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Sample records for adult cf cells

  1. SERCA2 Regulates Non-CF and CF Airway Epithelial Cell Response to Ozone

    PubMed Central

    Ahmad, Shama; Nichols, David P.; Strand, Matthew; Rancourt, Raymond C.; Randell, Scott H.; White, Carl W.; Ahmad, Aftab

    2011-01-01

    Calcium mobilization can regulate a wide range of essential functions of respiratory epithelium, including ion transport, ciliary beat frequency, and secretion of mucus, all of which are modified in cystic fibrosis (CF). SERCA2, an important controller of calcium signaling, is deficient in CF epithelium. We conducted this study to determine whether SERCA2 deficiency can modulate airway epithelial responses to environmental oxidants such as ozone. This could contribute to the pathogenesis of pulmonary exacerbations, which are important and frequent clinical events in CF. To address this, we used air-liquid interface (ALI) cultures of non-CF and CF cell lines, as well as differentiated cultures of cells derived from non-CF and CF patients. We found that ozone exposure caused enhanced membrane damage, mitochondrial dysfunction and apoptotic cell death in CF airway epithelial cell lines relative to non-CF. Ozone exposure caused increased proinflammatory cytokine production in CF airway epithelial cell lines. Elevated proinflammatory cytokine production also was observed in shRNA-mediated SERCA2 knockdown cells. Overexpression of SERCA2 reversed ozone-induced proinflammatory cytokine production. Ozone-induced proinflammatory cytokine production was NF-κB- dependent. In a stable NF-κB reporter cell line, SERCA2 inhibition and knockdown both upregulated cytomix-induced NF-κB activity, indicating importance of SERCA2 in modulating NF-κB activity. In this system, increased NF-κB activity was also accompanied by increased IL-8 production. Ozone also induced NF-κB activity and IL-8 release, an effect that was greater in SERCA2-silenced NF-κB-reporter cells. SERCA2 overexpression reversed cytomix-induced increased IL-8 release and total nuclear p65 in CFTR-deficient (16HBE-AS) cells. These studies suggest that SERCA2 is an important regulator of the proinflammatory response of airway epithelial cells and could be a potential therapeutic target. PMID:22096575

  2. Increasing Discharge Capacities of Li-(CF)(sub n) Cells

    NASA Technical Reports Server (NTRS)

    Whitacre, Jay; West, William

    2008-01-01

    An electrolyte additive has shown promise as a means of increasing the sustainable rates of discharge and, hence, the discharge capacities, of lithiumpoly(carbon monofluoride) electrochemical power cells. Lithium-poly(carbon monofluoride) [Li-(CF)n] cells and batteries offer very high specific energies practical values of about 600 W.h/g and a theoretical maximum value of 2,180 W.h/kg. However, because Li-(CF)n cells and batteries cannot withstand discharge at high rates, they have been relegated to niche applications that involve very low discharge currents over times of the order of hundreds to thousands of hours. Increasing the discharge capacities of Li- (CF)n batteries while maintaining high practical levels of specific energy would open new applications for these batteries. During the discharge of a Li-(CF)n cell, one of the electrochemical reactions causes LiF to precipitate at the cathode. LiF is almost completely insoluble in most non-aqueous solvents, including those used in the electrolyte solutions of Li-(CF)n cells. LiF is electrochemically inactive and can block the desired transport of ions at the cathode, and, hence, the precipitation of LiF can form an ever-thickening film on the cathode that limits the rate of discharge.

  3. Using spirituality after an adult CF diagnosis: cognitive reframing and adherence motivation.

    PubMed

    Grossoehme, Daniel H; Ragsdale, Judith R; Cotton, Sian; Meyers, Melenie A; Clancy, John P; Seid, Michael; Joseph, Patricia M

    2012-01-01

    Chronic illness is a significant stressor; the majority of Americans cope utilizing spirituality. Numerous studies demonstrate links between spiritual coping and health outcomes. The purpose of this study was to determine whether persons diagnosed with cystic fibrosis (CF) as adults use spirituality to cope and influence disease management. Semi-structured interviews were completed and analyzed using grounded theory. Data saturation was reached following twelve interviews (83% female); representing 100% participation of those approached and 48% of eligible adults. Persons with late-life CF diagnoses used spirituality to make meaning, understanding themselves in a collaborative partnership with their pulmonologist and God. Supporting themes were: (a) God's intervention depended on treatment adherence and (b) spiritual meaning was constructed through positively reframing their experience. The constructed meaning differed from that of adult parents of children with CF. Late-life diagnosed adults focused on personal responsibility for health. Clinical and research implications for chaplains are presented. PMID:23094612

  4. PERCEPTIONS OF BARRIERS AND FACILITATORS: SELF-MANAGEMENT DECISIONS BY OLDER ADOLESCENTS AND ADULTS WITH CF

    PubMed Central

    George, Maureen; Rand-Giovannetti, Devin; Eakin, Michelle N.; Borrelli, Belinda; Zettler, Melissa; Riekert, Kristin A.

    2010-01-01

    Background Adherence to CF treatments is poor, which can lead to negative health outcomes. The objective of our study was to qualitatively investigate the barriers and facilitators of self management among older adolescents and adults with CF. Methods Individual semi-structured interviews were conducted, audio-taped, transcribed verbatim and coded to identify common themes. Results Twenty-five patients were interviewed. Four broad themes were identified: Barriers to Self-Management (e.g., treatment burden (identified by 64% of patients), accidental or purposeful forgetting (60%), no perceived benefit (56%)), Facilitators of Self-Management (e.g., CF clinic visits (76%), social support (68%), perceived benefit (68%)), Substitution of Alternative Approaches to Conventional Management (36%) and Planned Nonadherence (32%). Conclusions Older adolescents and adults with CF identified many barriers and facilitators of adherence that may be amenable to self-management counseling strategies, particularly the use of health feedback. PMID:20846910

  5. Evaluation of Li/CF(x)Cells For Aerospace Applications

    NASA Technical Reports Server (NTRS)

    Vaidyanathan, Hari; Rao, Gopalakrishna M.

    2007-01-01

    Panasonic commercialized LiICF(x) cell technology in the 1970's. This technology was a promising primary battery for Aerospace applications such as: Exploration missions, Launch vehicles, Tools and more. This technology offers Wide operation temperature range, Low self-discharge and High specific energy CF(x) cathode material has a theoretical specific energy of 2260 Wh/Kg. Specific energy however achieved as of now is only 10% of theoretical value unless used at a very low rate of C/1000. Research both at Government Labs and Industries is currently in progress to improve the performance. This viewgraph presentation describes the cells, and reviews the results of some of the research using tables and charts.

  6. Examination of the discharge mechanism of Li/CF(x) cells: Comparison of the electrochemical reduction mechanisms of PTFE and (CF(x))n by lithium

    NASA Technical Reports Server (NTRS)

    Baxam, Carl C.; Margalit, N.

    1991-01-01

    Swelling of (CF(x))(sub n) electrodes in commercial Li/(CF(x))(sub n) cells presents a limiting factor in cell design optimization. Examination of cathodes from such cells, after discharge, reveals a relation between cell operating temperatures and cathode swelling. Attempts to explain the swelling using the prevailing model for the cathode reaction have failed. A more suitable reaction mechanism is proposed based on the observed behavior of (CF(x))(sub n) electrodes on discharge and a comparison of the reaction products of (CF(x))(sub n) and polytetra fluoroethylene (PTFE) with lithium amalgams. The proposed mechanism is in agreement with the experimental data found in the literature.

  7. Aggregates of mutant CFTR fragments in airway epithelial cells of CF lungs: new pathologic observations.

    PubMed

    Du, Kai; Karp, Philip H; Ackerley, Cameron; Zabner, Joseph; Keshavjee, Shaf; Cutz, Ernest; Yeger, Herman

    2015-03-01

    Cystic fibrosis (CF) is caused by a mutation in the CF transmembrane conductance regulator (CFTR) gene resulting in a loss of Cl(-) channel function, disrupting ion and fluid homeostasis, leading to severe lung disease with airway obstruction due to mucus plugging and inflammation. The most common CFTR mutation, F508del, occurs in 90% of patients causing the mutant CFTR protein to misfold and trigger an endoplasmic reticulum based recycling response. Despite extensive research into the pathobiology of CF lung disease, little attention has been paid to the cellular changes accounting for the pathogenesis of CF lung disease. Here we report a novel finding of intracellular retention and accumulation of a cleaved fragment of F508del CFTR in concert with autophagic like phagolysosomes in the airway epithelium of patients with F508del CFTR. Aggregates consisting of poly-ubiquitinylated fragments of only the N-terminal domain of F508del CFTR but not the full-length molecule accumulate to appreciable levels. Importantly, these undegraded intracytoplasmic aggregates representing the NT-NBD1 domain of F508del CFTR were found in ciliated, in basal, and in pulmonary neuroendocrine cells. Aggregates were found in both native lung tissues and ex-vivo primary cultures of bronchial epithelial cells from CF donors, but not in normal control lungs. Our findings present a new, heretofore, unrecognized innate CF gene related cell defect and a potential contributing factor to the pathogenesis of CF lung disease. Mutant CFTR intracytoplasmic aggregates could be analogous to the accumulation of misfolded proteins in other degenerative disorders and in pulmonary "conformational protein-associated" diseases. Consequently, potential alterations to the functional integrity of airway epithelium and regenerative capacity may represent a critical new element in the pathogenesis of CF lung disease. PMID:25453871

  8. Low-conductance chloride channels in IEC-6 and CF nasal cells expressing CFTR.

    PubMed

    Bijman, J; Dalemans, W; Kansen, M; Keulemans, J; Verbeek, E; Hoogeveen, A; De Jonge, H; Wilke, M; Dreyer, D; Lecocq, J P

    1993-03-01

    The properties of the cystic fibrosis gene product (CFTR) were studied by expression of cloned cDNA in different cell systems. Infection of both simian fibroblast (Vero) cells and immortalized CF nasal polyp cells (NCF3A) with a vaccinia virus encoding CFTR induced forskolin-induced Cl- permeability and low-conductance (8 pS) Cl- channels. By stable transfection of the rat intestinal crypt-derived cell line IEC-6 we have isolated a clone, IEC-CF7, which expresses CFTR mRNA and antigen. IEC-CF7 cells, but not IEC-6, display forskolin-induced Cl- permeability and multiple linear low-conductance (+/- 8 pS) Cl- channels in cell-attached membrane patches. In excised patches of IEC-CF7 cells, low-conductance Cl- channels could be activated by addition of the catalytic subunit of the adenosine 3',5'-cyclic monophosphate-dependent protein kinase A (PKA) plus ATP. During bath fluid replacement studies, the activated low-conductance channel remained active in the absence of ATP at room temperature and showed saturation kinetics. Rectifying (32 pS) Cl- channels were not observed in either IEC-6 cells or IEC-CF7 cells, indicating that there is no relation between CFTR expression and the incidence of this channel. Our data strongly support the conclusion that CFTR can act as a low-conductance Cl- channel, gated by PKA. The IEC-6-derived cell line IEC-CF7 may prove to be a useful model in the study of CFTR function because of the absence of 32-pS Cl- channel activity and its potential for differentiation. PMID:7681632

  9. Expression and functionality of TRPV1 receptor in human MCF-7 and canine CF.41 cells.

    PubMed

    Vercelli, C; Barbero, R; Cuniberti, B; Odore, R; Re, G

    2015-06-01

    As canine mammary tumours (CMT) and human breast cancer share clinical and prognostic features, the former have been proposed as a model to study carcinogenesis and improved therapeutic treatment in human breast cancer. In recent years, it has been shown that transient receptor potential vanilloid 1 (TRPV1) is expressed in different neoplastic tissues and its activation has been associated with regulation of cancer growth and progression. The aim of the present research was to demonstrate the presence of TRPV1 in human and canine mammary cancer cells, MCF-7 and CF.41, respectively, and to study the role of TRPV1 in regulating cell proliferation. The images obtained by Western blot showed a signal at 100 kDa corresponding to the molecular weight of TRPV1 receptor. All tested TRPV1 agonists and antagonists caused a significant decrease (P < 0.05) of cell growth rate in MCF-7 cells. By contrast, in CF.41 cells capsaicin and capsazepine induced a significant increase (P < 0.05) in cell proliferation, whereas resiniferatoxin (RTX) and 5-iodo-resiniferatoxin (5-I-RTX) had no influence on CF.41 cell proliferation. Further studies are needed to elucidate the underlying molecular mechanism responsible for the different effects evoked by TRPV1 activation in MCF-7 and CF.41 cells. PMID:23510405

  10. SERCA and PMCA pumps contribute to the deregulation of Ca2+ homeostasis in human CF epithelial cells.

    PubMed

    Philippe, Réginald; Antigny, Fabrice; Buscaglia, Paul; Norez, Caroline; Becq, Frédéric; Frieden, Maud; Mignen, Olivier

    2015-05-01

    Cystic Fibrosis (CF) disease is caused by mutations in the CFTR gene (CF transmembrane conductance regulator). F508 deletion is the most represented mutation, and F508del-CFTR is absent of plasma membrane and accumulates into the endoplasmic reticulum (ER) compartment. Using specific Ca2+ genetics cameleon probes, we showed in the human bronchial CF epithelial cell line CFBE that ER Ca2+ concentration was strongly increased compared to non-CF (16HBE) cells, and normalized by the F508del-CFTR corrector agent, VX-809. We also showed that ER F508del-CFTR retention increases SERCA (Sarcoplasmic/Reticulum Ca2+ ATPase) pump activity whereas PMCA (Plasma Membrane Ca2+ ATPase) activities were reduced in these CF cells compared to corrected CF cells (VX-809) and non-CF cells. We are showing for the first time CFTR/SERCA and CFTR/PMCA interactions that are modulated in CF cells and could explain part of Ca2+ homeostasis deregulation due to mislocalization of F508del-CFTR. Using ER or mitochondria genetics Ca2+ probes, we are showing that ER Ca2+ content, mitochondrial Ca2+ uptake, SERCA and PMCA pump, activities are strongly affected by the localization of F508del-CFTR protein. PMID:25661196

  11. Internalization of Sambucus nigra agglutinins I and II in insect midgut CF-203 cells.

    PubMed

    Shahidi-Noghabi, Shahnaz; Van Damme, Els J M; De Vos, Winnok H; Smagghe, Guy

    2011-04-01

    In this project, the uptake mechanisms and localization of two lectins from Sambucus nigra, further referred to as S. nigra agglutinin (SNA)-I and SNA-II, into insect midgut CF-203 cells were studied. SNA-I is a chimeric lectin belonging to the class of ribosome-inactivating proteins, whereas SNA-II is a hololectin devoid of enzymatic activity. Internalization of the fluorescein isothiocyanate-labeled lectin was investigated using confocal microscopy. Both lectins were internalized into the cytoplasm of CF-203 cells at similar rates. Preexposure of the insect midgut cells to specific inhibitors of clathrin- and caveolae-mediated endocytosis resulted in an inhibition of lectin uptake in CF-203 cells and caspase-induced cytotoxicity caused by SNA-I and SNA-II, confirming the involvement of both endocytosis pathways. Further studies demonstrated that the uptake mechanism(s) for both lectins required phosphoinositide 3-kinases, but did not depend on the actin cytoskeleton. Since the hololectin SNA-II apparently uses a similar endocytosis pathway as the chimerolectin SNA-I, it can be concluded that the endocytosis process mainly relies on the carbohydrate-binding activity of the lectins under investigation. © 2011 Wiley Periodicals, Inc. PMID:21254203

  12. Decision Making about Risk of Infection by Young Adults with CF

    PubMed Central

    Reynolds, Lisa; Latchford, Gary; Duff, Alistair J. A.; Denton, Miles; Lee, Tim; Peckham, Daniel

    2013-01-01

    Young people with cystic fibrosis (CF) are asked to avoid a number of environments associated with increased infection risk, but in practice they need to balance this with competing priorities such as building and sustaining relationships with friends and family. This study explored the process by which young people make these decisions. Mixed methods were used: a vignette study presenting choices around engaging in activities involving a degree of infection risk and a thematic analysis of participant's accounts of their decision making. The eight participants chose to engage in high risk behaviours in 59% of the choices. All participants chose to engage in at least one risky behavior, though this was less likely when the risk was significant. Thematic analysis revealed large areas of misunderstanding and lack of knowledge, leading to some potentially worrying misconceptions about the nature of infections and risk. Young people with CF are not currently making informed decisions around activities that involve increased risk of infection, and there is an urgent need for CF teams to address this in information provision. PMID:23365742

  13. Additive for Low-Temperature Operation of Li-(CF)n Cells

    NASA Technical Reports Server (NTRS)

    West, William; Whitacre, Jay

    2009-01-01

    Some progress has been reported in continuing research on the use of anion-receptor compounds as electrolyte additives to increase the sustainable rates of discharge and, hence, the discharge capacities, of lithium-poly(carbon monofluoride) [Li-(CF)n, where n >1] primary electrochemical power cells. Some results of this research at a prior stage were summarized in Increasing Discharge Capacities of Li(CF)n Cells (NPO-42346), NASA Tech Briefs, Vol. 32, No. 2 (February 2008), page 37. A major difference between the present and previously reported results is that now there is some additional focus on improving performance at temperatures from ambient down to as low as 40 C. To recapitulate from the cited prior article: During the discharge of a Li-(CF)n cell, one of the electrochemical reactions causes LiF to precipitate at the cathode. LiF is almost completely insoluble in most non-aqueous solvents, including those used in the electrolyte solutions of Li- (CF)n cells. LiF is electrochemically inactive and can block the desired transport of electrons at the cathode, and, hence, the precipitation of LiF can form an ever-thickening film on the cathode that limits the rate of discharge. An anion-receptor electrolyte additive helps to increase the discharge capacity in two ways: It renders LiF somewhat soluble in the non-aqueous electrolyte solution, thereby delaying precipitation until a high concentration of LiF in solution has been reached. When precipitation occurs, it promotes the formation of large LiF grains that do not conformally coat the cathode. The net effect is to reduce the blockage caused by precipitation of LiF, thereby maintaining a greater degree of access of electrolyte to the cathode and greater electronic conductivity.

  14. EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6

    PubMed Central

    Zhou, Li; Hao, Jin; Yuan, Yue; Peng, Rui; Wang, Honglian; Ni, Dongsheng; Gu, Yuping; Huang, Liyuan; Mao, Zhaomin; Lyu, Zhongshi; Du, Yao; Liu, Zhicheng; Li, Yiman; Ju, Pan; Long, Yaoshui; Liu, Jianing; Zhou, Qin

    2016-01-01

    Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy. PMID:27231908

  15. EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6.

    PubMed

    Zhou, Li; Hao, Jin; Yuan, Yue; Peng, Rui; Wang, Honglian; Ni, Dongsheng; Gu, Yuping; Huang, Liyuan; Mao, Zhaomin; Lyu, Zhongshi; Du, Yao; Liu, Zhicheng; Li, Yiman; Ju, Pan; Long, Yaoshui; Liu, Jianing; Zhou, Qin

    2016-01-01

    Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy. PMID:27231908

  16. A randomized controlled trial of a new behavioral home-based nutrition education program, "Eat Well with CF," in adults with cystic fibrosis.

    PubMed

    Watson, Helen; Bilton, Diana; Truby, Helen

    2008-05-01

    Cystic fibrosis (CF) remains the most common genetically inherited disease in the white population and its prognosis is affected by nutritional status. Adults with the disease are now surviving longer and new strategies are required to ensure that they maintain optimal nutrition. This article reports preliminary data from a randomized controlled trial of a 10-week home-based behavioral nutrition intervention, "Eat Well with CF." Outcome measures of weight change over 6 and 12 months and changes in CF-specific nutrition knowledge score, self-efficacy score, reported dietary fat intake and health-related quality-of-life score were compared between the intervention group (n=34) and a standard care control group (n=34). The hypotheses to be tested were that adults with CF completing "Eat Well with CF" would have an improved nutritional status, improvement in specific nutrition knowledge, and an improvement in self-efficacy regarding their ability to cope with a special diet, compared to those receiving standard care. There were substantial improvements in the intervention group's specific CF nutrition knowledge score, self-efficacy score, and reported fat intake compared to control, but no substantial change in body mass index or health-related quality of life over time. Home-based nutrition education incorporating behavioral strategies can be an effective way to support adults with CF, enabling improvement in self-management skills in relation to diet and pancreatic enzyme replacement therapy. This study revealed gaps in basic nutrition knowledge and skills, inadequate knowledge of diet-disease links and pancreatic enzyme replacement therapy. These need to be identified when subjects progress from pediatric to adult care, and programs such as "Eat Well with CF" are a useful adjunct for registered dietitians trying to manage this diverse but growing population. PMID:18442509

  17. Fourier Transform Infrared Spectroscopy of CF4 on the GEC Reference Cell

    NASA Technical Reports Server (NTRS)

    Rao, M. V. V. S.; Sharma, S. P.; Meyyappan, M.; Cruden, Brett A.; Arnold, Jim (Technical Monitor)

    2001-01-01

    Fourier Transform Infrared Spectroscopy (FTIR) has been used to characterize inductively coupled CF4 plasmas in a GEC Reference Cell in-situ In examining these FTIR spectra, several assumptions and approximations of FTIR analysis are addressed. This includes the density dependence of cross-sections, non-linear effects in the addition of overlapping bands and the effect of spatial variations in density and temperature, This analysis demonstrates that temperatures extracted from MR spectra may provide a poor estimate of the true neutral plasma temperature. The FTIR spectra are dominated by unreacted CF, accounting for 40-60% of the gas products. The amount of CF4 consumption is found to have a marked dependence on power, and is nearly independent of pressure in the range of 10-50 mtorr. Small amounts of C2F6 are observed at low power. Also observed are etching products from the quartz window SiF4 COF2 and CO which occur in approximately equal ratios and together account for less than 10% of the gas. The concentrations of these species are nearly independent of pressure. CFx radicals are below the detection limit of this apparatus (approx. 1012/cc).

  18. The coordination chemistry of perfluorovinyl substituted phosphine ligands, a crystallographic and spectroscopic study. Co-crystallisation of both cis- and trans-isomers of [PtCl2{P(i)pr2(CF=CF2)}2] within the same unit cell.

    PubMed

    Barnes, Nicholas A; Brisdon, Alan K; Brown, F R William; Cross, Wendy I; Herbert, Christopher J; Pritchard, Robin G; Sadiq, Ghazala

    2008-01-01

    The coordination chemistry of the perfluorovinyl phosphines PEt2(CF=CF2), P(i)Pr2(CF=CF2), PCy,(CF=CF2) and PPh(CF=CF2)2 to rhodium(I), palladium(II), and platinum(II) centres has been investigated. The electronic properties of the ligands are estimated based on v(CO) and 1J(Rh-P) values. X-Ray diffraction data for the square-planar Pd(II) and Pt(II) perfluorovinyl-phosphine containing complexes allow estimates of the steric demand for the series of ligands PPh2(CF=CF2), PEt2(CF=CF2), P(i)Pr2(CF=CF2), PCy2(CF=CF2) and PPh(CF=CF2)2 to be determined. The (CF=CF2) fragment is found to be more electron withdrawing than (C6F5) yet sterically less demanding. These ligands therefore provide a range of electron-neutral to phosphite-like electronic properties combined with a range of steric demands. This study also reveals that short intramolecular interactions from the metal centre to the beta-fluorine atom cis to phosphorus of the CF=CF2 groups are observed in all-trans square planar complexes of the ligands. Unusually, the complex [PtCl2{P(i)Pr2(CF=CF2)}2] crystallises with both cis- and trans-isomers present in the unit cell. It appears that co-crystallisation of both isomers occurs in order to maximise fluorous regions in the crystal packing, and the extended structure displays short fluorine-fluorine contacts. The generation of mixed geometries seems to be a phenomenon of crystallisation, as solution phase NMR studies reveal the presence of only the trans-isomer. PMID:18399236

  19. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

    The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

  20. Identification of genes required for Cf-dependent hypersensitive cell death by combined proteomic and RNA interfering analyses

    PubMed Central

    Xu, Qiu-Fang; Cheng, Wei-Shun; Zhang, Zhi-Xin; Xu, You-Ping; Zhou, Xue-Ping; Cai, Xin-Zhong

    2012-01-01

    Identification of hypersensitive cell death (HCD) regulators is essential to dissect the molecular mechanisms underlying plant disease resistance. In this study, combined proteomic and RNA interfering (RNAi) analyses were employed to identify genes required for the HCD conferred by the tomato resistance gene Cf-4 and the Cladosporium fulvum avirulence gene Avr4. Forty-nine proteins differentially expressed in the tomato seedlings mounting and those not mounting Cf-4/Avr4-dependent HCD were identified through proteomic analysis. Among them were a variety of defence-related proteins including a cysteine protease, Pip1, an operative target of another C. fulvum effector, Avr2. Additionally, glutathione-mediated antioxidation is a major response to Cf-4/Avr4-dependent HCD. Functional analysis through tobacco rattle virus-induced gene silencing and transient RNAi assays of the chosen 16 differentially expressed proteins revealed that seven genes, which encode Pip1 homologue NbPip1, a SIPK type MAP kinase Nbf4, an asparagine synthetase NbAsn, a trypsin inhibitor LeMir-like protein NbMir, a small GTP-binding protein, a late embryogenesis-like protein, and an ASR4-like protein, were required for Cf-4/Avr4-dependent HCD. Furthermore, the former four genes were essential for Cf-9/Avr9-dependent HCD; NbPip1, NbAsn, and NbMir, but not Nbf4, affected a nonadaptive bacterial pathogen Xanthomonas oryzae pv. oryzae-induced HCD in Nicotiana benthamiana. These data demonstrate that Pip1 and LeMir may play a general role in HCD and plant immunity and that the application of combined proteomic and RNA interfering analyses is an efficient strategy to identify genes required for HCD, disease resistance, and probably other biological processes in plants. PMID:22275387

  1. Circulating Tumor Cells (CTC) and Cell-Free DNA (cfDNA) Workshop 2016: Scientific Opportunities and Logistics for Cancer Clinical Trial Incorporation.

    PubMed

    Lowes, Lori E; Bratman, Scott V; Dittamore, Ryan; Done, Susan; Kelley, Shana O; Mai, Sabine; Morin, Ryan D; Wyatt, Alexander W; Allan, Alison L

    2016-01-01

    Despite the identification of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) as potential blood-based biomarkers capable of providing prognostic and predictive information in cancer, they have not been incorporated into routine clinical practice. This resistance is due in part to technological limitations hampering CTC and cfDNA analysis, as well as a limited understanding of precisely how to interpret emergent biomarkers across various disease stages and tumor types. In recognition of these challenges, a group of researchers and clinicians focused on blood-based biomarker development met at the Canadian Cancer Trials Group (CCTG) Spring Meeting in Toronto, Canada on 29 April 2016 for a workshop discussing novel CTC/cfDNA technologies, interpretation of data obtained from CTCs versus cfDNA, challenges regarding disease evolution and heterogeneity, and logistical considerations for incorporation of CTCs/cfDNA into clinical trials, and ultimately into routine clinical use. The objectives of this workshop included discussion of the current barriers to clinical implementation and recent progress made in the field, as well as fueling meaningful collaborations and partnerships between researchers and clinicians. We anticipate that the considerations highlighted at this workshop will lead to advances in both basic and translational research and will ultimately impact patient management strategies and patient outcomes. PMID:27618023

  2. Detection of Chamber Conditioning by CF4 in the GEC Cell

    NASA Technical Reports Server (NTRS)

    Cruden, Brett A.; Rao, M. V. V. S.; Sharma, S. P.; Meyyappan, M.; Arnold, James (Technical Monitor)

    2001-01-01

    During oxide etch processes, buildup of fluorocarbon residues on reactor sidewalks can cause to drift and will necessitate time for conditioning and cleaning of the reactor. Various measurements in CF4 and Ar plasmas are made in an attempt to identify a metric able to indicate the chamber condition. Mass spectrometry and a Langmuir probe shows that the buildup of fluorocarbon films on the reactor surface causes a decrease in plasma floating potential, plasma potential, and ion energy in argon plasmas. This change in floating potential is also observed in CF4 plasma operation, and occurs primarily during the first hour and a half of plasma operation. A slight rise in electron density is also observed in the argon plasmas. Because the change is seen in an argon plasma, it is indicative of altered physical, not chemical, plasma-surface interactions. Specifically, the insulating films deposited on metal surfaces alter the electromagnetic fields seen by the plasma, affecting various parameters including the floating potential and electron density. An impedance probe placed on the inductive coil shows a slight reduction in plasma impedance due to this rising electron density. The optical emission of several species, including CF, C2, atomic Si and atomic C, is also monitored for changes in density resulting from the buildup of film on the chamber wall. Changes in the optical emission spectrum are comparable to the noise levels in their measurement.

  3. [Langerhans cell histiocytosis in adults].

    PubMed

    Néel, A; Artifoni, M; Donadieu, J; Lorillon, G; Hamidou, M; Tazi, A

    2015-10-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies. PMID:26150351

  4. TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs.

    PubMed

    Suzuki, Shingo; Sargent, R Geoffrey; Illek, Beate; Fischer, Horst; Esmaeili-Shandiz, Alaleh; Yezzi, Michael J; Lee, Albert; Yang, Yanu; Kim, Soya; Renz, Peter; Qi, Zhongxia; Yu, Jingwei; Muench, Marcus O; Beyer, Ashley I; Guimarães, Alessander O; Ye, Lin; Chang, Judy; Fine, Eli J; Cradick, Thomas J; Bao, Gang; Rahdar, Meghdad; Porteus, Matthew H; Shuto, Tsuyoshi; Kai, Hirofumi; Kan, Yuet W; Gruenert, Dieter C

    2016-01-01

    Cystic fibrosis (CF) is a recessive inherited disease associated with multiorgan damage that compromises epithelial and inflammatory cell function. Induced pluripotent stem cells (iPSCs) have significantly advanced the potential of developing a personalized cell-based therapy for diseases like CF by generating patient-specific stem cells that can be differentiated into cells that repair tissues damaged by disease pathology. The F508del mutation in airway epithelial cell-derived CF-iPSCs was corrected with small/short DNA fragments (SDFs) and sequence-specific TALENs. An allele-specific PCR, cyclic enrichment strategy gave ~100-fold enrichment of the corrected CF-iPSCs after six enrichment cycles that facilitated isolation of corrected clones. The seamless SDF-based gene modification strategy used to correct the CF-iPSCs resulted in pluripotent cells that, when differentiated into endoderm/airway-like epithelial cells showed wild-type (wt) airway epithelial cell cAMP-dependent Cl ion transport or showed the appropriate cell-type characteristics when differentiated along mesoderm/hematopoietic inflammatory cell lineage pathways. PMID:26730810

  5. Sertoli cells in the testis of caecilians, Ichthyophis tricolor and Uraeotyphlus cf. narayani (Amphibia: Gymnophiona): light and electron microscopic perspective.

    PubMed

    Smita, Mathew; Oommen, Oommen V; George, Jancy M; Akbarsha, M A

    2003-12-01

    The caecilians have evolved a unique pattern of cystic spermatogenesis in which cysts representing different stages in spermatogenesis coexist in a testis lobule. We examined unsettled issues relating to the organization of the caecilian testis lobules, including the occurrence of a fatty matrix, the possibility of both peripheral and central Sertoli cells, the origin of Sertoli cells from follicular cells, and the disengagement of older Sertoli cells to become loose central Sertoli cells. We subjected the testis of Ichthyophis tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani (Uraeotyphliidae) from the Western Ghats of Kerala, India, to light and transmission electron microscopic studies. Irrespective of the functional state of the testis, whether active or regressed, Sertoli cells constitute a permanent feature of the lobules. The tall Sertoli cells adherent to the basal lamina with basally located pleomorphic nuclei extend deeper into the lobule to meet at the core. There they provide for association of germ cells at different stages of differentiation, an aspect that has earlier been misconceived as the fatty matrix. Germ cells up to the 4-cell stage remain in the intercalating region of the Sertoli cells and they are located at the apices of the Sertoli cells from the 8-cell stage onwards. The developing germ cells are intimately associated with the Sertoli cell adherent to the basal lamina until spermiation. There are ameboid cells in the core of the lobules that appear to interact with the germ cells at the face opposite to their attachment with the Sertoli cells. Adherence of the Sertoli cells to the basal lamina is a permanent feature of the caecilian testicular lobules. The ameboid cells in the core are neither Sertoli cells nor their degeneration products. PMID:14584033

  6. The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells.

    PubMed

    Stanke, Frauke; van Barneveld, Andrea; Hedtfeld, Silke; Wölfl, Stefan; Becker, Tim; Tümmler, Burkhard

    2014-05-01

    The three-base-pair deletion c.1521_1523delCTT (p.Phe508del, F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most frequent disease-causing lesion in cystic fibrosis (CF). The CFTR gene encodes a chloride and bicarbonate channel at the apical membrane of epithelial cells. Altered ion transport of CFTR-expressing epithelia can be used to differentiate manifestations of the so-called CF basic defect. Recently, an 11p13 region has been described as a CF modifier by the North American CF Genetic Modifier Study Consortium. Selecting the epithelial-specific transcription factor EHF (ets homologous factor) as the likely candidate gene on 11p13, we have genotyped two intragenic microsatellites in EHF to replicate the 11p13 finding in the patient cohort of the European CF Twin and Sibling Study. We could observe an association of rare EHF haplotypes among homozygotes for c.1521_1523delCTT in CFTR, which exhibit a CF-untypical manifestation of the CF basic defect such as CFTR-mediated residual chloride secretion and low response to amiloride. We have reviewed transcriptome data obtained from intestinal epithelial samples of homozygotes for c.1521_1523delCTT in CFTR, which were stratified for their EHF genetic background. Transcripts that were upregulated among homozygotes for c.1521_1523delCTT in CFTR, who carry two rare EHF alleles, were enriched for genes that alter protein glycosylation and trafficking, both mechanisms being pivotal for the effective targeting of fully functional p.Phe508del-CFTR to the apical membrane of epithelial cells. We conclude that EHF modifies the CF phenotype by altering capabilities of the epithelial cell to correctly process the folding and trafficking of mutant p.Phe508del-CFTR. PMID:24105369

  7. Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr−/− transgenic mice

    PubMed Central

    Zaman, Munir M.; Martin, Camilia R.; Andersson, Charlotte; Bhutta, Abdul Q.; Cluette-Brown, Joanne E.; Laposata, Michael

    2010-01-01

    Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2α secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/− Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators. PMID:20656894

  8. CF.sub.4 laser

    DOEpatents

    Wittig, Curt; Tiee, Joe J.

    1979-01-01

    A CF.sub.4 laser for producing near 16 .mu.m radiation utilizing a line tunable CO.sub.2 laser as an optical pumping source. The device uses a cryogenically cooled optically pumped cell containing molecular CF.sub.4 gas. An optical resonant cavity formed around the optically pumped cell induces oscillations of near 16 .mu.m radiation from the .nu..sub.2 +.nu..sub.4 .fwdarw..nu..sub.2 transition in the molecular CF.sub.4 gas.

  9. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  10. CF Mutation Panel

    MedlinePlus

    ... page: Was this page helpful? Also known as: Cystic Fibrosis Genotyping; CF DNA Analysis; CF Gene Mutation Panel; CF Molecular Genetic Testing Formal name: Cystic Fibrosis Gene Mutation Panel Related tests: Sweat Test ; Trypsinogen ; ...

  11. Adult stem cells and tissue repair.

    PubMed

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells. PMID:12931235

  12. Race-Specific Elicitors of Cladosporium fulvum Induce Changes in Cell Morphology and the Synthesis of Ethylene and Salicylic Acid in Tomato Plants Carrying the Corresponding Cf Disease Resistance Gene.

    PubMed Central

    Hammond-Kosack, K. E.; Silverman, P.; Raskin, I.; Jones, JDG.

    1996-01-01

    Defense responses mediated by the genetically unlinked Cf-9 and Cf-2 genes were compared with those involving no Cf gene (Cf0). Compatible tomato (Lycopersicon esculentum)-Cladosporium fulvum intercellular washing fluids were injected into tomato cotyledons, and the kinetics of responses was monitored under conditions of 70 and 98% relative humidity. The latter conditions suppressed the normal macroscopic responses. For the Cf-9-Avr9 interaction, stomatal opening was induced within 3 to 4 h and after 9 h mesophyll cell death commenced. A burst of ethylene production occurred between 9 and 12.5 h and remained elevated. Free salicylic acid levels increased after 12 h, peaked at 24 h, and thereafter declined. For the Cf-2-Avr2 interaction, stomata became plugged after 8 h, and salicylic acid and ethylene levels increased by 12 and 18 h, respectively, and thereafter declined. Host cell death commenced around vascular tissue by 24 h. Cell death in both incompatible interactions was frequently preceded by cell enlargement. For Cf0-injected plants, no significant responses were detected. High humidity delayed and reduced the Cf-Avr-gene-dependent cell death and ethylene synthesis, whereas induced salicylic acid levels were unaffected for Cf-2-Avr2 and reduced in magnitude only for Cf-9-Avr9. PMID:12226268

  13. Safety evaluation of an electronic totalizer containing a Li/(CF)x cell

    NASA Astrophysics Data System (ADS)

    Davis, P. B.; Bis, R. F.; Barnes, J. A.; Buchholz, S. E.; Debold, F. C.

    1983-11-01

    A safety review and test program has been conducted on the Electronic Totalizer Model 799806-212 manufactured by Veeder-Root containing the Panasonic Lithium Polycarbonmonofluoride battery (one cell) BR-2/3A. The cell is used for the LCD display of the totalizer. Tests were conducted on the cell both inside the totalizer and alone. Tests included short circuit, forced discharge into voltage reversal, charging, heat tape, and gas sample collection of combustion products. The tests were run on both fresh cells and partially discharged cells. The forced discharge and charging tests were conducted at both the 250mA and 1 amp level. No fire or flame was noted during the tests with the exception of the heat tape runs. During heat tape tests fire was noted at 450 C.

  14. Progenitor cells in the adult pancreas.

    PubMed

    Holland, Andrew M; Góñez, L Jorge; Harrison, Leonard C

    2004-01-01

    The beta-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or beta-cell progenitors and the molecular mechanisms underlying beta-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, beta-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of beta-cells. PMID:14737742

  15. Toxicity and mode of action of insecticidal Cry1A proteins from Bacillus thuringiensis in an insect cell line, CF-1.

    PubMed

    Portugal, Leivi; Gringorten, J Lawrence; Caputo, Guido F; Soberón, Mario; Muñoz-Garay, Carlos; Bravo, Alejandra

    2014-03-01

    Bacillus thuringiensis Cry toxins are insecticidal proteins used to control insect pests. The interaction of Cry toxins with the midgut of susceptible insects is a dynamic process involving activation of the toxin, binding to midgut receptors in the apical epithelium and conformational changes in the toxin molecule, leading to pore formation and cell lysis. An understanding of the molecular events underlying toxin mode of action is essential for the continued use of Cry toxins. In this work, we examined the mechanism of action of Cry1A toxins in the lepidopteran cell line CF-1, using native Cry1Ab and mutant forms of this protein that interfer with different steps in the mechanism of action, specifically, receptor binding, oligomerization or pore formation. These mutants lost activity against both Manduca sexta larvae and CF-1 cells. We also analyzed a mutation created in domain I of Cry1Ab, in which helix α-1 and part of helix α-2 were deleted (Cry1AbMod). Cry1AbMod is able to oligomerize in the absence of toxin receptors, and although it shows reduced activity against some susceptible insects, it kills insect pests that have developed resistance to native Cry1Ab. Cry1AbMod showed enhanced toxicity to CF-1, suggesting that oligomerization of native Cry1Ab may be a limiting step in its activity against CF-1 cells. The toxicity of Cry1Ac and Cry1AcMod were also analyzed. Our results suggest that some of the steps in the mode of action of Cry1A toxins are conserved in vivo in insect midgut cells and in vitro in an established cell line, CF-1. PMID:24189038

  16. Experimental and theoretical study of RF capacitively coupled plasma in Ar-CF4-CF3I mixtures

    NASA Astrophysics Data System (ADS)

    Proshina, O. V.; Rakhimova, T. V.; Lopaev, D. V.; Šamara, V.; Baklanov, M. R.; de Marneffe, J.-F.

    2015-10-01

    Radio frequency capacitively coupled plasma (RF CCP) sustained at RF frequencies of 27 MHz in an Ar-CF4-CF3I gas mixture is studied experimentally and theoretically. The RF CCP in Ar-CF4-CF3I is simulated by using a 1D hybrid particle-in-cell-fluid numerical model. We pay special attention to the changes in plasma structure and fluxes to the electrode, negative ion and neutral radical production with admixture of CF3I in Ar-CF4 plasma. With CF3I admixture the plasma becomes strongly electronegative as a result of the high electron attachment rate to the CF3I molecule. The atomic fluorine density becomes extremely low with addition of CF3I molecules due to the large volume loss in the reaction CF3I + F  →  CF3 + IF. Optical emission spectrometry data on CF2 emission at the wavelength of 250 nm indicate the essential sources of CF2 in CF3I-containing plasma in the studied conditions, although direct dissociation channels for the CF3I molecule with CF2 production have not been studied. Evaluation of CF2 density in Ar-CF4-CF3I plasma was first carried out on the basis of the actinometry technique and numerical simulation. The possible mechanism of ultra-low-k film damage in the studied conditions is also discussed.

  17. Fluorinated Peptide Nucleic Acids with Fluoroacetyl Side Chain Bearing 5-(F/CF3)-Uracil: Synthesis and Cell Uptake Studies.

