculoskeletal disease mechanism and provides a potential therapeutic target for debilitating muscle contractures. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Preferential Ty1 retromobility in mother cells and nonquiescent stationary phase cells is associated with increased concentrations of total Gag or processed Gag and is inhibited by exposure to a high concentration of calcium.

Science.gov (United States)

Peifer, Andrew C; Maxwell, Patrick H

2018-03-21

Retrotransposons are abundant mobile DNA elements in eukaryotic genomes that are more active with age in diverse species. Details of the regulation and consequences of retrotransposon activity during aging remain to be determined. Ty1 retromobility in Saccharomyces cerevisiae is more frequent in mother cells compared to daughter cells, and we found that Ty1 was more mobile in nonquiescent compared to quiescent subpopulations of stationary phase cells. This retromobility asymmetry was absent in mutant strains lacking BRP1 that have reduced expression of the essential Pma1p plasma membrane proton pump, lacking the mRNA decay gene LSM1 , and in cells exposed to a high concentration of calcium. Mother cells had higher levels of Ty1 Gag protein than daughters. The proportion of protease-processed Gag decreased as cells transitioned to stationary phase, processed Gag was the dominant form in nonquiescent cells, but was virtually absent from quiescent cells. Treatment with calcium reduced total Gag levels and the proportion of processed Gag, particularly in mother cells. We also found that Ty1 reduced the fitness of proliferating but not stationary phase cells. These findings may be relevant to understanding regulation and consequences of retrotransposons during aging in other organisms, due to conserved impacts and regulation of retrotransposons.

FREQUENCY OF QUIESCENT FUNGI AND POST-HARVEST ALTERNATIVE MANAGEMENT OF STEM END ROT IN PAPAYA

Directory of Open Access Journals (Sweden)

DANIELA DAMBROS AMARAL

2017-01-01

Full Text Available The aim of this study was to evaluate the frequency of quiescent fungi and the effect of phosphites under modified atmosphere on Lasiodiplodia theobromae in papaya. The fruits were treated with a range of doses of phosphites and their actions evaluated under conditions of ambient and modified atmosphere. Of the eight fungal genera found, Lasiodiplodia was the most common. No interaction was observed between the evaluated factors and only atmosphere and dose were independently significant. The usage of phosphites and modified atmosphere reduced the severity of the disease, and did not affect the chemical properties of the fruits.

Taxonomic separation of hippocampal networks: principal cell populations and adult neurogenesis

Directory of Open Access Journals (Sweden)

Roelof Maarten evan Dijk

2016-03-01

Full Text Available While many differences in hippocampal anatomy have been described between species, it is typically not clear if they are specific to a particular species and related to functional requirements or if they are shared by species of larger taxonomic units. Without such information, it is difficult to infer how anatomical differences may impact on hippocampal function, because multiple taxonomic levels need to be considered to associate behavioral and anatomical changes. To provide information on anatomical changes within and across taxonomic ranks, we present a quantitative assessment of hippocampal principal cell populations in 20 species or strain groups, with emphasis on rodents, the taxonomic group that provides most animals used in laboratory research. Of special interest is the importance of adult hippocampal neurogenesis in species-specific adaptations relative to other cell populations. Correspondence analysis of cell numbers shows that across taxonomic units, phylogenetically related species cluster together, sharing similar proportions of principal cell populations. CA3 and hilus are strong separators that place rodent species into a tight cluster based on their relatively large CA3 and small hilus while non-rodent species (including humans and non-human primates are placed on the opposite side of the spectrum. Hilus and CA3 are also separators within rodents, with a very large CA3 and rather small hilar cell populations separating mole-rats from other rodents that, in turn, are separated from each other by smaller changes in the proportions of CA1 and granule cells. When adult neurogenesis is included, the relatively small populations of young neurons, proliferating cells and hilar neurons become main drivers of taxonomic separation within rodents. The observations provide challenges to the computational modeling of hippocampal function, suggest differences in the organization of hippocampal information streams in rodent and non

Density and temperature profile modifications with electron cyclotron power injection in quiescent double barrier discharges on DIII-D

International Nuclear Information System (INIS)

Casper, T A; Burrell, K H; Doyle, E J; Gohil, P; Lasnier, C J; Leonard, A W; Moller, J M; Osborne, T H; Snyder, P B; Thomas, D M; Weiland, J; West, W P