    PubMed

    Ellipilli, Satheesh; Palvai, Sandeep; Ganesh, Krishna N

    2016-08-01

    Fluorine incorporation into organic molecules imparts favorable physicochemical properties such as lipophilicity, solubility and metabolic stability necessary for drug action. Toward such applications using peptide nucleic acids (PNA), we herein report the chemical synthesis of fluorinated PNA monomers and biophysical studies of derived PNA oligomers containing fluorine in in the acetyl side chain (-CHF-CO-) bearing nucleobase uracil (5-F/5-CF3-U). The crystal structures of fluorinated racemic PNA monomers reveal interesting base pairing of enantiomers and packing arrangements directed by the chiral F substituent. Reverse phase HPLC show higher hydrophobicity of fluorinated PNA oligomers, dependent on the number and site of the fluorine substitution: fluorine on carbon adjacent to the carbonyl group induces higher lipophilicity than fluorine on nucleobase or in the backbone. The PNA oligomers containing fluorinated bases form hybrids with cDNA/RNA with slightly lower stability compared to that of unmodified aeg PNA, perhaps due to electronic effects. The uptake of fluorinated homooligomeric PNAs by HeLa cells was as facile as that of nonfluorinated PNA. In conjunction with our previous work on PNAs fluorinated in backbone and at N-terminus, it is evident that the fluorinated PNAs have potential to emerge as a new class of PNA analogues for applications in functional inhibition of RNA. PMID:27391099

  18. Clinical grade adult stem cell banking

    PubMed Central

    Thirumala, Sreedhar; Goebel, W Scott

    2009-01-01

    There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

  19. Ion Energy and Ion Flux Distributions of CF4/Ar/O2 Inductively Coupled Plasmas in a GEC Cell

    NASA Technical Reports Server (NTRS)

    Rao, M. V. V. S.; Cruden, Brett; Sharma, Surendra; Meyyappan, Meyya

    2001-01-01

    Knowledge of ion kinetics in plasma processing gas mixtures, such as CF4:Ar:O2, is important for understanding plasma assisted etching and deposition of materials. Ion energies and ion fluxes were measured in this mixture for 80:10:10, 60:20:20, and 40:30:30 mixture ratios in the pressure range of 10-50 mTorr, and at 200 and 300 W of RF power. Ions from plasma, sampled through a 10 micron orifice in the center of the lower plane electrode, were energy and mass analyzed by a combination of electrostatic energy and quadrupole mass filters. CFx(+) (x = 1 - 3), F2(+), F(+), C(+) from CF4, Ar(+) from Ar, and O2(+) and O(+) from O2, and by-product ions SiFx(+)(x = 1 - 3) from etching of quartz coupling window, COFx(+)(x = 1 - 3), CO(+), CO2(+), and OF(+) were detected. In all conditions ion flux decreases with increase of pressure but increase with increase of RF power. Ar(+) signal decreases with increase of pressure while CF3(+), which is the dominant ion at all conditions, increases with increase in pressure. The loss mechanism for Ar(+) and increase of CF3(+) is due to large cross section for Ar(+) + CF4 yields Ar + CF3(+) + F. Ion energies, which range from 15-25 eV depending on plasma operating conditions, are nearly Gaussian. By-product ion signals are higher at lower pressures indicating stronger plasma interaction with quartz window.

  20. Mef2c-F10N enhancer driven β-galactosidase (LacZ) and Cre recombinase mice facilitate analyses of gene function and lineage fate in neural crest cells.

    PubMed

    Aoto, Kazushi; Sandell, Lisa L; Butler Tjaden, Naomi E; Yuen, Kobe C; Watt, Kristin E Noack; Black, Brian L; Durnin, Michael; Trainor, Paul A

    2015-06-01

    Neural crest cells (NCC) comprise a multipotent, migratory stem cell and progenitor population that gives rise to numerous cell and tissue types within a developing embryo, including craniofacial bone and cartilage, neurons and glia of the peripheral nervous system, and melanocytes within the skin. Here we describe two novel stable transgenic mouse lines suitable for lineage tracing and analysis of gene function in NCC. Firstly, using the F10N enhancer of the Mef2c gene (Mef2c-F10N) linked to LacZ, we generated transgenic mice (Mef2c-F10N-LacZ) that express LacZ in the majority, if not all migrating NCC that delaminate from the neural tube. Mef2c-F10N-LacZ then continues to be expressed primarily in neurogenic, gliogenic and melanocytic NCC and their derivatives, but not in ectomesenchymal derivatives. Secondly, we used the same Mef2c-F10N enhancer together with Cre recombinase to generate transgenic mice (Mef2c-F10N-Cre) that can be used to indelibly label, or alter gene function in, migrating NCC and their derivatives. At early stages of development, Mef2c-F10N-LacZ and Mef2c-F10N-Cre label NCC in a pattern similar to Wnt1-Cre mice, with the exception that Mef2c-F10N-LacZ and Mef2c-F10N-Cre specifically label NCC that have delaminated from the neural plate, while premigratory NCC are not labeled. Thus, our Mef2c-F10N-LacZ and Mef2c-F10N-Cre transgenic mice provide new resources for tracing migratory NCC and analyzing gene function in migrating and differentiating NCC independently of NCC formation. PMID:25794678

  1. Mef2c-F10N enhancer driven β-galactosidase (LacZ) and Cre recombinase mice facilitate analyses of gene function and lineage fate in neural crest cells

    PubMed Central

    Aoto, Kazushi; Sandell, Lisa L.; Butler Tjaden, Naomi E.; Yuen, Kobe C.; Noack Watt, Kristin E.; Black, Brian L.; Durnin, Michael; Trainor, Paul A.

    2015-01-01

    Neural crest cells (NCC) comprise a multipotent, migratory stem cell and progenitor population that gives rise to numerous cell and tissue types within a developing embryo, including craniofacial bone and cartilage, neurons and glia of the peripheral nervous system, and melanocytes within the skin. Here we describe two novel stable transgenic mouse lines suitable for lineage tracing and analysis of gene function in NCC. Firstly, using the F10N enhancer of the Mef2c gene (Mef2c-F10N) linked to LacZ, we generated transgenic mice (Mef2c-F10N-LacZ) that express LacZ in the majority, if not all migrating NCC that delaminate from the neural tube. Mef2c-F10N-LacZ then continues to be expressed primarily in neurogenic, gliogenic and melanocytic NCC and their derivatives, but not in ectomesenchymal derivatives. Secondly, we used the same Mef2c-F10N enhancer together with Cre recombinase to generate transgenic mice (Mef2c-F10N-Cre) that can be used to indelibly label, or alter gene function in, migrating NCC and their derivatives. At early stages of development, Mef2c-F10N-LacZ and Mef2c-F10N-Cre label NCC in a pattern similar to Wnt1-Cre mice, with the exception that Mef2c-F10N-LacZ and Mef2c-F10N-Cre specifically label NCC that have delaminated from the neural plate, while premigratory NCC are not labeled. Thus, our Mef2c-F10N-LacZ and Mef2c-F10N-Cre transgenic mice provide new resources for tracing migratory NCC and analyzing gene function in migrating and differentiating NCC independently of NCC formation. PMID:25794678

  2. Adult stem-like cells in kidney.

    PubMed

    Hishikawa, Keiichi; Takase, Osamu; Yoshikawa, Masahiro; Tsujimura, Taro; Nangaku, Masaomi; Takato, Tsuyoshi

    2015-03-26

    Human pluripotent cells are promising for treatment for kidney diseases, but the protocols for derivation of kidney cell types are still controversial. Kidney tissue regeneration is well confirmed in several lower vertebrates such as fish, and the repair of nephrons after tubular damages is commonly observed after renal injury. Even in adult mammal kidney, renal progenitor cell or system is reportedly presents suggesting that adult stem-like cells in kidney can be practical clinical targets for kidney diseases. However, it is still unclear if kidney stem cells or stem-like cells exist or not. In general, stemness is defined by several factors such as self-renewal capacity, multi-lineage potency and characteristic gene expression profiles. The definite use of stemness may be obstacle to understand kidney regeneration, and here we describe the recent broad findings of kidney regeneration and the cells that contribute regeneration. PMID:25815133

  3. Sleep Disorders in Adult Sickle Cell Patients

    PubMed Central

    Sharma, Sunil; Efird, Jimmy T.; Knupp, Charles; Kadali, Renuka; Liles, Darla; Shiue, Kristin; Boettger, Peter; Quan, Stuart F.

    2015-01-01

    Study Objectives: While sleep apnea has been studied in children with sickle cell disease (SCD), little is known about sleep disorders in adult sickle cell patients. The objective of this study was to evaluate sleep disordered breathing and its polysomnographic characteristics in adult patients with sickle cell disease. Methods: The analysis cohort included 32 consecutive adult SCD patients who underwent a comprehensive sleep evaluation and overnight polysomnography in an accredited sleep center after reporting symptoms suggesting disordered sleep or an Epworth Sleepiness Scale score ≥ 10. Epworth score, sleep parameters, comorbid conditions, and narcotic use were reviewed and compared in patients with and without sleep disordered breathing. SCD complication rates in the two groups also were compared. Results: In adult SCD patients who underwent overnight polysomnography, we report a high prevalence (44%) of sleep disordered breathing. Disease severity was mild to moderate (mean apnea-hypopnea index = 17/h (95% CI: 10–24/h). Concomitant sleep disorders, including insomnia complaints (57%) and delayed sleep-phase syndrome (57%), also were common in this population. In this limited cohort, we did not find increased SCD complications associated with sleep disordered breathing in adult patients with sickle cell disease. Conclusions: A high burden of sleep disordered breathing and other sleep-related complaints were identified in the adult sickle cell population. Our results provide important information on this unique population. Citation: Sharma S, Efird JT, Knupp C, Kadali R, Liles D, Shiue K, Boettger P, Quan SF. Sleep disorders in adult sickle cell patients. J Clin Sleep Med 2015;11(3):219–223. PMID:25515282

  4. Adult Stem Cell Responses to Nanostimuli

    PubMed Central

    Tsimbouri, Penelope M.

    2015-01-01

    Adult or mesenchymal stem cells (MSCs) have been found in different tissues in the body, residing in stem cell microenvironments called “stem cell niches”. They play different roles but their main activity is to maintain tissue homeostasis and repair throughout the lifetime of an organism. Their ability to differentiate into different cell types makes them an ideal tool to study tissue development and to use them in cell-based therapies. This differentiation process is subject to both internal and external forces at the nanoscale level and this response of stem cells to nanostimuli is the focus of this review. PMID:26193326

  5. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  6. Adult Stem Cells and Diseases of Aging.

    PubMed

    Boyette, Lisa B; Tuan, Rocky S

    2014-01-21

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  7. 28. Embryonic and adult stem cell therapy.

    PubMed

    Henningson, Carl T; Stanislaus, Marisha A; Gewirtz, Alan M

    2003-02-01

    Stem cells are characterized by the ability to remain undifferentiated and to self-renew. Embryonic stem cells derived from blastocysts are pluripotent (able to differentiate into many cell types). Adult stem cells, which were traditionally thought to be monopotent multipotent, or tissue restricted, have recently also been shown to have pluripotent properties. Adult bone marrow stem cells have been shown to be capable of differentiating into skeletal muscle, brain microglia and astroglia, and hepatocytes. Stem cell lines derived from both embryonic stem and embryonic germ cells (from the embryonic gonadal ridge) are pluripotent and capable of self-renewal for long periods. Therefore embryonic stem and germ cells have been widely investigated for their potential to cure diseases by repairing or replacing damaged cells and tissues. Studies in animal models have shown that transplantation of fetal, embryonic stem, or embryonic germ cells may be able to treat some chronic diseases. In this review, we highlight recent developments in the use of stem cells as therapeutic agents for three such diseases: Diabetes, Parkinson disease, and congestive heart failure. We also discuss the potential use of stem cells as gene therapy delivery cells and the scientific and ethical issues that arise with the use of human stem cells. PMID:12592319

  8. Adult neural stem cells stake their ground

    PubMed Central

    Lim, Daniel A.; Alvarez-Buylla, Arturo

    2014-01-01

    The birth of new neurons in the walls of the adult brain lateral ventricles has captured the attention of many neuroscientists for over two decades, yielding key insights into the identity and regulation of neural stem cells (NSCs). In the adult ventricular-subventricular zone (V-SVZ), NSCs are a specialized form of astrocyte that generates several types of neurons for the olfactory bulb. Here we discuss recent findings regarding the unique organization of the V-SVZ NSCs niche, the multiple regulatory controls of neuronal production, the distinct regional identities of adult NSCs, and the epigenetic mechanisms that maintain adult neurogenesis. Understanding how V-SVZ NSCs establish and maintain lifelong neurogenesis continues to provide surprising insights into the cellular and molecular regulation of neural development. PMID:25223700

  9. Tissue engineering using adult stem cells.

    PubMed

    Eberli, Daniel; Atala, Anthony

    2006-01-01

    Patients with a variety of diseases may be treated with transplanted tissues and organs. However, there is a shortage of donor tissues and organs, which is worsening yearly because of the aging population. Scientists in the field of tissue engineering are applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new options for cellular therapy and tissue engineering. The use of adult stem cells for tissue engineering applications is promising. This chapter discusses applications of these new technologies for the engineering of tissues and organs. The first part provides an overview of regenerative medicine and tissue engineering techniques; the second highlights different adult stem cell populations used for tissue regeneration. PMID:17161702

  10. Epigenetic regulation in adult stem cells and cancers

    PubMed Central

    2013-01-01

    Adult stem cells maintain tissue homeostasis by their ability to both self-renew and differentiate to distinct cell types. Multiple signaling pathways have been shown to play essential roles as extrinsic cues in maintaining adult stem cell identity and activity. Recent studies also show dynamic regulation by epigenetic mechanisms as intrinsic factors in multiple adult stem cell lineages. Emerging evidence demonstrates intimate crosstalk between these two mechanisms. Misregulation of adult stem cell activity could lead to tumorigenesis, and it has been proposed that cancer stem cells may be responsible for tumor growth and metastasis. However, it is unclear whether cancer stem cells share commonalities with normal adult stem cells. In this review, we will focus on recent discoveries of epigenetic regulation in multiple adult stem cell lineages. We will also discuss how epigenetic mechanisms regulate cancer stem cell activity and probe the common and different features between cancer stem cells and normal adult stem cells. PMID:24172544

  11. Unique multipotent cells in adult human mesenchymal cell populations

    PubMed Central

    Kuroda, Yasumasa; Kitada, Masaaki; Wakao, Shohei; Nishikawa, Kouki; Tanimura, Yukihiro; Makinoshima, Hideki; Goda, Makoto; Akashi, Hideo; Inutsuka, Ayumu; Niwa, Akira; Shigemoto, Taeko; Nabeshima, Yoko; Nakahata, Tatsutoshi; Nabeshima, Yo-ichi; Fujiyoshi, Yoshinori; Dezawa, Mari

    2010-01-01

    We found adult human stem cells that can generate, from a single cell, cells with the characteristics of the three germ layers. The cells are stress-tolerant and can be isolated from cultured skin fibroblasts or bone marrow stromal cells, or directly from bone marrow aspirates. These cells can self-renew; form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency; and can differentiate into endodermal, ectodermal, and mesodermal cells both in vitro and in vivo. When transplanted into immunodeficient mice by local or i.v. injection, the cells integrated into damaged skin, muscle, or liver and differentiated into cytokeratin 14-, dystrophin-, or albumin-positive cells in the respective tissues. Furthermore, they can be efficiently isolated as SSEA-3(+) cells. Unlike authentic ES cells, their proliferation activity is not very high and they do not form teratomas in immunodeficient mouse testes. Thus, nontumorigenic stem cells with the ability to generate the multiple cell types of the three germ layers can be obtained through easily accessible adult human mesenchymal cells without introducing exogenous genes. These unique cells will be beneficial for cell-based therapy and biomedical research. PMID:20421459

  12. Atmospheric chemistry of CF3CF2OCH3

    NASA Astrophysics Data System (ADS)

    Østerstrøm, Freja F.; Nielsen, Ole John; Wallington, Timothy J.

    2016-06-01

    Smog chamber Fourier transform infrared techniques were used to investigate the kinetics of the reaction of CF3CF2OCH3 with Cl atoms and OH radicals: k(Cl + CF3CF2OCH3) = (1.09 ± 0.16) × 10-13 and k(OH + CF3CF2OCH3) = (1.28 ± 0.19) × 10-14 cm3 molecule-1 s-1 in 700 Torr total pressure of N2/O2 at 296 ± 2 K. The Cl-initiated oxidation of CF3CF2OCH3 gives CF3CF2OCHO in a yield indistinguishable from 100%. An estimate of k(Cl + CF3CF2OCHO) = (1.18 ± 0.34) × 10-14 cm3 molecule-1 s-1 is provided. Based on the OH reaction rate, the atmospheric lifetime of CF3CF2OCH3 is estimated to be 5.0 years. The 100-year time horizon global warming potential of CF3CF2OCH3 is estimated to be 585. The atmospheric impact of CF3CF2OCH3 is discussed.

  13. Adult stem cells in the knifefish cerebellum.

    PubMed

    Sîrbulescu, Ruxandra F; Ilieş, Iulian; Vitalo, Antonia G; Trull, Krystal; Zhu, Jenny; Traniello, Ian M; Zupanc, Günther K H

    2015-01-01

    Adult neurogenesis has been described in dozens of brain regions in teleost fish, with the largest number of new neurons being generated in the cerebellum. Here, we characterized the cerebellar neural stem/progenitor cells (NSPCs) in the brown ghost knifefish (Apteronotus leptorhynchus), an established model system of adult neurogenesis. The majority of the new cerebellar cells arise from neurogenic niches located medially, at the interface of the dorsal/ventral molecular layers and the granular layer. NSPCs within these niches give rise to transit-amplifying progenitors which populate the molecular layer, where they continue to proliferate during their migration toward target areas in the granular layer. At any given time, the majority of proliferating cells are located in the molecular layer. Immunohistochemical staining revealed that the stem cell markers Sox2, Meis1/2/3, Islet1, and, to a lesser extent, Pax6, are widely expressed in all regions of the adult cerebellum. A large subpopulation of these NSPCs coexpress S100, GFAP, and/or vimentin, indicating astrocytic identity. This is further supported by the specific effect of the gliotoxin l-methionine sulfoximine, which leads to a targeted decrease in the number of GFAP+ cells that coexpress Sox2 or the proliferation marker PCNA. Pulse-chase analysis of the label size associated with new cells after administration of 5-bromo-2'-deoxyuridine demonstrated that, on average, two additional cell divisions occur after completion of the initial mitotic cycle. Overall numbers of NSPCs in the cerebellum niches increase consistently over time, presumably in parallel with the continuous growth of the brain. PMID:25044932

  14. VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITY, AND CRITICAL PROPERTIES OF CF3OCF2CF2CF3, c-CF2CF2CF2CF2O, CF3OCF2OCF3, AND CF3OCF2CF2H

    EPA Science Inventory

    New measurements of the thermophysical properties of CF3OCF2CF2CF3 and c -CF2CF2CF2CF2O are reported from T ≈ 235 K to the critical region. Liquid-phase volumetric results for CF3OCF2OCF3 and CF3OCF2CF2H (235 < T/K < 303) are reported to supplement the information already availab...

  15. Progesterone induces adult mammary stem cell expansion.

    PubMed

    Joshi, Purna A; Jackson, Hartland W; Beristain, Alexander G; Di Grappa, Marco A; Mote, Patricia A; Clarke, Christine L; Stingl, John; Waterhouse, Paul D; Khokha, Rama

    2010-06-10

    Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer. PMID:20445538

  16. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics.

    PubMed

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T; Sorensen, Staci A; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-02-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell type-specific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties. PMID:26727548

  17. Adult Mouse Cortical Cell Taxonomy by Single Cell Transcriptomics

    PubMed Central

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T.; Sorensen, Staci A.; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M.; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-01-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. Here, we construct a cellular taxonomy of one cortical region, primary visual cortex, in adult mice based on single cell RNA-sequencing. We identify 49 transcriptomic cell types including 23 GABAergic, 19 glutamatergic and seven non-neuronal types. We also analyze cell-type specific mRNA processing and characterize genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we show that some of our transcriptomic cell types display specific and differential electrophysiological and axon projection properties, thereby confirming that the single cell transcriptomic signatures can be associated with specific cellular properties. PMID:26727548

  18. Molecular Hallmarks of Adult T Cell Leukemia

    PubMed Central

    Yamagishi, Makoto; Watanabe, Toshiki

    2012-01-01

    The molecular hallmarks of adult T cell leukemia (ATL) comprise outstanding deregulations of signaling pathways that control the cell cycle, resistance to apoptosis, and proliferation of leukemic cells, all of which have been identified by early excellent studies. Nevertheless, we are now confronted the therapeutic difficulties of ATL that is a most aggressive T cell leukemia/lymphoma. Using next-generation strategies, emerging molecular characteristics such as specific surface markers and an additional catalog of signals affecting the fate of leukemic cells have been added to the molecular hallmarks that constitute an organizing principle for rationalizing the complexities of ATL. Although human T cell leukemia virus type 1 is undoubtedly involved in ATL leukemogenesis, most leukemic cells do not express the viral protein Tax. Instead, cellular gene expression changes dominate homeostasis disorders of infected cells and characteristics of ATL. In this review, we summarize the state of the art of ATL molecular pathology, which supports the biological properties of leukemic cells. In addition, we discuss the recent discovery of two molecular hallmarks of potential generality; an abnormal microRNA pattern and epigenetic reprogramming, which strongly involve the imbalance of the molecular network of lymphocytes. Global analyses of ATL have revealed the functional impact of crosstalk between multifunctional pathways. Clinical and biological studies on signaling inhibitory agents have also revealed novel oncogenic drivers that can be targeted in future. ATL cells, by deregulation of such pathways and their interconnections, may become masters of their own destinies. Recognizing and understanding of the widespread molecular applicability of these concepts will increasingly affect the development of novel strategies for treating ATL. PMID:23060864

  19. Adult Mesenchymal Stem Cells and Radiation Injury.

    PubMed

    Kiang, Juliann G

    2016-08-01

    Recent understanding of the cellular and molecular signaling activations in adult mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal for tissue repair and recovery after radiation injury. Thus far, MSCs have been characterized extensively and shown to be useful in mitigation and therapy for acute radiation syndrome and cognitive dysfunction. Use of MSCs for treating radiation injury alone or in combination with additional trauma is foreseeable. PMID:27356065

  20. Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors.

    PubMed

    Yan, Weixin; Zhang, Aiguo; Powell, Michael J

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural tumors of the gastrointestinal tract. The identification of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the efficacy of cancer therapy by matching targeted drugs to specific mutations. Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A (PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by the KIT gene. Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs, yet the prevalence and size of subpopulations remain largely unexplored. Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods, such as polymerase chain reaction (PCR) target amplification technology, is hampered by the high abundance of wild-type alleles, which limit the sensitivity of detection of these minor mutant alleles. This is especially true in the case of mutant tumor DNA derived "driver" and "drug-resistant" alleles that are present in the circulating cell-free tumor DNA (cfDNA) in the peripheral blood circulation of GIST patients. So-called "liquid biopsy" allows for the dynamic monitoring of the patients' tumor status during treatment using minimally invasive sampling. New methodologies, such as a technology that employs a xenonucleic acid (XNA) clamping probe to block the PCR amplification of wild-type templates, have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA. These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs. PMID:27443349

  1. Adult stem cell-based apexogenesis

    PubMed Central

    Li, Yao; Shu, Li-Hong; Yan, Ming; Dai, Wen-Yong; Li, Jun-Jun; Zhang, Guang-Dong; Yu, Jin-Hua

    2014-01-01

    Generally, the dental pulp needs to be removed when it is infected, and root canal therapy (RCT) is usually required in which infected dental pulp is replaced with inorganic materials (paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth are destined to be devitalized, brittle and susceptible to postoperative fracture. Recently, the advances and achievements in the field of stem cell biology and regenerative medicine have inspired novel biological approaches to apexogenesis in young patients suffering from pulpitis or periapical periodontitis. This review mainly focuses on the benchtop and clinical regeneration of root apex mediated by adult stem cells. Moreover, current strategies for infected pulp therapy are also discussed here. PMID:25332909

  2. Adult stem cell-based apexogenesis.

    PubMed

    Li, Yao; Shu, Li-Hong; Yan, Ming; Dai, Wen-Yong; Li, Jun-Jun; Zhang, Guang-Dong; Yu, Jin-Hua

    2014-06-26

    Generally, the dental pulp needs to be removed when it is infected, and root canal therapy (RCT) is usually required in which infected dental pulp is replaced with inorganic materials (paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth are destined to be devitalized, brittle and susceptible to postoperative fracture. Recently, the advances and achievements in the field of stem cell biology and regenerative medicine have inspired novel biological approaches to apexogenesis in young patients suffering from pulpitis or periapical periodontitis. This review mainly focuses on the benchtop and clinical regeneration of root apex mediated by adult stem cells. Moreover, current strategies for infected pulp therapy are also discussed here. PMID:25332909

  3. [Pulmonary Langerhans cell histiocytosis in adults].

    PubMed

    Feuillet, Séverine; Giroux-Leprieur, Bénédicte; Tazi, Abdellatif

    2010-01-01

    Pulmonary Langerhans-cell histiocytosis in adults is a rare condition of unknown etiology characterized by the accumulation of Langerhans cells organized in granulomas involving the distal bronchioles and destroying their walls. It occurs in young subjects who smoke, with frequency peaking between 20 and 40 years. High-resolution thoracic CT is essential for diagnosis; in typical forms it shows a combination of nodules, cavitary nodules, thick-walled cysts, and thin-walled cysts. Diagnostic certainty requires a surgical lung biopsy, by videothoracoscopy, but only if a specialist considers it indicated. It is difficult to predict the disease course for any given patient. A prospective multicenter cohort study currently underway should provide more information about the natural history of this disease. Management is empirical, for efficacy has not been proved for any treatment. Stopping smoking is especially important to prevent the added development of chronic obstructive pulmonary disease (COPD), cardiovascular complications, or the onset of bronchopulmonary cancer, the frequency of which appears elevated in these patients. Oral corticosteroids are used to treat disease progression, especially in the symptomatic mainly nodular forms, but their efficacy for respiratory function has not been shown. Vinblastine, the reference treatment for multisystem forms of Langerhans-cell histiocytosis, is not indicated for pulmonary involvement in adults. Better knowledge of the pathogenic mechanisms involved in this condition should eventually make it possible to develop innovative treatment strategies. The creation of the national reference center for Langerhans-cell histiocytosis has given new momentum to clinical and pathophysiologic research on this orphan disease. PMID:19959324

  4. Sertoli Cells Maintain Leydig Cell Number and Peritubular Myoid Cell Activity in the Adult Mouse Testis

    PubMed Central

    Monteiro, Ana; Milne, Laura; Cruickshanks, Lyndsey; Jeffrey, Nathan; Guillou, Florian; Freeman, Tom C.; Mitchell, Rod T.; Smith, Lee B.

    2014-01-01

    The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR) specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health. PMID:25144714

  5. Persistent Disparities in Adult Hematopoietic Cell Transplantation.

    PubMed

    Crockett, David G; Loberiza, Fausto R

    2015-09-01

    The use of large databases has provided advancements in the understanding of racial, ethnic, and socioeconomic disparities in the field of adult hematopoietic cell transplants (HCT). Disparities exist on individual, institutional, and systemic levels for both allogeneic and autologous HCT. We reviewed the most recent publications that utilized large databases to elucidate disparities in HCT and placed them into historical context of the other major studies in the field. Two emerging themes were identified. These themes are persistent inequalities in both allogeneic HCT and autologous HCT for myeloma and the importance of improving homogeneity of care in HCT. Minimization of inequalities can be achieved only with an understanding of the persistent barriers that exist in the field. PMID:26104908

  6. CF6 performance improvement

    NASA Technical Reports Server (NTRS)

    Lennard, D. J.

    1978-01-01

    Potential CF6 engine performance improvements directed at reduced fuel consumption were identified and screened relative to airline acceptability and are reviewed. The screening process developed to provide evaluations of fuel savings and economic factors including return on investment and direct operating cost is described. In addition, assessments of development risk and production potential are made. Several promising concepts selected for full-scale development based on a ranking involving these factors are discussed.

  7. A new perfluorinated peroxynitrate, CF3CF2CF2CF2OONO2. Synthesis, characterization and atmospheric implications

    NASA Astrophysics Data System (ADS)

    Bossolasco, Adriana G.; Vila, Jesús A.; Burgos Paci, Maxi A.; Malanca, Fabio E.; Argüello, Gustavo A.

    2014-09-01

    CF3CF2CF2CF2OONO2 was synthesized from the photolysis of CF3CF2CF2CF2I, in presence of NO2 and O2. Alkyl peroxynitrates (CxF2x+1OONO2) could be formed in the atmospheric degradation of chlorofluorocarbons, hydrofluorocarbons and hydrofluoroethers. We present here the synthesis and characterization (IR and UV absorption cross sections) of CF3CF2CF2CF2OONO2 and its comparison with those corresponding to other perfluoro alkyl peroxynitrates. The thermal stability was studied as a function of total pressure (from 9.0 to 417 mbar) and temperature (from 283 to 293 K) using infrared spectroscopy. Kinetic parameters measured for the thermal dissociation were Ea = (81 ± 4) kJ/mol and A = 4.8 × 1012. DFT calculations at the B3LYP/6-311+G∗ level were used to explore the ground state potential energy surface. Geometrical parameters, conformer populations and vibrational spectra are presented. The calculated activation energy was 81.3 kJ mol-1 in excellent agreement with experimental results. Atmospheric implications are discussed.

  8. NASA Li/CF(x) cell problem analysis: Scanning electron microscopy with energy dispersive x ray spectrometry

    NASA Technical Reports Server (NTRS)

    Baker, John

    1991-01-01

    An analysis was made of Lithium/carbon fluoride cell parts for possible chloride contamination induced by exposure to thionyl chloride (SOCl2); various samples were submitted for analysis. Only a portion of the analysis which has been conducted is covered, herein, namely analysis by scanning electron microscopy with energy dispersive x ray spectrometry (SEM/EDS). A strip of nickel was exposed to SOCl2 vapors to observe variations in surface concentrations of sulfur and chlorine with time. By detecting chlorine one can not infer contamination by SOCl2 only that contamination is present. Six samples of stainless steel foil were analyzed for chlorine using EDS. Chlorine was not detected on background samples but was detected on the samples which had been handled including those which had been cleaned. Cell covers suspected of being contaminated while in storage and covers which were not exposed to the same storage conditions were analyzed for chlorine. Although no chlorine was found on the covers from cells, it was found on all stored covers. Results are presented with techniques shown for analysis and identification. Relevant photomicrographs are presented.

  9. [Pulmonary complications in adult sickle cell disease].

    PubMed

    Maître, B; Mekontso-Dessap, A; Habibi, A; Bachir, D; Parent, F; Godeau, B; Galacteros, F

    2011-02-01

    Sickle cell disease is an autosomal genetic condition which represents the most frequent genetic disease in Île-de-France and Caribbean islands. The main clinical manifestations can be divided into infectious disease, hemolytic anemia and vaso-occlusive events. Pulmonary complications represent 20 to 30% of mortality due to sickle cell and can be divided into acute and chronic events. Acute chest syndrome (ACS) is an acute lung injury often preceded by a vaso-occlusive crisis and triggered by different factors including: hypoventilation, pulmonary infectious disease and vascular occlusions. These occlusions can be secondary to fat embolism, thrombosis or sickling. Treatment is mainly supportive combining oxygen supplementation adequate hydration analgesia and sedation. Exchange transfusion may be indicated in severe forms of ACS, characterized by a right ventricular dysfunction and acute respiratory failure. Pulmonary hypertension is the most serious chronic complication. Its frequency is estimated at 6% in adult patients and is more often described in patients with venous ulcers and higher levels of chronic hemolysis. Prognosis is poor with 12.5% of patients dying in the first two years following diagnosis irrespective of the actual pulmonary artery pressure level. There are currently limited data on the effects of any treatment modality. Other respiratory complications such as sleep disorders and nocturnal hypoxemia, infiltrative lung disease and exertional dyspnea are described and should be considered. PMID:21402228

  10. [Progress in treating diabetes mellitus with adult stem cells].

    PubMed

    Zhang, Lixin; Teng, Chunbo; An, Tiezhu

    2008-02-01

    Diabetes mellitus is a metabolic diseases, mainly including type 1 and type 2 diabetes. Treatment for type 1 and part of type 2 often involves regular insulin injection. However, this treatment neither precisely controls the blood sugar levels, nor prevents the diabetes complications. Transplantation of islets of Langerhans offers an attractive strategy for diabetes therapies, but its wide application has been limited by donor shortage and immunological rejection after transplantation. Stem cells with strong proliferation capacity and multipotential may be potential cell sources in diabetes therapies. For this, adult stem cells are interesting because of absence of teratoma formation and ethnical problems. Adult pancreatic stem cells (PSCs) really exist and could produce insulin-secreting cells both under the condition of pancreatic injury and in vitro culture, but lack of effective markers to enrich PSCs hampers the studies of exploring the expanding and differentiating conditions in vitro. Some other adult stem cells, such as hepatic stem cells, marrow stem cells or intestine stem cells, were also suggested to transdifferentiate into insulin-producing cells under special culture conditions in vitro or by genetic modifications. Moreover, transplanting these adult stem cells-derived insulin-secreting cells into the diabetic mouse could cure diabetes. Thus, adult stem cells would supply the abundant beta-cell sources for cell replacement therapy of diabetes. PMID:18464596

  11. Infectious hematopoietic necrosis virus detected by separation and incubation of cells from salmonid cavity fluid.

    USGS Publications Warehouse

    Mulcahy, D.; Batts, W.N.

    1987-01-01

    Infectious hematopoietic necrosis (IHN) virus is usually detected by inoculating susceptible cell cultures with cavity ("ovarian") fluid (CF) from spawning females. We identified additional adult carriers of virus in spawning populations of steelhead trout (Salmo gairdneri) and sockeye salmon (Oncorhynchus nerka) by collecting nonerythrocytic cells from CF samples by low-speed centrifugation, culturing the cells for at least 7 d at 15 °C, and then testing the culture medium for virus. Virus appeared in the cultured cells from some samples of CF that remained negative during incubation. In additional samples of CF from these species, the virus titer increased in cultured cells compared with the titer in the original CF sample. With chinook salmon (O.tshawytscha), no negative samples converted to positive during incubation, but the virus titer was retained in incubated CF cells, but not in cell-free CF.

  12. Adult T-cell leukemia-lymphoma.

    PubMed

    Tsukasaki, Kunihiro

    2012-04-01

    Adult T-cell leukemia-lymphoma (ATL) was first described in 1977 as a distinct clinico-pathological entity with a suspected viral etiology. Subsequently, a novel RNA retrovirus, human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) was isolated from a cell line established from the leukemic cells of an ATL patient, and the finding of a clear association with ATL led to its inclusion among human carcinogenic pathogens. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. HTLV-1 infection early in life, presumably from breast feeding, is crucial in the development of ATL. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types defined by organ involvement, and LDH and calcium values. In cases of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy such as VCAP-AMP-VECP is usually recommended. In cases of favorable chronic or smoldering ATL (indolent ATL), watchful waiting until disease progression has been recommended although the long term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation is also promising for the treatment of aggressive ATL possibly reflecting graft vs. ATL effect. Several new agent-trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody. Two steps should be considered for the prevention of HTLV-1-associated ATL. The first is the prevention of HTLV-1 infections and the second is the prevention of ATL among HTLV-1 carriers. So far, no agent has been found to be

  13. Cell Phone Use by Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Bryen, Diane Nelson; Carey, Allison; Friedman, Mark

    2007-01-01

    Although cell phone use has grown dramatically, there is a gap in cell phone access between people with disabilities and the general public. The importance of cell phone use among people with intellectual disabilities and studies about use of cell phones by adults with intellectual disabilities was described. Our goal was to determine the extent…

  14. Hepatic cancer stem cells may arise from adult ductal progenitors

    PubMed Central

    Nikolaou, Kostas C; Talianidis, Iannis

    2016-01-01

    Cancer stem cells (CSCs) are defined as cells within tumors that can self-renew and differentiate into heterogeneous lineages of cancerous cells. The origin of CSCs is not well understood. Recent evidence suggests that CSCs in hepatocellular carcinoma could be generated via oncogenic transformation and partial differentiation of adult hepatic ductal progenitor cells.

  15. Delivery of genes into the CF airway.

    PubMed

    Gill, Deborah R; Hyde, Stephen C

    2014-10-01

    Gene therapy was suggested as a potential treatment for cystic fibrosis (CF), even before the identification of the CFTR gene. Initial enthusiasm has been tempered as it became apparent that reintroduction of the CFTR gene into the cells of the lung is more difficult than anticipated. Here, we review the major gene delivery vectors evaluated clinically, and suggest that advances in either plasmid DNA design and/or hybrid lentivirus biology may finally facilitate lung gene transfer with efficiencies sufficient for CF gene therapy to offer clinical benefit. PMID:25015239

  16. VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITIES, AND CRITICAL PROPERTIES OF SOME FLUORINATED ETHERS: CF3OCF2OCF3, CF3OCF2 CF2H, c-CF2CF2CF2O, CF3OCF2H, AND CF3OCH3; AND OF CCl3F AND CF2ClH

    EPA Science Inventory

    Vapor pressures, compressibilities, expansivities, and molar volumes of the liquid phase have been measured between room temperature and the critical temperature for a series of fluorinated ethers: CF3OCF2OCF3, CF3OCF2CF2H, c-CF2CF2CF2O, CF3OCF2H, and CF3OCH3. Vapor-phase non-ide...

  17. Anonymous sources: where do adult β cells come from?

    PubMed

    German, Michael S

    2013-05-01

    Evidence that the pool of insulin-producing β cells in the pancreas is reduced in both major forms of diabetes mellitus has led to efforts to understand β cell turnover in the adult pancreas. Unfortunately, previous studies have reached opposing conclusions regarding the source of new β cells during regeneration in the adult pancreas. In this issue of the JCI, Xiao et al. use a novel mouse model for detecting new β cells derived from non-β cells to demonstrate the absence of β cell neogenesis from non-β cells during normal postnatal growth and in models of β cell regeneration. This work adds to mounting evidence that in most physiological and pathological conditions, β cell neogenesis may not make large contributions to the postnatal β cell pool - at least not in rodents. PMID:23619356

  18. HIV is inactivated after transepithelial migration via adult oral epithelial cells but not fetal epithelial cells

    PubMed Central

    Tugizov, Sharof M.; Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

    2010-01-01

    Oral transmission of human immunodeficiency virus (HIV) in adult populations is rare. However, HIV spread across fetal/neonatal oropharyngeal epithelia could be important in mother-to-child transmission. Analysis of HIV transmission across polarized adult and fetal oral epithelial cells revealed that HIV transmigrates through both adult and fetal cells. However, only virions that passed through the fetal cells – and not those that passed through the adult cells – remained infectious. Analysis of expression of anti-HIV innate proteins beta-defensins 2 and 3, and secretory leukocyte protease inhibitor in adult, fetal, and infant oral epithelia showed that their expression is predominantly in the adult oral epithelium. Retention of HIV infectivity after transmigration correlated inversely with the expression of these innate proteins. Inactivation of innate proteins in adult oral keratinocytes restored HIV infectivity. These data suggest that high-level innate protein expression may contribute to the resistance of the adult oral epithelium to HIV transmission. PMID:21056450

  19. The adult human brain harbors multipotent perivascular mesenchymal stem cells.

    PubMed

    Paul, Gesine; Özen, Ilknur; Christophersen, Nicolaj S; Reinbothe, Thomas; Bengzon, Johan; Visse, Edward; Jansson, Katarina; Dannaeus, Karin; Henriques-Oliveira, Catarina; Roybon, Laurent; Anisimov, Sergey V; Renström, Erik; Svensson, Mikael; Haegerstrand, Anders; Brundin, Patrik

    2012-01-01

    Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain. PMID:22523602

  20. High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

    PubMed Central

    Kong, Chae-Gwan; Kim, Man Soo; Park, Eun-Young

    2014-01-01

    Study Design In vitro cell culture. Purpose The purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells. Overview of Literature Diabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells. Methods Nucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified. Results Two high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner. Conclusions The results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus. PMID:25346805

  1. Muscle stem cells contribute to myofibers in sedentary adult mice

    PubMed Central

    Keefe, Alexandra C.; Lawson, Jennifer A.; Flygare, Steven D.; Fox, Zachary D.; Colasanto, Mary P.; Mathew, Sam J.; Yandell, Mark; Kardon, Gabrielle

    2015-01-01

    Skeletal muscle is essential for mobility, stability, and whole body metabolism, and muscle loss, for instance during sarcopenia, has profound consequences. Satellite cells (muscle stem cells) have been hypothesized, but not yet demonstrated, to contribute to muscle homeostasis and a decline in their contribution to myofiber homeostasis to play a part in sarcopenia. To test their role in muscle maintenance, we genetically labeled and ablated satellite cells in adult sedentary mice. We demonstrate via genetic lineage experiments that even in the absence of injury, satellite cells contribute to myofibers in all adult muscles, although the extent and timing differs. However, genetic ablation experiments showed that satellite cells are not globally required to maintain myofiber cross-sectional area of uninjured adult muscle. PMID:25971691

  2. Signaling mechanisms regulating adult neural stem cells and neurogenesis

    PubMed Central

    Faigle, Roland; Song, Hongjun

    2012-01-01

    Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

  3. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  4. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  5. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  6. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  7. Therapeutics from Adult Stem Cells and the Hype Curve.

    PubMed

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment. PMID:27190588

  8. Tax fingerprint in adult T-cell leukemia.

    PubMed

    Bazarbachi, Ali

    2016-04-01

    In this issue of Blood, Fujikawa et al demonstrate that the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax induces an epigenetic-dependent global modification of host gene expression in adult T-cell leukemia-lymphoma (ATL). Hence, the fingerprint of Tax is all over ATL and this may be used for finally capturing ATL. PMID:27056993

  9. Adult stem cells: the therapeutic potential of skeletal muscle.

    PubMed

    Saini, Amarjit; Stewart, Claire E H

    2006-05-01

    Embryonic stem cells have revolutionised our understanding of normal and deregulated growth and development. The potential to produce cells and tissues as needed offers enormous therapeutic potential. The use of these cells, however, is accompanied by ongoing ethical, religious and biomedical issues. The expansion potential and plasticity of adult stem cells have therefore received much interest. Adult skeletal muscle is highly adaptable, responding to both the hypertrophic and degenerative stresses placed upon it. This extreme plasticity is in part regulated by resident stem cells. In addition to regenerating muscle, if exposed to osteogenic or adipogenic inducers, these cells spontaneously form osteoblasts or adipocytes. The potential for and heterogeneity of muscle stem cells is underscored by the observation that CD45+ muscle side population cells are capable of reconstituting bone marrow in lethally irradiated mice and of contributing to neo-vascularisation of regenerating muscle. Finally, first attempts to replace infarcted myocardium relied on injection of skeletal myoblasts into the heart. Cells successfully engrafted and cardiac function was improved. Harnessing their differentiation/trans-differentiation capacity provides enormous potential for adult stem cells. In this review, current understanding of the different stem cells within muscle will be discussed as will their potential utility for regenerative medicine. PMID:18220864

  10. Engineering of the Embryonic and Adult Stem Cell Niches

    PubMed Central

    Hosseinkhani, Mohsen; Shirazi, Reza; Rajaei, Farzad; Mahmoudi, Masoud; Mohammadi, Navid; Abbasi, Mahnaz

    2013-01-01

    Context Stem cells have the potential to generate a renewable source of cells for regenerative medicine due to their ability to self-renew and differentiate to various functional cell types of the adult organism. The extracellular microenvironment plays a pivotal role in controlling stem cell fate responses. Therefore, identification of appropriate environmental stimuli that supports cellular proliferation and lineage-specific differentiation is critical for the clinical application of the stem cell therapies. Evidence Acquisition Traditional methods for stem cells culture offer limited manipulation and control of the extracellular microenvironment. Micro engineering approaches are emerging as powerful tools to control stem cell-microenvironment interactions and for performing high-throughput stem cell experiments. Results In this review, we provided an overview of the application of technologies such as surface micropatterning, microfluidics, and engineered biomaterials for directing stem cell behavior and determining the molecular cues that regulate cell fate decisions. Conclusions Stem cells have enormous potential for therapeutic and pharmaceutical applications, because they can give rise to various cell types. Despite their therapeutic potential, many challenges, including the lack of control of the stem cell microenvironment remain. Thus, a greater understanding of stem cell biology that can be used to expand and differentiate embryonic and adult stem cells in a directed manner offers great potential for tissue repair and regenerative medicine. PMID:23682319

  11. Identification of Neutrophil Activation Markers as Novel Surrogate Markers of CF Lung Disease

    PubMed Central

    Hage, Lisa; Kügler, Marion; Menendez, Katrin; Naehrlich, Lutz; Schulz, Richard; Roderfeld, Martin; Roeb, Elke

    2014-01-01

    Background and aims Cystic Fibrosis (CF) lung disease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lung disease and the occurrence of pulmonary exacerbations (PEx) are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lung disease. Methods 54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lung disease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001. Results Adults and children with moderate to severe CF lung disease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency. Conclusions MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lung disease and PEx. PMID:25545245

  12. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells

    PubMed Central

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  13. Optimized cell transplantation using adult rag2 mutant zebrafish

    PubMed Central

    Tang, Qin; Abdelfattah, Nouran S.; Blackburn, Jessica S.; Moore, John C.; Martinez, Sarah A.; Moore, Finola E.; Lobbardi, Riadh; Tenente, Inês M.; Ignatius, Myron S.; Berman, Jason N.; Liwski, Robert S.; Houvras, Yariv; Langenau, David M.

    2014-01-01

    Cell transplantation into adult zebrafish has lagged behind mouse due to the lack of immune compromised models. Here, we have created homozygous rag2E450fs mutant zebrafish that have reduced numbers of functional T and B cells but are viable and fecund. Mutant fish engraft zebrafish muscle, blood stem cells, and cancers. rag2E450fs mutant zebrafish are the first immune compromised zebrafish model that permits robust, long-term engraftment of multiple tissues and cancer. PMID:25042784

  14. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells.

    PubMed

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  15. Adult T-cell leukaemia lymphoma in an aborigine.

    PubMed

    Kirkland, M A; Frasca, J; Bastian, I

    1991-10-01

    A 44-year-old Aborigine with Adult T-cell Leukaemia/Lymphoma (ATLL) due to HTLV-I is reported. He presented with transverse myelitis of subacute onset, and subsequently developed frank T-cell leukaemia complicated by splenomegaly and hypercalcaemia. Cell surface marker studies showed a phenotype of CD3+ CD4+ CD8- CD25+, and serological and molecular studies confirmed HTLV-I infection. This is the first report of ATLL in an Australian Aborigine. PMID:1759923

  16. Young Adult Perspectives on a Successful Transition from Pediatric to Adult Care in Sickle Cell Disease

    PubMed Central

    Sobota, Amy E.; Umeh, Emeka; Mack, Jennifer W.

    2016-01-01

    Objective This qualitative study sought to learn from young adults with sickle cell disease (SCD) about their experience leaving pediatric care and perspective on what makes a successful transition. Methods Fifteen young adults with SCD who had left pediatric care within the previous five years participated in focus groups led by a trained moderator. Transcripts were analyzed using grounded theory. Results Four main themes emerged from the analysis: facilitators of transition (meeting the adult provider prior to transfer, knowing what to expect, gradually taking over disease self-management and starting the process early), barriers to transition (negative perceived attitude of adult staff, lack of SCD specific knowledge by both patients and staff, and competing priorities interfering with transition preparation), what young adults wished for in a transition program (opportunities to meet more staff prior to transfer, more information about the differences between pediatric and adult care, learning from a peer who has been through the process, more SCD teaching, and flexibility in transition preparation) and how they define a successful transition (gradually assuming responsibility for self-management of their SCD). Conclusion Our findings present unique opportunities to learn from young adults with SCD about ways to improve current transition programs. PMID:27175364

  17. Adult granulosa cell tumor of the testis masquerading as hydrocele

    PubMed Central

    Vallonthaiel, Archana George; Kakkar, Aanchal; Singh, Animesh; Dogra, Prem N; Ray, Ruma

    2015-01-01

    ABSTRACT Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view. PMID:26742984

  18. Properties of Adult Lung Stem and Progenitor Cells.

    PubMed

    Bertoncello, Ivan

    2016-12-01

    The last decade has seen significant progress in understanding the organisation of regenerative cells in the adult lung. Cell-lineage tracing and in vitro clonogenic assays have enabled the identification and characterisation of endogenous lung epithelial stem and progenitor cells. Selective lung injury models, and genetically engineered mice have revealed highly conserved gene networks, factors, signalling pathways, and cellular interactions important in maintaining lung homeostasis and regulating lung regeneration and repair following injury. This review describes the current models of lung epithelial stem and progenitor cell organisation in adult mice, and the impediments encountered in translational studies aiming to identify and characterise their human homologs. J. Cell. Physiol. 231: 2582-2589, 2016. © 2016 Wiley Periodicals, Inc. PMID:27062064

  19. Adult stem cells and their ability to differentiate.

    PubMed

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue. PMID:16865077

  20. Adult stem cells underlying lung regeneration

    PubMed Central

    2012-01-01

    Despite the massive toll in human suffering imparted by degenerative lung disease, including COPD, idiopathic pulmonary fibrosis and ARDS, the scientific community has been surprisingly agnostic regarding the potential of lung tissue and, in particular, the alveoli, to regenerate. However, there is circumstantial evidence in humans and direct evidence in mice that ARDS triggers robust regeneration of lung tissue rather than irreversible fibrosis. The stem cells responsible for this remarkable regenerative process has garnered tremendous attention, most recently yielding a defined set of cloned human airway stem cells marked by p63 expression but with distinct commitment to differentiated cell types typical of the upper or lower airways, the latter of which include alveoli-like structures in vitro and in vivo. These recent advances in lung regeneration and distal airway stem cells and the potential of associated soluble factors in regeneration must be harnessed for therapeutic options in chronic lung disease. PMID:22333577

  1. Embryonic and adult stem cell therapy.

    PubMed

    Brignier, Anne C; Gewirtz, Alan M

    2010-02-01

    There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID:20061008

  2. Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin.

    PubMed

    Golub, Justin S; Tong, Ling; Ngyuen, Tot B; Hume, Cliff R; Palmiter, Richard D; Rubel, Edwin W; Stone, Jennifer S

    2012-10-24

    We developed a transgenic mouse to permit conditional and selective ablation of hair cells in the adult mouse utricle by inserting the human diphtheria toxin receptor (DTR) gene into the Pou4f3 gene, which encodes a hair cell-specific transcription factor. In adult wild-type mice, administration of diphtheria toxin (DT) caused no significant hair cell loss. In adult Pou4f3(+/DTR) mice, DT treatment reduced hair cell numbers to 6% of normal by 14 days post-DT. Remaining hair cells were located primarily in the lateral extrastriola. Over time, hair cell numbers increased in these regions, reaching 17% of untreated Pou4f3(+/DTR) mice by 60 days post-DT. Replacement hair cells were morphologically distinct, with multiple cytoplasmic processes, and displayed evidence for active mechanotransduction channels and synapses characteristic of type II hair cells. Three lines of evidence suggest replacement hair cells were derived via direct (nonmitotic) transdifferentiation of supporting cells: new hair cells did not incorporate BrdU, supporting cells upregulated the pro-hair cell gene Atoh1, and supporting cell numbers decreased over time. This study introduces a new method for efficient conditional hair cell ablation in adult mouse utricles and demonstrates that hair cells are spontaneously regenerated in vivo in regions where there may be ongoing hair cell turnover. PMID:23100430

  3. Intestinal stem cells in the adult Drosophila midgut

    SciTech Connect

    Jiang, Huaqi; Edgar, Bruce A.

    2011-11-15

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.

  4. In Vivo Dedifferentiation of Adult Adipose Cells

    PubMed Central

    Lu, Feng; Dong, Ziqing; Chang, Qiang; Gao, Jianhua

    2015-01-01

    Introduction Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown. Methods A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histological, cytological, ultrastructural, and gene expression analyses were conducted. In a separate experiment, purified green fluorescent protein+ adipocytes were transplanted into C57 mice and collected at various time points. The transplanted adipocytes were assessed by bioluminescence imaging and whole-mount staining. Results The expanded fat pad was obviously thinner than the untreated fat pad on the opposite side. It was also tougher in texture and with more blood vessels attached. Hematoxylin and eosin staining and transmission electron microscopy indicated there were fewer monolocular adipocytes in the expanded fat pad and the morphology of these cells was altered, most notably their lipid content was discarded. Immunohistochemistry showed that the expanded fat pad contained an increased number of proliferative cells, which may have been derived from adipocytes. Following removal of the tissue expander, many small adipocytes were observed. Bioluminescence imaging suggested that some adipocytes survived when transplanted into an ischemic-hypoxic environment. Whole-mount staining revealed that surviving adipocytes underwent a process similar to adipocyte dedifferentiation in vitro. Monolocular adipocytes became multilocular adipocytes and then fibroblast-like cells. Conclusions Mature adipocytes may be able to dedifferentiate in vivo, and this may be an adipose tissue self-repair mechanism. The capacity of adipocytes to dedifferentiate into stem cell-like cells may also have a

  5. EMPOWERING ADULT STEM CELLS FOR MYOCARDIAL REGENERATION

    PubMed Central

    Mohsin, Sadia; Siddiqi, Sailay; Collins, Brett; Sussman, Mark A.

    2012-01-01

    Treatment strategies for heart failure remain a high priority for ongoing research due to the profound unmet need in clinical disease coupled with lack of significant translational progress. The underlying issue is the same whether the cause is acute damage, chronic stress from disease, or aging: progressive loss of functional cardiomyocytes and diminished hemodynamic output. To stave off cardiomyocyte losses, a number of strategic approaches have been embraced in recent years involving both molecular and cellular approaches to augment myocardial structure and performance. Resultant excitement surrounding regenerative medicine in the heart has been tempered by realizations that reparative processes in the heart are insufficient to restore damaged myocardium to normal functional capacity and that cellular cardiomyoplasty is hampered by poor survival, proliferation, engraftment and differentiation of the donated population. To overcome these limitations, a combination of molecular and cellular approaches needs to be adopted involving use of genetic engineering to enhance resistance to cell death and increase regenerative capacity. This review will highlight biological properties of approached to potentiate stem cell-mediated regeneration to promote enhanced myocardial regeneration, persistence of donated cells, and long lasting tissue repair. Optimizing cell delivery and harnessing the power of survival signaling cascades for ex vivo genetic modification of stem cells prior to reintroduction into the patient will be critical to enhance the efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based therapy has great promise for treatment of heart failure to combat the loss of cardiac structure and function associated with acute damage, chronic disease or aging. PMID:22158649

  6. Isolation, culture and analysis of adult subependymal neural stem cells.

    PubMed

    Belenguer, Germán; Domingo-Muelas, Ana; Ferrón, Sacri R; Morante-Redolat, José Manuel; Fariñas, Isabel

    2016-01-01

    Individual cells dissected from the subependymal neurogenic niche of the adult mouse brain proliferate in medium containing basic fibroblast growth factor (bFGF) and/or epidermal growth factor (EGF) as mitogens, to produce multipotent clonal aggregates called neurospheres. These cultures constitute a powerful tool for the study of neural stem cells (NSCs) provided that they allow the analysis of their features and potential capacity in a controlled environment that can be modulated and monitored more accurately than in vivo. Clonogenic and population analyses under mitogen addition or withdrawal allow the quantification of the self-renewing and multilineage potency of these cells and the identification of the mechanisms involved in these properties. Here, we describe a set of procedures developed and/or modified by our group including several experimental options that can be used either independently or in combination for the ex vivo assessment of cell properties of NSCs obtained from the adult subependymal niche. PMID:27016251

  7. Medical perspectives of adults and embryonic stem cells.

    PubMed

    Cavazzana-Calvo, Marina; André-Schmutz, Isabelle; Lagresle, Chantal; Fischer, Alain

    2002-10-01

    In the last 30 years, allogeneic bone marrow transplantation has become the treatment of choice for many hematologic malignancies or inherited disorders and a number of changes have been registered in terms of long-term survival rate of transplanted patients as well as of available sources of hematopoietic stem cell (HSC). In parallel to the publication of better results in HSC transplantation, several recent discoveries have opened a scientific and ethical debate on the therapeutical potential of stem cells isolated from adult or embryonic tissues. One of the major discoveries in this field is the capacity of bone marrow-derived stem cells to treat a genetic liver disease in a mouse model, thus justifying the concept of transdifferentiation of adult stem cell and raising hopes on its possible therapeutical applications. We have tried here to summarise the advances in this field and to discuss the limits of these biological data. PMID:12494504

  8. Langerhans' cell histiocytosis in an adult.

    PubMed

    Lindelöf, B; Forslind, B; Hilliges, M; Johansson, O; Aström, L

    1991-01-01

    A woman with typical skin lesions of histiocytosis X is reported. Electron microscopic and immunohistochemical investigations revealed a large number of markedly long Birbeck Langerhans' cell granulae. During treatment with Interferon alpha -2b, the patient developed infarctus cerebri and died. PMID:1675535

  9. Adult stem cells for chronic lung diseases.

    PubMed

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  10. New Nerve Cells for the Adult Brain.

    ERIC Educational Resources Information Center

    Kempermann, Gerd; Gage, Fred H.

    1999-01-01

    Contrary to dogma, the human brain does produce new nerve cells in adulthood. The mature human brain spawns neurons routinely in the hippocampus, an area important to memory and learning. This research can make it possible to ease any number of disorders involving neurological damage and death. (CCM)

  11. Live Imaging of Adult Neural Stem Cells in Rodents

    PubMed Central

    Ortega, Felipe; Costa, Marcos R.

    2016-01-01

    The generation of cells of the neural lineage within the brain is not restricted to early development. New neurons, oligodendrocytes, and astrocytes are produced in the adult brain throughout the entire murine life. However, despite the extensive research performed in the field of adult neurogenesis during the past years, fundamental questions regarding the cell biology of adult neural stem cells (aNSCs) remain to be uncovered. For instance, it is crucial to elucidate whether a single aNSC is capable of differentiating into all three different macroglial cell types in vivo or these distinct progenies constitute entirely separate lineages. Similarly, the cell cycle length, the time and mode of division (symmetric vs. asymmetric) that these cells undergo within their lineage progression are interesting questions under current investigation. In this sense, live imaging constitutes a valuable ally in the search of reliable answers to the previous questions. In spite of the current limitations of technology new approaches are being developed and outstanding amount of knowledge is being piled up providing interesting insights in the behavior of aNSCs. Here, we will review the state of the art of live imaging as well as the alternative models that currently offer new answers to critical questions. PMID:27013941

  12. Calcium exchange, structure, and function in cultured adult myocardial cells

    SciTech Connect

    Langer, G.A.; Frank, J.S.; Rich, T.L.; Orner, F.B.

    1987-02-01

    Cells digested from adult rat heart and cultured for 14 days demonstrate all the structural elements, in mature form, associated with the process of excitation-contraction (EC) coupling. The transverse tubular (TT) system is well developed with an extensive junctional sarcoplasmic reticulum (JSR). In nonphosphate-containing buffer contraction of the cells is lost as rapidly as zero extracellular Ca concentration ((Ca)/sup 0/) solution is applied and a negative contraction staircase is produced on increase of stimulation frequency. Structurally and functionally the cells have the characteristics of adult cells in situ. /sup 45/Ca exchange and total /sup 45/Ca measurement in N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid (HEPES)-buffered perfusate define three components of cellular Ca: 1) a rapidly exchangeable component accounting for 36% of total Ca, 2) a slowly exchangeable component (t/sub 1/2/ 53 min) accounting for 7% total Ca, and 3) the remaining 57% cellular Ca is inexchangeable (demonstrates no significant exchange within 60 min). The slowly exchangeable component can be increased 10-fold within 60 min by addition of phosphate to the perfusate. The Ca distribution and exchange characteristics are little different from those of 3-day cultures of neonatal rat heart previously studied. The results suggest that the cells are representative of adult cells in situ and that both sarcolemmal-bound and sarcoplasmic reticular Ca contribute to the component of Ca that is rapidly exchangeable.

  13. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    PubMed Central

    Webb, Carol F.; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. PMID:26111446

  14. Wnt signaling in adult intestinal stem cells and cancer.

    PubMed

    Krausova, Michaela; Korinek, Vladimir

    2014-03-01

    Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physiological range. In addition, the Wnt pathway involves various feedback loops that balance the opposing processes of cell proliferation and differentiation. Today, we have compelling evidence that mutations causing aberrant activation of the Wnt pathway promote expansion of undifferentiated progenitors and lead to cancer. The review summarizes recent advances in characterization of adult epithelial stem cells in the gut. We mainly focus on discoveries related to molecular mechanisms regulating the output of the Wnt pathway. Moreover, we present novel experimental approaches utilized to investigate the epithelial cell signaling circuitry in vivo and in vitro. Pivotal aspects of tissue homeostasis are often deduced from studies of tumor cells; therefore, we also discuss some latest results gleaned from the deep genome sequencing studies of human carcinomas of the colon and rectum. PMID:24308963

  15. Intraganglionic interactions between satellite cells and adult sensory neurons.

    PubMed

    Christie, Kimberly; Koshy, Dilip; Cheng, Chu; Guo, GuiFang; Martinez, Jose A; Duraikannu, Arul; Zochodne, Douglas W

    2015-07-01

    Perineuronal satellite cells have an intimate anatomical relationship with sensory neurons that suggests close functional collaboration and mutual support. We examined several facets of this relationship in adult sensory dorsal root ganglia (DRG). Collaboration included the support of process outgrowth by clustering of satellite cells, induction of distal branching behavior by soma signaling, the capacity of satellite cells to respond to distal axon injury of its neighboring neurons, and evidence of direct neuron-satellite cell exchange. In vitro, closely adherent coharvested satellite cells routinely clustered around new outgrowing processes and groups of satellite cells attracted neurite processes. Similar clustering was encountered in the pseudounipolar processes of intact sensory neurons within intact DRG in vivo. While short term exposure of distal growth cones of unselected adult sensory neurons to transient gradients of a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma induced early and substantial growth of their distant neurites and branches, an example of local soma signaling. In turn, satellite cells sensed when distal neuronal axons were injured by enlarging and proliferating. We also observed that satellite cells were capable of internalizing and expressing a neuron fluorochrome label, diamidino yellow, applied remotely to distal injured axons of the neuron and retrogradely transported to dorsal root ganglia sensory neurons. The findings illustrate a robust interaction between intranganglionic neurons and glial cells that involve two way signals, features that may be critical for both regenerative responses and ongoing maintenance. PMID:25979201

  16. Ecological consequence of the introduction of the polychaete Marenzelleria cf. viridis into a shallow-water biotope of the northern Baltic Sea

    NASA Astrophysics Data System (ADS)

    Kotta, Jonne; Orav, Helen; Sandberg-Kilpi, Eva

    2001-12-01

    Effects of the North American polychaete Marenzelleria cf. viridis on a simple shallow-water benthic community of the northern Baltic Sea were studied in a field experiment combining natural densities of dominating macrofaunal species. The presence of M. cf. viridis increased benthic production (chlorophyll a) and reduced the survival of the native polychaete Nereis diversicolor. Adult Macoma balthica caused a significant mortality on M. cf. viridis whereas adult Cerastoderma glaucum had no effect on M. cf. viridis. We suggest that the competitive interactions between M. cf. viridis and M. balthica are a possible key factor determining the distribution pattern of M. cf. viridis in the Baltic Sea.

  17. Langerhans cell histiocytosis in the adult.

    PubMed

    Malpas, J S; Norton, A J

    1996-12-01

    A study of 47 well-documented patients with Langerhans cell histiocytosis (LCH) showed a slight female preponderance, with onset as late as the ninth decade. The skin was the commonest site of presentation, but pulmonary and bone involvement was frequent. Patients with single-site disease did best. The worst prognosis was seen in the elderly or those with organ dysfunction. A high incidence of associated malignant disease was seen, which could precede, be coincidental with, or occur after a diagnosis of LCH. PMID:8888814

  18. Satellite cell proliferation in adult skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  19. Axonal Control of the Adult Neural Stem Cell Niche

    PubMed Central

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  20. Axonal control of the adult neural stem cell niche.

    PubMed

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D; Tecott, Laurence H; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-04-01

    The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain's neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  1. Germ Cell Tumors in Adolescents and Young Adults.

    PubMed

    Calaminus, Gabriele; Joffe, Jonathan

    2016-01-01

    Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs. PMID:27595361

  2. In vivo cell tracking and quantification method in adult zebrafish

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Alt, Clemens; Li, Pulin; White, Richard M.; Zon, Leonard I.; Wei, Xunbin; Lin, Charles P.

    2012-03-01

    Zebrafish have become a powerful vertebrate model organism for drug discovery, cancer and stem cell research. A recently developed transparent adult zebrafish using double pigmentation mutant, called casper, provide unparalleled imaging power in in vivo longitudinal analysis of biological processes at an anatomic resolution not readily achievable in murine or other systems. In this paper we introduce an optical method for simultaneous visualization and cell quantification, which combines the laser scanning confocal microscopy (LSCM) and the in vivo flow cytometry (IVFC). The system is designed specifically for non-invasive tracking of both stationary and circulating cells in adult zebrafish casper, under physiological conditions in the same fish over time. The confocal imaging part in this system serves the dual purposes of imaging fish tissue microstructure and a 3D navigation tool to locate a suitable vessel for circulating cell counting. The multi-color, multi-channel instrument allows the detection of multiple cell populations or different tissues or organs simultaneously. We demonstrate initial testing of this novel instrument by imaging vasculature and tracking circulating cells in CD41: GFP/Gata1: DsRed transgenic casper fish whose thrombocytes/erythrocytes express the green and red fluorescent proteins. Circulating fluorescent cell incidents were recorded and counted repeatedly over time and in different types of vessels. Great application opportunities in cancer and stem cell researches are discussed.

  3. Recent advances in bone regeneration using adult stem cells.

    PubMed

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration. PMID:25914769

  4. Adsorption of CF4 on graphite preplated with a monolayer of CF3Cl

    NASA Astrophysics Data System (ADS)

    Thomas, Petros; Velazquez, Daniel; Hess, George B.

    2011-03-01

    We report a study of the adsorption of CF4 on graphite preplated with a monolayer of CF3Cl, using infrared reflection absorption spectroscopy combined with ellipsometry. The saturated vapor pressure of CF3Cl is nearly 3 orders of magnitude smaller than that of CF4 at the same temperature, so the main control variables are the temperature and the pressure (or chemical potential) of CF4, together with the initial coverage of CF3Cl. The temperature range covered is 60-105 K. We find that, if the initial monolayer of CF3Cl is liquid, CF4 continuously displaces CF3Cl by substitution in the monolayer. If the initial monolayer of CF3Cl is solid, due to either lower temperature or compression, CF4 condenses as a second layer on the top of the CF3Cl layer, with only slight mixing with the original layer. This behavior persists to multiple layers of CF4.

  5. Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila.

    PubMed

    Ma, Meifang; Zhao, Hang; Zhao, Hanfei; Binari, Richard; Perrimon, Norbert; Li, Zhouhua

    2016-03-15

    Adult stem cells or residential progenitor cells are critical to maintain the structure and function of adult tissues (homeostasis) throughout the lifetime of an individual. Mis-regulation of stem cell proliferation and differentiation often leads to diseases including cancer, however, how wildtype adult stem cells and cancer cells respond to cellular damages remains unclear. We find that in the adult Drosophila midgut, intestinal stem cells (ISCs), unlike tumor intestinal cells, are resistant to various cellular damages. Tumor intestinal cells, unlike wildtype ISCs, are easily eliminated by apoptosis. Further, their proliferation is inhibited upon autophagy induction, and autophagy-mediated tumor inhibition is independent of caspase-dependent apoptosis. Interestingly, inhibition of tumorigenesis by autophagy is likely through the sequestration and degradation of mitochondria, as compromising mitochondria activity in these tumor models mimics the induction of autophagy and increasing the production of mitochondria alleviates the tumor-suppression capacity of autophagy. Together, these data demonstrate that wildtype adult stem cells and tumor cells show dramatic differences in sensitivity to cellular damages, thus providing potential therapeutic implications targeting tumorigenesis. PMID:26845534

  6. Loss of Fbw7 Reprograms Adult Pancreatic Ductal Cells into α, δ, and β Cells

    PubMed Central

    Sancho, Rocio; Gruber, Ralph; Gu, Guoqiang; Behrens, Axel

    2014-01-01

    Summary The adult pancreas is capable of limited regeneration after injury but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here, we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into α, δ, and β cells. Loss of Fbw7 stabilized the transcription factor Ngn3, a key regulator of endocrine cell differentiation. The induced β cells resemble islet β cells in morphology and histology, express genes essential for β cell function, and release insulin after glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type. PMID:25105579

  7. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies.

    PubMed

    Parmesar, Kevon; Raj, Kavita

    2016-01-01

    Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients. PMID:27313619

  8. [Hypercalcemia of T-cell leukemia in adults].

    PubMed

    Jean-Baptiste, G; Arfi, S; Plumelle, Y; Panelatti, G; Mangin, J L; Pascaline, N

    1993-04-01

    A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells. PMID:8167627

  9. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    PubMed Central

    Parmesar, Kevon; Raj, Kavita

    2016-01-01

    Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients. PMID:27313619

  10. Regeneration through reprogramming adult cell identity in vivo.

    PubMed

    Smith, Derek K; Zhang, Chun-Li

    2015-10-01

    The discovery and in vivo application of cell fate reprogramming concepts have jumpstarted new technologies aimed at the functional regeneration of damaged tissues. As most adult organ systems retain only a limited potential for self-regeneration after trauma, the production of fate-specific cells by in vivo transdifferentiation offers a targeted method for tissue bioengineering. Proof-of-principle studies have demonstrated the induction of neural precursor cells, neurons, cardiomyocytes, and insulin-producing β islet cells. Each of these induced cell types survive, mature, and integrate into the local environment in a functionally meaningful manner. Here, we briefly highlight recent advances in the in vivo reprogramming of cell identity and the current challenges that face the clinical relevance of these methods. PMID:26056931

  11. Abnormal tracheal smooth muscle function in the CF mouse

    PubMed Central

    Wallace, Helen L; Southern, Kevin W; Connell, Marilyn G; Wray, Susan; Burdyga, Theodor

    2013-01-01

    Increased airway smooth muscle (ASM) contractility is thought to underlie symptoms of airway hyperresponsiveness (AHR). In the cystic fibrosis (CF) airway, ASM anomalies have been reported, but have not been fully characterized and the underlying mechanisms are largely unknown. We examined ASM in an adult CF mouse tracheal ring preparation, and determined whether changes in contractility were associated with altered ASM morphology. We looked for inherent changes in the cellular pathways involved in contractility, and characterized trachea morphology in the adult trachea and in an embryonic lung culture model during development. Results showed that that there was a reduction in tracheal caliber in CF mice as indicated by a reduction in the number of cartilage rings; proximal cross-sectional areas of cftr−/− tracheas and luminal areas were significantly smaller, but there was no difference in the area or distribution of smooth muscle. Morphological differences observed in adult trachea were not evident in the embryonic lung at 11.5 days gestation or after 72 h in culture. Functional data showed a significant reduction in the amplitude and duration of contraction in response to carbachol (CCh) in Ca-free conditions. The reduction in contraction was agonist specific, and occurred throughout the length of the trachea. These data show that there is a loss in the contractile capacity of the CF mouse trachea due to downregulation of the pathway specific to acetylcholine (ACh) activation. This reduction in contraction is not associated with changes in the area or distribution of ASM. PMID:24400140

  12. Dendritic cells in humans--from fetus to adult.

    PubMed

    McGovern, Naomi; Chan, Jerry K Y; Ginhoux, Florent

    2015-02-01

    The human immune system evolves continuously during development from the embryo into the adult, reflecting the ever-changing environment and demands of our body. This ability of our immune system to sense external cues and adapt as we develop is just as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DCs), the professional antigen-sensing and antigen-presenting components of the immune system, play a crucial role in this process where they act as sentinels, both initiating and regulating immune responses. Here, we provide an overview of the human immune system in the developing fetus and the adult, with a focus on DC ontogeny and function during these discrete but intimately linked life stages. PMID:25323843

  13. Adult stem cell plasticity: will engineered tissues be rejected?

    PubMed Central

    Fang, Te-Chao; Alison, Malcolm R; Wright, Nicholas A; Poulsom, Richard

    2004-01-01

    The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. PMID:15255965

  14. Differentiation of embryonic and adult stem cells into insulin producing cells.

    PubMed

    Zulewski, H

    2008-03-01

    Replacement of insulin producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans is successful in experienced centers. The wider application of this therapy, however, is limited by the lack of donor organs. Insulin producing cells generated from stem cells represent an attractive alternative. Stem cells with the potential to differentiate into insulin producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns but research with human ESC may help us to decipher important steps in the differentiation process in vitro since almost all information available on pancreas development are based on animal studies. The present review summarizes the current knowledge on the development of insulin producing cells from embryonic and adult stem cells with special emphasis on pancreatic, hepatic and human mesenchymal stem cells. PMID:18427390

  15. IMMATURE RAT LEYDIG CELLS ARE INTRINSICALLY LESS SENSITIVE THAN ADULT LEYDIG CELLS TO ETHANE DIMETHANESULFONATE

    EPA Science Inventory

    Leydig cells from immature rat tests appear to be insensitive to doses of ethane-1,2-dimethanesulfonate (EDS) which eliminate Leydig cells from adult rat testes. e sought to determine whether this differential response to EDS is intrinsic to the Leydig cell or mediated by other i...

  16. Modeling The CF4 Laser

    NASA Astrophysics Data System (ADS)

    Patterson, C. W.; McDowell, R. S.; Krohn, B. J.; Nereson, N. G.

    1981-12-01

    The CO2-pumped CF4 laser is a potentially useful source of line-tunable infrared radiation in the region 605-655 cm 1, and the spectroscopy of CF4 has been carried to the point that the laser frequencies that will result from any given pump line can be calculated to better than 0.01 cm 1. We now report quantitative intensity and line-broadening studies on CF4 and their application to modeling the laser gain. First, absorption measurements on isolated lines in the ν2 + ν4 pump band at a series of pressures yield an effective transition dipole moment for this band of 0.010 Debye. At the same time the transition moment for the (ν2 + ν4) - ν2 laser band has been calculated and agrees well with the results of laser self-absorption measurements. Finally, linewidths determined as a function of pressure yield a pressure-broadening coefficient of ca. 10 MHz/torr, significantly greater than that expected from a hard-sphere gas-kinetic model. From these data the gain of the CF4 laser can be calculated at various pressures and temperatures; the results are in reasonable agreement with measured values.

  17. Symptoms, Diagnosis, Treatment & Living with CF | NIH MedlinePlus the Magazine

    MedlinePlus

    ... a sign of infection. Transition of Care Because people today with CF are living longer than ever the move from pediatric to adult care is very important. Children should learn as much as possible about their condition and ...

  18. Symptoms, Diagnosis, Treatment & Living with CF | NIH MedlinePlus the Magazine

    MedlinePlus

    ... A fever, which is a sign of infection. Transition of Care Because people today with CF are ... age-appropriate treatment. They also will support the transition to adult care by balancing medical needs with ...

  19. Prolactin Stimulates Precursor Cells in the Adult Mouse Hippocampus

    PubMed Central

    Walker, Tara L.; Vukovic, Jana; Koudijs, Margaretha M.; Blackmore, Daniel G.; Mackay, Eirinn W.; Sykes, Alex M.; Overall, Rupert W.; Hamlin, Adam S.; Bartlett, Perry F.

    2012-01-01

    In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL) can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80%) in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory. PMID:22973440

  20. Stem cell niches in the adult mouse heart

    PubMed Central

    Urbanek, Konrad; Cesselli, Daniela; Rota, Marcello; Nascimbene, Angelo; De Angelis, Antonella; Hosoda, Toru; Bearzi, Claudia; Boni, Alessandro; Bolli, Roberto; Kajstura, Jan; Anversa, Piero; Leri, Annarosa

    2006-01-01

    Cardiac stem cells (CSCs) have been identified in the adult heart, but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and fibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs–lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of α4-integrin, which colocalizes with the α2-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base–midregion of the ventricle. PMID:16754876

  1. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    SciTech Connect

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  2. Genetic landscape of adult T-cell leukemia/lymphoma.

    PubMed

    Kataoka, Keisuke; Ogawa, Seishi

    2016-04-01

    Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy associated with HTLV-1 infection. To decipher the genetic landscape of ATL, we performed an integrated molecular analysis, which included whole-genome, whole-exome, transcriptome and targeted sequencing, as well as array-based copy number and methylation analyses. The somatic alterations are highly enriched for T-cell receptor/NF-κB signaling, the G-protein coupled receptor associated with T-cell migration, and other T-cell-related pathways as well as immune surveillance related genes. Among these, PLCG1, PRKCB, CARD11, VAV1, IRF4, CCR4, and CCR7 activating mutations and CTLA4-CD28 and ICOS-CD28 fusion genes have been identified. In addition, these genes significantly overlap with HTLV-1 Tax interactome. These results provide an important basis for the development of new ATL diagnostics and therapeuticsregimens. PMID:27169444

  3. Adult mesenchymal stem cells: differentiation potential and therapeutic applications.

    PubMed

    Jackson, L; Jones, D R; Scotting, P; Sottile, V

    2007-01-01

    Adult mesenchymal stem cells (MSCs) are a population of multipotent cells found primarily in the bone marrow. They have long been known to be capable of osteogenic, adipogenic and chondrogenic differentiation and are currently the subject of a number of trials to assess their potential use in the clinic. Recently, the plasticity of these cells has come under close scrutiny as it has been suggested that they may have a differentiation potential beyond the mesenchymal lineage. Myogenic and in particular cardiomyogenic potential has been shown in vitro. MSCs have also been shown to have the ability to form neural cells both in vitro and in vivo, although the molecular mechanisms underlying these apparent transdifferentiation events are yet to be elucidated. We describe here the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for future applications in regenerative medicine. PMID:17495381

  4. Adult langerhans cell histiocytosis with hepatic and pulmonary involvement.

    PubMed

    Araujo, Bruno; Costa, Francisco; Lopes, Joanne; Castro, Ricardo

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment. PMID:25977828

  5. Adult stem cell lineage tracing and deep tissue imaging

    PubMed Central

    Fink, Juergen; Andersson-Rolf, Amanda; Koo, Bon-Kyoung

    2015-01-01

    Lineage tracing is a widely used method for understanding cellular dynamics in multicellular organisms during processes such as development, adult tissue maintenance, injury repair and tumorigenesis. Advances in tracing or tracking methods, from light microscopy-based live cell tracking to fluorescent label-tracing with two-photon microscopy, together with emerging tissue clearing strategies and intravital imaging approaches have enabled scientists to decipher adult stem and progenitor cell properties in various tissues and in a wide variety of biological processes. Although technical advances have enabled time-controlled genetic labeling and simultaneous live imaging, a number of obstacles still need to be overcome. In this review, we aim to provide an in-depth description of the traditional use of lineage tracing as well as current strategies and upcoming new methods of labeling and imaging. [BMB Reports 2015; 48(12): 655-667] PMID:26634741

  6. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve

    PubMed Central

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N.; Samuvel, Devadoss J.; Panganiban, Clarisse H.; Havens, Luke T.; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L.; Barth, Jeremy L.

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  7. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells.

    PubMed

    Jacobs, Sandra A; Roobrouck, Valerie D; Verfaillie, Catherine M; Van Gool, Stefaan W

    2013-01-01

    Somatic, also termed adult, stem cells are highly attractive biomedical cell candidates because of their extensive replication potential and functional multilineage differentiation capacity. They can be used for drug and toxicity screenings in preclinical studies, as in vitro model to study differentiation or for regenerative medicine to aid in the repair of tissues or replace tissues that are lost upon disease, injury or ageing. Multipotent adult progenitor cells (MAPCs) and mesenchymal stem cells (MSCs) are two types of adult stem cells derived from bone marrow that are currently being used clinically for tissue regeneration and for their immunomodulatory and trophic effects. This review will give an overview of the phenotypic and functional differences between human MAPCs and MSCs, with a strong emphasis on their immunological characteristics. Finally, we will discuss the clinical studies in which MSCs and MAPCs are already used. PMID:23295415

  8. Adult Stem Cells as a Renewable Source of Insulin-Producing Cells

    PubMed Central

    Jun, Hee-Sook; Park, Eun-Young

    2009-01-01

    Diabetes mellitus is a metabolic disorder resulting from an inadequate mass of insulin-producing pancreatic beta cells. The replacement or restoration of damaged beta cells would be considered the optimal therapeutic options. Islet transplantation seems to be a promising approach for replacement therapy; however, the main obstacle is the shortage of organ donors. As mature beta cells have been shown to be difficult to expand in vitro, regeneration of beta cells from embryonic or adult stem cells or pancreatic progenitor cells is an attractive method to restore the islet cell mass. So far, multiple studies using various strategies have shown direct differentiation of stem and progenitor cells toward insulin-producing cells. The important issue to be solved is how to differentiate these cells into mature functional insulin-producing cells. Further research is required to understand how endogenous beta cells differentiate and to develop methods to regenerate enough functional beta cells for clinically applicable therapies for diabetes. PMID:24855530

  9. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  10. Switching roles: the functional plasticity of adult tissue stem cells.

    PubMed

    Wabik, Agnieszka; Jones, Philip H

    2015-05-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  11. Switching roles: the functional plasticity of adult tissue stem cells

    PubMed Central

    Wabik, Agnieszka; Jones, Philip H

    2015-01-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  12. Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model.

    PubMed

    Potash, Andrea E; Wallen, Tanner J; Karp, Philip H; Ernst, Sarah; Moninger, Thomas O; Gansemer, Nicholas D; Stoltz, David A; Zabner, Joseph; Chang, Eugene H

    2013-05-01

    Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis. PMID:23511247

  13. Adult stem cells in bone and cartilage tissue engineering.

    PubMed

    Salgado, António J; Oliveira, João T; Pedro, Adriano J; Reis, Rui L

    2006-09-01

    The progressive increase in life expectancy within the last century has led to the appearance of novel health related problems, some of those within the musculoskeletal field. Among the latter, one can find diseases such as osteoporosis, rheumatoid arthritis and bone cancer, just to mention some of the most relevant. Other related problems are those that arise from serious injuries, often leading to non-recoverable critical size defects. The therapies currently used to treat this type of diseases/injuries are based on the use of pharmaceutical agents, auto/allotransplant and synthetic materials. However, such solutions present a number of inconveniences and therefore, there is a constant search for novel therapeutic solutions. The appearance of a novel field of science called Tissue engineering brought some hope for the solution of the above mentioned problems. In this field, it is believed that by combining a 3D porous template--scaffold--with an adequate cell population, with osteo or chondrogenic potential, it will be possible to develop bone and cartilage tissue equivalents that when implanted in vivo, could lead to the total regeneration of the affected area. This ideal cell population should have a series of properties, namely a high osteo and chondrogenic potential and at the same time, should be easily expandable and maintained in cultures for long periods of time. Due to its natural and intrinsic properties, stem cells are one of the best available cell types. However, after this sentence, the readers may ask, "Which Stem Cells?". During the last 10/15 years, the scientific community witnessed and reported the appearance of several sources of stem cells with both osteo and chondrogenic potential. Therefore, the present review intends to make an overview of data reported on different sources of adult stem cells (bone marrow, periosteum, adipose tissue, skeletal muscle and umbilical cord) for bone and cartilage regenerative medicine, namely those focusing on

  14. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults.