2006-01-01

Quiescent double barrier (QDB) conditions often form when an internal transport barrier is created with high-power neutral-beam injection into a quiescent H-mode (QH) plasma. These QH-modes offer an attractive, high-performance operating scenario for burning plasma experiments due to their quasi-stationarity and lack of edge localized modes. Our initial experiments and modelling using ECH/ECCD in QDB shots were designed to control the current profile and, indeed, we have observed a strong dependence on the q-profile when EC-power is used inside the core transport barrier region. While strong electron heating is observed with EC power injection, we also observe a drop in the other core parameters, namely ion temperature and rotation, electron density and impurity concentration. At onset and termination of the EC pulse, dynamically changing conditions are induced that provide a rapid evolution of T e /T i profiles accessible with 0.3 e /T i ) axis e /T i ratio as the ion temperature and density profiles flatten with this change in transport. The change in transport is consistent with a destabilization of ITG turbulence as inferred from the reduction of the stability threshold due to the change in T e /T i

Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Dai, Jiawen [Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research (Singapore); Itahana, Koji, E-mail: koji.itahana@duke-nus.edu.sg [Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School (Singapore); Baskar, Rajamanickam, E-mail: r.baskar@nccs.com.sg [Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research (Singapore); Department of Radiation Oncology, National Cancer Centre (Singapore)

2015-02-27

Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G{sub 1}/S or G{sub 2}/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G{sub 0}, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10–1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. - Highlights: • p53 response by irradiation was similar between proliferating and quiescent cells. • Quiescent cells showed similar profiles of cell cycle proteins after irradiation. • Radioprotection of GSK-3β inhibitor caused similar effects between these cells. • Quiescence did not affect p53 response despite its

Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts

International Nuclear Information System (INIS)

Dai, Jiawen; Itahana, Koji; Baskar, Rajamanickam

2015-01-01

Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G 1 /S or G 2 /M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G 0 , therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10–1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. - Highlights: • p53 response by irradiation was similar between proliferating and quiescent cells. • Quiescent cells showed similar profiles of cell cycle proteins after irradiation. • Radioprotection of GSK-3β inhibitor caused similar effects between these cells. • Quiescence did not affect p53 response despite its known role in

Comparisons of Force Measurement Methods for DBD Plasma Actuators in Quiescent Air

Science.gov (United States)

Hoskinson, Alan R.; Hershkowitz, Noah; Ashpis, David E.

2009-01-01

We have performed measurements of the force induced by both single (one electrode insulated) and double (both electrodes insulated) dielectric barrier discharge plasma actuators in quiescent air. We have shown that, for single barrier actuators with cylindrical exposed electrodes, as the electrode diameter decrease the force efficiencies increase much faster than a previously reported linear trend. This behavior has been experimentally verified using two different measurement techniques: stagnation probe measurements of the induced flow velocity and direct measurement of the force using an electronic balance. Actuators with rectangular cross-section exposed electrodes do not show the same rapid increase at small thicknesses. We have also shown that the induced force is independent of the material used for the exposed electrode. The same techniques have shown that the induced force of a double barrier actuator increases with decreasing narrow electrode diameter.

Mechanism of derivation of radioresistance in HeLa cell population after repeated x-irradiation

International Nuclear Information System (INIS)

Kubo, Kihei; Koiwai, Soichiro; Morita, Kazuo

1982-01-01

The Radioresistant strain (X-8-5) was obtained from HeLa-SC population X-irradiated repeatedly for five times with 800 rad. The mean lethal dose (D 0 ) was 196 rad for X-8-5 cells, while it was 166 rad for control HeLa-SC cells. The fraction of cells containing an unusually long acrocentric chromosome (LA 2) exclusively increased with increasing number of irradiation of HeLa-SC population. A clonal strain with LA 2 marker was isolated from X-8-5 population and named RC-355. Since the RC-355 cells were more resistant (D 0 = 220 rad)than parental X-8-5 cells (D 0 = 196 rad), it was suggested that the cells with LA 2 were responsible for the radioresistance of X-8-5 population. The RC-355 cells were further subjected to the analysis of Q-banded karyotypes and it was observed that 18 types of specific markers (rm 1-17 and LA 2) were included in RC-355 cells in addition to 12 types of markers observed in most of HeLa-SC cells. Since the analysis of Q-banded karyotypes of RC-355 cells showed that RC-355 specific markers were not produced by radiation-induced rearrangements of HeLa-SC chromosomes, because twelve kinds of HeLa-SC markers were presented in RC-355 cells without any change, it was concluded that a small number of cells with LA 2 marker were originally presented in the control population and the relative fraction of them occupied increased after irradiation. (author)

Heterogenous populations of cytotoxic cells in the peritoneal cavity of BALB/c mice immunized with allogeneic EL4 leukemia cells

International Nuclear Information System (INIS)

Zighelboim, J.; Bonavida, B.; Fahey, J.L.

1974-01-01

Adherent cells, presumably macrophages, obtained from the peritoneal cavity shortly after rejection of the allogeneic leukemia EL4, produced effective cell-mediated cytotoxicity (CMC) in vitro. These cytotoxic cells were sensitive to anti-macrophage serum and resistant to anti-thymocyte serum and 10,000 roentgen irradiation. In contrast, a second population of specifically cytotoxic cells were nonadherent, sensitive to x-rays and anti-thymocyte serum, but not to anti-macrophage serum. The two cell populations had a cooperative cytotoxic effect in vitro against allogeneic tumor cells

Recovery of the Erythropoietin-Sensitive Stem-Cell Population following Total-Body X-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Byron, J. W. [Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (United Kingdom)

1968-08-15

Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. This effect may be used in polycythaemic mice to estimate changes in the erythropoietin-sensitive stem-cell population following total-body irradiation (TBR). Generally, single doses of erythropoietin, less than that needed for maximum stem-cell response, are used to estimate changes in the stem-cell population. The validity of results using this test is based upon accepting several assumptions regarding erythropoietin kinetics. These are: (a) the contribution of endogenous erythropoietin is always negligible; (b) the origin of the dose-response curve to erythropoietin alters only because of changes in stem-cell numbers; (c) the proportion of stem cells responding to a given concentration of erythropoietin is independent of stem-cell numbers; (d) the slope of the dose-response curve does not alter; and (e) competition between erythropoietin and other factors for the stem cells remains unchanged. The studies to be reported indicate that some of these assumptions m a y not always be valid. Following 150 rad TBR, changes in erythropoietin dose-response curves were not always due to changes in the size of the stem-cell population, but also due to changes in erythropoietin kinetics. Changes in erythropoietin kinetics could be corrected for by using doses of erythropoietin which at any particular time after TBR gave maximum stem-cell response; through full dose-response studies, the nature of changes in erythropoietin kinetics following TBR could be established. These studies appear to explain discrepancies in results obtained in different laboratories using the erythropoietin test. The effect of 150 rad TBR on the erythropoietin-sensitive stem-cell population is an initial depression within 30 min to 20% of normal followed by a second depression (post-irradiation dip) at about 12 h. Twenty-four hours after TBR there is a recovery to the initial depression. This

Bet-hedging in bacteriocin producing Escherichia coli populations: the single cell perspective

Science.gov (United States)

Bayramoglu, Bihter; Toubiana, David; van Vliet, Simon; Inglis, R. Fredrik; Shnerb, Nadav; Gillor, Osnat

2017-02-01

Production of public goods in biological systems is often a collaborative effort that may be detrimental to the producers. It is therefore sustainable only if a small fraction of the population shoulders the cost while the majority reap the benefits. We modelled this scenario using Escherichia coli populations producing colicins, an antibiotic that kills producer cells’ close relatives. Colicin expression is a costly trait, and it has been proposed that only a small fraction of the population actively expresses the antibiotic. Colicinogenic populations were followed at the single-cell level using time-lapse microscopy, and showed two distinct, albeit dynamic, subpopulations: the majority silenced colicin expression, while a small fraction of elongated, slow-growing cells formed colicin-expressing hotspots, placing a significant burden on expressers. Moreover, monitoring lineages of individual colicinogenic cells showed stochastic switching between expressers and non-expressers. Hence, colicin expressers may be engaged in risk-reducing strategies—or bet-hedging—as they balance the cost of colicin production with the need to repel competitors. To test the bet-hedging strategy in colicin-mediated interactions, competitions between colicin-sensitive and producer cells were simulated using a numerical model, demonstrating a finely balanced expression range that is essential to sustaining the colicinogenic population.

The diet, physical activity and accommodation of patients with quiescent pulmonary tuberculosis in a poor South Indian community. A four-year follow-up study.