    PubMed

    Speziali, Craig; Paulson, Kristjan; Seftel, Matthew

    2016-06-01

    The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improved. Emerging data show substantially improved outcomes for young adults treated with pediatric-inspired chemotherapy regimens that question the role of HCT in the upfront setting. In this review, we review the data supporting the role of allogeneic transplantation in adult acute lymphoblastic leukemia (ALL), and we propose a therapeutic algorithm for upfront therapy of adults with ALL. PMID:26984203

  15. Graphite moderated (252)Cf source.

    PubMed

    Sajo-Bohus, Laszlo; Barros, Haydn; Greaves, Eduardo D; Vega-Carrillo, Hector Rene

    2015-06-01

    The Thorium molten-salt reactor is an attractive and affordable nuclear power option for developing countries with insufficient infrastructure and limited technological capability. In the aim of personnel training and experience gathering at the Universidad Simon Bolivar there is in progress a project of developing a subcritical thorium liquid-fuel reactor. The neutron source to run this subcritical reactor is a (252)Cf source and the reactor will use high-purity graphite as moderator. Using the MCNP5 code the neutron spectra of the (252)Cf in the center of the graphite moderator has been estimated along the channel where the liquid thorium salt will be inserted; also the ambient dose equivalent due to the source has been determined around the moderator. PMID:25770393

  16. Modeling the CF4 laser

    NASA Astrophysics Data System (ADS)

    Patterson, C. W.; McDowell, R. S.; Krohn, B. J.; Nereson, N. G.

    Quantitative intensity and line broadening studies on CF4 and their application to modeling the laser gain is presented. First, absorption measurements on isolated lines in the v sub 2 + v sub 4 pump band at a series of pressures yield an effective transition dipole moment for this band of 0.010 Debye. At the same time the transition moment for the v sub 2 + v sub 4 - v sub 2 laser band are calculated and agrees well with the results of laser self-absorption measurements. Finally, linewidths determined as a function of pressure yield a pressure broadening coefficient of ca, 10 MHz/torr, significantly greater than that expected from a hard sphere gas kinetic model. From these data the gain of the CF4 laser are calculated at various pressures and temperatures; the results are in reasonable agreement with measured values.

  17. Quantitative and semi-quantitative immunoassay of growth factors and cytokines in the conditioned medium of STO and CF-1 mouse feeder cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Feeder-cells of irradiated mouse fibroblasts are commonly used for, and are generally necessary for, the in vitro maintenance and growth of many fastidious cell types, particularly embryonic stem cells or induced pluripotent stem cells. Quantitative and semi-quantitative immunoassays were performed...

  18. Simulation and Experimental Measurements of Inductively Coupled CF4 and CF4/Ar Plasmas

    NASA Technical Reports Server (NTRS)

    Hash, D. B.; Bose, D.; Rao, M. V. V. S.; Cruden, B. A.; Meyyappan, M.; Sharma, S. P.; Arnold, James O. (Technical Monitor)

    2000-01-01

    The recently developed code SEMS (semiconductor equipment modeling software)is applied to the simulation of CF4 and CF4/Ar inductively coupled plasmas (ICP). This work builds upon the earlier nitrogen, transformer coupled plasma (TCP) SEMS research by demonstrating its accuracy for more complex reactive mixtures, moving closer to the realization of a virtual plasma reactor. Attention is given to the etching of and/or formation of carbonaceous films on the quartz dielectric window and diagnostic aperatures. The simulations are validated through comparisons with experimental measurements using FTIR (Fourier Transform Infrared) and UV absorption spectroscopy for CFx and SiFx neutral radicals, QMS (quadrupole mass spectrometry) for the ions, and Langmuir probe measurements of electron number density and temperature in an ICP GEC reference cell.

  19. cfDNA analysis from blood in melanoma.

    PubMed

    Molina-Vila, Miguel A; de-Las-Casas, Clara Mayo; Bertran-Alamillo, Jordi; Jordana-Ariza, Nuria; González-Cao, María; Rosell, Rafael

    2015-11-01

    Testing of tumor tissue remains the recommended method for detecting the presence of somatic mutations in human malignancies. V600E is the most frequent somatic point mutation in metastatic melanoma, providing a unique molecular marker for this malignancy. In addition, tumors carrying this mutation are primary candidates for BRAF-targeted therapy. Although metastatic melanoma patients usually have sufficient tumor tissue available for genetic analyses, the detection of V600E in blood can have prognostic and predictive value. In addition, patients are rarely re-biopsied and genetic testing in blood can be useful for monitoring response to therapy. Cell-free DNA (cfDNA) and cell-free RNA (cfRNA), RNA associated to platelets and circulating tumor cells (CTCs) are some of the materials that can be derived from the blood of cancer patients. cfDNA can be easily purified from serum and plasma and contains DNA fragments of tumor origin. For this reason, it is the most widely used material for the detection of somatic mutations in blood. Several methodologies have been used to determine V600E status in the cfDNA of metastatic melanoma and some studies have demonstrated that the identification and follow-up of V600E in cfDNA can have prognostic and predictive value. PMID:26697469

  20. Purkinje Cell Ataxin-1 Modulates Climbing Fiber Synaptic Input in Developing and Adult Mouse Cerebellum

    PubMed Central

    Ebner, Blake A.; Ingram, Melissa A.; Barnes, Justin; Duvick, Lisa A.; Frisch, Jill L.; Clark, H. Brent; Zoghbi, Huda Y.; Ebner, Timothy J.; Orr, Harry T.

    2013-01-01

    Previous studies indicate that while transgenic mice with ATXN1[30Q]-D776-induced disease share pathological features caused by ATXN1[82Q] having an expanded polyglutamine tract, they fail to manifest the age-related progressive neurodegeneration seen in SCA1. The shared features include morphological alterations in climbing fiber (CF) innervation of Purkinje cells (PCs). To further investigate the ability of ATXN1 to impact CF/PC innervation, this study used morphological and functional approaches to examine CF/PC innervation during postnatal development in ATXN1[30Q]-D776 and ATXN1[82Q] cerebella. Notably, ATXN1[30Q]-D776 induced morphological alterations consistent with the development of the innervation of PCs by CFs being compromised, including a reduction of CF translocation along the PC dendritic tree, and decreased pruning of CF terminals from the PC soma. Like previously shown for ATXN1[82Q], ATXN1[30Q]-D776 must enter the nucleus of PCs to induce these alterations. Experiments using conditional ATXN1[30Q]-D776 mice demonstrate that both the levels and specific timing of mutant ATXN1expression are critical for alteration of the CF-PC synapse. Together these observations suggest that ATXN1, expressed exclusively in PCs, alters expression of a gene(s) in the postsynaptic PC that are critical for its innervation by CFs. To investigate whether ATXN1[30Q]-D776 curbs the progressive disease in ATXN1[82Q]-S776 mice, we crossed ATXN1[30Q]-D776 and ATXN1[82Q]-S776 mice and found that double transgenic mice developed progressive PC atrophy. Thus, the results also show that to develop progressive cerebellar degeneration requires expressing ATXN1 with an expanded polyglutamine tract. PMID:23536093

  1. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    PubMed Central

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  2. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking.

    PubMed

    Ratajczak, M Z

    2015-04-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  3. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells.

    PubMed

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; MacLellan, W Robb; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  4. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

    PubMed Central

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  5. Vacuum-UV negative photoion spectroscopy of CF3Cl, CF3Br, and CF3I

    NASA Astrophysics Data System (ADS)

    Simpson, M. J.; Tuckett, R. P.; Dunn, K. F.; Hunniford, C. A.; Latimer, C. J.

    2009-05-01

    Using synchrotron radiation, negative ions are detected by mass spectrometry following vacuum-UV photoexcitation of trifluorochloromethane (CF3Cl), trifluorobromomethane (CF3Br), and trifluoroiodomethane (CF3I). The anions F-, X-, F2-, FX-, CF-, CF2-, and CF3- are observed from all three molecules, where X =Cl, Br, or I, and their ion yields recorded in the range of 8-35 eV. With the exception of Br- and I-, the anions observed show a linear dependence of signal with pressure, showing that they arise from unimolecular ion-pair dissociation. Dissociative electron attachment, following photoionization of CF3Br and CF3I as the source of low-energy electrons, is shown to dominate the observed Br- and I- signals, respectively. Cross sections for ion-pair formation are put onto an absolute scale by calibrating the signal strengths with those of F- from both SF6 and CF4. These anion cross sections are normalized to vacuum-UV absorption cross sections, where available, and the resulting quantum yields are reported. Anion appearance energies are used to calculate upper limits to 298 K bond dissociation energies for Do(CF3-X), which are consistent with literature values. We report new data for Do(CF2I+-F)≤2.7±0.2 eV and ΔfH298o(CF2I+)≤(598±22) kJ mol-1. No ion-pair formation is observed below the ionization energy of the parent molecule for CF3Cl and CF3Br, and only weak signals (in both I- and F-) are detected for CF3I. These observations suggest that neutral photodissociation is the dominant exit channel to Rydberg state photoexcitation at these lower energies.

  6. Robust G2 pausing of adult stem cells in Hydra.

    PubMed

    Buzgariu, Wanda; Crescenzi, Marco; Galliot, Brigitte

    2014-01-01

    Hydra is a freshwater hydrozoan polyp that constantly renews its two tissue layers thanks to three distinct stem cell populations that cannot replace each other, epithelial ectodermal, epithelial endodermal, and multipotent interstitial. These adult stem cells, located in the central body column, exhibit different cycling paces, slow for the epithelial, fast for the interstitial. To monitor the changes in cell cycling in Hydra, we established a fast and efficient flow cytometry procedure, which we validated by confirming previous findings, as the Nocodazole-induced reversible arrest of cell cycling in G2/M, and the mitogenic signal provided by feeding. Then to dissect the cycling and differentiation behaviors of the interstitial stem cells, we used the AEP_cnnos1 and AEP_Icy1 transgenic lines that constitutively express GFP in this lineage. For the epithelial lineages we used the sf-1 strain that rapidly eliminates the fast cycling cells upon heat-shock and progressively becomes epithelial. This study evidences similar cycling patterns for the interstitial and epithelial stem cells, which all alternate between the G2 and S-phases traversing a minimal G1-phase. We also found interstitial progenitors with a shorter G2 that pause in G1/G0. At the animal extremities, most cells no longer cycle, the epithelial cells terminally differentiate in G2 and the interstitial progenitors in G1/G0. At the apical pole ~80% cells are post-mitotic differentiated cells, reflecting the higher density of neurons and nematocytes in this region. We discuss how the robust G2 pausing of stem cells, maintained over weeks of starvation, may contribute to regeneration. PMID:24703763

  7. YM155 suppresses cell proliferation and induces cell death in human adult T-cell leukemia/lymphoma cells.

    PubMed

    Sasaki, Ryousei; Ito, Shigeki; Asahi, Maki; Ishida, Yoji

    2015-12-01

    Adult T-cell leukemia (ATL) is an aggressive malignancy of peripheral T cells infected with human T-cell leukemia virus type 1 (HTLV-1). The prognosis of patients with aggressive ATL remains poor because ATL cells acquire resistance to conventional cytotoxic agents. Therefore, development of novel agents is urgently needed. We examined the effects of YM155, sepantronium bromide, on cell proliferation and survival of ATL or HTLV-1-infected T-cell lines, S1T, MT-1, and MT-2. We found that YM155 suppressed cell proliferation in these cells and induced cell death in S1T and MT-1 cells. Both real-time quantitative polymerase chain reaction and immunoblot analyses showed suppression of survivin expression in S1T, MT-1, and MT-2 cells. In addition, we observed the cleavage of caspase-3 and poly(ADP-ribose) polymerase in YM155-treated S1T and MT-1 cells, indicating that YM155 induces caspase-dependent apoptosis in these cells. To clarify the mechanism of drug tolerance of MT-2 cells in terms of YM155-induced cell death, we examined intracellular signaling status in these cells. We found that STAT3, STAT5, and AKT were constitutively phosphorylated in MT-2 cells but not in S1T and MT-1 cells. Treatment with YM155 combined with the STAT3 inhibitor S3I-201 significantly suppressed cell proliferation compared to that with either YM155 or S3I-201 in MT-2 cells, indicating that STAT3 may play a role in tolerance of MT-2 cells to YM155 and that STAT3 may therefore be a therapeutic target for YM155-resistant ATL cells. These results suggest that YM155 presents potent antiproliferative and apoptotic effects via suppression of survivin in ATL cells in which STAT3 is not constitutively phosphorylated. YM155 merits further investigation as a potential chemotherapeutic agent for ATL. PMID:26547260

  8. TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation.

    PubMed

    Hillje, A-L; Pavlou, M A S; Beckmann, E; Worlitzer, M M A; Bahnassawy, L; Lewejohann, L; Palm, T; Schwamborn, J C

    2013-01-01

    In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts differentiate slower and show gene expression profiles that are characteristic of immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice. These results highlight the function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process. PMID:24357807

  9. DNA Damage Response in Neonatal and Adult Stromal Cells Compared With Induced Pluripotent Stem Cells

    PubMed Central

    Liedtke, Stefanie; Biebernick, Sophie; Radke, Teja Falk; Stapelkamp, Daniela; Coenen, Carolin; Zaehres, Holm; Fritz, Gerhard; Kogler, Gesine

    2015-01-01

    Comprehensive analyses comparing individual DNA damage response (DDR) of induced pluripotent stem cells (iPSCs) with neonatal stromal cells with respect to their developmental age are limited. The imperative necessity of providing developmental age-matched cell sources for meaningful toxicological drug safety assessments in replacement of animal-based testing strategies is evident. Here, DDR after radiation or treatment with N-methyl-N-nitrosurea (MNU) was determined in iPSCs compared with neonatal and bone marrow stromal cells. Neonatal and adult stromal cells showed no significant morphologically detectable cytotoxicity following treatment with 1 Gy or 1 mM MNU, whereas iPSCs revealed a much higher sensitivity. Foci analyses revealed an effective DNA repair in stromal cell types and iPSCs, as reflected by a rapid formation and disappearance of phosphorylated ATM and γH2AX foci. Furthermore, quantitative polymerase chain reaction analyses revealed the highest basic expression level of DDR and repair-associated genes in iPSCs, followed by neonatal stromal cells and adult stromal cells with the lowest expression levels. In addition, the influence of genotoxic stress prior to and during osteogenic differentiation of neonatal and adult stromal cells was analyzed applying common differentiation procedures. Experiments presented here suggest a developmental age-dependent basic expression level of genes involved in the processing of DNA damage. In addition a differentiation-dependent downregulation of repair genes was observed during osteogenesis. These results strongly support the requirement to provide adequate cell sources for toxicological in vitro drug testing strategies that match to the developmental age and differentiation status of the presumptive target cell of interest. Significance The results obtained in this study advance the understanding of DNA damage processing in human neonatal stromal cells as compared with adult stromal cells and induced pluripotent

  10. Optimizing Management of Patients with Adult T Cell Leukemia-Lymphoma

    PubMed Central

    Yared, Jean A.; Kimball, Amy S.

    2015-01-01

    Adult T cell leukemia-lymphoma is a rare disease with a high mortality rate, and is challenging for the clinician. Early allogeneic stem cell transplant can confer durable remission. As novel therapeutic agents become available to treat T cell malignancies, it is increasingly important that medical oncologists, hematologists, and hematopathologists recognize and accurately diagnose adult T cell leukemia-lymphoma. There is no uniform standard of treatment of adult T cell leukemia-lymphoma, and clinical trials remain critical to improving outcomes. Here we present one management approach based on the recent advances in treatment for adult T cell leukemia-lymphoma patients. PMID:26610571

  11. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras.

    PubMed

    Keighren, Margaret A; Flockhart, Jean H; West, John D

    2016-01-01

    The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1(-/-) null mouse embryos die but a previous study showed that some homozygous Gpi1(-/-) null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1(-/-)↔Gpi1(c/c) chimaera with functional Gpi1(-/-) null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1(-/-) null cells in adult Gpi1(-/-)↔Gpi1(c/c) chimaeras and determine if Gpi1(-/-) null germ cells are functional. Analysis of adult Gpi1(-/-)↔Gpi1(c/c) chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1(-/-) null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1(-/-) null oocytes in one female Gpi1(-/-)↔Gpi1(c/c) chimaera were functional and provided preliminary evidence that one male putative Gpi1(-/-)↔Gpi1(c/c) chimaera produced functional spermatozoa from homozygous Gpi1(-/-) null germ cells. Although the male chimaera was almost certainly Gpi1(-/-)↔Gpi1(c/c), this part of the study is considered preliminary because only blood was typed for GPI. Gpi1(-/-) null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1(-/-) null germ cells, it successfully identified functional Gpi1(-/-) null oocytes and revealed that some Gpi1(-/-) null cells could survive in many adult tissues. PMID:27103217

  12. Simultaneous characterization of progenitor cell compartments in adult human liver.

    PubMed

    Porretti, Laura; Cattaneo, Alessandra; Colombo, Federico; Lopa, Raffaella; Rossi, Giorgio; Mazzaferro, Vincenzo; Battiston, Carlo; Svegliati-Baroni, Gianluca; Bertolini, Francesco; Rebulla, Paolo; Prati, Daniele

    2010-01-01

    The human liver is a complex tissue consisting of epithelial, endothelial, hematopoietic, and mesenchymal elements that probably derive from multiple lineage-committed progenitors, but no comprehensive study aimed at identifying and characterizing intrahepatic precursors has yet been published. Cell suspensions for this study were obtained by enzymatic digestion of liver specimens taken from 20 patients with chronic liver disease and 13 multiorgan donors. Stem and progenitor cells were first isolated, amplified, and characterized ex vivo according to previously validated methods, and then optimized flow cytometry was used to assess their relative frequencies and characterize their immunophenotypes in the clinical specimens. Stem and progenitor cells committed to hematopoietic, endothelial, epithelial, and mesenchymal lineages were clearly identifiable in livers from both healthy and diseased subjects. Within the mononuclear liver cell compartment, epithelial progenitors [epithelial cell adhesion molecule (EpCAM)(+)/CD49f(+)/CD29(+)/CD45(-)] accounted for 2.7-3.5% whereas hematopoietic (CD34(+)/CD45(+)), endothelial [vascular endothelial growth factor-2 (KDR)(+)/CD146(+)/CD45(-)], and mesenchymal [CD73(+)/CD105(+)/CD90 (Thy-1)(+)/CD45 (-)] stem cells and progenitors accounted for smaller fractions (0.02-0.6%). The patients' livers had higher percentages of hematopoietic and endothelial precursors than those of the donors. In conclusion, we identified and characterized precursors committed to four different lineages in adult human liver. We also optimized a flow cytometry approach that will be useful in exploring the contribution of these cells to the pathogenesis of liver disease. PMID:19960544

  13. Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population

    PubMed Central

    Giachino, Claudio; Basak, Onur; Lugert, Sebastian; Knuckles, Philip; Obernier, Kirsten; Fiorelli, Roberto; Frank, Stephan; Raineteau, Olivier; Alvarez–Buylla, Arturo; Taylor, Verdon

    2014-01-01

    Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP+ NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP+ NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and sub-ventricular progenitors in the fetal and postnatal human brain. Loss of BLBP+ stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging. PMID:23964022

  14. Sustained Arc expression in adult-generated granule cells.

    PubMed

    Meconi, Alicia; Lui, Erika; Marrone, Diano F

    2015-08-31

    The dentate gyrus (DG) plays a critical role in memory formation and maintenance. Fitting this specialized role, the DG has many unique characteristics. In addition to being one of the few places in which new neurons are continually added in adulthood, the region also shows a unique long-term sustained transcriptional response of the immediate-early gene Arc to sensory input. Although we know that adult-generated granule cells are reliably recruited into behaviorally-driven neuronal network, it remains unknown whether they display robust late-phase sustained transcription in response to activity like their developmentally-generated counterparts. Since this late-phase of transcription is required for enduring plasticity, knowing if sustained transcription appears as soon as these cells are incorporated provides information on their potential for plasticity. To address this question, adult F344 rats were injected with BrdU (50mg/kg/day for 5 days) and 4 weeks later explored a novel environment. Arc expression in both BrdU- and BrdU+ neurons was determined 0.5h, 1h, 2h, 6h, 8h, 12h, or 24h following this behavior. Recently-generated granule cells showed a robust sustained Arc expression following a discrete behavioral experience. These data provide information on a potential mechanism to sculpt the representations of events occurring within hours of each other to create uncorrelated representations of episodes despite a highly excitable population of neurons. PMID:26219984

  15. Adult human adipose tissue contains several types of multipotent cells.

    PubMed

    Tallone, Tiziano; Realini, Claudio; Böhmler, Andreas; Kornfeld, Christopher; Vassalli, Giuseppe; Moccetti, Tiziano; Bardelli, Silvana; Soldati, Gianni

    2011-04-01

    Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria. PMID:21327755

  16. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    PubMed Central

    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. PMID:22952666

  17. Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?

    PubMed Central

    Markel, Troy A.; Crisostomo, Paul R.; Manukyan, Maiuxi C.; Al-Azzawi, Dalia; Herring, Christine M.; Lahm, Tim; Novotny, Nathan M.; Meldrum, Daniel R.

    2009-01-01

    Background Bone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that: 1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium; and 2) neonatal stem cells would enhance post-ischemic myocardial recovery above that seen with adult stem cell therapy. Materials and Methods Female adult Sprague-Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 minutes equilibration, 25 minutes ischemia, and 60 minutes reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37 C, 5% CO2/air). Immediately prior to ischemia, one million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded. Results Pretreatment with adult BMSCs significantly increased post-ischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia. Conclusion Neonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of “super stem cells” that provide maximum protection to ischemic tissues. PMID:18805555

  18. Kinetics of gas-phase reactions of cyc-CF2CF2CF2CHFCH2sbnd and trans-cyc-CF2CF2CF2CHFCHFsbnd with OH radicals between 253 and 328 K

    NASA Astrophysics Data System (ADS)

    Zhang, Ni; Chen, Liang; Uchimaru, Tadafumi; Qing, Feiyao; Mizukado, Junji; Quan, Hengdao; Suda, Hiroyuki

    2015-10-01

    Rate constants for the reactions of cyc-CF2CF2CF2CHFCH2sbnd (k1) and trans-cyc-CF2CF2CF2CHFCHFsbnd (k2) with OH radicals were assessed by a relative rate method. The values were determined as (9.35 ± 5.83) × 10-13 exp[-(1197 ± 180)/T] and (8.02 ± 2.17) × 10-13 exp[-(1198 ± 80)/T] between 253 and 328 K; and (1.72 ± 0.05) × 10-14 and (1.43 ± 0.03) × 10-14 cm3 molecule-1 s-1 at 298 K, respectively. The atmospheric lifetimes were 2.8 and 3.2 years; the 100-year time horizon global warming potentials were estimated to be 211 and 241, respectively.

  19. Cytogenesis in the adult monkey motor cortex: Perivascular NG2 cells are the major adult born cell type

    PubMed Central

    Stanton, Gregory B; Kohler, Shawn J; Boklweski, Jennifer; Cameron, Judy L; Greenough, William T

    2015-01-01

    We used confocal microscopy and immunohistochemistry (IHC) to look for new cells in the motor cortex of adult macaque monkeys that might form the cellular bases of improved brain function from exercise. Twenty-four female Macaca fascicularis monkeys divided into groups by age (10–12 years, 15–17 years), postexercise survival periods, and controls, received 10 weekly injections of the thymidine analog, bromodeoxyuridine (BrdU) to mark new cells. Sixteen monkeys survived 15 weeks (5 weeks postexercise) and 8 monkeys survived 27 weeks (12 weeks postexercise) after initial BrdU injections. Additionally, five Macaca mulatta female monkeys (∼5.5–7 years) received single injections of BrdU and survived 2 days, 2 weeks, and 6 weeks after BrdU injections. Neural and glial antibodies were used to identify new cell phenotypes and to look for changes in proportions of these cells with respect to time and experimental conditions. No BrdU+/DCx+ cells were found but about 7.5% of new cells were calretinin-positive (Cr+). BrdU+/GABA+ (gamma-aminobutyric acid) cells were also found but no new Cr+ or GABA+ cells colabeled with a mature neuron marker, NeuN or chondroitin sulfate antibody, NG2. The proportion of new cells that were NG2+ was about 85% for short and long survival monkeys of which two, newly described perivascular phenotypes (Pldv and Elu) and a small percentage of pericytes (2.5%) comprised 44% and 51% of the new NG2+ cells, respectively. Proportions of NG2+ phenotypes were affected by post-BrdU survival periods, monkey age, and possibly a postexercise sedentary period but no direct effect of exercise was found. PMID:25308320

  20. Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis.

    PubMed

    Reynolds, A J; Jahoda, C A

    1992-06-01

    Adult rat pelage follicle dermal papilla cells induced follicle neogenesis and external hair growth when associated with adult footpad skin epidermis. They thus demonstrated a capacity to completely change the structural arrangement and gene expression of adult epidermis--an ability previously undocumented for cultured adult cells. Isolation chambers ensured that de novo follicle formation must have occurred by eliminating the possibility of cellular contributions, and/or inductive influences, from local skin follicles. These findings argue against previous suggestions of vibrissa follicle specificity, and imply that the potential for hair follicle induction may be common to all adult papilla cells. PMID:1425341

  1. Late adult onset of Langerhans cell histiocytosis mimicking glioblastoma multiforme.

    PubMed

    Perren, F; Fankhauser, L; Thiévent, B; Pache, J-C; Delavelle, J; Rochat, T; Landis, T; Chizzolini, C

    2011-02-15

    Langerhans cell histiocytosis (LCH) with multiple organ involvement is a rare disorder in adults. Extrapituitary involvement of the central nervous system (CNS) is uncommon. We report the unusual case of a 55-year-old woman presenting with a left-sided hemiataxia-hemiparesis, left hemisensory loss and short-lasting episodes of an alien left hand due to lesions of the internal capsule and the right thalamus, extending into the mesencephalon associated with extensive surrounding edema, without pituitary involvement. The neuroradiological image suggested glioblastoma multiforme. Brain biopsy revealed inflammatory tissue and "pseudotumoral" multiple sclerosis was suspected. Biopsy of concomitant lung and bone lesions disclosed Langerhans cell histiocytosis. The treatment with pulsed steroids in association with mycophenolate mofetil led to a sustained, clinical neurological remission. PMID:21131007

  2. Adult somatic stem cells in the human parasite, Schistosoma mansoni

    PubMed Central

    Collins, James J.; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla; Iyer, Harini; Newmark, Phillip A.

    2013-01-01

    Summary Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide1. The etiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (e.g., planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here, we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites. PMID:23426263

  3. Regenerative capacity of adult cortical thymic epithelial cells.

    PubMed

    Rode, Immanuel; Boehm, Thomas

    2012-02-28

    Involution of the thymus is accompanied by a decline in the number of thymic epithelial cells (TECs) and a severely restricted peripheral repertoire of T-cell specificities. TECs are essential for T-cell differentiation; they originate from a bipotent progenitor that gives rise to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors. Upon acute selective near-total ablation during embryogenesis, regeneration of TECs fails, suggesting that losses from the pool of TEC progenitors are not compensated. However, it is unclear whether this is also true for the compartment-specific progenitors. The decline of cTECs is a prominent feature of thymic involution. Because cTECs support early stages of T-cell development and hence determine the overall lymphopoietic capacity of the thymus, it is possible that the lack of sustained regenerative capacity of cTEC progenitor cells underlies the process of thymic involution. Here, we examine this hypothesis by cell-type-specific conditional ablation of cTECs. Expression of the human diphtheria toxin receptor (hDTR) gene under the regulatory influence of the chemokine receptor Ccx-ckr1 gene renders cTECs sensitive to the cytotoxic effects of diphtheria toxin (DT). As expected, DT treatment of preadolescent and adult mice led to a dramatic loss of cTECs, accompanied by a rapid demise of immature thymocytes. Unexpectedly, however, the cTEC compartment regenerated after cessation of treatment, accompanied by the restoration of T-cell development. These findings provide the basis for the development of targeted interventions unlocking the latent regenerative potential of cTECs to counter thymic involution. PMID:22331880

  4. High-repetition-rate CF/sub 4/ laser

    SciTech Connect

    Telle, J.

    1981-01-01

    A 16 ..mu..m CF/sub 4/ laser oscillator has operated at 1 kHz in a cooled static cell. Threshold pump energies required from the low pressure, Q-switched, cw discharge CO/sub 2/ laser were as low as 60 ..mu..J. The laser cavity employed the multiple-pass off-axis path resonator in a ring configuration. CF/sub 4/ laser power at 615 cm/sup -1/ and a 1 kHz repetition rate exceeded 300 ..mu..W.

  5. Ex vivo Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics

    PubMed Central

    Paré, JF; Sherley, JL

    2013-01-01

    Transplantation therapy for type I diabetes (T1D) might be improved if pancreatic stem cells were readily available for investigation. Unlike macroscopic islets, pancreatic tissue stem cells could more easily access the retroperitoneal pancreatic environment and thereby might achieve more effective pancreatic regeneration. Unfortunately, whether the adult pancreas actually contains renewing stem cells continues as a controversial issue in diabetes research. We evaluated a new method developed in our lab for expanding renewing distributed stem cells (DSCs) from adult tissues as a means to provide more evidence for adult pancreatic stem cells, and potentially advance their availability for future clinical investigation. The new method was designed to switch DSCs from asymmetric self-renewal to symmetric self-renewal, which promotes their exponential expansion in culture with reduced production of differentiated cells. Called suppression of asymmetric cell kinetics (SACK), the method uses natural purine metabolites to accomplish the self-renewal pattern shift. The SACK purine metabolites xanthine, xanthosine, and hypoxanthine were evaluated for promoting expansion of DSCs from the pancreas of adult human postmortem donors. Xanthine and xanthosine were effective for deriving both pooled and clonal populations of cells with properties indicative of human pancreatic DSCs. The expanded human cell strains had signature SACK agent-suppressible asymmetric cell kinetics, produced Ngn3+ bipotent precursors for α-cells and β-cells, and were non-tumorigenic in immunodeficient mice. Our findings support the existence of pancreatic DSCs in the adult human pancreas and indicate a potential path to increasing their availability for future clinical evaluation. PMID:25197614

  6. Measurement of the 250Cf component in a 252Cf neutron source at KRISS.

    PubMed

    Kim, Jungho; Park, Hyeonseo; Choi, Kil-Oung

    2014-10-01

    Neutron emission rate measurements have been carried out at the Korea Research Institute of Standards and Science using a manganese sulphate bath system for (252)Cf and (241)Am-Be sources since 2004. The relative measurement method was chosen in 2012, and the neutron emission rates agreed with those by the absolute measurement method within uncertainties. The neutron emission rate of an old (252)Cf source has been measured three times: in 2004, 2009 and 2012. The (250)Cf component was fitted to a double-exponential function of (252)Cf+(250)Cf, and the ratio of the (250)Cf component to the (252)Cf component was estimated to be 7.8 % in 2004 and 46.8 % in 2012. Underestimation of the neutron emission rates of old (252)Cf sources can be corrected if the neutron emission rate of the (250)Cf component is taken into account. PMID:24344350

  7. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  8. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process.

    PubMed

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix-only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications. PMID

  9. Pluripotency of adult stem cells derived from human and rat pancreas

    NASA Astrophysics Data System (ADS)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  10. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    PubMed

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  11. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    PubMed Central

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  12. Surgical and Obstetric Outcomes in Adults with Sickle Cell Disease

    PubMed Central

    Adam, Soheir; Jonassaint, Jude; Kruger, Hillary; Kail, Melanie; Orringer, Eugene P.; Eckman, James R.; Ashley-Koch, Allison; Telen, Marilyn J.; De Castro, Laura M.

    2013-01-01

    BACKGROUND Sickle cell disease patients are more likely than the general population to undergo surgery and usually do so at a younger age. Female sickle cell disease patients also have special gynecological and obstetric issues related to their disease. METHODS We collected data through standardized clinical report forms, patient interviews, and medical records from 509 adult sickle cell disease patients. Logistic regression was used to estimate the association between multiple variables and each of the surgery types. We also determined the prevalence and outcomes of pregnancy in 284 women with sickle cell disease in this population. RESULTS Almost 50% of patients aged 18–27 years had had a cholecystectomy. Mean corpuscular hemoglobin, total bilirubin, and lactate dehydrogenase were significantly higher in the postcholecystectomy group; 9.5% of 504 individuals had undergone splenectomy. Hematocrit, body mass index, and red blood cell count were significantly higher in the postsplenectomy group. Hip replacement had been performed in 9.2% of individuals, with the prevalence increasing as early as the fourth decade and continuing to increase through the sixth decade of life. A history of pregnancy was present in 190 women (67%). Of 410 pregnancies, only 53.9% resulted in live births, 16.6% were voluntarily terminated, and 29.5% were complicated by miscarriage, still birth, or ectopic implantation. CONCLUSIONS Sickle cell disease continues to have a strong effect on the mean age for common surgeries and impacts pregnancy outcomes. We conclude that this population has a unique surgical and obstetric history that should be further studied to provide insight into potentially more effective preventive approaches to end-organ damage. PMID:18823864

  13. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    SciTech Connect

    Greene, Carol Ann Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  14. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.

    PubMed

    Thorel, Fabrizio; Népote, Virginie; Avril, Isabelle; Kohno, Kenji; Desgraz, Renaud; Chera, Simona; Herrera, Pedro L

    2010-04-22

    Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration. PMID:20364121

  15. LEM-CF Premixed Tool Kit

    2015-01-19

    The purpose of LEM-CF Premixed Tool Kit is to process premixed flame simulation data from the LEM-CF solver (https://fileshare.craft-tech.com/clusters/view/lem-cf) into a large-eddy simulation (LES) subgrid model database. These databases may be used with a user-defined-function (UDF) that is included in the Tool Kit. The subgrid model UDF may be used with the ANSYS FLUENT flow solver or other commercial flow solvers.

  16. Label-Retaining Cells in the Adult Murine Salivary Glands Possess Characteristics of Adult Progenitor Cells

    PubMed Central

    Chibly, Alejandro M.; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H.

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction. PMID:25238060

  17. Trifluoromethoxycarbonyl peroxynitrate, CF3OCOOONO2.

    PubMed

    von Ahsen, Stefan; García, Plácido; Willner, Helge; Argüello, Gustavo A

    2005-08-01

    The trioxide, CF(3)OC(O)OOOC(O)OCF(3), reacts with NO(2) at 0 degrees C to yield the new peroxynitrate, CF(3)OC(O)OONO(2), which is stable for hours at room temperature. It is spectroscopically characterized and some thermal properties are reported. From the vapor pressure, ln(p/p(0)) = 14.06 - 4565/T, of the liquid above the melting point of -89 degrees C, the extrapolated boiling point is 52 degrees C. CF(3)OC(O)OONO(2) dissociates at higher temperatures and low pressures into the radicals CF(3)OC(O)OO and NO(2) as demonstrated by matrix isolation experiments. The matrix-isolated peroxy radicals consist in a rotameric mixture of trans,trans,trans-CF(3)OC(O)OO and trans,trans,cis-CF(3)OC(O)OO, where trans and cis denote dihedral angles of ca. 180 degrees and 0 degree, respectively, around beta F-C-O-C, beta C-O-C-O, and beta O-C-O-O, with an equilibrium composition dependent on the thermolysis temperature. The radical trans,trans,cis-CF(3)OC(O)OO is found to be ca. 3 kJ mol(-1) higher in enthalpy than trans,trans,trans-CF(3)OC(O)OO. DFT calculations are performed to support the vibrational assignments and to provide structural information about CF(3)OC(O)OONO(2). PMID:16060622

  18. Adsorption of CF4 on graphite preplated with a monolayer of CF3Cl.

    PubMed

    Thomas, Petros; Velazquez, Daniel; Hess, George B

    2011-03-21

    We report a study of the adsorption of CF(4) on graphite preplated with a monolayer of CF(3)Cl, using infrared reflection absorption spectroscopy combined with ellipsometry. The saturated vapor pressure of CF(3)Cl is nearly 3 orders of magnitude smaller than that of CF(4) at the same temperature, so the main control variables are the temperature and the pressure (or chemical potential) of CF(4), together with the initial coverage of CF(3)Cl. The temperature range covered is 60-105 K. We find that, if the initial monolayer of CF(3)Cl is liquid, CF(4) continuously displaces CF(3)Cl by substitution in the monolayer. If the initial monolayer of CF(3)Cl is solid, due to either lower temperature or compression, CF(4) condenses as a second layer on the top of the CF(3)Cl layer, with only slight mixing with the original layer. This behavior persists to multiple layers of CF(4). PMID:21428651

  19. Adult Mesenchymal Stem Cells: When, Where, and How

    PubMed Central

    Caplan, Arnold I.

    2015-01-01

    Adult mesenchymal stem cells (MSCs) have profound medicinal effects at body sites of tissue injury, disease, or inflammation as either endogenously or exogenously supplied. The medicinal effects are either immunomodulatory or trophic or both. When to deliver these mediators of regeneration, where, and by what delivery apparatus or mechanism will directly determine their medical efficacy. The MSCs help manage the innate regenerative capacity of almost every body tissue and the MSCs have only recently been fully appreciated. Perhaps the most skilled physician-manager of the body's innate regenerative capacity is in orthopedics where the vigorous regeneration and repair capacity of bone through local MSCs-titers is expertly managed by the orthopaedic physician. The challenge is to extend MSCs expertise to address other tissue dysfunctions and diseases. The medicine of tomorrow will encompass optimizing the tissues' intrinsic regenerative potential through management of local MSCs. PMID:26273305

  20. Asymptomatic Primary Merkel Cell Polyomavirus Infection among Adults

    PubMed Central

    Tolstov, Yanis L.; Knauer, Alycia; Chen, Jian Guo; Kensler, Thomas W.; Kingsley, Lawrence A.; Moore, Patrick S.

    2011-01-01

    Merkel cell polyomavirus (MCV) is a recently discovered virus that causes 80% of Merkel cell carcinomas. We examined data for 564 gay/bisexual male participants >18 years of age in the Multicenter AIDS Cohort Study in Pittsburgh, Pennsylvania, USA, and found that 447 (79.3%) were MCV-antibody positive at initial enrollment. Of the 117 MCV-seronegative men, 31 subsequently seroconverted over a 4-year follow-up period, corresponding to a 6.6% annual conversion rate. MCV immunoglobulin G levels remained detectable up to 25 years after exposure. No signs, symptoms, or routine diagnostic test results were associated with MCV infection, and no correlation between HIV infection or AIDS progression and MCV infection was noted. An initial correlation between chronic hepatitis B virus infection and MCV prevalence could not be confirmed among MCV seroconverters or in studies of a second hepatitis B virus–hyperendemic cohort from Qidong, China. In adults, MCV is typically an asymptomatic, common, and commensal viral infection that initiates rare cancers after virus (rather than host cell) mutations. PMID:21801612

  1. Langerhans cell histiocytosis of the atlas in an adult.

    PubMed

    Zhong, Wo Quan; Jiang, Liang; Ma, Qing Jun; Liu, Zhong Jun; Liu, Xiao Guang; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting

    2010-01-01

    Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is a rare disorder (approximately 1:1,500,000 inhabitants) characterized by clonal proliferation and excess accumulation of pathologic Langerhans cells causing local or systemic effects. The exact etiology of LCH is still unknown. LCH could affect patients of any age, although most present when they are children. The most frequent sites of the bony lesions are the skull, femur, mandible, pelvis and spine. A variety of treatment modalities has been reported, but there was no evidence suggesting that any one treatment was more advantageous than another. We present an adult with LCH of the atlas. A 26-year-old young man presented with a 2-month history of neck pain and stiffness. CT revealed osteolytic lesion in the left lateral mass of atlas with compression fracture. Histopathological diagnosis was Langerhans cell histiocytosis by percutaneous needle biopsy under CT guidance. The patient underwent conservative treatment, including Halo-vest immobilization and radiotherapy. At 7-year follow-up, the patient was asymptomatic except for mild motion restriction of the neck. CT revealed a significant reconstruction of the C1 lateral mass. PMID:19844749

  2. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras

    PubMed Central

    Keighren, Margaret A.; Flockhart, Jean H.

    2016-01-01

    ABSTRACT The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1−/− null mouse embryos die but a previous study showed that some homozygous Gpi1−/− null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1−/−↔Gpi1c/c chimaera with functional Gpi1−/− null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1−/− null cells in adult Gpi1−/−↔Gpi1c/c chimaeras and determine if Gpi1−/− null germ cells are functional. Analysis of adult Gpi1−/−↔Gpi1c/c chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1−/− null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1−/− null oocytes in one female Gpi1−/−↔Gpi1c/c chimaera were functional and provided preliminary evidence that one male putative Gpi1−/−↔Gpi1c/c chimaera produced functional spermatozoa from homozygous Gpi1−/− null germ cells. Although the male chimaera was almost certainly Gpi1−/−↔Gpi1c/c, this part of the study is considered preliminary because only blood was typed for GPI. Gpi1−/− null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1−/− null germ cells, it successfully identified functional Gpi1−/− null oocytes and revealed that some Gpi1−/− null cells could survive in many adult tissues. PMID:27103217

  3. Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

    PubMed

    Young, Henry E; Duplaa, Cecile; Katz, Ryan; Thompson, Tina; Hawkins, Kristina C; Boev, Angel N; Henson, Nicholas L; Heaton, Matthew; Sood, Rajiv; Ashley, Dennis; Stout, Christopher; Morgan, Joe H; Uchakin, Peter N; Rimando, Marylen; Long, Gypsy F; Thomas, Crystal; Yoon, Jee-In; Park, Ji Eun; Hunt, Darren J; Walsh, Nancy M; Davis, Josh C; Lightner, Joel E; Hutchings, Anna M; Murphy, Meredith L; Boswell, Elizabeth; McAbee, Jessica A; Gray, Brandon M; Piskurich, Janet; Blake, Lisa; Collins, Julie A; Moreau, Catherine; Hixson, Douglas; Bowyer, Frank P; Black, Asa C

    2005-01-01

    This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine. PMID:16202227

  4. Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions

    PubMed Central

    Özdoğu, Hakan; Boğa, Can

    2015-01-01

    Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD), and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD. PMID:25912490

  5. A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal.

    PubMed

    Gilbert, Penney M; Corbel, Stephane; Doyonnas, Regis; Havenstrite, Karen; Magnusson, Klas E G; Blau, Helen M

    2012-04-01

    The goal of regenerative medicine is to restore form and function to damaged and aging tissues. Adult stem cells, present in tissues such as skeletal muscle, comprise a reservoir of cells with a remarkable capacity to proliferate and repair tissue damage. Muscle stem cells, known as satellite cells, reside in a quiescent state in an anatomically distinct compartment, or niche, ensheathed between the membrane of the myofiber and the basal lamina. Recently, procedures for isolating satellite cells were developed and experiments testing their function upon transplantation into muscles revealed an extraordinary potential to contribute to muscle fibers and access and replenish the satellite cell compartment. However, these properties are rapidly lost once satellite cells are plated in culture. Accordingly, elucidating the role of extrinsic factors in controlling muscle stem cell fate, in particular self-renewal, is critical. Through careful design of bioengineered culture platforms, analysis of specific proteins presented to stem cells is possible. Critical to the success of the approach is single cell analysis, as more rapidly proliferating progenitors may mask the behavior of stem cells that proliferate slowly. Bioengineering approaches provide a potent means of gaining insight into the role of extrinsic factors in the stem cell microenvironment on stem cell function and the mechanisms that control their diverse fates. Ultimately, the multidisciplinary approach presented here will lead to novel therapeutic strategies for degenerative diseases. PMID:22327505

  6. Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes.

    PubMed

    Li, Xiaoheng; Wang, Zhao; Jiang, Zhenming; Guo, Jingjing; Zhang, Yuxi; Li, Chenhao; Chung, Jinyong; Folmer, Janet; Liu, June; Lian, Qingquan; Ge, Renshan; Zirkin, Barry R; Chen, Haolin

    2016-03-01

    Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry. PMID:26929346

  7. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    PubMed

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics. PMID:26068799

  8. Culture and proliferation of highly purified adult Schwann cells from rat, dog, and man.

    PubMed

    Haastert-Talini, Kirsten

    2012-01-01

    This chapter presents fast and easy protocols to obtain highly purified cultures of proliferating adult rat, canine, and human Schwann cells. Cell preparation from predegenerated adult sciatic nerves combined with the use of melanocyte growth medium supplemented with forskolin, fibroblast growth factor-2, pituitary extract, and heregulin as selective, serum-free culture medium and two methods for a consecutive cell-enrichment step are described. Our protocols result in approximately 90% pure Schwann cell cultures (or higher). The average time to obtain highly purified in vitro cultures of adult Schwann cells is 21 days. PMID:22367812

  9. Zika Kills Vital Nervous System Cells in Adult Mice, Study Finds

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160505.html Zika Kills Vital Nervous System Cells in Adult Mice, ... 2016 THURSDAY, Aug. 18, 2016 (HealthDay News) -- The Zika virus kills neural stem cells in the brains ...

  10. Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

    PubMed Central

    Kilcoyne, Karen R.; Smith, Lee B.; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S.; Chambers, Thomas J. G.; De Gendt, Karel; Verhoeven, Guido; O’Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathália L. M.; Anderson, Richard A.; Sharpe, Richard M.

    2014-01-01

    Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk. PMID:24753613

  11. Duct Cells Contribute to Regeneration of Endocrine and Acinar Cells Following Pancreatic Damage in Adult Mice

    PubMed Central

    CRISCIMANNA, ANGELA; SPEICHER, JULIE A.; HOUSHMAND, GOLBAHAR; SHIOTA, CHIYO; PRASADAN, KRISHNA; Ji, BAOAN; LOGSDON, CRAIG D.; GITTES, GEORGE K.; ESNI, FARZAD

    2015-01-01

    BACKGROUND & AIMS There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response. METHODS To target specific types of pancreatic cells, we crossed R26DTR or R26dtR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters. RESULTS Exposure of PdxCre;R26DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCre-ERT2;R26DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage. CONCLUSIONS In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process. PMID:21763240

  12. Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

    PubMed Central

    Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

    2013-01-01

    Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

  13. Isolation and purification of islet cells from adult pigs.

    PubMed

    Qiao, A-Y; Zhang, W-H; Chen, X-J; Zhang, J; Xiao, G-H; Hu, Y-X; Tang, D-C

    2010-06-01

    We used in situ perfusion and a multiple-organ harvesting technique to collect islets from adult pig pancreata. The tissues were digested with collagenase P followed by purification in a lympholyte discontinuous gradient using a COBE2991 cell separator. The yield and purity of isolated islets were evaluated with a light microscope after dithizone (DTZ) staining. Islet function was assessed using an in vitro insulin release assay. The results showed that before purification 275,000 +/- 20,895 islet equivalents (IEQ) were obtained from 1 digested pancreas. After purification with gradient centrifugation, the islet yield was 230,350 +/- 26,679 IEQ/pancreas. Each gram of the purified pancreatic tissues yielded 2710 +/- 229 IEQ with an average purity of 50.2 +/- 2.0%. The purified islet cells responded to stimulation with high glucose concentrations (16.7 mmol/L), namely, 4.74-fold greater than the insulin secretion with exposure to the basal level of glucose (3.3 mmol/L; P < .001). These results suggested that the established isolation method can be applied to large-scale purification of fully functional islets from pig pancreata. PMID:20620533

  14. Management of chronic rhinosinusitis in CF.

    PubMed

    Mainz, Jochen G; Koitschev, Assen

    2009-06-01

    Routine CF management often does not include upper airway (UAW) assessment although CFTR defects equally affect the sinonasal mucosa. Up to 50% of CF patients have chronic rhinosinusitis (CRS) and/or nasal polyps, and almost 100% reveal UAW abnormalities on CT scan. CRS impairs quality of life. UAW dysfunction in filtering, humidifying, and warming inspired air affects lower airways and the UAW is a potential site of first colonization and a reservoir for opportunistic bacteria. Therefore, UAW pathology substantially affects overall health in CF. Standard treatments are scarce and mostly lack evidence. Nasal douche can remove mucus and crusts. Recently, delivery of dornase alfa using a vibrating aerosol has shown potential as treatment for CF-related CRS. Surgery is indicated when conservative approaches fail but postoperative relapse is frequent. In summary, upper airway involvement in CF is undertreated and requires prospective investigation and an interdisciplinary consensus on diagnosis and therapy. PMID:19460681

  15. Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells.

    PubMed

    Ye, Lei; Haider, Husnain Kh; Sim, Eugene K W

    2006-01-01

    The real promise of a stem cell-based approach for cardiac regeneration and repair lies in the promotion of myogenesis and angiogenesis at the site of the cell graft to achieve both structural and functional benefits. Despite all of the progress and promise in this field, many unanswered questions remain; the answers to these questions will provide the much-needed breakthrough to harness the real benefits of cell therapy for the heart in the clinical perspective. One of the major issues is the choice of donor cell type for transplantation. Multiple cell types with varying potentials have been assessed for their ability to repopulate the infarcted myocardium; however, only the adult stem cells, that is, skeletal myoblasts (SkM) and bone marrow-derived stem cells (BMC), have been translated from the laboratory bench to clinical use. Which of these two cell types will provide the best option for clinical application in heart cell therapy remains arguable. With results pouring in from the long-term follow-ups of previously conducted phase I clinical studies, and with the onset of phase II clinical trials involving larger population of patients, transplantation of stem cells as a sole therapy without an adjunct conventional revascularization procedure will provide a deeper insight into the effectiveness of this approach. The present article discusses the pros and cons of using SkM and BMC individually or in combination for cardiac repair, and critically analyzes the progress made with each cell type. PMID:16380640

  16. Clinical Trials of Adult Stem Cell Therapy in Patients with Ischemic Stroke

    PubMed Central

    2016-01-01

    Stem cell therapy is considered a potential regenerative strategy for patients with neurologic deficits. Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. With current advances in the understanding regarding the effects of introducing stem cells and their mechanisms of action, several clinical trials of stem cell therapy have been conducted in patients with stroke since 2005, including studies using mesenchymal stem cells, bone marrow mononuclear cells, and neural stem/progenitor cells. In addition, several clinical trials of the use of adult stem cells to treat ischemic stroke are ongoing. This review presents the status of our understanding of adult stem cells and results from clinical trials, and introduces ongoing clinical studies of adult stem cell therapy in the field of stroke. PMID:26610894

  17. Comparison of Mesenchymal Stem Cell Markers in Multiple Human Adult Stem Cells

    PubMed Central

    Maleki, Masoud; Ghanbarvand, Farideh; Reza Behvarz, Mohammad; Ejtemaei, Mehri; Ghadirkhomi, Elham

    2014-01-01

    Objectives: Mesenchymal stem cells (MSCs) are adult stem cells which identified by adherence to plastic, expression of cell surface markers including CD44, CD90, CD105, CD106, CD166, and Stro-1, lack of the expression of hematopoietic markers, no immunogenic effect and replacement of damaged tissues. These properties led to development of progressive methods to isolation and characterization of MSCs from various sources for therapeutic applications in regenerative medicine. Methods: We isolated MSC-like cells from testis biopsies, ovary, hair follicle and umbilical cord Wharton’s jelly and investigated the expression of specific cell surface antigens using flow cytometry in order to verify stemness properties of these cells. Results: All four cell types adhered to plastic culture flask a few days after primary culture. All our cells positively expressed common MSC- specific cell surface markers. Moreover, our results revealed the expression of CD19and CD45 antigens in these cells. Conclusion: According to our results, high expression of CD44 in spermatogonial stem cells (SSCs), hair follicle stem cells (HFSCs),granulosa cells (GCs)and Wharton’s jelly- MSCs (WJ-MSCs)may help them to maintain stemness properties. Furthermore, we suggest that CD105+SSCs, HFSCs and WJ-MSCs revealed the osteogenic potential of these cells. Moreover, high expression of CD90 in SSCs and HFSCs may associate to higher growth and differentiation potential of these cells. Further, the presence of CD19 on SSCs and GCs may help them to efficiency in response to trans-membrane signals. Thus, these four types of MSCs may be useful in clinical applications and cell therapy. PMID:25473449

  18. Alloproliferation of purified CD4+ T cells to adult human heart endothelial cells, and study of second-signal requirements.

    PubMed Central

    McDouall, R M; Page, C S; Hafizi, S; Yacoub, M H; Rose, M L

    1996-01-01

    Human endothelial cells have been shown to be capable of causing direct allostimulation of T cells. However, the majority of immunological studies of human endothelial cells have been performed on cells of fetal origin. Here we use endothelial cells isolated from the adult human heart, both large vessel (coronary artery, pulmonary artery and aorta) and also microvascular. We have examined the ability of all these endothelial cells to cause direct allostimulation of T cells, and show that purified CD4+ T cells can proliferate in response to adult human heart endothelial cells, the response being dependent on pretreatment of the endothelial cells with interferon-gamma (IFN-gamma) and inhibited by anti-HLA-DR monoclonal antibody. The proliferative responses of CD8+ T cells to adult but not fetal endothelial cells was inconsistent and weak. Proliferative responses were not blocked by CTLA4-Ig, which inhibits T-cell responses to "classical' antigen-presenting cells (APC), but > 50% inhibition was achieved with monoclonal antibody to lymphocyte function-associated antigen-3 (LFA-3). These results show that adult human cardiovascular endothelial cells are capable of causing allostimulation of resting CD4+ T cells, using a different second signal to classical APC. In view of these findings endothelial cells should be considered as APC following solid organ transplantation. PMID:8943718

  19. Electrochemically Preadsorbed Collagen Promotes Adult Human Mesenchymal Stem Cell Adhesion.

    PubMed

    Benavidez, Tomás E; Wechsler, Marissa E; Farrer, Madeleine M; Bizios, Rena; Garcia, Carlos D

    2016-01-01

    The present article reports on the effect of electric potential on the adsorption of collagen type I (the most abundant component of the organic phase of bone) onto optically transparent carbon electrodes (OTCE) and its mediation on subsequent adhesion of adult, human, mesenchymal stem cells (hMSCs). For this purpose, adsorption of collagen type I was investigated as a function of the protein concentration (0.01, 0.1, and 0.25 mg/mL) and applied potential (open circuit potential [OCP; control], +400, +800, and +1500 mV). The resulting substrate surfaces were characterized using spectroscopic ellipsometry, atomic force microscopy, and cyclic voltammetry. Adsorption of collagen type I onto OTCE was affected by the potential applied to the sorbent surface and the concentration of protein. The higher the applied potential and protein concentration, the higher the adsorbed amount (Γcollagen). It was also observed that the application of potential values higher than +800 mV resulted in the oxidation of the adsorbed protein. Subsequent adhesion of hMSCs on the OTCEs (precoated with the collagen type I films) under standard cell culture conditions for 2 h was affected by the extent of collagen preadsorbed onto the OTCE substrates. Specifically, enhanced hMSCs adhesion was observed when the Γcollagen was the highest. When the collagen type I was oxidized (under applied potential equal to +1500 mV), however, hMSCs adhesion was decreased. These results provide the first correlation between the effects of electric potential on protein adsorption and subsequent modulation of anchorage-dependent cell adhesion. PMID:26549607

  20. NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration

    SciTech Connect

    Zhang, Lei; Wang, Huaxi; Yang, Yan; Liu, Hui; Zhang, Qihao; Xiang, Qi; Ge, Renshan; Su, Zhijian; Huang, Yadong

    2013-06-28

    Highlights: •Nerve growth factor has shown significant changes on mRNA levels during Adult Leydig cells regeneration. •We established the organ culture model of rat seminiferous tubules with ethane dimethyl sulphonate (EDS) treatment. •Nerve growth factor has shown proliferation and differentiation-promoting effects on Adult stem Leydig cells. •Nerve growth factor induces progenitor Leydig cells to proliferate and differentiate and immature Leydig cells to proliferate. -- Abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful

  1. Role for protein geranylgeranylation in adult T-cell leukemia cell survival

    SciTech Connect

    Nonaka, Mizuho; Uota, Shin; Saitoh, Yasunori; Takahashi, Mayumi; Sugimoto, Haruyo; Amet, Tohti; Arai, Ayako; Miura, Osamu; Yamamoto, Naoki; Yamaoka, Shoji

    2009-01-15

    Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL.

  2. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells.

    PubMed

    Hiwarkar, Prashant; Qasim, Waseem; Ricciardelli, Ida; Gilmour, Kimberly; Quezada, Sergio; Saudemont, Aurore; Amrolia, Persis; Veys, Paul

    2015-12-24

    Unrelated cord blood transplantation (CBT) without in vivo T-cell depletion is increasingly used to treat high-risk hematologic malignancies. Following T-replete CBT, naïve CB T cells undergo rapid peripheral expansion with memory-effector differentiation. Emerging data suggest that unrelated CBT, particularly in the context of HLA mismatch and a T-replete graft, may reduce leukemic relapse. To study the role of CB T cells in mediating graft-versus-tumor responses and dissect the underlying immune mechanisms for this, we compared the ability of HLA-mismatched CB and adult peripheral blood (PB) T cells to eliminate Epstein-Barr virus (EBV)-driven human B-cell lymphoma in a xenogeneic NOD/SCID/IL2rg(null) mouse model. CB T cells mediated enhanced tumor rejection compared with equal numbers of PB T cells, leading to improved survival in the CB group (P < .0003). Comparison of CB T cells that were autologous vs allogeneic to the lymphoma demonstrated that this antitumor effect was mediated by alloreactive rather than EBV-specific T cells. Analysis of tumor-infiltrating lymphocytes demonstrated that CB T cells mediated this enhanced antitumor effect by rapid infiltration of the tumor with CCR7(+)CD8(+) T cells and prompt induction of cytotoxic CD8(+) and CD4(+) T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies. PMID:26450984

  3. Longitudinal analysis of pulmonary function in adults with sickle cell disease

    PubMed Central

    Field, Joshua J.; Glassberg, Jeffrey; Gilmore, Annette; Howard, Joanna; Patankar, Sameer; Yan, Yan; Davies, Sally C.; DeBaun, Michael R.; Strunk, Robert C.

    2013-01-01

    Among adults with sickle cell disease (SCD), pulmonary complications are a leading cause of death. Yet, the natural history of lung function in adults with SCD is not well established. We conducted a retrospective cohort study of adults with SCD who had repeated pulmonary function tests performed over 20 years of age. Ninety-two adults were included in this cohort. Rate of decline in FEV1 for men and women with SCD was 49 cc/year (compared with 20–26 cc/year in the general population). Further studies are needed to identify factors which impact the rate of lung function decline in adults with SCD. PMID:18383325

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

    SciTech Connect

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

    2014-07-18

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1{sup +} or nestin{sup +} 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{sup +} 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{sup +} cells, very few are mash1{sup +} or nestin{sup +} 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{sup +} 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.

  5. Normal Glucagon Signaling and β-Cell Function After Near-Total α-Cell Ablation in Adult Mice

    PubMed Central

    Thorel, Fabrizio; Damond, Nicolas; Chera, Simona; Wiederkehr, Andreas; Thorens, Bernard; Meda, Paolo; Wollheim, Claes B.; Herrera, Pedro L.

    2011-01-01

    OBJECTIVE To evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis. RESEARCH DESIGN AND METHODS We generated a new transgenic model allowing near-total α-cell removal specifically in adult mice. Massive α-cell ablation was triggered in normally grown and healthy adult animals upon diphtheria toxin (DT) administration. The metabolic status of these mice was assessed in 1) physiologic conditions, 2) a situation requiring glucagon action, and 3) after β-cell loss. RESULTS Adult transgenic mice enduring extreme (98%) α-cell removal remained healthy and did not display major defects in insulin counter-regulatory response. We observed that 2% of the normal α-cell mass produced enough glucagon to ensure near-normal glucagonemia. β-Cell function and blood glucose homeostasis remained unaltered after α-cell loss, indicating that direct local intraislet signaling between α- and β-cells is dispensable. Escaping α-cells increased their glucagon content during subsequent months, but there was no significant α-cell regeneration. Near-total α-cell ablation did not prevent hyperglycemia in mice having also undergone massive β-cell loss, indicating that a minimal amount of α-cells can still guarantee normal glucagon signaling in diabetic conditions. CONCLUSIONS An extremely low amount of α-cells is sufficient to prevent a major counter-regulatory deregulation, both under physiologic and diabetic conditions. We previously reported that α-cells reprogram to insulin production after extreme β-cell loss and now conjecture that the low α-cell requirement could be exploited in future diabetic therapies aimed at regenerating β-cells by reprogramming adult α-cells. PMID:21926270

  6. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution

    PubMed Central

    Spiewak, Jessica E.

    2014-01-01

    Summary Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage and mate choice and have played important roles in speciation. Here, we review recent studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns. PMID:25421288

  7. Isolation and culture of adult epithelial stem cells from human skin.

    PubMed

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

    The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue. Epithelial stem cells have been identified in the epidermis, hair follicle, and intestine as cells with a high in vitro proliferative potential and as slow-cycling label-retaining cells in vivo (1-3). Adult, tissue-specific stem cells are responsible for the regeneration of the tissues in which they reside during normal physiologic turnover as well as during times of stress (4-5). Moreover, stem cells are generally considered to be multi-potent, possessing the capacity to give rise to multiple cell types within the tissue (6). For example, rodent hair follicle stem cells can generate epidermis, sebaceous glands, and hair follicles (7-9). We have shown that stem cells from the human hair follicle bulge region exhibit multi-potentiality (10). Stem cells have become a valuable tool in biomedical research, due to their utility as an in vitro system for studying developmental biology, differentiation, tumorigenesis and for their possible therapeutic utility. It is likely that adult epithelial stem cells will be useful in the treatment of diseases such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa and alopecias (11-13). Additionally, other skin problems such as burn wounds, chronic wounds and ulcers will benefit from stem cell related therapies (14,15). Given the potential for reprogramming of adult cells into a pluripotent state (iPS cells)(16,17), the readily accessible and expandable adult stem cells in human skin may provide a valuable source of cells for induction and downstream therapy for a wide range of disease including diabetes and

  8. Cardiomyogenic potential of c-kit+ expressing cells derived from neonatal and adult mouse hearts

    PubMed Central

    Zaruba, Marc-Michael; Soonpaa, Mark; Reuter, Sean; Field, Loren J.

    2010-01-01

    Summary Background c-kit is a receptor tyrosine kinase family member expressed in hematopoietic stem cells. c-kit is also transiently expressed in cardiomyocyte precursors during development, and in a rare cell population in the normal adult heart. Here, the cardiomyogenic potential of c-kit+ cells isolated from normal neonatal, normal adult and infarcted adult mouse hearts was evaluated. Methods and Results Magnetic activated cell sorting (MACS) was used to prepare c-kit+ cells from the hearts of ACT-EGFP/MHC-nLAC double transgenic mice. These animals exhibit widespread enhanced green fluorescent protein (EGFP) expression and cardiomyocyte-restricted nuclear β-galactosidase activity, thus permitting simultaneous tracking of cell survival and differentiation. A subset of the c-kit+ cells from double transgenic neonatal hearts acquired a cardiomyogenic phenotype when co-cultured with fetal cardiomyocytes (2.4% of all EGFP+ cells screened), but not when cultured alone or when co-cultured with mouse fibroblasts (0.03% and 0.05% of the EGFP+ cells screened, respectively). In contrast, c-kit+ cells from normal adult double transgenic hearts failed to undergo cardiomyogenic differentiation when co-cultured with non-transgenic fetal cardiomyocytes (>18,000 EGFP+ cells screened) or when transplanted into normal or infarcted adult mouse hearts (14 EGFP+ grafts examined). A single c-kit+ cell from an infarcted double transgenic adult heart was observed to acquire a cardiomyogenic phenotype in co-culture (>37,000 EGFP+ cells screened). Conclusions These data suggest that the ability of cardiac-resident c-kit+ cells to acquire a cardiomyogenic phenotype is subject to temporal limitations, or alternatively that the cardiomyogenic population is lost. Elucidation of the underlying molecular basis may permit robust cardiomyogenic induction in adult-derived cardiac c-kit+ cells. PMID:20421520

  9. A Case of Adult Granulosa Cell Tumor of the Testis

    PubMed Central

    Tanner, Stephen B.; Morilla, Dan B.; Schaber, John D.

    2014-01-01

    Patient: Female, 22 Final Diagnosis: Testis granulosa cell tumor Symptoms: Pain in testicles • swelling of epididymides • tenderness of epididymiides Medication: — Clinical Procedure: — Specialty: Urology Objective: Rare disease Background: Adult granulosa cell tumors of the testis (AGCTT) are classified as sex cord-stromal tumors. Only 31 cases have been reported. Typical presentation includes a slowly enlarging, painless testicular mass. Associated findings are gynecomastia, decreased libido, and erectile dysfunction. Immunohistochemistry can be used to confirm the diagnosis. Case Rrport: A 22-year-old male presented with complaint of mild pain in both testicles. A testicular ultrasound revealed a 4.0×3.8×4.6 mm hypoechoic lesion within the left testicle. Serum tumor markers (STM) included lactate dehydrogenase (LDH) measuring 146 IU/L (98–192), serum alpha-1-fetoprotein (AFP), 2.89 ng/mL (0–9), and plasma beta human chorionic gonadotropin (Beta HCG) measuring less than 0.50 mIU/mL (<0.50–2.67). Computed tomography (CT) of the abdomen and pelvis with oral and intravenous contrast was normal. A radical orchiectomy was recommended but the patient refused. He agreed to surveillance with imaging and serum tumor markers (STM). The patient’s testicular ultrasound showed the mass to be stable in size and STMs remained negative. The patient agreed to an orchiectomy 9 months after his diagnosis. This case is the first reported with c-kit-positive immunohistochemistry. His post-operative course has been unremarkable. Conclusions: AGCTT is a rare tumor and information regarding its presentation, gross and microscopic morphology, and immunohistochemical characteristics is lacking. This report provides an update of the immunohistochemical findings and adds to the available data concerning this tumor. Based on the results of this case, future reports that include c-kit immunohistochemistry would be beneficial to evaluate its utility in diagnosing AGCTT. PMID

  10. Specific ablation of thyroid follicle cells in adult transgenic mice.

    PubMed

    Wallace, H; Ledent, C; Vassart, G; Bishop, J O; al-Shawi, R

    1991-12-01

    The coding region of the herpes simplex type 1 virus thymidine kinase gene was coupled to the promoter of the bovine thyroglobulin gene and introduced into the genome of mice. The viral thymidine kinase (HSV1-TK) was expressed mainly in the thyroid glands and testis. Upon treatment of transgenic females with the antiherpetic agent Ganciclovir the thyroid regressed, while the parathyroid gland was unaffected. The number of thyroid follicle cells was greatly reduced after 3 days, and they were completely absent after 7 days of treatment. After 14 days, the levels of circulating T4 and T3 were below the limits of detection, total soluble protein recovered from the thyroid and parathyroid glands together was 10% of the control value, and the level of thyroid HSV1-TK was more than 100-fold lower than that in transgenic controls. Levels of circulating PTH and calcitonin remained normal. At the time of treatment the mice were adults. Thus, the thyroid follicle cells were selectively ablated after normal development with a functional thyroid gland. When treatment with Ganciclovir was terminated after 14 days, no circulating T4 or T3 or other indications of thyroid regeneration were detected for a subsequent period of 90 days. During this time the mice gained weight more slowly than controls, at a rate consistent with the suppression of GH synthesis by thyroid deficiency. The production of mouse major urinary protein (MUP) ceased in the treated mice and was completely restored by the administration of T4. MUP production was not restored by GH, demonstrating that the expression of the Mup genes requires T4 in addition to GH. PMID:1659524

  11. Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary.

    PubMed

    Ma, Qing; de Cuevas, Margaret; Matunis, Erika L

    2016-03-01

    Sexual identity is continuously maintained in specific differentiated cell types long after sex determination occurs during development. In the adult Drosophila testis, the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo) acts with the canonical male sex determinant DoublesexM (Dsx(M)) to maintain the male identity of somatic cyst stem cells and their progeny. Here we find that ectopic expression of chinmo is sufficient to induce a male identity in adult ovarian somatic cells, but it acts through a Dsx(M)-independent mechanism. Conversely, the feminization of the testis somatic stem cell lineage caused by loss of chinmo is enhanced by expression of the canonical female sex determinant Dsx(F), indicating that chinmo acts in parallel with the canonical sex determination pathway to maintain the male identity of testis somatic cells. Consistent with this finding, ectopic expression of female sex determinants in the adult testis disrupts tissue morphology. The miRNA let-7 downregulates chinmo in many contexts, and ectopic expression of let-7 in the adult testis is sufficient to recapitulate the chinmo loss-of-function phenotype, but we find no apparent phenotypes upon removal of let-7 in the adult ovary or testis. Our finding that chinmo is necessary and sufficient to promote a male identity in adult gonadal somatic cells suggests that the sexual identity of somatic cells can be reprogrammed in the adult Drosophila ovary as well as in the testis. PMID:26811385

  12. Lysophosphatidic Acid Receptor Is a Functional Marker of Adult Hippocampal Precursor Cells

    PubMed Central

    Walker, Tara L.; Overall, Rupert W.; Vogler, Steffen; Sykes, Alex M.; Ruhwald, Susann; Lasse, Daniela; Ichwan, Muhammad; Fabel, Klaus; Kempermann, Gerd

    2016-01-01

    Summary Here, we show that the lysophosphatidic acid receptor 1 (LPA1) is expressed by a defined population of type 1 stem cells and type 2a precursor cells in the adult mouse dentate gyrus. LPA1, in contrast to Nestin, also marks the quiescent stem cell population. Combining LPA1-GFP with EGFR and prominin-1 expression, we have enabled the prospective separation of both proliferative and non-proliferative precursor cell populations. Transcriptional profiling of the isolated proliferative precursor cells suggested immune mechanisms and cytokine signaling as molecular regulators of adult hippocampal precursor cell proliferation. In addition to LPA1 being a marker of this important stem cell population, we also show that the corresponding ligand LPA is directly involved in the regulation of adult hippocampal precursor cell proliferation and neurogenesis, an effect that can be attributed to LPA signaling via the AKT and MAPK pathways. PMID:27050949

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

    PubMed Central

    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

  14. Roles of neural stem cells and adult neurogenesis in adolescent alcohol use disorders

    PubMed Central

    Nixon, K.; Morris, S.A.; Liput, D.J.; Kelso, M.L.

    2009-01-01

    This review discusses the contributions of a newly considered form of plasticity, the ongoing production of new neurons from neural stem cells, or adult neurogenesis, within the context of neuropathologies that occur with excessive alcohol intake in the adolescent. Neural stem cells and adult neurogenesis are now thought to contribute to the structural integrity of the hippocampus, a limbic system region involved in learning, memory, behavioral control, and mood. In adolescents with alcohol use disorders, the hippocampus appears to be particularly vulnerable to the neurodegenerative effects of alcohol, but the role of neural stem cells and adult neurogenesis in alcoholic neuropathology has only recently been considered. This review encompasses a brief overview of neural stem cells and the processes involved in adult neurogenesis, how neural stem cells are affected by alcohol, and possible differences in the neurogenic niche between adults and adolescents. Specifically, what is known about developmental differences in adult neurogenesis between the adult and adolescent is gleaned from the literature, as well as how alcohol affects this process differently between the age groups. And finally, this review suggests differences that may exist in the neurogenic niche between adults and adolescents and how these differences may contribute to the susceptibility of the adolescent hippocampus to damage. However, many more studies are needed to discern whether these developmental differences contribute to the vulnerability of the adolescent to developing an alcohol use disorder. PMID:20113873

  15. Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain

    PubMed Central

    Deng, Wei; Saxe, Michael D.; Gallina, Iryna S.; Gage, Fred H.

    2009-01-01

    Adult-born dentate granule cells (DGCs) contribute to learning and memory, yet it remains unknown when adult-born DGCs become involved in the cognitive processes. During neurogenesis, immature dentate granule cells (DGCs) display distinctive physiological characteristics while undergoing morphological maturation before final integration into the neural circuits. The survival and activity of the adult-born DGCs can be influenced by the experience of the animal during a critical period when newborn DGCs are still immature. To assess the temporal importance of adult neurogenesis, we developed a transgenic mouse model that allowed us to transiently reduce the numbers of adult-born DGCs in a temporally regulatable manner. We found that mice with a reduced population of adult-born DGCs at the immature stage were deficient in forming robust, long-term spatial memory and displayed impaired performance in extinction tasks. These results suggest that immature DGCs that undergo maturation make important contributions to learning and memory. PMID:19864566

  16. Fetal PGC-1α Overexpression Programs Adult Pancreatic β-Cell Dysfunction

    PubMed Central

    Valtat, Bérengère; Riveline, Jean-Pierre; Zhang, Ping; Singh-Estivalet, Amrit; Armanet, Mathieu; Venteclef, Nicolas; Besseiche, Adrien; Kelly, Daniel P.; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Bréant, Bernadette; Blondeau, Bertrand

    2013-01-01

    Adult β-cell dysfunction, a hallmark of type 2 diabetes, can be programmed by adverse fetal environment. We have shown that fetal glucocorticoids (GCs) participate in this programming through inhibition of β-cell development. Here we have investigated the molecular mechanisms underlying this regulation. We showed that GCs stimulate the expression of peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), a coregulator of the GCs receptor (GR), and that the overexpression of PGC-1α represses genes important for β-cell development and function. More precisely, PGC-1α inhibited the expression of the key β-cell transcription factor pancreatic duodenal homeobox 1 (Pdx1). This repression required the GR and was mediated through binding of a GR/PGC-1α complex to the Pdx1 promoter. To explore PGC-1α function, we generated mice with inducible β-cell PGC-1α overexpression. Mice overexpressing PGC-1α exhibited at adult age impaired glucose tolerance associated with reduced insulin secretion, decreased β-cell mass, and β-cell hypotrophy. Interestingly, PGC-1α expression in fetal life only was sufficient to impair adult β-cell function whereas β-cell PGC-1α overexpression from adult age had no consequence on β-cell function. Altogether, our results demonstrate that the GR and PGC-1α participate in the fetal programming of adult β-cell function through inhibition of Pdx1 expression. PMID:23274887

  17. Benign mast cell hyperplasia and atypical mast cell infiltrates in penile lichen planus in adult men.

    PubMed

    Regauer, Sigrid; Beham-Schmid, Christine

    2014-08-01

    Introduction. Lichen planus (LP) is a chronic cytokine-mediated disease of possible auto-immune etiology. 25% of men have anogenital manifestations. Erosive penile LP causes a scarring phimosis of the foreskin in uncircumcised men. Mast cells as potent immune modulators have been implicated in a number of autoimmune and chronic inflammatory diseases, but have not been investigated in LP. Material and Methods. Formalin-fixed tissues of 117 circumcision specimens of adult men affected by LP were evaluated for the extent of mast cell and lymphocyte infiltrates, characterized immunohistochemically with antibodies to CD 3, 4, 8, 20, 21, 25, 30, 117c and human mast cell tryptase. Specimens with dense mast cell infiltrates were analyzed for point mutations of the c-kit gene (D816V). Results. Unaffected skin and modified mucosa of foreskins contained ⟨5 mast cells/mm². The inflammatory infiltrate of LP-lesions displayed ⟨15 mast cells/mm² in 33/117 foreskins, 16-40 mast cells/mm² in 22/117 and ⟩40 mast cells/mm² (average 70, range 40-100) in 62/117 foreskins. Lesional mast cells of 29/117 (24%) foreskins showed aberrant CD25-expression and/or spindled morphology, with 11/29 men having erosive LP, 13/29 a lymphocytic vasculitis and 1/28 a systemic mastocytosis. Neither CD30-expression nor c-kit mutations were identified. Atypical mast cell infiltrates in LP correlated with high disease activity, erosive LP and presence of lymphocytic vasculitis Conclusions. Increased mast cells in penile LP, mostly representing a benign hyperplasia/activation syndrome, suggests them as targets for innovative therapy options for symptomatic LP-patients not responding to corticosteroid therapy. Presently, the biological implications of atypical mast cell infiltrates in penile LP are unknown. PMID:24402730

  18. Analysis of gene expression in fetal and adult cells infected with rubella virus

    SciTech Connect

    Adamo, Maria Pilar; Zapata, Marta; Frey, Teryl K.

    2008-01-05

    Congenital infection with rubella virus (RUB) leads to persistent infection and congenital defects and we showed previously that primary human fetal fibroblasts did not undergo apoptosis when infected with RUB, which could promote fetal virus persistence [Adamo, P., Asis, L., Silveyra, P., Cuffini, C., Pedranti, M., Zapata, M., 2004. Rubella virus does not induce apoptosis in primary human embryo fibroblasts cultures: a possible way of viral persistence in congenital infection. Viral Immunol. 17, 87-100]. To extend this observation, gene chip analysis was performed on a line of primary human fetal fibroblasts (10 weeks gestation) and a line of human adult lung fibroblasts (which underwent apoptosis in response to RUB infection) to compare gene expression in infected and uninfected cells. A total of 632 and 516 genes were upregulated or downregulated in the infected fetal and adult cells respectively in comparison to uninfected cells, however only 52 genes were regulated in both cell types. Although the regulated genes were different, across functional gene categories the patterns of gene regulation were similar. In general, regulation of pro- and anti-apoptotic genes following infection appeared to favor apoptosis in the adult cells and lack of apoptosis in the fetal cells, however there was a greater relative expression of anti-apoptotic genes and reduced expression of pro-apoptotic genes in uninfected fetal cells versus uninfected adult cells and thus the lack of apoptosis in fetal cells following RUB infection was also due to the prevailing background of gene expression that is antagonistic to apoptosis. In support of this hypothesis, it was found that of a battery of five chemicals known to induce apoptosis, two induced apoptosis in the adult cells, but not in fetal cells, and two induced apoptosis more rapidly in the adult cells than in fetal cells (the fifth did not induce apoptosis in either). A robust interferon-stimulated gene response was induced

  19. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  20. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells.

    PubMed

    Pfenninger, Cosima V; Roschupkina, Teona; Hertwig, Falk; Kottwitz, Denise; Englund, Elisabet; Bengzon, Johan; Jacobsen, Sten Eirik; Nuber, Ulrike A

    2007-06-15

    Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133. PMID:17575139

  1. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

    ... Cystic Fibrosis (CF) Chloride Sweat Test Lungs and Respiratory System Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition Lungs and Respiratory System Contact Us Print Resources Send to a friend ...

  2. YAP Regulates Cell Proliferation, Migration, and Steroidogenesis in Adult Granulosa Cell Tumors

    PubMed Central

    Fu, David; Lv, Xiangmin; Hua, Guohua; He, Chunbo; Dong, Jixin; Lele, Subodh M.; Li, David Wan-Cheng; Zhai, Qiongli; Davis, John S.; Wang, Cheng

    2014-01-01

    The Hippo signaling pathway has been implicated as a conserved regulator of organ size in both Drosophila and mammals. Yes associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargement of ovary, excess production of estrogen, high frequency of recurrence and potential of malignancy and metastasis. Whether the Hippo pathway plays a role in the pathogenesis of GCT is unknown. This study was conducted to examine the expression of YAP in human adult GCTs and to determine the role of YAP in the proliferation and steroidogenesis of GCT cells. Compared with age-matched normal human ovaries, GCT tissues exhibited higher levels of YAP expression. YAP protein was predominantly expressed in the nucleus of tumor cells, whereas the non-tumor ovarian stromal cells expressed very low levels of YAP. YAP was also expressed in cultured primary human granulosa cells and in KGN and COV434 GCT cell lines. siRNA-mediated knockdown of YAP in KGN cells resulted in a significant reduction in cell proliferation (P<0.001). Conversely, overexpression of wild-type YAP or a constitutively active YAP mutant resulted in a significant increase in KGN cell proliferation and migration. Moreover, YAP knockdown reduced FSH-induced aromatase (CYP19A1) protein expression and estrogen production in KGN cells. These results demonstrate that YAP plays an important role in regulating GCT cell proliferation, migration and steroidogenesis. Targeting the Hippo/YAP pathway may provide a novel therapeutic approach for GCT. PMID:24389730

  3. Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner

    PubMed Central

    Kolahgar, Golnar; Suijkerbuijk, Saskia J.E.; Kucinski, Iwo; Poirier, Enzo Z.; Mansour, Sarah; Simons, Benjamin D.; Piddini, Eugenia

    2015-01-01

    Summary Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization. Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute−/+ cells in response to chronic JNK stress signaling. PMID:26212135

  4. Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.

    PubMed

    Kolahgar, Golnar; Suijkerbuijk, Saskia J E; Kucinski, Iwo; Poirier, Enzo Z; Mansour, Sarah; Simons, Benjamin D; Piddini, Eugenia

    2015-08-10

    Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization. Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute(-/+) cells in response to chronic JNK stress signaling. PMID:26212135

  5. RNA-Seq Reveals the Angiogenesis Diversity between the Fetal and Adults Bone Mesenchyme Stem Cell.

    PubMed

    Zhao, Xin; Han, Yingmin; Liang, Yu; Nie, Chao; Wang, Jian

    2016-01-01

    In this research, we used RNA sequencing (RNA-seq) to analyze 23 single cell samples and 2 bulk cells sample from human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. The results from the research demonstrated that there were big differences between two cell lines. Adult bone mesenchyme stem cell lines showed a strong trend on the blood vessel differentiation and cell motion, 48/49 vascular related differential expressed genes showed higher expression in adult bone mesenchyme stem cell lines (Abmsc) than fetal bone mesenchyme stem cell lines (Fbmsc). 96/106 cell motion related genes showed the same tendency. Further analysis showed that genes like ANGPT1, VEGFA, FGF2, PDGFB and PDGFRA showed higher expression in Abmsc. This work showed cell heterogeneity between human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. Also the work may give an indication that Abmsc had a better potency than Fbmsc in the future vascular related application. PMID:26901069

  6. RNA-Seq Reveals the Angiogenesis Diversity between the Fetal and Adults Bone Mesenchyme Stem Cell

    PubMed Central

    Zhao, Xin; Han, Yingmin; Liang, Yu; Nie, Chao; Wang, Jian

    2016-01-01

    In this research, we used RNA sequencing (RNA-seq) to analyze 23 single cell samples and 2 bulk cells sample from human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. The results from the research demonstrated that there were big differences between two cell lines. Adult bone mesenchyme stem cell lines showed a strong trend on the blood vessel differentiation and cell motion, 48/49 vascular related differential expressed genes showed higher expression in adult bone mesenchyme stem cell lines (Abmsc) than fetal bone mesenchyme stem cell lines (Fbmsc). 96/106 cell motion related genes showed the same tendency. Further analysis showed that genes like ANGPT1, VEGFA, FGF2, PDGFB and PDGFRA showed higher expression in Abmsc. This work showed cell heterogeneity between human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. Also the work may give an indication that Abmsc had a better potency than Fbmsc in the future vascular related application. PMID:26901069

  7. GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

    PubMed Central

    Young, Stephanie Z.; Bordey, Angélique

    2010-01-01

    Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA's presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity. PMID:19509127

  8. Adult equine bone marrow stromal cells produce a cartilage-like ECM mechanically superior to animal-matched adult chondrocytes.