Science.gov (United States)

Ramakrishnan, C V; Rajendran, K; Mohan, K; Fox, W; Radhakrishna, S

1966-01-01

A previous report from the Tuberculosis Chemotherapy Centre, Madras, has shown that, if standard chemotherapy is given for one year, the response of patients treated at home in very poor environmental circumstances is nearly as good as that of those treated in sanatorium under much more favourable conditions. This paper reports on a four-year follow-up of all the patients whose disease was bacteriologically quiescent at the end of the year's treatment. During this period, all the patients were managed on a domiciliary basis; about a quarter of them received chemotherapy with isoniazid alone for two years, another quarter received the drug for one year and the rest received no specific chemotherapy. Despite adverse environmental factors (poor diet; long hours of work often involving strenuous physical activity; overcrowded living conditions; and, for the sanatorium patients, the stresses of returning suddenly to the unfavourable home environment), the great majority of patients in both series maintained quiescent disease throughout the follow-up period. Furthermore, the few patients whose disease relapsed bacteriologically were at no special dietary disadvantage in comparison with those who maintained quiescent disease throughout, nor did they show any appreciable differences in occupation, physical activity or living accommodation. These findings, together with the earlier ones, indicate that, despite adverse environmental circumstances, standard chemotherapy for an adequate period of time is sufficient in the great majority of patients for the attainment of bacteriological quiescence and its maintenance thereafter.

Destruction of radiation-resistant cell populations by hyperthermia

International Nuclear Information System (INIS)

Roettinger, E.M.; Gerweck, L.E.

1979-01-01

Animal experiments with local hyperthermia have shown that the radiauion dose necessary for the local control of 50% of the tumours examined was essentially reduced by heating to 42,5 0 C. In-vitro experients indicated selective destruction of relatively radiation-resistent cell populations by the combination of hyperthermie and reduced hydrogen ion concentration. Experiments with glioblastoma cells confirmed these results qualitatively, but showed quantitatively considerably lower sensitivity towards hyperthermia. (orig.) 891 MG/orig. 892 RDG [de

Multiwavelength study of quiescent states of MRK 421 with unprecedented hard x-ray coverage provided by NuSTAR in 2013

DEFF Research Database (Denmark)

Baloković, M.; Paneque, D.; Madejski, G.

2016-01-01

V. For the first time, we observed both the synchrotron and the inverse-Compton peaks of the spectral energy distribution (SED) simultaneously shifted to frequencies below the typical quiescent state by an order of magnitude. The fractional variability as a function of photon energy shows a double-bump structure...

An experimental and numerical study of diffusion flames in cross-flow and quiescent environment at smoke point condition

Science.gov (United States)

Goh, Sien Fong

An experimental and numerical study of a turbulent smoke point diffusion flame in a quiescent and cross-flow condition was performed. The fuel mass flow rate of a turbulent smoke point flame was determined at a quiescent condition and in cross-flow with velocity ranging from 2 to 4 m/s. This fuel mass flow rate is defined as the Critical Fuel Mass Flow Rate (CFMFR). At a fuel mass flow rate below the CFMFR the flame produces smoke. In the dilution study, an amount of inert gas (nitrogen) was added to the fuel stream to achieve the smoke point condition for ten different fractions of CFMFR. From this dilution study, three regions were defined, the chemically-dominated region, transition region, and momentum-dominated region. The first objective of this study was to determine the factors behind the distinction of these three regions. The second objective was to understand the effect of cross-flow velocity on the smoke point flame structure. The flame temperature, radiation, geometrical dimension of flame, velocity, and global emissions and in-flame species concentration were measured. The third objective was to study a numerical model that can simulate the turbulent smoke point flame structure. The dilution study showed that the flames in quiescent condition and in the 3.5 and 4 m/s cross-flow condition had the chemically-dominated region at 5% to 20% CFMFR, the transition region at 20% to 40% CFMFR, and the momentum-dominated region at 40% to 100% CFMFR. On the other hand, the flame in cross-flow of 2 to 3 m/s showed the chemically-dominated region at 5% to 10% CFMFR, the transition region at 10% to 30% CFMFR, and the momentum-dominated region at 30% to 100% CFMFR. The chemically-dominated flame had a sharp dual-peak structure for the flame temperature, CO2 and NO concentration profiles at 25% and 50% flame length. However, the momentum-dominated region flame exhibited a dual peak structure only at 25% flame length. The decrease of flow rate from 30% to 10% CFMFR

High-frequency coherent edge fluctuations in a high-pedestal-pressure quiescent H-mode plasma.