    PubMed

    Kopesky, P W; Lee, H-Y; Vanderploeg, E J; Kisiday, J D; Frisbie, D D; Plaas, A H K; Ortiz, C; Grodzinsky, A J

    2010-06-01

    Our objective was to evaluate the age-dependent mechanical phenotype of bone marrow stromal cell- (BMSC-) and chondrocyte-produced cartilage-like neo-tissue and to elucidate the matrix-associated mechanisms which generate this phenotype. Cells from both immature (2-4 month-old foals) and skeletally-mature (2-5 year-old adults) mixed-breed horses were isolated from animal-matched bone marrow and cartilage tissue, encapsulated in self-assembling-peptide hydrogels, and cultured with and without TGF-beta1 supplementation. BMSCs and chondrocytes from both donor ages were encapsulated with high viability. BMSCs from both ages produced neo-tissue with higher mechanical stiffness than that produced by either young or adult chondrocytes. Young, but not adult, chondrocytes proliferated in response to TGF-beta1 while BMSCs from both age groups proliferated with TGF-beta1. Young chondrocytes stimulated by TGF-beta1 accumulated ECM with 10-fold higher sulfated-glycosaminoglycan content than adult chondrocytes and 2-3-fold higher than BMSCs of either age. The opposite trend was observed for hydroxyproline content, with BMSCs accumulating 2-3-fold more than chondrocytes, independent of age. Size-exclusion chromatography of extracted proteoglycans showed that an aggrecan-like peak was the predominant sulfated proteoglycan for all cell types. Direct measurement of aggrecan core protein length and chondroitin sulfate chain length by single molecule atomic force microscopy imaging revealed that, independent of age, BMSCs produced longer core protein and longer chondroitin sulfate chains, and fewer short core protein molecules than chondrocytes, suggesting that the BMSC-produced aggrecan has a phenotype more characteristic of young tissue than chondrocyte-produced aggrecan. Aggrecan ultrastructure, ECM composition, and cellular proliferation combine to suggest a mechanism by which BMSCs produce a superior cartilage-like neo-tissue than either young or adult chondrocytes. PMID:20153827

  9. Expression of nestin-GFP transgene marks oval cells in the adult liver

    PubMed Central

    Gleiberman, Anatoli S.; Encinas, Juan M.; Mignone, John L.; Michurina, Tatyana; Rosenfeld, Michael G.; Enikolopov, Grigori

    2009-01-01

    Oval cells which become apparent in the liver after chronic injury, serve as bi-potent progenitors for differentiated hepatocytes and cholangiocytes. We found that in the liver of adult transgenic mice in which expression of green fluorescent protein (GFP) is driven by regulatory elements of the nestin gene, the GFP signal marks a subpopulation of small epithelial cells which meet the criteria for oval cells, including morphology, localization, antigenic profile, and reactivity in response to injury. In the regenerating and developing liver we also found nestin-GFP-positive cells which express hepatocyte markers; such cells may correspond to transiently appearing differentiating progeny of oval cells. During development, GFP-expressing cells in the liver emerge relatively late, after the appearance of differentiated hepatocytes and cholangiocytes. Our results suggest that nestin-GFP cells in the liver correspond to a specialized cell type whose primary function may be to serve as a reserve for adult liver epithelial cell types. PMID:16127706

  10. In vitro generation of pancreatic endocrine cells from human adult fibroblast-like limbal stem cells.

    PubMed

    Criscimanna, Angela; Zito, Giovanni; Taddeo, Annalisa; Richiusa, Pierina; Pitrone, Maria; Morreale, Daniele; Lodato, Gaetano; Pizzolanti, Giuseppe; Citarrella, Roberto; Galluzzo, Aldo; Giordano, Carla

    2012-01-01

    Stem cells might provide unlimited supply of transplantable cells for β-cell replacement therapy in diabetes. The human limbus is a highly specialized region hosting a well-recognized population of epithelial stem cells, which sustain the continuous renewal of the cornea, and the recently identified stromal fibroblast-like stem cells (f-LSCs), with apparent broader plasticity. However, the lack of specific molecular markers for the identification of the multipotent limbal subpopulation has so far limited the investigation of their differentiation potential. In this study we show that the human limbus contains uncommitted cells that could be potentially harnessed for the treatment of diabetes. Fourteen limbal biopsies were obtained from patients undergoing surgery for ocular diseases not involving the conjunctiva or corneal surface. We identified a subpopulation of f-LSCs characterized by robust proliferative capacity, expressing several pluripotent stem cell markers and exhibiting self-renewal ability. We then demonstrated the potential of f-LSCs to differentiate in vitro into functional insulin-secreting cells by developing a four-step differentiation protocol that efficiently directed f-LSCs towards the pancreatic endocrine cell fate. The expression of specific endodermal, pancreatic, islet, and β-cell markers, as well as functional properties of f-LSC-derived insulin-producing cells, were evaluated during differentiation. With our stage-specific approach, up to 77% of f-LSCs eventually differentiated into cells expressing insulin (also assessed as C-peptide) and exhibited phenotypic features of mature β-cells, such as expression of critical transcription factors and presence of secretory granules. Although insulin content was about 160-fold lower than what observed in adult islets, differentiated cells processed ∼98% of their proinsulin content, similar to mature β-cells. Moreover, they responded in vitro in a regulated manner to multiple secretory stimuli

  11. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

    SciTech Connect

    Capkovic, Katie L.; Stevenson, Severin; Johnson, Marc C.; Thelen, Jay J.; Cornelison, D.D.W.

    2008-04-15

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression.

  12. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation.

    PubMed

    Capkovic, Katie L; Stevenson, Severin; Johnson, Marc C; Thelen, Jay J; Cornelison, D D W

    2008-04-15

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression. PMID:18308302

  13. CF6-6D engine performance deterioration

    NASA Technical Reports Server (NTRS)

    Wulf, R. H.; Kramer, W. H.; Pass, J. E.; Smith, J. J.

    1980-01-01

    Cruise cockpit recordings and test cell performance data in conjunction with hardware inspection data from airline overhaul shops were analyzed to define the extent and magnitude of performance deterioration of the General Electric CF6-6D model engine. These studies successfully isolated short-term deterioration from the longer term, and defined areas where a significant reduction in aircraft energy requirements for the 1980's can be realized. Unrestored losses which remain after engine refurbishment represent over 70% of the loss at engine shop visit. Sixty-three percent of the unrestored losses are cost-effective to restore which could reduce fuel consumed by CF6-6D engines in 1980 by 10.9 million gallons.

  14. Cell swelling impairs dye coupling in adult rat ventricular myocytes. Cell volume as a regulator of cell communication

    PubMed Central

    De Mello, WC

    2013-01-01

    The influence of cell swelling on cell communication was investigated in cardiomyocytes isolated from the ventricle of adult rats. Measurements of dye coupling were performed in cell pairs using intracellular dialysis of Lucifer Yellow CH. The pipette was attached to one cell of the pair and after a gig ohm seal was achieved, the membrane was ruptured by a brief suction allowing the dye to diffuse from the pipette into the cell. Fluorescence of the dye in the injected as well as in non-dialyzed cell of the pair was continuously monitored. The results indicate that in cell pairs exposed to hypotonic solution the cell volume was increased by about 60% within 35 min and the dye coupling was significantly reduced by cell swelling. Calculation of gap junction permeability (P(j)) assuming an the intracellular volume accessible to intracellular diffusion of the dye as 12% of total cell volume, showed an average P(j) value of 0.16 ± 0.04 × 10−4 cm/s (n = 35) in the control and 0.89 ± 1.1 × 10−5 cm (n = 40) for cells exposed to hypotonic solution (P < 0.05). Similar results were found assuming intracellular volumes accessible to the dye of 20 and 30% of total cell volume, respectively. Cell swelling did not change the rate of intracellular diffusion of the dye. The results, which indicate that cell volume is an important regulator of gap junction permeability, have important implications to myocardial ischemia and heart failure as well as to heart pharmacology because changes in cell volume caused by drugs and transmitters can impair cell communication with consequent generation of slow conduction and cardiac arrhythmias. PMID:20512611

  15. The influence of hypoxic physical activity on cfDNA as a new marker of vascular inflammation

    PubMed Central

    Zembron-Lacny, Agnieszka; Baldy-Chudzik, Katarzyna; Orysiak, Joanna; Sitkowski, Dariusz; Banach, Maciej

    2015-01-01

    The phenomenon of circulating cell-free DNA (cfDNA) is important for many biomedical disciplines including the field of exercise biochemistry and physiology. It is likely that cfDNA is released into the plasma by apoptosis of endothelial cells and circulating endothelial progenitor cells (EPCs), and/or by NETosis of immune cells induced by strenuous exercise. Increases of cfDNA are described to be a potential hallmark for the overtraining syndrome, and might be related to aseptic vascular inflammation in athletes. Yet, the relevance of systemic inflammation and cfDNA with endothelial dysfunction in athletes still remains unclear. In this review article, we provide a current overview of exercise-induced cfDNA release to the circulation with special emphasis on its relationship with apoptosis and NETosis and the effect of hypoxic physical activity on vascular inflammation in athletes. PMID:26788076

  16. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation

    PubMed Central

    Kolf, Catherine M; Cho, Elizabeth; Tuan, Rocky S

    2007-01-01

    Recent advances in understanding the cellular and molecular signaling pathways and global transcriptional regulators of adult mesenchymal stem cells have provided new insights into their biology and potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal and regulation of lineage-specific differentiation of mesenchymal stem cells. In addition we review recent research on the concept of stem cell niche, and its relevance to adult mesenchymal stem cells. PMID:17316462

  17. Reserve stem cells: Reprogramming of differentiated cells fuels repair, metaplasia, and neoplasia in the adult gastrointestinal tract

    PubMed Central

    Mills, Jason C.; Sansom, Owen J.

    2016-01-01

    It has long been known that differentiated cells can switch fates, especially in vitro, but only recently has there been a critical mass of publications describing the mechanisms adult, post-mitotic cells use in vivo to reverse their differentiation state. We propose that this sort of cellular reprogramming is a fundamental cellular process akin to apoptosis or mitosis. Because reprogramming can invoke regenerative cells from mature cells, it is critical to the longterm maintenance of tissues like the pancreas, which encounter large insults during adulthood but lack constitutively active adult stem cells to repair the damage. However, even in tissues with adult stem cells, like stomach and intestine, reprogramming may allow mature cells to serve as reserve (“quiescent”) stem cells when normal stem cells are compromised. We propose that the potential downside to reprogramming is that it increases risk for cancers that occur late in adulthood. Mature, long-lived cells may have years of exposure to mutagens. Mutations that affect the physiological function of differentiated, post-mitotic cells may lead to apoptosis, but mutations in genes that govern proliferation might not be selected against. Hence, reprogramming with reentry into the cell cycle might unmask those mutations, causing an irreversible progenitor-like, proliferative state. We review recent evidence showing that reprogramming fuels irreversible metaplastic and precancerous proliferations in stomach and pancreas. Finally, we illustrate how we think reprogrammed differentiated cells are likely candidates as cells of origin for cancers of the intestine. PMID:26175494

  18. Kinetics and genomic profiling of adult human and mouse β-cell maturation.

    PubMed

    Szabat, Marta; Pourghaderi, Poya; Soukhatcheva, Galina; Verchere, C Bruce; Warnock, Garth L; Piret, James M; Johnson, James D

    2011-01-01

    Diabetes is a multifactorial metabolic disorder defined by the loss of functional pancreatic insulin-producing β-cells. The functional maturation and dedifferentiation of adult β-cells is central to diabetes pathogenesis and to β-cell replacement therapy for the treatment of diabetes. Despite its importance, the dynamics and mechanisms of adult β-cell maturation remain poorly understood. Using a novel Pdx1/Ins1 dual fluorescent reporter lentiviral vector, we previously found that individual adult human and mouse β-cells exist in at least two differentiation states distinguishable by the activation of the rat Ins1 promoter and performed the first real-time imaging of the maturation of individual cultured β-cells. Our previous study focused on transformed (MIN6) β-cells as a model to investigatethe kinetics of β-cell maturation. In the present study, we investigated the kinetics of the maturation process in primary human and mouse β-cells and performed gene expression profiling. Gene expression profiling of FACS purified immature Pdx1 (+) /Ins1 (low) cells and mature Pdx1 (high) /Ins1 (high ) cells from cultures of human islets, mouse islets and MIN6 cells revealed that Pdx1 (+) /Ins1 (low) cells are enriched for multiple genes associated with β-cell development/progenitor cells, proliferation, apoptosis, as well as genes coding for other islet cell hormones such as glucagon. We also demonstrated that the heterogeneity in β-cell maturation states previously observed in vitro, can also be found in vivo. Collectively, these experiments contribute to the understanding of maturation, dedifferentiation and plasticity of adult pancreatic β-cells. The results have significant implications for islet regeneration and for in vitro generation of functional β-cells to treat diabetes. PMID:21633187

  19. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-01-01

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases. PMID:27098178

  20. Horizontal transmission of Symbiodinium cells between adult and juvenile corals is aided by benthic sediment

    NASA Astrophysics Data System (ADS)

    Nitschke, Matthew R.; Davy, Simon K.; Ward, Selina

    2016-03-01

    Of all reef-building coral species, 80-85 % initially draw their intracellular symbionts (dinoflagellates of the genus Symbiodinium) from the environment. Although Symbiodinium cells are crucial for the growth of corals and the formation of coral reefs, little is known about how corals first encounter free-living Symbiodinium cells. We report how the supply of free-living Symbiodinium cells to the benthos by adult corals can increase the rate of horizontal symbiont acquisition for conspecific recruits. Three species of newly settled aposymbiotic (i.e., symbiont-free) corals were maintained in an open aquarium system containing: sterilized sediment and adult coral fragments combined; adult coral fragments alone; sterilized sediment alone; or seawater at Heron Island, Great Barrier Reef, Australia. In all instances, the combination of an adult coral and sediment resulted in the highest symbiont acquisition rates by juvenile corals (up to five-fold greater than seawater alone). Juvenile corals exposed to individual treatments of adult coral or sediment produced an intermediate acquisition response (<52 % of recruits), and symbiont acquisition from unfiltered seawater was comparatively low (<20 % of recruits). Additionally, benthic free-living Symbiodinium cells reached their highest densities in the adult coral + sediment treatment (up to 1.2 × 104 cells mL-1). Our results suggest that corals seed microhabitats with free-living Symbiodinium cells suitable for many coral species during the process of coral recruitment.

  1. Lin-28 promotes symmetric stem cell division and drives adaptive growth in the adult Drosophila intestine.

    PubMed

    Chen, Ching-Huan; Luhur, Arthur; Sokol, Nicholas

    2015-10-15

    Stem cells switch between asymmetric and symmetric division to expand in number as tissues grow during development and in response to environmental changes. The stem cell intrinsic proteins controlling this switch are largely unknown, but one candidate is the Lin-28 pluripotency factor. A conserved RNA-binding protein that is downregulated in most animals as they develop from embryos to adults, Lin-28 persists in populations of adult stem cells. Its function in these cells has not been previously characterized. Here, we report that Lin-28 is highly enriched in adult intestinal stem cells in the Drosophila intestine. lin-28 null mutants are homozygous viable but display defects in this population of cells, which fail to undergo a characteristic food-triggered expansion in number and have reduced rates of symmetric division as well as reduced insulin signaling. Immunoprecipitation of Lin-28-bound mRNAs identified Insulin-like Receptor (InR), forced expression of which completely rescues lin-28-associated defects in intestinal stem cell number and division pattern. Furthermore, this stem cell activity of lin-28 is independent of one well-known lin-28 target, the microRNA let-7, which has limited expression in the intestinal epithelium. These results identify Lin-28 as a stem cell intrinsic factor that boosts insulin signaling in intestinal progenitor cells and promotes their symmetric division in response to nutrients, defining a mechanism through which Lin-28 controls the adult stem cell division patterns that underlie tissue homeostasis and regeneration. PMID:26487778

  2. CRIPTO/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo.

    PubMed

    Spike, Benjamin T; Kelber, Jonathan A; Booker, Evan; Kalathur, Madhuri; Rodewald, Rose; Lipianskaya, Julia; La, Justin; He, Marielle; Wright, Tracy; Klemke, Richard; Wahl, Geoffrey M; Gray, Peter C

    2014-04-01

    Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these cultures and yields colonies with enhanced mammary gland reconstitution capacity. Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and adult mammary epithelial cells, and deletion of GRP78 from adult mammary epithelial cells blocks their mammary gland reconstitution potential. Together, these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers. PMID:24749068

  3. The role of CD44 in fetal and adult hematopoietic stem cell regulation

    PubMed Central

    Cao, Huimin; Heazlewood, Shen Y.; Williams, Brenda; Cardozo, Daniela; Nigro, Julie; Oteiza, Ana; Nilsson, Susan K.

    2016-01-01

    Throughout development, hematopoietic stem cells migrate to specific microenvironments, where their fate is, in part, extrinsically controlled. CD44 standard as a member of the cell adhesion molecule family is extensively expressed within adult bone marrow and has been previously reported to play important roles in adult hematopoietic regulation via CD44 standard-ligand interactions. In this manuscript, CD44 expression and function are further assessed and characterized on both fetal and adult hematopoietic stem cells. Using a CD44−/− mouse model, conserved functional roles of CD44 are revealed throughout development. CD44 is critical in the maintenance of hematopoietic stem and progenitor pools, as well as in hematopoietic stem cell migration. CD44 expression on hematopoietic stem cells as well as other hematopoietic cells within the bone marrow microenvironment is important in the homing and lodgment of adult hematopoietic stem cells isolated from the bone/bone marrow interface. CD44 is also involved in fetal hematopoietic stem cell migration out of the liver, via a process involving stromal cell-derived factor-1α. The absence of CD44 in neonatal bone marrow has no impact on the size of the long-term reconstituting hematopoietic stem cell pool, but results in an enhanced long-term engraftment potential of hematopoietic stem cells. PMID:26546504

  4. Atmospheric Chemistry of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3.

    PubMed

    Østerstrøm, Freja From; Wallington, Timothy J; Sulbaek Andersen, Mads P; Nielsen, Ole John

    2015-10-22

    Smog chambers with in situ FTIR detection were used to measure rate coefficients in 700 Torr of air and 296 ± 2 K of: k(Cl+(CF3)2CHOCH3) = (5.41 ± 1.63) × 10(-12), k(Cl+(CF3)2CHOCHO) = (9.44 ± 1.81) × 10(-15), k(Cl+CF3C(O)OCH3) = (6.28 ± 0.98) × 10(-14), k(OH+(CF3)2CHOCH3) = (1.86 ± 0.41) × 10(-13), and k(OH+(CF3)2CHOCHO) = (2.08 ± 0.63) × 10(-14) cm(3) molecule(-1) s(-1). The Cl atom initiated oxidation of (CF3)2CHOCH3 gives (CF3)2CHOCHO in a yield indistinguishable from 100%. The OH radical initiated oxidation of (CF3)2CHOCH3 gives the following products (molar yields): (CF3)2CHOCHO (76 ± 8)%, CF3C(O)OCH3 (16 ± 2)%, CF3C(O)CF3 (4 ± 1)%, and C(O)F2 (45 ± 5)%. The primary oxidation product (CF3)2CHOCHO reacts with Cl atoms to give secondary products (molar yields): CF3C(O)CF3 (67 ± 7)%, CF3C(O)OCHO (28 ± 3)%, and C(O)F2 (118 ± 12)%. CF3C(O)OCH3 reacts with Cl atoms to give: CF3C(O)OCHO (80 ± 8)% and C(O)F2 (6 ± 1)%. Atmospheric lifetimes of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 were estimated to be 62 days, 1.5 years, and 220 days, respectively. The 100-year global warming potentials (GWPs) for (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 are estimated to be 6, 121, and 46, respectively. A comprehensive description of the atmospheric fate of (CF3)2CHOCH3 is presented. PMID:26439469

  5. Adult neurogenesis: can analysis of cell cycle proteins move us "Beyond BrdU"?

    PubMed

    Eisch, Amelia J; Mandyam, Chitra D

    2007-06-01

    One of the greatest scientific discoveries of the 20th century is that the mammalian brain can give rise to new neurons throughout the lifespan. The phenomenon of adult neurogenesis raises hopes of harnessing neural stem cell for brain repair, and has sparked interest in novel roles for these new neurons, such as olfaction, spatial memory, and even regulation of mood. Traditionally, studies on adult neurogenesis have relied on exogenous markers of DNA synthesis, such as bromodeoxyuridine (BrdU), to label and track the birth of new cells. However, the exponential increase in our knowledge of endogenous markers of cycling cells has ushered in a new era of stem cell biology. Here we review the strides made in using endogenous cell cycle proteins to study adult neurogenesis in vivo. We (1) discuss the distribution of endogenous cell cycle proteins in proliferative regions of the adult mammalian brain; (2) review cell cycle phase-specific information gained from analyzing a combination of endogenous cell cycle proteins; and (3) provide data on the regulation of cell cycle proteins by a robust inhibitor of proliferation, morphine. The ability of BrdU to birthdate cells ensures it will always serve a role in studies of adult neurogenesis, thus preventing us from moving entirely 'beyond BrdU'. However, it is hoped that this review will provide interested researchers with the tools needed to apply the powerful and relatively novel approach of analyzing endogenous cell cycle proteins to the study of stem cells in general and adult neurogenesis in particular. PMID:17584088

  6. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-01-01

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed. PMID:24476362

  7. Novel small-molecule SIRT1 inhibitors induce cell death in adult T-cell leukaemia cells

    PubMed Central

    Kozako, Tomohiro; Suzuki, Takayoshi; Yoshimitsu, Makoto; Uchida, Yuichiro; Kuroki, Ayako; Aikawa, Akiyoshi; Honda, Shin-ichiro; Arima, Naomichi; Soeda, Shinji

    2015-01-01

    Adult T-cell leukaemia/lymphoma (ATL) is an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukaemia virus (HTLV)-1. The identification of new molecular targets for ATL prevention and treatment is desired. SIRT1, a nicotinamide adenine dinucleotide+ -dependent histone/protein deacetylase, plays crucial roles in various physiological processes, including aging and apoptosis. We previously reported that ATL patients had significantly higher SIRT1 protein levels than healthy controls. Here, we demonstrate that two novel small-molecule SIRT1 inhibitors, NCO-01/04, reduced cell viability and enhanced apoptotic cells in peripheral blood monocyte cells of patients with acute ATL, which has a poor prognosis. NCO-01/04 also reduced the cell viability with DNA fragmentation, Annexin V-positive cells, and caspase activation. However, a caspase inhibitor did not inhibit this caspase-dependent cell death. NCO-01/04 enhanced the endonuclease G level in the nucleus with loss of the mitochondrial transmembrane potential, which can promote caspase-independent death. Interestingly, NCO-01/04 increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation as well as autophagy. Thus, NCO-01/04 simultaneously caused caspase activation and autophagy. These results suggest that NCO-01/04 is highly effective against ATL cells in caspase-dependent or -independent manners with autophagy, and that its clinical application might improve the prognosis of patients with this fatal disease. PMID:26091232

  8. Insights from a chimpanzee adipose stromal cell population: opportunities for adult stem cells to expand primate functional genomics.

    PubMed

    Pfefferle, Lisa W; Wray, Gregory A

    2013-01-01

    Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs with three comparable human cell lines. Consistent with previous studies on ASCs in humans, the chimpanzee cells have fibroblast-like morphology and express genes encoding components of the extracellular matrix at high levels. Differentially expressed genes are enriched for distinct functional classes between species: immunity and protein processing are higher in chimpanzees, whereas cell cycle and DNA processing are higher in humans. Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution. In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates. By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling. PMID:24092797

  9. Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells

    PubMed Central

    Shin, Jae-Won; Spinler, Kyle R.; Swift, Joe; Chasis, Joel A.; Mohandas, Narla; Discher, Dennis E.

    2013-01-01

    Hematopoietic stem and progenitor cells, as well as nucleated erythroblasts and megakaryocytes, reside preferentially in adult marrow microenvironments whereas other blood cells readily cross the endothelial barrier into the circulation. Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34+ cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. In particular, erythroid differentiation is promoted by high lamin-A and low lamin-B1 expression whereas megakaryocytes of high ploidy are inhibited by lamin suppression. Lamins thus contribute to both trafficking and differentiation. PMID:24191023

  10. Adult T-Cell Leukemia/Lymphoma (HTLV-1)

    MedlinePlus

    ... gentic material made of DNA, but instead carry RNA. These viruses selectively infect only T-cells. Only ... potential to inject its genetic material (DNA or RNA) into normal cells. Once inside the normal cells, ...

  11. Developmental and psychosocial issues in CF

    PubMed Central

    Ernst, Michelle M.; Johnson, Mark C.; Stark, Lori J.

    2010-01-01

    Synopsis Cystic Fibrosis (CF) is a multi-systemic life-limiting genetic disorder, primarily impacting respiratory functioning. Most patients with CF are diagnosed by 2 years of age, and the current median predicted survival rate is 37.4 years old, with 95% of patients dying from complications relate to pulmonary infection. Given the chronic, progressive and disabling nature of CF, multiple treatments are prescribed, most on a daily basis. Thus, this illness requires children, with the aid of their families, to adopt multiple health-related behaviors in addition to managing more typical developmental demands. The morbidity and mortality factors pose cognitive, emotional and behavioral challenges for many children with CF and their families. This article will apply a developmental perspective to describing the psychosocial factors impacting psychological adjustment and health-related behaviors relevant to infants, preschool and school age children, and adolescents with CF. Topics particularly pertinent to developmental periods and medical milestones will be noted, with clinical implications highlighted. PMID:20478499

  12. Studies on density function theory for the F -+CF 3SO 3CF 2CF 3S N2 reaction

    NASA Astrophysics Data System (ADS)

    Gao, Hongwei; Zhou, Zhengyu; Yu, Zhongheng

    2002-09-01

    The reaction mechanism of the sulfur oxygen and/or carbon oxygen bond breaking in sulfonates during nucleophilic substitution has been studied using DFT (B3LYP) method at 6-31G level. Through the analysis of the kinetics and thermodynamics, we conclude that halide ion (F -) easily attacks the sulfur atom of perfluoroalkanesulfonic ester, causing the S-O bond cleavage to give CF 3SO 2F and -OCF2CF3. In contrast to the S-O bond cleavage it has been found that the C-O bond scission in perfluoroalkanesulfonic ester is difficult to take place. This conclusion is in good agreement with experiment.

  13. Ostreopsis cf. ovata dynamics in the NW Mediterranean Sea in relation to biotic and abiotic factors.

    PubMed

    Carnicer, Olga; Guallar, Carles; Andree, Karl B; Diogène, Jorge; Fernández-Tejedor, Margarita

    2015-11-01

    An expansion of the distribution of Ostreopsis cf. ovata, a dinoflagellate which produces palytoxin-like compounds, has been reported in recent years. Economical and social interests are affected by blooms, as they are responsible for respiratory and skin problems in humans and may cause damage to marine organisms. In order to identify the most influential environmental factors that trigger proliferations of O. cf. ovata in the area of the adjacent shallow rocky coast of the Ebro Delta (NW Mediterranean Sea) a three-year survey was performed on the metaphytic microalgae community growing on the macrophytes Jania rubens and Corallina elongata. Small-size diatoms were more abundant than dinoflagellates; O. cf. ovata was identified as the only species present from the genus. Seawater temperature was the primary driver defining the ecological niche of O. cf. ovata. Freshwater and groundwater fluxes were more pronounced in southern than in northern sites, which may have resulted in a distinct O. cf. ovata spatial distribution, with the highest records of abundance and more frequent blooms in the north. In consequence, negative correlations between the abundance of O. cf. ovata and nitrate concentrations and significant positive correlation with salinity were observed. The temporal pattern of O. cf. ovata dynamics from mid-July to early-November is probably due to the fact that this species is observed only above a certain threshold temperature of seawater. Metaphytic cells of O. cf. ovata were smaller in the northern site than in the south, possibly as a result of an increase in cell division, coinciding with higher abundance, and this could be an indicator of favorable conditions. Toxicity in planktonic cells was negatively correlated with cell abundance in the water column, achieving maximum concentrations of 25pg. PLTX eqcell(-1). PMID:26365038

  14. Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus.

    PubMed

    Szabat, Marta; Luciani, Dan S; Piret, James M; Johnson, James D

    2009-04-01

    The enigmatic process of beta-cell maturation has significant implications for diabetes pathogenesis, and potential diabetes therapies. This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. The majority of fluorescent cells were highly positive for both Pdx1 and insulin. Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. Time-lapse imaging demonstrated that Pdx1(+)/Ins(low) primary beta-cells and MIN6 cells could convert to Pdx1(+)/Ins(+) cells without cell division. Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. Long-term phenotype tracking of Pdx1(+)/Ins(low) cells showed two groups, one that matured into Pdx1(+)/Ins(+) cells and one that remained immature. These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. At a given time, a proportion of adult beta-cells share similar characteristics to functionally immature embryonic beta-cell progenitors. The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. These results have implications for harnessing the maturation process for therapeutic purposes. PMID:19095744

  15. Cardiorespiratory measurements during field tests in CF: use of an ambulatory monitoring system.

    PubMed

    Bradley, Judy M; Kent, Lisa; O'Neill, Brenda; Nevill, Alan; Boyle, Lesley; Elborn, J Stuart

    2011-03-01

    Respiratory inductive plethysmography (e.g., LifeShirt) may offer in-depth study of the cardiorespiratory responses during field exercise tests. The aims of this study were to assess the reliability, discriminate validity, and responsiveness of cardiorespiratory measurements recorded by the LifeShirt during field exercise tests in adults with CF. To assess reliability and discriminate validity, participants with CF and stable lung disease and healthy participants performed the 6-Minute Walk Test (6MWT) and Modified Shuttle Test (MST) on two occasions. To assess responsiveness, participants with CF experiencing an exacerbation performed the 6MWT at the start and end of an admission for intravenous antibiotics. The LifeShirt was worn during all exercise tests. Reliability and discriminate validity were assessed in 18 participants with CF (mean (SD) age: 26 (10) years; FEV1 %predicted: 69.2 (23)%) and 18 healthy participants (age: 24 (5) years, FEV1 % predicted: 92 (8)%). There was no difference in 6MWT and MST performance between days and reliability of cardiorespiratory measures was acceptable (bias: P > 0.05; CV < 10%). Participants with CF demonstrated a significantly greater response to exercise (e.g., ventilation, respiratory rate) compared to healthy participants indicating discriminate validity. Responsiveness was assessed in 12 participants with CF: clinical measurements and 6MWT performance improved (61 (81) min; P < 0.05) however, cardiorespiratory measurements recorded by the LifeShirt remained the same (bias: P > 0.05; CV < 10%). This study provides evidence that cardiorespiratory responses can be measured non-invasively during field exercise tests in adults with CF. Reliability and discriminate validity of key cardiorespiratory measurements recorded by the LifeShirt were demonstrated. Some information on responsiveness is reported. PMID:20967834

  16. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

    PubMed Central

    Wang, Hua; Lau, Benson Wui-Man; Wang, Ning-li; Wang, Si-ying; Lu, Qing-jun; Chang, Raymond Chuen-Chung; So, Kwok-fai

    2015-01-01

    Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID:26889185

  17. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia.

    PubMed Central

    Lois, C; Alvarez-Buylla, A

    1993-01-01

    Subventricular zone (SVZ) cells proliferate spontaneously in vivo in the telencephalon of adult mammals. Several studies suggest that SVZ cells do not differentiate after mitosis into neurons or glia but die. In the present work, we show that SVZ cells labeled in the brains of adult mice with [3H]thymidine differentiate directly into neurons and glia in explant cultures. In vitro labeling with [3H]thymidine shows that 98% of the neurons that differentiate from the SVZ explants are derived from precursor cells that underwent their last division in vivo. This report identifies the SVZ cells as neuronal precursors in an adult mammalian brain. Images Fig. 1 Fig. 2 Fig. 3 PMID:8446631

  18. Bis(trifluoroacetyl) peroxide, CF(3)C(O)OOC(O)CF(3).

    PubMed

    Kopitzky, R; Willner, H; Hermann, A; Oberhammer, H

    2001-06-01

    Pure, highly explosive CF(3)C(O)OOC(O)CF(3) is prepared for the first time by low-temperature reaction between CF(3)C(O)Cl and Na(2)O(2). At room temperature CF(3)C(O)OOC(O)CF(3) is stable for days in the liquid or gaseous state. The melting point is -37.5 degrees C, and the boiling point is extrapolated to 44 degrees C from the vapor pressure curve log p = -1875/T + 8.92 (p/mbar, T/K). Above room temperature the first-order unimolecular decay into C(2)F(6) + CO(2) occurs with an activation energy of 129 kJ mol(-1). CF(3)C(O)OOC(O)CF(3) is a clean source for CF(3) radicals as demonstrated by matrix-isolation experiments. The pure compound is characterized by NMR, vibrational, and UV spectroscopy. The geometric structure is determined by gas electron diffraction and quantum chemical calculations (HF, B3PW91, B3LYP, and MP2 with 6-31G basis sets). The molecule possesses syn-syn conformation (both C=O bonds synperiplanar to the O-O bond) with O-O = 1.426(10) A and dihedral angle phi(C-O-O-C) = 86.5(32) degrees. The density functional calculations reproduce the experimental structure very well. PMID:11375681

  19. Shunt Diode Designs in Li/cf Shuttle Batteries

    NASA Technical Reports Server (NTRS)

    Miller, D.; Higgins, R.

    1984-01-01

    Although Li/CF cells and batteries have an excellent safety record, they are included with other battery systems that require additional safety precautions. One precaution suggested is the inclusion of shunt diodes into these batteries. The benefits of this addition are examined. All cells tested at elevated temperatures vent regardless of length of time between being fully discharged and reversed or inclusion of the diode in the system. Cells discharged at ambient temperatures all show a relatively quick reversal, but stabilize at voltages that are high enough that the diodes are not functioning. Cells tested at depressed temperatures reverse the deepest of all cells tested, with the deepest reversal occurring very early in the test and voltages recovering to above -0.60 volts near the end of the tests. Anode limited cells will eliminate the venting during hot reversal.

  20. Shunt diode designs in Li/CF Shuttle batteries

    NASA Astrophysics Data System (ADS)

    Miller, D.; Higgins, R.

    1984-09-01

    Although Li/CF cells and batteries have an excellent safety record, they are included with other battery systems that require additional safety precautions. One precaution suggested is the inclusion of shunt diodes into these batteries. The benefits of this addition are examined. All cells tested at elevated temperatures vent regardless of length of time between being fully discharged and reversed or inclusion of the diode in the system. Cells discharged at ambient temperatures all show a relatively quick reversal, but stabilize at voltages that are high enough that the diodes are not functioning. Cells tested at depressed temperatures reverse the deepest of all cells tested, with the deepest reversal occurring very early in the test and voltages recovering to above -0.60 volts near the end of the tests. Anode limited cells will eliminate the venting during hot reversal.

  1. Effect of High Glucose on Stress-Induced Senescence of Nucleus Pulposus Cells of Adult Rats

    PubMed Central

    Kong, Jae-Gwan; Lee, Donghwan; Park, Eun-Young

    2015-01-01

    Study Design In vitro cell culture model. Purpose We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells. Overview of Literature DM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells. Methods Adult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-β-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways. Results The mean SA-β-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations. Conclusions The current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM. PMID:25901224

  2. Observations on the migratory behaviour of Schwann cells from adult peripheral nerve explant cultures.

    PubMed

    Crang, A J; Blakemore, W F

    1987-06-01

    The migration of Schwann cells from adult sciatic nerve explant cultures has been examined by time-lapse photomicrography. Analysis of Schwann cell migratory behaviour indicates that the initial outwandering by individual Schwann cells was random. Although chance cell-cell contacts resulted in temporary immobilization of pairs of cells, stable multicellular structures did not form during this initial phase. As local cell densities increased, Schwann cells assembled networks within which Schwann cell movement continued to be observed. A second form of Schwann cell outgrowth was observed from degenerating fibres in which arrays of highly oriented Schwann cells migrated away from their basal lamina tubes onto the culture dish. These observations of Schwann cell random migration, network self-assembly and coordinated extratubal migration are considered to highlight aspects of Schwann cell behaviour, independent of axonal influences, which may have relevance to their role in peripheral nerve repair following nerve section. PMID:3612187

  3. Location and phenotype of human adult keratinocyte stem cells of the skin.

    PubMed

    Webb, Angela; Li, Amy; Kaur, Pritinder

    2004-10-01

    The location and identity of interfollicular epidermal stem cells of adult human skin remain undefined. Based on our previous work in both adult murine and neonatal human foreskin, we demonstrate that cell surface levels of the alpha6 integrin and the transferrin receptor (CD71) are valid markers for resolving a putative stem cell, transit amplifying and differentiating compartment in adult human skin by flow cytometry. Specifically, epidermal cells expressing high levels of alpha6 integrin and low levels of the transferrin receptor CD71 (phenotype alpha6 (bri)CD71(dim)) exhibit several stem cell characteristics, comprising a minor population (2%-5%) of the K14(bri) fraction, enriched for quiescent and small blast-like cells with high clonogenic capacity, lacking the differentiation marker K10. Conversely, the majority of K14(bri) K10(neg) epidermal cells express high levels of CD71 (phenotype alpha6 (bri)CD71(bri)), and represent the actively cycling fraction of keratinocytes displaying greater cell size due to an increase in cytoplasmic area, consistent with their being transient amplifying cells. The alpha6 (bri)CD71(bri) population exhibited intermediate clonogenic capacity. A third population of K14(dim) but K10 positive epidermal cells could be identified by their low levels of alpha6 integrin expression (i.e. alpha6 (dim) cells), representing the differentiation compartment; predictably, this subpopulation exhibited poor clonogenic efficiency. Flow cytometric analysis for the hair follicle bulge region (stem cell) marker K15 revealed preferential expression of this keratin in alpha6 (bri) cells (i.e., both stem and transient amplifying fractions), but not the alpha6 (dim) population. Given that K15 positive cells could only be detected in the deep rete ridges of adult skin in situ, we conclude that stem and transient amplifying cells reside in this location, while differentiating (K15 negative) cells are found in the shallow rete ridges. PMID:15606498

  4. Two modes of capacitively coupled rf discharge in CF4

    NASA Astrophysics Data System (ADS)

    Proshina, O. V.; Rakhimova, T. V.; Rakhimov, A. T.; Voloshin, D. G.

    2010-12-01

    Capacitively coupled rf discharge in pure CF4 was studied using a one-dimensional self-consistent particle-in-cell Monte Carlo model. Two different discharge modes are observed depending on the discharge conditions: the regime of electronegative plasma with high-electron temperatures in the bulk, and the regime of electropositive plasma with abnormally low electron temperatures in the bulk. The characteristic features of the two discharge modes are considered. A sharp transition from the former to the latter mode is observed with an increase in applied voltage. The dependence of the transition voltage on gas pressure is analyzed. In the studied range of gas pressures, the existence of a high-temperature mode in an electronegative gas like CF4 is suggested by the balance between the ionization rate and attachment rate in the bulk region. As a result, the transition voltage increases with gas pressure because of the increased relative role of electron attachment. It is shown that the differences in the used electron cross-section sets may noticeably affect the simulation results and the discharge properties. Three different electron cross-section sets for CF4 are considered. In particular, the transition voltage between the two discharge modes differs essentially for different cross-sections used. In order to analyze the fundamental causes of this difference, a detailed comparison of three cross-section sets was done on the basis of the Monte Carlo calculation of swarm parameters in constant electric fields.

  5. Engine diagnostics program: CF6-50 engine performance deterioration

    NASA Technical Reports Server (NTRS)

    Wulf, R. H.

    1980-01-01

    Cockpit cruise recordings and test cell data in conjunction with hardware inspection results from airline overhaul shops were analyzed to define the extent and magnitude of performance deterioration of the General Electric CF6-50 high bypass turbofan engine. The magnitude of short term deterioration was isolated from the long term, and the individual damage mechanisms that were the cause for the majority of the performance deterioration was identified. It was determined that the long term engine performance deterioration characteristics were different for the 3 aircraft types currently powered by the CF6-50 engine, but these differences were due to operational considerations (flight length and takeoff derate) and not to differences associated with the aircraft type. Unrestored losses, that is, performance deterioration which remains after engine refurbishment, represents over 70 percent of the total performance deterioration at engine shop visit. Superficial damage, such as, increased surface roughness, leading edge shape changes on airfoils, and increases in the average clearances between rotating and stationary components is the major contributor to these losses. Seventy one percent of the unrestored losses are cost effective to restore, and if implemented could reduce fuel consumed by CF6-50 engines by 26 million gallons in 1980.

  6. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis.

    PubMed

    Zhang, Juan; Jiao, Jianwei

    2015-01-01

    The procedure of neurogenesis has made numerous achievements in the past decades, during which various molecular biomarkers have been emerging and have been broadly utilized for the investigation of embryonic and adult neural stem cell (NSC). Nevertheless, there is not a consistent and systematic illustration to depict the functional characteristics of the specific markers expressed in distinct cell types during the different stages of neurogenesis. Here we gathered and generalized a series of NSC biomarkers emerging during the procedures of embryonic and adult neural stem cell, which may be used to identify the subpopulation cells with distinguishing characters in different timeframes of neurogenesis. The identifications of cell patterns will provide applications to the detailed investigations of diverse developmental cell stages and the extents of cell differentiation, which will facilitate the tracing of cell time-course and fate determination of specific cell types and promote the further and literal discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization of comprehensive applications under the aiding of the systematic knowledge framework, researchers may broaden their insights into the derivation and establishment of novel technologies to analyze the more detailed process of embryogenesis and adult neurogenesis. PMID:26421301

  7. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis

    PubMed Central

    Zhang, Juan; Jiao, Jianwei

    2015-01-01

    The procedure of neurogenesis has made numerous achievements in the past decades, during which various molecular biomarkers have been emerging and have been broadly utilized for the investigation of embryonic and adult neural stem cell (NSC). Nevertheless, there is not a consistent and systematic illustration to depict the functional characteristics of the specific markers expressed in distinct cell types during the different stages of neurogenesis. Here we gathered and generalized a series of NSC biomarkers emerging during the procedures of embryonic and adult neural stem cell, which may be used to identify the subpopulation cells with distinguishing characters in different timeframes of neurogenesis. The identifications of cell patterns will provide applications to the detailed investigations of diverse developmental cell stages and the extents of cell differentiation, which will facilitate the tracing of cell time-course and fate determination of specific cell types and promote the further and literal discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization of comprehensive applications under the aiding of the systematic knowledge framework, researchers may broaden their insights into the derivation and establishment of novel technologies to analyze the more detailed process of embryogenesis and adult neurogenesis. PMID:26421301

  8. Lgr5+ amacrine cells possess regenerative potential in the retina of adult mice

    PubMed Central

    Chen, Mengfei; Tian, Shenghe; Glasgow, Nathan G; Gibson, Gregory; Yang, Xiaoling; Shiber, Christen E; Funderburgh, James; Watkins, Simon; Johnson, Jon W; Schuman, Joel S; Liu, Hongjun

    2015-01-01

    Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5+ cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5+ amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5+ amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5+ amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases. PMID:25990970

  9. NASA CF6 jet engine diagnostics program: Long-term CF6-6D low-pressure turbine deterioration

    NASA Technical Reports Server (NTRS)

    Smith, J. J.

    1979-01-01

    Back-to-back performance tests were run on seven airline low pressure turbine (LPT) modules and four new CF6-6D modules. Back-to-back test cell runs, in which an airline LPT module was directly compared to a new production module, were included. The resulting change, measured in fuel burn, equaled the level of LPT module deterioration. Three of the LPT modules were analytically inspected followed by a back-to-back test cell run to evaluate current refurbishment techniques.

  10. Mathematical model of adult stem cell regeneration with cross-talk between genetic and epigenetic regulation

    PubMed Central

    Lei, Jinzhi; Levin, Simon A.; Nie, Qing

    2014-01-01

    Adult stem cells, which exist throughout the body, multiply by cell division to replenish dying cells or to promote regeneration to repair damaged tissues. To perform these functions during the lifetime of organs or tissues, stem cells need to maintain their populations in a faithful distribution of their epigenetic states, which are susceptible to stochastic fluctuations during each cell division, unexpected injury, and potential genetic mutations that occur during many cell divisions. However, it remains unclear how the three processes of differentiation, proliferation, and apoptosis in regulating stem cells collectively manage these challenging tasks. Here, without considering molecular details, we propose a genetic optimal control model for adult stem cell regeneration that includes the three fundamental processes, along with cell division and adaptation based on differential fitnesses of phenotypes. In the model, stem cells with a distribution of epigenetic states are required to maximize expected performance after each cell division. We show that heterogeneous proliferation that depends on the epigenetic states of stem cells can improve the maintenance of stem cell distributions to create balanced populations. A control strategy during each cell division leads to a feedback mechanism involving heterogeneous proliferation that can accelerate regeneration with less fluctuation in the stem cell population. When mutation is allowed, apoptosis evolves to maximize the performance during homeostasis after multiple cell divisions. The overall results highlight the importance of cross-talk between genetic and epigenetic regulation and the performance objectives during homeostasis in shaping a desirable heterogeneous distribution of stem cells in epigenetic states. PMID:24501127

  11. Establishing the reference intervals of NK cell functions in healthy adults.

    PubMed

    Hou, Hongyan; Mao, Lie; Wang, Juan; Liu, Weiyong; Lu, Yanfang; Yu, Jing; Zhou, Yu; Mao, Liyan; Wang, Feng; Sun, Ziyong

    2016-08-01

    Natural killer (NK) cells play a key role in host defense against microbial pathogens. Establishing the reference intervals (RIs) of NK cell functions would be valuable in assessing the immune status of hosts. We evaluated the NK cell activity in healthy adults. We further established and validated the RIs of representative NK cell functions. Flow cytometry was used to evaluate the cytokine production and CD107a degranulation of NK cells. Levels of soluble IFN-γ in the culture supernatants were evaluated by ELISA. Our results demonstrated that the intracellular IFN-γ production of NK cells was positively correlated with CD107a expression and soluble IFN-γ levels. There were no significant differences in NK cell functions between different age and gender groups. The mean values and RIs of representative NK cell functions are as following: IFN-γ(+) NK cells (%): 28.09 (11.3-51.95); CD107a(+) NK cells (%): 17.90 (9.852-27.56); soluble IFN-γ (pg/ml): 330.4 (41.38-717.8). In addition, the intracellular IFN-γ production and degranulation activity of NK cells in patients with colorectal cancer were significantly lower than that in healthy adults. Our study has established the RIs of NK cell functions in healthy adults, which might be used for monitoring the immune status of the hosts. PMID:27236137

  12. EFFECTS OF ETHANE DIMETHANESULFONATE (EDS) ON ADULT AND IMMATURE RABBIT LEYDIG CELLS: COMPARISON WITH EDS-TREATED RAT LEYDIG CELLS

    EPA Science Inventory

    Ethane-dimethanesulfonate (EDS) has been shown to selectively kill Leydig cells and depress testosterone production in adult rats. ecent study has shown that immature rat leydig cells are less sensitive to EDS exposure. here is evidence that the rabbit metabolizes EDS to methane ...

  13. The CF6 engine performance improvement

    NASA Technical Reports Server (NTRS)

    Fasching, W. A.

    1982-01-01

    As part of the NASA-sponsored Engine Component Improvement (ECI) Program, a feasibility analysis of performance improvement and retention concepts for the CF6-6 and CF6-50 engines was conducted and seven concepts were identified for development and ground testing: new fan, new front mount, high pressure turbine aerodynamic performance improvement, high pressure turbine roundness, high pressure turbine active clearance control, low pressure turbine active clearance control, and short core exhaust nozzle. The development work and ground testing are summarized, and the major test results and an enomic analysis for each concept are presented.

  14. Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.

    PubMed

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Alix, Philippe; Leprince, Pierre; Glejzer, Aneta; Poulet, Christophe; Hennuy, Benoit; Sommer, Lukas; Shakhova, Olga; Rogister, Bernard

    2012-08-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. PMID:22349262

  15. GATAe regulates intestinal stem cell maintenance and differentiation in Drosophila adult midgut.

    PubMed

    Okumura, Takashi; Takeda, Koji; Kuchiki, Megumi; Akaishi, Marie; Taniguchi, Kiichiro; Adachi-Yamada, Takashi

    2016-02-01

    Adult intestinal tissues, exposed to the external environment, play important roles including barrier and nutrient-absorption functions. These functions are ensured by adequately controlled rapid-cell metabolism. GATA transcription factors play essential roles in the development and maintenance of adult intestinal tissues both in vertebrates and invertebrates. We investigated the roles of GATAe, the Drosophila intestinal GATA factor, in adult midgut homeostasis with its first-generated knock-out mutant as well as cell type-specific RNAi and overexpression experiments. Our results indicate that GATAe is essential for proliferation and maintenance of intestinal stem cells (ISCs). Also, GATAe is involved in the differentiation of enterocyte (EC) and enteroendocrine (ee) cells in both Notch (N)-dependent and -independent manner. The results also indicate that GATAe has pivotal roles in maintaining normal epithelial homeostasis of the Drosophila adult midgut through interaction of N signaling. Since recent reports showed that mammalian GATA-6 regulates normal and cancer stem cells in the adult intestinal tract, our data also provide information on the evolutionally conserved roles of GATA factors in stem-cell regulation. PMID:26719127

  16. Role of C{sub 2}F{sub 4}, CF{sub 2}, and ions in C{sub 4}F{sub 8}/Ar plasma discharges under active oxide etch conditions in an inductively coupled GEC cell reactor

    SciTech Connect

    Barela, Marcos J.; Anderson, Harold M.; Oehrlein, Gottlieb S.

    2005-05-01

    Utilizing infrared diode-laser absorption spectroscopy (IRDLAS) and UV-Visible absorption spectroscopy (UV-Vis), we show that it is possible to make a near complete mass balance of etch reactants and products in a GEC inductively coupled fluorocarbon discharge while actively etching SiO{sub 2} substrates. Langmuir probe measurements were performed to measure the total ion current density. C{sub 2}F{sub 4} and CF{sub 2} are shown to be the main dissociation products in a C{sub 4}F{sub 8} plasma discharge. The C{sub 2}F{sub 4} concentration decreases as the SiO{sub 2} etching rate increases, along with CF{sub 2} and CF radicals, suggesting a role in the SiO{sub 2} etching process. The addition of Ar to the C{sub 4}F{sub 8} discharge increased the ion flux at the wafer surface, and the consumption rate of C{sub 2}F{sub 4} relative to CF{sub 2}. The increased ion flux enhanced the SiO{sub 2} etching rate, until at a very high degree of Ar dilution of C{sub 4}F{sub 8}/Ar the etching rate became neutral limited. We also monitored SiF{sub 2} using UV-Vis absorption and CO by IRDLAS. In our work we found SiF{sub 2} and CO to be the prevalent Si and C gas phase etch products for the SiO{sub 2} etching process.

  17. Catalog of gene expression in adult neural stem cells and their in vivo microenvironment

    SciTech Connect

    Williams, Cecilia; Wirta, Valtteri; Meletis, Konstantinos; Wikstroem, Lilian; Carlsson, Leif; Frisen, Jonas; Lundeberg, Joakim . E-mail: joakim.lundeberg@biotech.kth.se

    2006-06-10

    Stem cells generally reside in a stem cell microenvironment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique stemness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research.

  18. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    PubMed

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration. PMID:25977550

  19. Rfx6 maintains the functional identity of adult pancreatic β cells.

    PubMed

    Piccand, Julie; Strasser, Perrine; Hodson, David J; Meunier, Aline; Ye, Tao; Keime, Céline; Birling, Marie-Christine; Rutter, Guy A; Gradwohl, Gérard

    2014-12-24

    Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca(2+) channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of "disallowed" genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans. PMID:25497096

  20. Concise Review: Different Mesenchymal Stromal/Stem Cell Populations Reside in the Adult Kidney

    PubMed Central

    Bruno, Stefania; Chiabotto, Giulia

    2014-01-01

    During fetal life, mesenchymal stromal/stem cells (MSCs) surround glomeruli and tubules and contribute to the development of the renal interstitium by secretion of growth factors that drive nephron differentiation. In the adult, an MSC-like population has been demonstrated in different compartments of human and murine nephrons. After injury, these cells might provide support for kidney regeneration by recapitulating the role they have in embryonic life. In this short review, we discuss the evidence of an MSC presence within the adult kidney and their potential contribution to the turnover of renal cells and injury repair. PMID:25355731

  1. MAINTENANCE OF TESTOSTERONE PRODUCTION BY PURIFIED ADULT RAT LEYDIG CELLS FOR THREE DAYS IN VITRO

    EPA Science Inventory

    Using a preparation of highly purified, adult rat Leydig cells and conditions of culture which we found to optimize testosterone production during 24 h, we sought to maintain optimal testosterone production for 3 d. eydig cells cultured on Cytodex 3 beads at 19% O2 in Dulbecco's ...

  2. Cats cloned from fetal and adult somatic cells by nuclear transfer.

    PubMed

    Yin, X J; Lee, H S; Lee, Y H; Seo, Y I; Jeon, S J; Choi, E G; Cho, S J; Cho, S G; Min, W; Kang, S K; Hwang, W S; Kong, I K

    2005-02-01

    This work was undertaken in order to study the developmental competence of nuclear transfer (NT) into cat embryos using fetal fibroblast and adult skin fibroblast cells as donor nuclei. Oocytes were recovered by mincing the ovaries in Hepes-buffered TCM199 and selecting the cumulus oocyte complexes (COCs) with compact cumulus cell mass and dark color. Homogenous ooplasm was cultured for maturation in TCM199+10% fetal bovine serum (FBS) for 12 h and used as a source of recipient cytoplast for exogenous somatic nuclei. In experiment 1, we evaluated the effect of donor cell type on the reconstruction and development of cloned embryos. Fusion, first cleavage and blastocyst developmental rate were not different between fetal fibroblasts and adult skin cells (71.2 vs 66.8; 71.0 vs 57.6; 4.0 vs 6.1% respectively; P < 0.05). In experiment 2, cloned embryos were surgically transferred into the oviducts of recipient queens. One of the seven recipient queens was delivered naturally of 2 healthy cloned cats and 1 stillborn from fetal fibroblast cells of male origin 65 days after embryo transfer. One of three recipient queens was delivered naturally of 1 healthy cloned cat from adult skin cells of female origin 65 days after embryo transfer. The cloned cats showed genotypes identical to the donor cell lines, indicating that adult somatic cells can be used for feline cloning. PMID:15695619

  3. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    SciTech Connect

    Weinberger, Florian Mehrkens, Dennis Starbatty, Jutta Nicol, Philipp Eschenhagen, Thomas

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  4. Diabetes enhances the proliferation of adult pancreatic multipotent progenitor cells and biases their differentiation to more β-cell production.

    PubMed

    Razavi, Rozita; Najafabadi, Hamed S; Abdullah, Sarah; Smukler, Simon; Arntfield, Margot; van der Kooy, Derek

    2015-04-01

    Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for β-cell loss since their β-cell-producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that β-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward β-cells in mouse and human. These effects are dynamic and correlate with functional β-cell regeneration when conditions allow. PMID:25392245

  5. Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

    PubMed Central

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

  6. Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary.

    PubMed

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)⁺-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2⁺-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

  7. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    NASA Astrophysics Data System (ADS)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  8. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    SciTech Connect

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A.

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  9. Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone.

    PubMed

    Bunk, Eva C; Ertaylan, Gökhan; Ortega, Felipe; Pavlou, Maria A; Gonzalez Cano, Laura; Stergiopoulos, Athanasios; Safaiyan, Shima; Völs, Sandra; van Cann, Marianne; Politis, Panagiotis K; Simons, Mikael; Berninger, Benedikt; Del Sol, Antonio; Schwamborn, Jens C

    2016-08-01

    Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thus, our work uncovers a novel function of Prox1 as a fate determinant for oligodendrocytes in the adult mammalian brain. These data indicate that the neurogenic and oligodendrogliogenic lineages in the two adult neurogenic niches exhibit a distinct requirement for Prox1, being important for neurogenesis in the DG but being indispensable for oligodendrogliogenesis in the SVZ. Stem Cells 2016;34:2115-2129. PMID:27068685

  10. PRIMITIVE ADULT HEMATOPOIETIC STEM CELLS CAN FUNCTION AS OSTEOBLAST PRECURSORS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hem...

  11. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis.

    PubMed

    Kaftanovskaya, Elena M; Lopez, Carolina; Ferguson, Lydia; Myhr, Courtney; Agoulnik, Alexander I

    2015-06-01

    It is commonly accepted that androgen-producing fetal Leydig cells (FLC) are substituted by adult Leydig cells (ALC) during perinatal testis development. The mechanisms influencing this process are unclear. We used mice with a retinoid acid receptor 2 promoter-Cre recombinase transgene (Rarb-cre) expressed in embryonic FLC precursors, but not in postnatal testis, and a dual fluorescent Cre recombinase reporter to label FLC and ALC in vivo. All FLC in newborn testis had the recombinant, whereas the majority of LC in adult testis had the nonrecombinant reporter. Primary LC cultures from adult testis had either recombinant (20%) or nonrecombinant (80%) cells, demonstrating that the FLC survive in adult testis and their ontogeny is distinct from ALC. Conditional inactivation of androgen receptor (AR) allele using the Rarb-cre transgene resulted in a 50% increase of AR-negative LC in adult testis. The mutant males became infertile with age, with all LC in older testis showing signs of incomplete differentiation, such as a large number of big lipid droplets, an increase of finger-like protrusions, and a misexpression of steroidogenic or FLC- and ALC-specific genes. We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation. PMID:25713029

  12. In situ CF3 Detection in Low Pressure Inductive Discharges by Fourier Transform Infrared Spectroscopy

    NASA Technical Reports Server (NTRS)

    Kim, J. S.; Cappelli, M. A.; Sharma, S. P.; Arnold, J. O. (Technical Monitor)

    1998-01-01

    The detection of CF(x) (x=1-3) radicals in low pressure discharges using source gases such as CF4 and CHF3 is of importance to the understanding of their chemical structure and relevance in plasma based etching processes. These radicals are known to contribute to the formation of fluorocarbon polymer films, which affect the selectivity and anisotropy of etching. In this study, we present preliminary results of the quantitative measurement of trifluoromethyl radicals, CF3, in low pressure discharges. The discharge studied here is an inductively (transformer) coupled plasma (ICP) source in the GEC reference cell, operating on pure CF4 at pressures ranging from 10 - 100 mTorr, This plasma source generates higher electron number densities at lower operating pressures than obtainable with the parallel-plate capacitively coupled version of the GEC reference cell. Also, this expanded operating regime is more relevant to new generations of industrial plasma reactors being used by the microelectronics industry. Fourier transform infrared (FTIR) spectroscopy is employed to observe the absorption band of CF3 radicals in the electronic ground state X2Al in the region of 1233-1270/cm. The spectrometer is equipped with a high sensitivity HgCdTe (MCT) detector and has a fixed resolution of 0.125/cm. The CF3 concentrations are measured for a range of operating pressures and discharge power levels.

  13. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    SciTech Connect

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%.

  14. Sans study of spinach CF 1-ATPase

    NASA Astrophysics Data System (ADS)

    Calmettes, P.; Girault, G.; Berger, G.; Galmiche, J. M.

    1989-01-01

    SANS experiments were performed on solutions of spinach chloroplast CF 1-ATPase in heavy water. Removal of the ɛ subunit partially activates the enzyme and further addition of dithiothreitol fully activates it. Molar masses and gyration radii values are given for these different conditions.

  15. ANISOTROPY FACTORS FOR A 252Cf SOURCE

    SciTech Connect

    Veinot, K. G.; Bogard, James S

    2009-01-01

    A new 252Cf source has been procured for use at the Dosimetry Applications and Research (DOSAR) facility at the Oak Ridge National Laboratory (ORNL). This source was encapsulated by the Californium Facility at ORNL, however, the encapsulation differs from previous designs designated as SR-Cf-100. The new encapsulation, designated SR-Cf-3000, has a similar cylindrical radius to the previous generation, but is 1.6 cm longer. Since the encapsulation geometries differ the amount of internal scattering of neutrons will also differ leading to changes in anisotropy factors between the two designs. Additionally, the different encapsulations will affect the absorbed dose and dose equivalent delivered per neutron emitted by the source since both the quantity and energy distribution of the emitted neutrons will vary with irradiation angle. This work presents the fluence anisotropy factors for the SR-Cf-3000 series encapsulation as well as absorbed dose and dose equivalent values calculated for various angles of irradiation. The fluence anisotropy factors vary from a maximum of 1.037 to a minimum of 0.641 for irradiation angles perpendicular and parallel to the source axis, respectively. Anisotropy in absorbed dose varied from a maximum of 1.033 to a minimum of 0.676 while anisotropy of dose equivalent varied from 1.035 to 0.657.

  16. Xe-135 Production from Cf-252

    SciTech Connect

    C. A. McGrath; T. P. Houghton; J. K. Pfeiffer; R. K. Hague

    2012-03-01

    135Xe is a good indicator that fission has occurred and is a valuable isotope that helps enforce the Comprehensive Test Ban Treaty. Due to its rather short half life and minimal commercial interest, there are no known sources where 135Xe can be purchased. Readily available standards of this isotope for calibrating collection and analytical techniques would be very useful. 135Xe can be produced in the fissioning of actinide isotopes, or by neutron capture on 134Xe. Since the neutron capture cross section of 134Xe is 3 mB, neutron capture is a low yield, though potentially useful, production route. 135Xe is also produced by spontaneous fission of 252Cf. 252Cf has a spontaneous fission rate of about 6 x 1011 s-1g-1. The cumulative yield from the spontaneous fission of 252Cf is 4.19%; and the competing neutron capture reaction that depletes 135Xe in thermal reactor systems is negligible because the neutron capture cross-section is low for fast fission neutrons. At the INL, scientists have previously transported fission products from an electroplated 252Cf thin source for the measurement of nuclear data of short-lived fission products using a technique called He-Jet collection. We have applied a similar system to the collection of gaseous 135Xe, in order to produce valuable standards of this isotope.

  17. Spectroscopy Of The CF4 Laser

    NASA Astrophysics Data System (ADS)

    McDowell, R. S.; Patterson, C. W.; Jones, C. R.; Buchwald, M. I.; Telle, J. M.

    1980-11-01

    When v2+v4 of CF4 at 1066 cm-1 is pumped by the 9.4-µm CO2 laser, stimulated emission on the (v2+v4) + v2 transition produces many discrete laser lines in the region 605 to 655 cm-1. A comprehensive program of Doppler-limited absorption spectroscopy of CF4 has been carried out using tunable semiconductor diode lasers, and has led to a full understanding of the rovibrational energy levels involved in the laser process. The frequencies of 28 laser lines of 12CF4 have been measured with an accuracy of ±0.2 cm- 1, for 12C16O2 pump lines from P(14) to R(24). From the complete vibration-rotation analysis of the v2+v4 band, the pump and laser transitions have been identified. Using the spectroscopic constants determined in the band analyses, we can predict within ±0.2 cm-1 the laser lines to be expected from any given pumping frequency. All observed laser lines have been accounted for; in a few cases there is evidence for a relaxation of J-value and/or Coriolis sublevel in the upper state. Application of these results to improving the performance of the CF4 laser and for designing it to produce specific desired output frequencies is discussed.

  18. A CF4 based positron trap

    NASA Astrophysics Data System (ADS)

    Marjanovic, Srdjan; Bankovic, Ana; Dujko, Sasa; Deller, Adam; Cooper, Ben; Cassidy, David; Petrovic, Zoran

    2016-05-01

    All positron buffer gas traps in use rely on N2 as the primary trapping gas due to its conveniently placed a1 Π electronic excitation cross section that is large enough to compete with positronium (Ps) formation in the threshold region. Its energy loss of 8.5 eV is sufficient to capture positrons into a potential well upon a single collision. The competing Ps formation, however, limits the efficiency of the two stage trap to 25 %. As positron moderators produce beams with energies of several eV we have proposed to use CF4 in the first stage of the trap, due to its large vibrational excitation cross section, where several vibrational excitations would be sufficient to trap the positrons with small losses. Apart from the simulations we also report the results of attempts to apply this approach to an existing Surko-type positron trap. Operating the unmodified trap as a CF4 based device proved to be unsuccessful, due primarily to excessive scattering due to high CF4 pressure in the first stage. However, the performance was consistent with subsequent simulations using the real system parameters. This agreement indicates that an efficient CF4 based scheme may be realized in an appropriately designed trap. also at Serbian Academy of Sciences and Arts, Knez Mihajlova 35, 11000 Belgrade, Serbia.

  19. Variant Human T-cell Lymphotropic Virus Type 1c and Adult T-cell Leukemia, Australia

    PubMed Central

    Cassar, Olivier; Bardy, Peter; Kearney, Daniel; Gessain, Antoine

    2013-01-01

    Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c. PMID:24047544

  20. Large-scale live imaging of adult neural stem cells in their endogenous niche

    PubMed Central

    Dray, Nicolas; Bedu, Sébastien; Vuillemin, Nelly; Alunni, Alessandro; Coolen, Marion; Krecsmarik, Monika; Supatto, Willy; Beaurepaire, Emmanuel; Bally-Cuif, Laure

    2015-01-01

    Live imaging of adult neural stem cells (aNSCs) in vivo is a technical challenge in the vertebrate brain. Here, we achieve long-term imaging of the adult zebrafish telencephalic neurogenic niche and track a population of >1000 aNSCs over weeks, by taking advantage of fish transparency at near-infrared wavelengths and of intrinsic multiphoton landmarks. This methodology enables us to describe the frequency, distribution and modes of aNSCs divisions across the entire germinal zone of the adult pallium, and to highlight regional differences in these parameters. PMID:26395477

  1. Two distinct monooxygenases for alkane oxidation in Nocardioides sp. strain CF8.

    PubMed

    Hamamura, N; Yeager, C M; Arp, D J

    2001-11-01

    Alkane monooxygenases in Nocardioides sp. strain CF8 were examined at the physiological and genetic levels. Strain CF8 can utilize alkanes ranging in chain length from C(2) to C(16). Butane degradation by butane-grown cells was strongly inhibited by allylthiourea, a copper-selective chelator, while hexane-, octane-, and decane-grown cells showed detectable butane degradation activity in the presence of allylthiourea. Growth on butane and hexane was strongly inhibited by 1-hexyne, while 1-hexyne did not affect growth on octane or decane. A specific 30-kDa acetylene-binding polypeptide was observed for butane-, hexane-, octane-, and decane-grown cells but was absent from cells grown with octane or decane in the presence of 1-hexyne. These results suggest the presence of two monooxygenases in strain CF8. Degenerate primers designed for PCR amplification of genes related to the binuclear-iron-containing alkane hydroxylase from Pseudomonas oleovorans were used to clone a related gene from strain CF8. Reverse transcription-PCR and Northern blot analysis showed that this gene encoding a binuclear-iron-containing alkane hydroxylase was expressed in cells grown on alkanes above C(6). These results indicate the presence of two distinct monooxygenases for alkane oxidation in Nocardioides sp. strain CF8. PMID:11679317

  2. Sex hormones establish a reserve pool of adult muscle stem cells.

    PubMed

    Kim, Ji-Hoon; Han, Gi-Chan; Seo, Ji-Yun; Park, Inkuk; Park, Wookjin; Jeong, Hyun-Woo; Lee, Su Hyeon; Bae, Sung-Hwan; Seong, Jinwoo; Yum, Min-Kyu; Hann, Sang-Hyeon; Kwon, Young-Guen; Seo, Daekwan; Choi, Man Ho; Kong, Young-Yun

    2016-09-01

    Quiescent satellite cells, known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle following injury throughout life. Although they mainly originate from multipotent stem/progenitor cells of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb 1 (Mib1) expression in myofibres at puberty, which activates Notch signalling in cycling juvenile satellite cells and causes them to be converted into adult quiescent satellite cells. Myofibres lacking Mib1 fail to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Our findings reveal that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofibre niche. Moreover, the same axis regulates the re-establishment of quiescent satellite cell populations following injury. Our data show that sex hormones establish adult quiescent satellite cell populations by regulating the myofibre niche at puberty and re-establish them during regeneration. PMID:27548913

  3. Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

    PubMed Central

    2013-01-01

    Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibility to stimulate their in vivo differentiation or to use their ex vivo expanded progenies for cell replacement-based therapies with multiple applications in human. Among the human diseases that could be treated by the stem cell-based therapies, there are hematopoietic and immune disorders, multiple degenerative disorders, such as Parkinson’s and Alzeimeher’s diseases, type 1 or 2 diabetes mellitus as well as eye, liver, lung, skin and cardiovascular disorders and aggressive and metastatic cancers. In addition, the genetically-modified adult stem/progenitor cells could also be used as delivery system for expressing the therapeutic molecules in specific damaged areas of different tissues. Recent advances in cancer stem/progenitor cell research also offer the possibility to targeting these undifferentiated and malignant cells that provide critical functions in cancer initiation and progression and disease relapse for treating the patients diagnosed with the advanced and metastatic cancers which remain incurable in the clinics with the current therapies. PMID:18288619

  4. ESTABLISHING MEAN CD4+ T CELL VALUES AMONG HEALTHY JAVANESE ADULTS IN INDONESIA.

    PubMed

    Prasetyo, Afiono Agung; Zaini, Khilyat Ulin Nur

    2015-07-01

    The objective of this study was to establish mean CD4+ T cell values among healthy Javanese adults in Indonesia. Two hundred forty-one healthy adults (119 women and 122 men), aged 18-65 years, were enrolled in the study. CD4+ T cells were analyzed by immunophenotyping. The mean absolute CD4+ T cell count was 753.3 ± 270.3 cells/µl (median = 725.0 cells/µl) and the mean CD4+ T cell percentage was 32.6 ± 7.7%, (median = 31.0%). Women had a slightly higher mean absolute CD4+ T cell count and CD4+ T cell percentage (779.1 ± 271.0 cells/ µl; 33.4 ± 8.2%) than men (728.2 ± 268.3 cells/µl; 31.8 ± 7.1%), but the differences were not statistically significant (p = 0.126, p = 0.216, respectively). The mean absolute CD4+ T cell varied significantly by age group (p = 0.002). Sixty-one point seven percent of men studied (37/60) had a CD4+ T cell count less than 500 cells/µl (OR 1.8; 95% CI = 1.001-3.300). Absolute CD4+ T cell counts among Javanese Indonesians varied significantly by age. PMID:26867386

  5. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    SciTech Connect

    Ren, Zhenhua; Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin; Chen, Zhiguo; Zhang, Y. Alex

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  6. Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition.

    PubMed

    Mellough, Carla B; Cho, Seongeun; Wood, Andrew; Przyborski, Stefan

    2011-09-01

    Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS. PMID:21256909

  7. A novel isolation method for macrophage-like cells from mixed primary cultures of adult rat liver cells.

    PubMed

    Kitani, Hiroshi; Takenouchi, Takato; Sato, Mitsuru; Yoshioka, Miyako; Yamanaka, Noriko

    2010-08-31

    We report a simple and efficient method to obtain macrophage-like cells from the mixed primary cultures of adult rat liver cells. A parenchymal hepatocyte enriched fraction was prepared from adult rat livers and seeded into culture flasks. After 7 to 10 days of culture, when most hepatocytes were degenerated or transformed into fibroblastic cells, macrophage-like cells vigorously proliferated on the cell sheet. By shaking the flasks, macrophage-like cells were readily detached. Subsequent transfer and incubation in plastic dishes resulted in quick and selective adhesion of macrophage-like cells, while other contaminating cells remained suspended in the medium. After rinsing with saline, attached macrophage-like cells were harvested with 95 to 99% purity, as evaluated by flow cytometry or immunocytochemistry. These cells showed typical macrophage morphology and were strongly positive for markers of rat macrophages, such as ED-1, ED-3, and OX-41, but negative for cytokeratins and alpha-smooth muscle actin. They possessed functional properties of typical macrophages, including active phagocytosis of latex beads, proliferative response to recombinant GM-CSF, secretion of inflammatory and anti-inflammatory cytokines upon stimulation with LPS, and formation of multinucleated giant cells. As more than 10(6) cells can be recovered repeatedly from a T75 culture flask at two to three day intervals for more than two weeks, our procedure might implicate a novel alternative to obtain Kupffer cells in sufficient number and purity without complex equipment and skills. PMID:20600081

  8. Summary report for CF6 jet engine diagnostics program

    NASA Technical Reports Server (NTRS)

    Fasching, W. A.; Stricklin, R.

    1982-01-01

    Cockpit cruise recordings and test cell data in conjunction with hardware inspection results from airline overhaul shops were analyzed to define the extent and magnitude of performance deterioration of the General Electric CF6 high bypass turbofan engines. The magnitude of Short Term deterioration from the Long Term was isolated and the individual damage mechanisms that were the cause for the majority of the performance deterioration were identified. A potential for reduction in compressor clearance and a potential for improvement in turbine roundness, which corresponds to cruise SFC reductions of 0.38 and 0.36 percent, respectively, were identified.

  9. Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or Regulatory T Cell Responses in Adults

    PubMed Central

    Boer, Mardi C.; Prins, Corine; van Meijgaarden, Krista E.; van Dissel, Jaap T.; Joosten, Simone A.

    2015-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG), the only currently available vaccine against tuberculosis, induces variable protection in adults. Immune correlates of protection are lacking, and analyses on cytokine-producing T cell subsets in protected versus unprotected cohorts have yielded inconsistent results. We studied the primary T cell response, both proinflammatory and regulatory T cell responses, induced by BCG vaccination in adults. Twelve healthy adult volunteers who were tuberculin skin test (TST) negative, QuantiFERON test (QFT) negative, and BCG naive were vaccinated with BCG and followed up prospectively. BCG vaccination induced an unexpectedly dichotomous immune response in this small, BCG-naive, young-adult cohort: BCG vaccination induced either gamma interferon-positive (IFN-γ+) interleukin 2-positive (IL-2+) tumor necrosis factor α-positive (TNF-α+) polyfunctional CD4+ T cells concurrent with CD4+ IL-17A+ and CD8+ IFN-γ+ T cells or, in contrast, virtually absent cytokine responses with induction of CD8+ regulatory T cells. Significant induction of polyfunctional CD4+ IFN-γ+ IL-2+ TNF-α+ T cells and IFN-γ production by peripheral blood mononuclear cells (PBMCs) was confined to individuals with strong immunization-induced local skin inflammation and increased serum C-reactive protein (CRP). Conversely, in individuals with mild inflammation, regulatory-like CD8+ T cells were uniquely induced. Thus, BCG vaccination either induced a broad proinflammatory T cell response with local inflammatory reactogenicity or, in contrast, a predominant CD8+ regulatory T cell response with mild local inflammation, poor cytokine induction, and absent polyfunctional CD4+ T cells. Further detailed fine mapping of the heterogeneous host response to BCG vaccination using classical and nonclassical immune markers will enhance our understanding of the mechanisms and determinants that underlie the induction of apparently opposite immune responses and how these

  10. Pulmonary Alveolar Type II Epithelial Cells and Adult Respiratory Distress Syndrome

    PubMed Central

    Mason, Robert J.

    1985-01-01

    During the past ten years, functions of alveolar type II cells have been well characterized with isolated cells in vitro. Some of the functions were well known from studies in vivo, but others such as transepithelial sodium transport were unsuspected. A better understanding of this important pulmonary cell type improves our knowledge of the pathophysiology of adult respiratory distress syndrome and may in time lead to new therapeutic strategies. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:3909639

  11. Guiding principles on how to manage relevant psychological aspects within a CF team: interdisciplinary approaches.

    PubMed

    Nobili, Rita M; Duff, Alistair J A; Ullrich, Gerald; Smrekar, Ulrike; Havermans, Trudy; Bryon, Mandy; Borawska-Kowalczyk, Ula; Malmborg, Maria Sandberg

    2011-06-01

    Managing CF can be emotionally and physically challenging for patients and their relatives. The disease and its treatment influence the ability to tackle normal tasks of daily living and unexpected life events. The context within which psychologists work varies according to different cultural backgrounds and their professional and theoretical memberships. The benchmarks presented here focus on four crucial issues: (i) identifying a common base of tools and theoretical reflections through suggested readings, (ii) interdisciplinary work within a CF team and its importance for both persons with CF and other healthcare professionals, (iii) the benefits of an eclectic approach utilising cognitive-behavioural theories for specific psychological problems and, (iv) effective and evaluated transition programmes from paediatric to adult healthcare services. PMID:21658641

  12. Reduced Mucosal Associated Invariant T-Cells Are Associated with Increased Disease Severity and Pseudomonas aeruginosa Infection in Cystic Fibrosis

    PubMed Central

    Smith, Daniel J.; Hill, Geoffrey R.; Bell, Scott C.; Reid, David W.

    2014-01-01

    Background Primary defects in host immune responses have been hypothesised to contribute towards an inability of subjects with cystic fibrosis (CF) to effectively clear pulmonary infections. Innate T-lymphocytes provide rapid pathogen-specific responses prior to the development of classical MHC class I and II restricted T-cell responses and are essential to the initial control of pulmonary infection. We aimed to examine the relationship between peripheral blood lymphocyte phenotype and clinical outcomes in adults with CF. Methods We studied 41 subjects with CF and 22, age matched, non-smoking healthy control subjects. Lymphocytes were extracted from peripheral blood samples and phenotyped by flow-cytometry. Lymphocyte phenotype was correlated with sputum microbiology and clinical parameters. Results In comparison to healthy control subjects, mucosal associated invariant T (MAIT)-lymphocytes were significantly reduced in the peripheral blood of subjects with CF (1.1% versus 2.0% of T-lymphocytes, P = 0.002). MAIT cell concentration was lowest in CF subjects infected with P. aeruginosa and in subjects receiving treatment for a pulmonary exacerbation. Furthermore a reduced MAIT cell concentration correlated with severity of lung disease. Conclusion Reduced numbers of MAIT cells in subjects with CF were associated with P. aeruginosa pulmonary infection, pulmonary exacerbations and more severe lung disease. These findings provide the impetus for future studies examining the utility of MAIT cells in immunotherapies and vaccine development. Longitudinal studies of MAIT cells as biomarkers of CF pulmonary infection are awaited. PMID:25296025

  13. Single-cell in vivo imaging of adult neural stem cells in the zebrafish telencephalon.

    PubMed

    Barbosa, Joana S; Di Giaimo, Rossella; Götz, Magdalena; Ninkovic, Jovica

    2016-08-01

    Adult neural stem cells (aNSCs) in zebrafish produce mature neurons throughout their entire life span in both the intact and regenerating brain. An understanding of the behavior of aNSCs in their intact niche and during regeneration in vivo should facilitate the identification of the molecular mechanisms controlling regeneration-specific cellular events. A greater understanding of the process in regeneration-competent species may enable regeneration to be achieved in regeneration-incompetent species, including humans. Here we describe a protocol for labeling and repetitive imaging of aNSCs in vivo. We label single aNSCs, allowing nonambiguous re-identification of single cells in repetitive imaging sessions using electroporation of a red-reporter plasmid in Tg(gfap:GFP)mi2001 transgenic fish expressing GFP in aNSCs. We image using two-photon microscopy through the thinned skull of anesthetized and immobilized fish. Our protocol allows imaging every 2 d for a period of up to 1 month. This methodology allowed the visualization of aNSC behavior in vivo in their natural niche, in contrast to previously available technologies, which rely on the imaging of either dissociated cells or tissue slices. We used this protocol to follow the mode of aNSC division, fate changes and cell death in both the intact and injured zebrafish telencephalon. This experimental setup can be widely used, with minimal prior experience, to assess key factors for processes that modulate aNSC behavior. A typical experiment with data analysis takes up to 1.5 months. PMID:27362338

  14. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

    PubMed

    Bas, Esperanza; Van De Water, Thomas R; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M; Goldstein, Bradley J

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  15. PAX4 Defines an Expandable β-Cell Subpopulation in the Adult Pancreatic Islet

    PubMed Central

    Lorenzo, Petra I.; Fuente-Martín, Esther; Brun, Thierry; Cobo-Vuilleumier, Nadia; Jimenez-Moreno, Carmen María; G. Herrera Gomez, Irene; López Noriega, Livia; Mellado-Gil, José Manuel; Martin-Montalvo, Alejandro; Soria, Bernat; Gauthier, Benoit R.

    2015-01-01

    PAX4 is a key regulator of pancreatic islet development whilst in adult acute overexpression protects β-cells against stress-induced apoptosis and stimulates proliferation. Nonetheless, sustained PAX4 expression promotes β-cell dedifferentiation and hyperglycemia, mimicking β-cell failure in diabetic patients. Herein, we study mechanisms that allow stringent PAX4 regulation endowing favorable β-cell adaptation in response to changing environment without loss of identity. To this end, PAX4 expression was monitored using a mouse bearing the enhanced green fluorescent protein (GFP) and cre recombinase construct under the control of the islet specific pax4 promoter. GFP was detected in 30% of islet cells predominantly composed of PAX4-enriched β-cells that responded to glucose-induced insulin secretion. Lineage tracing demonstrated that all islet cells were derived from PAX4+ progenitor cells but that GFP expression was confined to a subpopulation at birth which declined with age correlating with reduced replication. However, this GFP+ subpopulation expanded during pregnancy, a state of active β-cell replication. Accordingly, enhanced proliferation was exclusively detected in GFP+ cells consistent with cell cycle genes being stimulated in PAX4-overexpressing islets. Under stress conditions, GFP+ cells were more resistant to apoptosis than their GFP- counterparts. Our data suggest PAX4 defines an expandable β-cell sub population within adult islets. PMID:26503027

  16. Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles.

    PubMed

    Lin, Vincent; Golub, Justin S; Nguyen, Tot Bui; Hume, Clifford R; Oesterle, Elizabeth C; Stone, Jennifer S

    2011-10-26

    The capacity of adult mammals to regenerate sensory hair cells is not well defined. To explore early steps in this process, we examined reactivation of a transiently expressed developmental gene, Atoh1, in adult mouse utricles after neomycin-induced hair cell death in culture. Using an adenoviral reporter for Atoh1 enhancer, we found that Atoh1 transcription is activated in some hair cell progenitors (supporting cells) 3 d after neomycin treatment. By 18 d after neomycin, the number of cells with Atoh1 transcriptional activity increased significantly, but few cells acquired hair cell features (i.e., accumulated ATOH1 or myosin VIIa protein or developed stereocilia). Treatment with DAPT, an inhibitor of γ-secretase, reduced notch pathway activity, enhanced Atoh1 transcriptional activity, and dramatically increased the number of Atoh1-expressing cells with hair cell features, but only in the striolar/juxtastriolar region. Similar effects were seen with TAPI-1, an inhibitor of another enzyme required for notch activity (TACE). Division of supporting cells was rare in any control or DAPT-treated utricles. This study shows that mature mammals have a natural capacity to initiate vestibular hair cell regeneration and suggests that regional notch activity is a significant inhibitor of direct transdifferentiation of supporting cells into hair cells following damage. PMID:22031879

  17. Mediastinal Tuberculosis in an Adult Patient with Cystic Fibrosis▿

    PubMed Central

    Morand, Philippe C.; Burgel, Pierre-Régis; Carlotti, Agnès; Desmazes-Dufeu, Nadine; Farhi, David; Martin, Clémence; Kanaan, Reem; Mangialavori, Luigi; Palangié, Estelle; Dusser, Daniel; Poyart, Claire; Hubert, Dominique

    2011-01-01

    Tuberculosis (TB) is rarely observed in cystic fibrosis (CF) patients. We report the first case of mediastinal TB, associated with leg pain and skin rash, in an adult patient with CF, and discuss factors suggestive of TB in the course of CF. PMID:21106788

  18. Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

    PubMed Central

    West, John D; Dorà, Natalie J; Collinson, J Martin

    2015-01-01

    In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed

  19. The cardiac stem cell compartment is indispensable for myocardial cell homeostasis, repair and regeneration in the adult.