Science.gov (United States)

Yan, Z; McKee, G R; Groebner, R J; Snyder, P B; Osborne, T H; Burrell, K H

2011-07-29

A set of high frequency coherent (HFC) modes (f=80-250 kHz) is observed with beam emission spectroscopy measurements of density fluctuations in the pedestal of a strongly shaped quiescent H-mode plasma on DIII-D, with characteristics predicted for kinetic ballooning modes (KBM): propagation in the ion-diamagnetic drift direction; a frequency near 0.2-0.3 times the ion-diamagnetic frequency; inferred toroidal mode numbers of n∼10-25; poloidal wave numbers of k(θ)∼0.17-0.4 cm(-1); and high measured decorrelation rates (τ(c)(-1)∼ω(s)∼0.5×10(6) s(-1)). Their appearance correlates with saturation of the pedestal pressure. © 2011 American Physical Society

A preliminary study measuring the number of T-cell receptor-rearrangement excision circles (TRECs) in peripheral blood T-cell populations of A-bomb survivors and control populations

International Nuclear Information System (INIS)

Kubo, Yoshiko; Yamaoka, Mika; Kusunoki, Yoichiro

2006-01-01

More than a half century after damage of the immune systems by the radiation from A-bomb, we can still observe significant decreases in the percentages of naieve CD4 and CD8 T cells among the survivors. To investigate whether the observed decreases in the naieve T-cell populations may have resulted from reduction in thymic T-cell production ability of survivors, we established a real-time polymerase chain reaction (PCR) method to examine the number of T-cell receptor-rearrangement excision circles (TRECs) in peripheral blood CD4 and CD8 T-cell populations. The real-time PCR quantitatively detected TREC sequences with a good reproducibility in human laboratory controls. In the 445 survivors so far been examined, multiple regression analysis indicated that the number of TRECs in the CD4 T-cell fraction was significantly higher in females than in males and decreased significantly with age in both males and females. This analysis also suggested a possible dose-dependent decrease in the number of TRECs in the CD4 T-cell fraction of the survivors who were less than 20 years of age at the time of bombing (p=0.09). A similar statistically significant trend for gender difference or age was observed in the CD8 T-cell fraction of the survivors. However, there was no effect of radiation exposure on the number of TRECs in the CD8-T cell fraction. The results indicate the possibility that A-bomb radiation exposure may have induced a long-term impairment in thymic CD4 T-cell production. Further investigations in a larger study population are necessary to test this hypothesis. (author)

Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations.

Science.gov (United States)

Cosette, Jérémie; Moussy, Alice; Onodi, Fanny; Auffret-Cariou, Adrien; Neildez-Nguyen, Thi My Anh; Paldi, Andras; Stockholm, Daniel

2015-12-09

Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the Treg fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population.

Microelectromechanical System-Based Sensing Arrays for Comparative in Vitro Nanotoxicity Assessment at Single Cell and Small Cell-Population Using Electrochemical Impedance Spectroscopy.

Science.gov (United States)

Shah, Pratikkumar; Zhu, Xuena; Zhang, Xueji; He, Jin; Li, Chen-zhong

2016-03-09

The traditional in vitro nanotoxicity assessment approaches are conducted on a monolayer of cell culture. However, to study a cell response without interference from the neighbor cells, a single cell study is necessary; especially in cases of neuronal, cancerous, and stem cells, wherein an individual cell's fate is often not explained by the whole cell population. Nonetheless, a single cell does not mimic the actual in vivo environment and lacks important information regarding cell communication with its microenvironment. Both a single cell and a cell population provide important and complementary information about cells' behaviors. In this research, we explored nanotoxicity assessment on a single cell and a small cell population using electrochemical impedance spectroscopy and a microelectromechanical system (MEMS) device. We demonstrated a controlled capture of PC12 cells in different-sized microwells (to capture a different number of cells) using a combined method of surface functionalization and dielectrophoresis. The present approach provides a rapid nanotoxicity response as compared to other conventional approaches. This is the first study, to our knowledge, which demonstrates a comparative response of a single cell and small cell colonies on the same MEMS platform, when exposed to metaloxide nanoparticles. We demonstrated that the microenvironment of a cell is also accountable for cells' behaviors and their responses to nanomaterials. The results of this experimental study open up a new hypothesis to be tested for identifying the role of cell communication in spreading toxicity in a cell population.

Reduced Ang2 expression in aging endothelial cells.

Science.gov (United States)

Hohensinner, P J; Ebenbauer, B; Kaun, C; Maurer, G; Huber, K; Wojta, J

2016-06-03

Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. Copyright © 2016 Elsevier Inc. All rights reserved.