    PubMed

    Nadal-Ginard, Bernardo; Ellison, Georgina M; Torella, Daniele

    2014-11-01

    Resident cardiac stem cells in embryonic, neonatal and adult mammalian heart have been identified by different membrane markers and transcription factors. However, despite a flurry of publications no consensus has been reached on the identity and actual regenerative effects of the adult cardiac stem cells. Intensive research on the adult mammalian heart's capacity for self-renewal of its muscle cell mass has led to a consensus that new cardiomyocytes (CMs) are indeed formed throughout adult mammalian life albeit at a disputed frequency. The physiological significance of this renewal, the origin of the new CMs, and the rate of adult CM turnover are still highly debated. Myocyte replacement, particularly after injury, was originally attributed to differentiation of a stem cell compartment. More recently, it has been reported that CMs are mainly replaced by the division of pre-existing post-mitotic CMs. These latter results, if confirmed, would shift the target of regenerative therapy toward boosting mature CM cell-cycle re-entry. Despite this controversy, it is documented that the adult endogenous c-kit(pos) cardiac stem cells (c-kit(pos) eCSCs) participate in adaptations to myocardial stress, and, when transplanted into the myocardium, regenerate most cardiomyocytes and microvasculature lost in an infarct. Nevertheless, the in situ myogenic potential of adult c-kit(pos) cardiac cells has been questioned. To revisit the regenerative potential of c-kit(pos) eCSCs, we have recently employed experimental protocols of severe diffuse myocardial damage in combination with several genetic murine models and cell transplantation approaches showing that eCSCs are necessary and sufficient for CM regeneration, leading to complete cellular, anatomical, and functional myocardial recovery. Here we will review the available data on adult eCSC biology and their regenerative potential placing it in the context of the different claimed mechanisms of CM replacement. These data are in

  20. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  1. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  2. The sexual identity of adult intestinal stem cells controls organ size and plasticity

    PubMed Central

    Hudry, Bruno; Khadayate, Sanjay; Miguel-Aliaga, Irene

    2016-01-01

    SUMMARY Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realisation that cell-intrinsic mechanisms play important and persistent roles1,2. Here we use the Drosophila melanogaster intestine to investigate the nature and significance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncover its key roles in controlling organ size, its reproductive plasticity and its response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms, which control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognised. PMID:26887495

  3. The sexual identity of adult intestinal stem cells controls organ size and plasticity.

    PubMed

    Hudry, Bruno; Khadayate, Sanjay; Miguel-Aliaga, Irene

    2016-02-18

    Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles. Here we use the Drosophila melanogaster intestine to investigate the nature and importance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncovers the key role this identity has in controlling organ size, reproductive plasticity and response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognized. PMID:26887495

  4. PROGRESSION OF REGULATORY GENE EXPRESSION STATES IN FETAL AND ADULT PRO-T CELL DEVELOPMENT

    PubMed Central

    David-Fung, Elizabeth-Sharon; Yui, Mary A.; Morales, Marissa; Wang, Hua; Taghon, Tom; Diamond, Rochelle A.; Rothenberg, Ellen V.

    2014-01-01

    Precursors entering the T-cell developmental pathway traverse a progression of states characterized by distinctive patterns of gene expression. Of particular interest are regulatory genes, which ultimately control the dwell time of cells in each state and establish the mechanisms that propel them forward to subsequent states. Under particular genetic and developmental circumstances, the transitions between these states occur with different timing, and environmental feedbacks may shift the steady-state accumulations of cells in each state. The fetal transit through pro-T cell stages is faster than in the adult, and subject to somewhat different genetic requirements. To explore causes of such variation, this review presents previously unpublished data on differentiation gene activation in pro-T cells of pre-TCR deficient mutant mice, and a quantitative comparison of the profiles of transcription factor gene expression in pro-T cell subsets of fetal and adult wildtype mice. Against a background of consistent gene expression, several regulatory genes show marked differences between fetal and adult expression profiles, including those encoding two bHLH antagonist Id factors, the Ets family factor SpiB, and the Notch target gene Deltex1. The results also reveal global differences in regulatory alterations triggered by the first TCR-dependent selection events in fetal and adult thymopoiesis. PMID:16448545

  5. Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

    PubMed Central

    Lee, Dong Joon; Park, Yonsil; Hu, Wei-Shou; Ko, Ching-Chang

    2016-01-01

    Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluated in vivo by the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formation in vitro and induced new bone formation by the effect of rMAPC aggregates in vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration. PMID:27239552

  6. Electron transport in CF3I and CF3I-N2 mixtures

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Satoru; Satoh, Kohki; Itoh, Hidenori

    2014-04-01

    Electron collision cross sections for CF3I are estimated using the electron swarm method. Electron drift velocity, effective ionisation coefficient, and longitudinal diffusion coefficient in CF3I are calculated using Monte Carlo method, and the calculated electron transport coefficients are compared with those measured. Calculated electron drift velocity agrees with measured data within the difference of 6% below 1600 Td, and calculated effective ionisation coefficient agrees with measured data within the difference of 10% above 460 Td. Further, those swarm parameters in CF3I-N2 mixtures are calculated, and calculated values of electron drift velocity and effective ionisation coefficient agree well with measured data in CF3I-N2 mixtures. This confirms the validity of the estimated set.

  7. Diversity of epithelial stem cell types in adult lung.

    PubMed

    Li, Feng; He, Jinxi; Wei, Jun; Cho, William C; Liu, Xiaoming

    2015-01-01

    Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer. PMID:25810726

  8. Diversity of Epithelial Stem Cell Types in Adult Lung

    PubMed Central

    Li, Feng; He, Jinxi; Wei, Jun; Cho, William C.; Liu, Xiaoming

    2015-01-01

    Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer. PMID:25810726

  9. Characterization of the tomato Cf-4 gene for resistance to Cladosporium fulvum identifies sequences that determine recognitional specificity in Cf-4 and Cf-9.

    PubMed Central

    Thomas, C M; Jones, D A; Parniske, M; Harrison, K; Balint-Kurti, P J; Hatzixanthis, K; Jones, J D

    1997-01-01

    In many interactions between plants and their pathogens, resistance to infection is specified by plant resistance (R) genes and corresponding pathogen avirulence (Avr) genes. In tomato, the Cf-4 and Cf-9 resistance genes map to the same location but confer resistance to Cladosporium fulvum through recognition of different avirulence determinants (AVR4 and AVR9) by a molecular mechanism that has yet to be determined. Here, we describe the cloning and characterization of Cf-4, which also encodes a membrane-anchored extracellular glycoprotein. Cf-4 contains 25 leucine-rich repeats, which is two fewer than Cf-9. The proteins have > 91% identical amino acids. DNA sequence comparison suggests that Cf-4 and Cf-9 are derived from a common progenitor sequence. Amino acid differences distinguishing Cf-4 and Cf-9 are confined to their N termini, delimiting a region that determines the recognitional specificity of ligand binding. The majority of these differences are in residues interstitial to those of the leucine-rich repeat consensus motif. Many of these residues are predicted to form a solvent-exposed surface that can interact with the cognate ligand. Both Cf-4 and Cf-9 are located within a 36-kb region comprising five tandemly duplicated homologous genes. These results provide further insight into the molecular basis of pathogen perception by plants and the organization of complex R gene loci. PMID:9437864

  10. Adult onset folliculocentric langerhans cell histiocytosis confined to the scalp.

    PubMed

    Hancox, John G; James, Asha Pardasani; Madden, Christopher; Wallace, Christopher A; McMichael, Amy J

    2004-04-01

    Langerhans cell histiocytosis (LCH) is a pleomorphic disease entity characterized by local or disseminated atypical Langerhans cells found most commonly in bone, lungs, mucocutaneous structures, and endocrine organs. Cutaneous disease occurs in approximately one quarter of all cases. Cutaneous findings include soft-tissue swelling, eczematous changes, a seborrheic dermatitis-like appearance, and ulceration. We report a rare case of LCH confined to the scalp with folliculocentric infiltrates. This 32-year-old male patient presented with follicularly based erythema, scale, and pustules unresponsive to topicals and oral antibiotics. The patient's lesions mimicked lichen planopilaris and folliculitis decalvans during the disease process. On hematoxylin and eosin stain, scalp biopsy showed a perivascular interstitial patchy lichenoid mononuclear cell infiltrate that focally abutted follicular infundibula. Prominent mononuclear cells having reniform nuclei were present, and immunoperoxidase stains for CD1a confirmed Langerhans cell differentiation. Serological and imaging workup failed to display systemic involvement. PMID:15024194

  11. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    PubMed

    Priller, Josef

    2003-08-01

    While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction. PMID:12898276

  12. Spontaneous electric fields in films of CF3Cl, CF2Cl2 and CFCl3.

    PubMed

    Cassidy, Andrew; Plekan, Oksana; Balog, Richard; Jones, Nykola C; Field, David

    2013-01-01

    Data are presented showing the spontaneous formation of electric fields within solid films of the chlorofluorocarbons (CFCs) CF(3)Cl, CF(2)Cl(2) and CFCl(3) as a function of film deposition temperature from 40 K and above. Electric fields, which arise through dipole alignment and lie in the range of a few times 10(7) V m(-1) to a few times 10(6) V m(-1), decrease as the degree of chlorination increases. Maximum deposition temperatures for display of an electric field lie at ~50 K, ~65 K and ~52 K for CF(3)Cl, CF(2)Cl(2) and CFCl(3) respectively. CFCl(3) films possess electric fields which show an onset of temporal metastability between deposition temperatures of 46 K and 50 K. CF(3)Cl and CF(2)Cl(2) demonstrate temperatures of ~65 K and ~80 K at which the electric field in the film is removed by heating, so-called Curie points, with decay of the field spread over more than 10 K. CFCl(3) displays a comparatively sharp Curie point at 55 K. This variety of behaviour arises despite the resemblance of these three species in terms of electronic structure and gas phase dipole moment, emphasising the requirement for detailed chemical models of this phenomenon. PMID:23147680

  13. High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells.

    PubMed

    Palmon, Aaron; David, Ran; Neumann, Yoav; Stiubea-Cohen, Raluca; Krief, Guy; Aframian, Doron J

    2012-02-01

    Isolation of highly pure specific cell types is crucial for successful adult stem cell-based therapy. As the number of such cells in adult tissue is low, an extremely efficient method is needed for their isolation. Here, we describe cell-separation methodologies based on magnetic-affinity cell sorting (MACS) MicroBeads with monoclonal antibodies against specific membrane proteins conjugated to superparamagnetic particles. Cells labeled with MACS MicroBeads are retained in a magnetic field within a MACS column placed in a MACS separator, allowing fast and efficient separation. Both positively labeled and non-labeled fractions can be used directly for downstream applications as the separated cell fractions remain viable with no functional impairment. As immunomagnetic separation depends on the interaction between a cell's membrane and the magnetically labeled antibody, separation of specific cells originating from solid tissues is more complex and demands a cell-dissociating pretreatment. In this paper, we detail the use of immunomagnetic separation for the purpose of regenerating damaged salivary gland (SG) function in animal and human models of irradiated head and neck cancer. Each year 500,000 new cases of head and neck cancer occur worldwide. Most of these patients lose SG function following irradiation therapy. SGs contain integrin α6β1-expressing epithelial stem cells. We hypothesized that these cells can be isolated, multiplied in culture and auto-implanted into the irradiated SGs to regenerate damaged SG function. PMID:22019721

  14. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium

    PubMed Central

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J.; Abreu Paiva, Marta S.; Habib, Josef; Macaulay, Iain; de Smith, Adam J.; al-Beidh, Farah; Sampson, Robert; Lumbers, R. Thomas; Rao, Pulivarthi; Harding, Sian E.; Blakemore, Alexandra I. F.; Eirik Jacobsen, Sten; Barahona, Mauricio; Schneider, Michael D.

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT–PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα+ cells. Clonal progeny of single Sca1+ SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα− cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα+/CD31− cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα−/CD31+ cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell. PMID:25980517

  15. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium.

    PubMed

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J; Abreu Paiva, Marta S; Habib, Josef; Macaulay, Iain; de Smith, Adam J; al-Beidh, Farah; Sampson, Robert; Lumbers, R Thomas; Rao, Pulivarthi; Harding, Sian E; Blakemore, Alexandra I F; Jacobsen, Sten Eirik; Barahona, Mauricio; Schneider, Michael D

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells. Clonal progeny of single Sca1(+) SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα(-) cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα(+)/CD31(-) cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα(-)/CD31(+) cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1(+) stem/progenitor cell. PMID:25980517

  16. B-cell production and differentiation in adult rats.

    PubMed Central

    Bazin, H; Platteau, B; Maclennan, I C; Johnson, G D

    1985-01-01

    The B-cell development in a group of rats was suppressed for the first 45 days of life by serial administration of rabbit anti-rat IgM and IgD antibody. Total or near total suppression of B lymphopoiesis was achieved. At 45 days, suppression was stopped by injection of IgM and IgD rat paraproteins. The sequence of B-cell and plasma cell development following suppression was assessed by immunohistological analysis of spleen lymph nodes and small intestinal lamina propria. The main findings are listed below. Complete reconstitution of B-cell numbers occurs within 8 days, at which stage germinal centres are also present. B lymphopoiesis in the red pulp of the spleen differs from that reported for bone marrow. Cells develop expressing surface sIgM and sIgM with IgA, but not sIgD. sIgD-positive cells first appear in splenic follicles 2 days after stopping suppression, but their appearance in lymph nodes is delayed until after 3 days. At this stage, sIgD-positive cells become apparent in the splenic red pulp. IgM plasma cells appear from day 4. IgA plasma cells in the gut appear in small numbers at day 6, and gradually increase to normal numbers by day 14. sIgG2c expression in the splenic marginal zone did not approach normal levels, even 2 weeks after suppression was stopped. Images Figure 4 Figure 2 Figure 3 PMID:3871730

  17. The molecular nature of very small embryonic-like stem cells in adult tissues.

    PubMed

    Kim, YongHwan; Jeong, Jaeho; Kang, Hyunsook; Lim, Jisun; Heo, Jinbeom; Ratajczak, Janina; Ratajczak, Mariusz Z; Shin, Dong-Myung

    2014-11-01

    Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (∼3-6 μm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells. PMID:25473442

  18. The Molecular Nature of Very Small Embryonic-Like Stem Cells in Adult Tissues

    PubMed Central

    Kim, YongHwan; Jeong, Jaeho; Kang, Hyunsook; Lim, Jisun; Heo, Jinbeom; Ratajczak, Janina; Ratajczak, Mariusz Z.; Shin, Dong-Myung

    2014-01-01

    Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4+ SSEA-1+Sca-1+Lin−CD45− very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (∼3–6 μm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells. PMID:25473442

  19. Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse.

    PubMed

    Furube, Eriko; Morita, Mitsuhiro; Miyata, Seiji

    2015-11-01

    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions. PMID:25994374

  20. Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands.

    PubMed

    Iakovenko, Roman O; Kazakova, Anna N; Muzalevskiy, Vasiliy M; Ivanov, Alexander Yu; Boyarskaya, Irina A; Chicca, Andrea; Petrucci, Vanessa; Gertsch, Jürg; Krasavin, Mikhail; Starova, Galina L; Zolotarev, Andrey A; Avdontceva, Margarita S; Nenajdenko, Valentine G; Vasilyev, Aleksander V

    2015-09-01

    4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells. PMID:26186675

  1. Adult stem cells and biocompatible scaffolds as smart drug delivery tools for cardiac tissue repair.

    PubMed

    Pagliari, Stefania; Romanazzo, Sara; Mosqueira, Diogo; Pinto-do-Ó, Perpetua; Aoyagi, Takao; Forte, Giancarlo

    2013-01-01

    The contribution of adult stem cells to cardiac repair is mostly ascribed to an indirect paracrine effect, rather than to their actual engraftment and differentiation into new contractile and vascular cells. This effect consists in a direct reduction of host cell death, promotion of neovascularization, and in a "bystander effect" on local inflammation. A number of cytokines secreted by adult stem/progenitor cells has been proposed to be responsible for the consistent beneficial effect reported in the early attempts to deliver different stem cell subsets to the injured myocardium. Aiming to maximize their beneficial activity on the diseased myocardium, the genetic modification of adult stem cells to enhance and/or control the secretion of specific cytokines would turn them into active drug delivery vectors. On the other hand, engineering biocompatible scaffolds as to release paracrine factors could result in multiple advantages: (1) achieve a local controlled release of the drug of interest, thus minimizing off-target effects, (2) enhance stem cell retention in the injured area and (3) boost the beneficial paracrine effects exerted by adult stem cells on the host tissue. In the present review, a critical overview of the state-of-the-art in the modification of stem cells and the functionalization of biocompatible scaffolds to deliver beneficial soluble factors to the injured myocardium is offered. Besides the number of concerns to be addressed before a clinical application can be foreseen for such concepts, this path could translate into the generation of active scaffolds as smart cell and drug delivery systems for cardiac repair. PMID:23745554

  2. Naïve adult stem cells isolation from primary human fibroblast cultures.

    PubMed

    Wenzel, Vera; Roedl, Daniela; Ring, Johannes; Djabali, Karima

    2013-01-01

    Over the last decade, several adult stem cell populations have been identified in human skin (1-4). The isolation of multipotent adult dermal precursors was first reported by Miller F. D laboratory (5, 6). These early studies described a multipotent precursor cell population from adult mammalian dermis (5). These cells--termed SKPs, for skin-derived precursors-- were isolated and expanded from rodent and human skin and differentiated into both neural and mesodermal progeny, including cell types never found in skin, such as neurons (5). Immunocytochemical studies on cultured SKPs revealed that cells expressed vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors, in addition to fibronectin and multipotent stem cell markers (6). Until now, the adult stem cells population SKPs have been isolated from freshly collected mammalian skin biopsies. Recently, we have established and reported that a population of skin derived precursor cells could remain present in primary fibroblast cultures established from skin biopsies (7). The assumption that a few somatic stem cells might reside in primary fibroblast cultures at early population doublings was based upon the following observations: (1) SKPs and primary fibroblast cultures are derived from the dermis, and therefore a small number of SKP cells could remain present in primary dermal fibroblast cultures and (2) primary fibroblast cultures grown from frozen aliquots that have been subjected to unfavorable temperature during storage or transfer contained a small number of cells that remained viable (7). These rare cells were able to expand and could be passaged several times. This observation suggested that a small number of cells with high proliferation potency and resistance to stress were present in human fibroblast cultures (7). We took advantage of these findings to establish a protocol for rapid isolation of adult stem cells from primary fibroblast cultures that are

  3. Differentiation of adult rat bone marrow stem cells into epithelial progenitor cells in culture.

    PubMed

    Shu, Chang; Li, Ting Yu; Tsang, Lai Ling; Fok, Kin Lam; Lo, Pui Shan; Zhu, Jin Xia; Ho, Lo Sze; Chung, Yiu Wa; Chan, Hsiao Chang

    2006-10-01

    We have previously obtained monoclonal bone marrow stem cells from adult rats (rMSCs) and induced them into phenotypic neurons. In the present study, we aimed to induce rMSCs into epithelial cells by culturing them onto compartmentalized permeable supports, which have been used for growing a variety of polarized epithelia in culture. Hematoxylin staining showed that after 4 days grown on permeable supports, rMSCs formed an epithelial-like monolayer. Immunofluorescence of the permeably-supported monolayers, but not the rMSCs grown in culture flasks, showed positive signals for epithelial markers, cytokeratin 5 & 8. RT-PCR results also showed the mRNA expression of epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR) as well as tight junction protein ZO-1 in the rMSC-derived monolayers grown on permeable supports but absent from those grown in culture flasks. However, western blot only detected protein expression of ZO-1 but not ENaC nor CFTR. The short-circuit current measurements showed that the rMSC-derived monolayers grown on permeable supports exhibited a trans-monolayer resistance of 30-50 Omega cm(2); however, the monolayers did not respond to activators or blockers of CFTR or ENaC. The results suggest that compartmentalized or polarized culture conditions provide a suitable environment for rMSCs to differentiate into epithelial progenitor cells with tight junction formation; however, this condition is not sufficient for functional expression of epithelial ion channels associated with well-differentiated epithelia. PMID:16877014

  4. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    PubMed

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches. PMID:16989722

  5. Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung.

    PubMed

    Liebler, Janice M; Marconett, Crystal N; Juul, Nicholas; Wang, Hongjun; Liu, Yixin; Flodby, Per; Laird-Offringa, Ite A; Minoo, Parviz; Zhou, Beiyun

    2016-01-15

    Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ∼ 20-30% of NKX2.1(+) (or thyroid transcription factor 1(+)) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1(+) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x (HOPX). Not all HOPX(+) cells colocalize with the AT1 cell marker aquaporin 5 (AQP5), and some AQP5(+) cells were NKX2.1(+). HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and HOPX or AQP5 colocalize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung. PMID:26545903

  6. Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers.

    PubMed

    He, Z P; Tan, W Q; Tang, Y F; Zhang, H J; Feng, M F

    2004-04-01

    Oval cells, putative hepatic stem cells, could potentially provide a novel solution to the severe shortage of donor livers, because of their ability to proliferate and differentiate into functional hepatocytes. We have previously demonstrated that oval cells can be induced to differentiate into cells with morphologic, phenotypic, and functional characteristics of mature hepatocytes. In this study, we have established a new model combining ethionine treatment with partial hepatectomy to activate oval cells, then developed a procedure utilizing selective enzymatic digestion and density gradient centrifugation to isolate and purify such cells from heterogeneous liver cell population. We identified oval cells by their morphological characteristics and phenotypic properties, thereby providing definitive evidence of the presence of hepatic stem-like cells in adult rat livers. Viewed by transmission electron microscopy, they were small cells with ovoid nuclei, a high nucleus/cytoplasm ratio and few organelles, including mitochondria and endoplasmic reticulum. Flow cytometric assay showed that these cells highly expressed OV-6, cytokeratin-19 (CK-19) and albumin. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis displayed that the freshly isolated cells co-expressed albumin, cytokeratin-7 (CK-7) and CK-19 mRNA, indicating that they were essentially bipotential hepatic stem-like cells. Furthermore, we set up a culture system containing growth factors and a fibroblast feeder layer, to provide nourishment to these cells. Thus, we were able to culture them in vitro for more than 3 months, with the number of cells doubling 100 times. Gene expressions of albumin, CK-7 and CK-19 in the cells derived from the expanding colonies at day 95 were confirmed by RT-PCR analysis. These data suggested that the hepatic oval cells derived from adult rat livers possess a high potential to proliferate in vitro with a large increase in number, while maintaining the bipotential

  7. Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process

    PubMed Central

    Galvao, Rui Pedro; Kasina, Anita; McNeill, Robert S.; Harbin, Jordan E.; Foreman, Oded; Verhaak, Roel G. W.; Nishiyama, Akiko; Miller, C. Ryan; Zong, Hui

    2014-01-01

    How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the premalignant events taking place between initial mutation and a fully developed tumor mass are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas. PMID:25246577

  8. Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults.

    PubMed

    Lutz, Charles T; Karapetyan, Anush; Al-Attar, Ahmad; Shelton, Brent J; Holt, Kimberly J; Tucker, Jason H; Presnell, Steven R

    2011-04-15

    NK cells are essential for health, yet little is known about human NK turnover in vivo. In both young and elderly women, all NK subsets proliferated and died more rapidly than T cells. CD56(bright) NK cells proliferated rapidly but died relatively slowly, suggesting that proliferating CD56(bright) cells differentiate into CD56(dim) NK cells in vivo. The relationship between CD56(dim) and CD56(bright) proliferating cells indicates that proliferating CD56(dim) cells both self-renew and are derived from proliferating CD56(bright) NK cells. Our data suggest that some dying CD56(dim) cells become CD16(+)CD56(-) NK cells and that CD16(-)CD56(low) NK cells respond rapidly to cellular and cytokine stimulation. We propose a model in which all NK cell subsets are in dynamic flux. About half of CD56(dim) NK cells expressed CD57, which was weakly associated with low proliferation. Surprisingly, CD57 expression was associated with higher proliferation rates in both CD8(+) and CD8(-) T cells. Therefore, CD57 is not a reliable marker of senescent, nonproliferative T cells in vivo. NKG2A expression declined with age on both NK cells and T cells. Killer cell Ig-like receptor expression increased with age on T cells but not on NK cells. Although the percentage of CD56(bright) NK cells declined with age and the percentage of CD56(dim) NK cells increased with age, there were no significant age-related proliferation or apoptosis differences for these two populations or for total NK cells. In vivo human NK cell turnover is rapid in both young and elderly adults. PMID:21402893

  9. Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

    PubMed Central

    Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

    2015-01-01

    Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

  10. Effects of addictive drugs on adult neural stem/progenitor cells.

    PubMed

    Xu, Chi; Loh, Horace H; Law, Ping-Yee

    2016-01-01

    Neural stem/progenitor cells (NSPCs) undergo a series of developmental processes before giving rise to newborn neurons, astrocytes and oligodendrocytes in adult neurogenesis. During the past decade, the role of NSPCs has been highlighted by studies on adult neurogenesis modulated by addictive drugs. It has been proven that these drugs regulate the proliferation, differentiation and survival of adult NSPCs in different manners, which results in the varying consequences of adult neurogenesis. The effects of addictive drugs on NSPCs are exerted via a variety of different mechanisms and pathways, which interact with one another and contribute to the complexity of NSPC regulation. Here, we review the effects of different addictive drugs on NSPCs, and the related experimental methods and paradigms. We also discuss the current understanding of major signaling molecules, especially the putative common mechanisms, underlying such effects. Finally, we review the future directions of research in this area. PMID:26468052

  11. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

    PubMed Central

    Knobloch, Marlen; Braun, Simon M. G.; Zurkirchen, Luis; von Schoultz, Carolin; Zamboni, Nicola; Arauzo-Bravo, Marcos J.; Kovacs, Werner J.; Karalay, Özlem; Suter, Ueli; Machado, Raquel A. C.; Roccio, Marta; Lutolf, Matthias P.; Semenkovich, Clay F.; Jessberger, Sebastian

    2013-01-01

    Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain1. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis2, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism3–5, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA6, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. PMID:23201681

  12. Neural stem cells, adult neurogenesis, and galectin-1: from bench to bedside.

    PubMed

    Sakaguchi, Masanori; Okano, Hideyuki

    2012-07-01

    Neural stem cells (NSCs) in the adult brain have been a consistent focus of biomedical research largely because of their potential clinical application. To fully exploit this potential, the molecular mechanisms that regulate NSCs must be clarified. Several lines of evidence show that a multifunctional protein, Galectin-1, is expressed and has a functional role in a subset of adult NSCs. Researchers, including our group, have explored the physiological role of Galectin-1 in NSCs and its application in the treatment of animal models of neurological disorders such as brain ischemia and spinal cord injury. Here, we summarize what is currently known regarding the role of Galectin-1 in adult NSCs. Furthermore, we discuss current issues in researching the role of Galectin-1 in adult NSCs under both physiological and pathological conditions. PMID:22488739

  13. ICP Reactor Modeling: CF4 Discharge

    NASA Technical Reports Server (NTRS)

    Bose, Deepak; Govindan, T. R.; Meyyappan, M.

    1999-01-01

    Inductively coupled plasma (ICP) reactors are widely used now for etching and deposition applications due to their simpler design compared to other high density sources. Plasma reactor modeling has been playing an important role since it can, in principle, reduce the number of trial and error iterations in the design process and provide valuable understanding of mechanisms. Fluorocarbon precursors have been the choice for oxide etching. We have data available on CF4 from our laboratory. These are current voltage characteristics, La.ngmuir probe data, UV-absorption, and mass spectrometry measurements in a GEC-ICP reactor. We have developed a comprehensive model for ICP reactors which couples plasma generation and transport and neutral species dynamics with the gas flow equations. The model has been verified by comparison with experimental results for a nitrogen discharge in an ICP reactor. In the present work, the model has been applied to CF4 discharge and compared to available experimental data.

  14. Identification and enrichment of colony-forming cells from the adult murine pituitary

    SciTech Connect

    Lepore, D.A.; Roeszler, K.; Wagner, J.; Ross, S.A.; Bauer, K.; Thomas, P.Q. , E-Mail: paul.thomas@mcri.edu.au

    2005-08-01

    Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, {beta}-Ala-Lys-N{epsilon}-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA{sup +} cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA{sup +} population contains rare cells that are GH{sup +} or PRL{sup +}. GH{sup +} cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH{sup +} cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments.

  15. Cl- Channels in CF: Lack of Activation by Protein Kinase C and cAMP-Dependent Protein Kinase

    NASA Astrophysics Data System (ADS)

    Hwang, Tzyh-Chang; Lu, Luo; Zeitlin, Pamela L.; Gruenert, Dieter C.; Huganir, Richard; Guggino, William B.

    1989-06-01

    Secretory chloride channels can be activated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in normal airway epithelial cells but not in cells from individuals with cystic fibrosis (CF). In excised, inside-out patches of apical membrane of normal human airway cells and airway cells from three patients with CF, the chloride channels exhibited a characteristic outwardly rectifying current-voltage relation and depolarization-induced activation. Channels from normal tissues were activated by both cAMP-dependent protein kinase and protein kinase C. However, chloride channels from CF patients could not be activated by either kinase. Thus, gating of normal epithelial chloride channels is regulated by both cAMP-dependent protein kinase and protein kinase C, and regulation by both kinases is defective in CF.

  16. Etiology of CF: knowns and unknowns.

    PubMed

    Riordan, J R

    1999-01-01

    It is still difficult to rationalize many of the features of CF with mutations in a single gene coding for a protein with one well-established function. The central question to be resolved is whether there are additional functions of CFTR to be discovered which better explain the poorly understood aspects of the molecular pathophysiology. Alternatively, each of the steps between primary chloride channel dysfunction and the different pathological processes must be elucidated. PMID:10093110

  17. Progress in cystic fibrosis and the CF Therapeutics Development Network

    PubMed Central

    Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

    2013-01-01

    Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised. PMID:22960984

  18. Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease

    PubMed Central

    Kaverina, Natalya V.; Eng, Diana G.; Krofft, Ronald D.; Glenn, Sean T.; Duffield, Jeremy S.; Gross, Kenneth W.; Shankland, Stuart J.

    2015-01-01

    Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease. PMID:26062877

  19. Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease.

    PubMed

    Pippin, Jeffrey W; Kaverina, Natalya V; Eng, Diana G; Krofft, Ronald D; Glenn, Sean T; Duffield, Jeremy S; Gross, Kenneth W; Shankland, Stuart J

    2015-08-15

    Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease. PMID:26062877

  20. Pluripotent embryonic stem cells and multipotent adult germline stem cells reveal similar transcriptomes including pluripotency-related genes.

    PubMed

    Meyer, S; Nolte, J; Opitz, L; Salinas-Riester, G; Engel, W

    2010-11-01

    DNA microarray analysis was performed with mouse multipotent adult germline stem cells (maGSCs) and embryonic stem cells (ESCs) from different genetic backgrounds cultured under standard ESC-culture conditions and under differentiation-promoting conditions by the withdrawal of the leukemia inhibitory factor (LIF) and treatment with retinoic acid (RA). The analyzed undifferentiated cell lines are very similar based on their global gene expression pattern and show 97-99% identity dependent on the analyzed background. Only 621 genes are differentially expressed in cells derived from mouse 129SV-background and 72 genes show differences in expression in cells generated from transgenic Stra8-EGFP/Rosa26-LacZ-background. Both maGSCs and ESCs express the same genes involved in the regulation of pluripotency and even show no differences in the expression level of these genes. When comparing maGSCs with previously published signature genes of other pluripotent cell lines, we found that maGSCs shared a very similar gene expression pattern with embryonic germ cells (EGCs). Also after differentiation of maGSCs and ESCs the transcriptomes of the cell lines are nearly identical which suggests that both cell types differentiate spontaneously in a very similar way. This is the first study, at transcriptome level, to compare ESCs and a pluripotent cell line derived from an adult organism (maGSCs). PMID:20624824

  1. Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles.

    PubMed

    Lei, Lei; Spradling, Allan C

    2013-05-21

    Whether or not mammalian females generate new oocytes during adulthood from germ-line stem cells to sustain the ovarian follicle pool has recently generated controversy. We used a sensitive lineage-labeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify active germ-line stem cells. Primordial follicles generated during fetal life are highly stable, with a half-life during adulthood of 10 mo, and thus are sufficient to sustain adult oogenesis without a source of renewal. Moreover, in normal mice or following germ-cell depletion with Busulfan, only stable, single oocytes are lineage-labeled, rather than cell clusters indicative of new oocyte formation. Even one germ-line stem cell division per 2 wk would have been detected by our method, based on the kinetics of fetal follicle formation. Thus, adult female mice neither require nor contain active germ-line stem cells or produce new oocytes in vivo. PMID:23630252

  2. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation.

    PubMed

    Foronda, Miguel; Morgado-Palacin, Lucia; Gómez-López, Gonzalo; Domínguez, Orlando; Pisano, David G; Blasco, Maria A

    2015-12-01

    Adult stem cells (ASCs) reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014). Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013). Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4 (cKO) mice), we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC) activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4 (cKO) mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014). Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155. PMID:26697322

  3. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation

    PubMed Central

    Foronda, Miguel; Morgado-Palacin, Lucia; Gómez-López, Gonzalo; Domínguez, Orlando; Pisano, David G.; Blasco, Maria A.

    2015-01-01

    Adult stem cells (ASCs) reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014). Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013). Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4cKO mice), we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC) activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4cKO mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014). Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155. PMID:26697322

  4. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage

    PubMed Central

    Fernandez Vallone, Valeria; Leprovots, Morgane; Strollo, Sandra; Vasile, Gabriela; Lefort, Anne; Libert, Frederick; Vassart, Gilbert; Garcia, Marie-Isabelle

    2016-01-01

    ABSTRACT Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2+ cells generating gastric spheroids differed from adult glandular Lgr5+ stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5+ stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2+ cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2+ cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program. PMID:26989172

  5. Heterogeneous generation of new cells in the adult echinoderm nervous system

    PubMed Central

    Mashanov, Vladimir S.; Zueva, Olga R.; García-Arrarás, José E.

    2015-01-01

    Adult neurogenesis, generation of new functional cells in the mature central nervous system (CNS), has been documented in a number of diverse organisms, ranging from humans to invertebrates. However, the origin and evolution of this phenomenon is still poorly understood for many of the key phylogenetic groups. Echinoderms are one such phylum, positioned as a sister group to chordates within the monophyletic clade Deuterostomia. They are well known for the ability of their adult organs, including the CNS, to completely regenerate after injury. Nothing is known, however, about production of new cells in the nervous tissue under normal physiological conditions in these animals. In this study, we show that new cells are continuously generated in the mature radial nerve cord (RNC) of the sea cucumber Holothuria glaberrima. Importantly, this neurogenic activity is not evenly distributed, but is significantly more extensive in the lateral regions of the RNC than along the midline. Some of the new cells generated in the apical region of the ectoneural neuroepithelium leave their place of origin and migrate basally to populate the neural parenchyma. Gene expression analysis showed that generation of new cells in the adult sea cucumber CNS is associated with transcriptional activity of genes known to be involved in regulation of various aspects of neurogenesis in other animals. Further analysis of one of those genes, the transcription factor Myc, showed that it is expressed, in some, but not all radial glial cells, suggesting heterogeneity of this CNS progenitor cell population in echinoderms. PMID:26441553

  6. Photoionisation study of Xe.CF4 and Kr.CF4 van-der-Waals molecules

    NASA Astrophysics Data System (ADS)

    Alekseev, V. A.; Garcia, G. A.; Kevorkyants, R.; Nahon, L.

    2016-05-01

    We report on photoionization studies of Xe.CF4 and Kr.CF4 van-der-Waals complexes produced in a supersonic expansion and detected using synchrotron radiation and photoelectron-photoion coincidence techniques. The ionization potential of CF4 is larger than those of the Xe and Kr atoms and the ground state of the Rg.CF4+ ion correlates with Rg+ (2P3/2) + CF4. The onset of the Rg.CF4+ signals was found to be only ˜0.2 eV below the Rg ionization potential. In agreement with experiment, complementary ab initio calculations show that vertical transitions originating from the potential minimum of the ground state of Rg.CF4 terminate at a part of the potential energy surfaces of Rg.CF4+, which are approximately 0.05 eV below the Rg+ (2P3/2) + CF4 dissociation limit. In contrast to the neutral complexes, which are most stable in the face geometry, for the Rg.CF4+ ions, the calculations show that the minimum of the potential energy surface is in the vertex geometry. Experiments which have been performed only with Xe.CF4 revealed no Xe.CF4+ signal above the first ionization threshold of Xe, suggesting that the Rg.CF4+ ions are not stable above the first dissociation limit.

  7. Potential implications of a monosynaptic pathway from mossy cells to adult-born granule cells of the dentate gyrus

    PubMed Central

    Scharfman, Helen E.; Bernstein, Hannah L.

    2015-01-01

    The dentate gyrus (DG) is important to many aspects of hippocampal function, but there are many aspects of the DG that are incompletely understood. One example is the role of mossy cells (MCs), a major DG cell type that is glutamatergic and innervates the primary output cells of the DG, the granule cells (GCs). MCs innervate the GCs as well as local circuit neurons that make GABAergic synapses on GCs, so the net effect of MCs on GCs – and therefore the output of the DG – is unclear. Here we first review fundamental information about MCs and the current hypotheses for their role in the normal DG and in diseases that involve the DG. Then we review previously published data which suggest that MCs are a source of input to a subset of GCs that are born in adulthood (adult-born GCs). In addition, we discuss the evidence that adult-born GCs may support the normal inhibitory ‘gate’ functions of the DG, where the GCs are a filter or gate for information from the entorhinal cortical input to area CA3. The implications are then discussed in the context of seizures and temporal lobe epilepsy (TLE). In TLE, it has been suggested that the DG inhibitory gate is weak or broken and MC loss leads to insufficient activation of inhibitory neurons, causing hyperexcitability. That idea was called the “dormant basket cell hypothesis.” Recent data suggest that loss of normal adult-born GCs may also cause disinhibition, and seizure susceptibility. Therefore, we propose a reconsideration of the dormant basket cell hypothesis with an intervening adult-born GC between the MC and basket cell and call this hypothesis the “dormant immature granule cell hypothesis.” PMID:26347618

  8. Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.

    PubMed

    Onifer, S M; Cannon, A B; Whittemore, S R

    1997-01-01

    Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI

  9. p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus.

    PubMed

    Yoshioka, Kento; Namiki, Kana; Sudo, Tatsuhiko; Kasuya, Yoshitoshi

    2015-01-01

    Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful long-term neurosphere culture of adult mouse hippocampal cells. Expanded neurospheres with high proliferative activity differentiated into the three neuronal lineages under differentiating conditions. Thus, inhibition of p38α can maintain adult hippocampal NSC activity in vitro. PMID:26101740

  10. p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus

    PubMed Central

    Yoshioka, Kento; Namiki, Kana; Sudo, Tatsuhiko; Kasuya, Yoshitoshi

    2015-01-01

    Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful long-term neurosphere culture of adult mouse hippocampal cells. Expanded neurospheres with high proliferative activity differentiated into the three neuronal lineages under differentiating conditions. Thus, inhibition of p38α can maintain adult hippocampal NSC activity in vitro. PMID:26101740

  11. Physicochemical Control of Adult Stem Cell Differentiation: Shedding Light on Potential Molecular Mechanisms

    PubMed Central

    Titushkin, Igor; Sun, Shan; Shin, Jennifer; Cho, Michael

    2010-01-01

    Realization of the exciting potential for stem-cell-based biomedical and therapeutic applications, including tissue engineering, requires an understanding of the cell-cell and cell-environment interactions. To this end, recent efforts have been focused on the manipulation of adult stem cell differentiation using inductive soluble factors, designing suitable mechanical environments, and applying noninvasive physical forces. Although each of these different approaches has been successfully applied to regulate stem cell differentiation, it would be of great interest and importance to integrate and optimally combine a few or all of the physicochemical differentiation cues to induce synergistic stem cell differentiation. Furthermore, elucidation of molecular mechanisms that mediate the effects of multiple differentiation cues will enable the researcher to better manipulate stem cell behavior and response. PMID:20379388

  12. C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence.

    PubMed

    Ye, Min; Zhang, Hong; Amabile, Giovanni; Yang, Henry; Staber, Philipp B; Zhang, Pu; Levantini, Elena; Alberich-Jordà, Meritxell; Zhang, Junyan; Kawasaki, Akira; Tenen, Daniel G

    2013-04-01

    In blood, the transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver haematopoietic stem cells (HSCs). However, its function in adult HSCs has remained unknown. Here, using an inducible knockout model we found that C/EBPa-deficient adult HSCs underwent a pronounced increase in number with enhanced proliferation, characteristics resembling fetal liver HSCs. Consistently, transcription profiling of C/EBPa-deficient HSCs revealed a gene expression program similar to fetal liver HSCs. Moreover, we observed that age-specific Cebpa expression correlated with its inhibitory effect on the HSC cell cycle. Mechanistically we identified N-Myc as a downstream target of C/EBPa, and loss of C/EBPa resulted in de-repression of N-Myc. Our data establish C/EBPa as a central determinant in the switch from fetal to adult HSCs. PMID:23502316

  13. Functional Myotube Formation from Adult Rat Satellite Cells in a Defined Serum-free System

    PubMed Central

    McAleer, Christopher W.; Rumsey, John W.; Stancescu, Maria; Hickman, James J.

    2016-01-01

    This manuscript describes the development of a culture system whereby mature contracting myotubes were formed from adult rat derived satellite cells. Satellite cells, extracted from the Tibialis Anterior (TA) of adult rats, were grown in defined serum-free growth and differentiation media, on a non-biological substrate, N-1[3-trimethoxysilyl propyl] diethylenetriamine. Myotubes were evaluated morphologically and immunocytochemically, using MyHC specific antibodies, as well as functionally using patch clamp electrophysiology to measure ion channel activity. Results indicated the establishment of the rapid expression of adult myosin isoforms that contrasts to their slow development in embryonic cultures. This culture system has applications in the understanding and treatment of age related muscle myopathy, muscular dystrophy, and for skeletal muscle engineering by providing a more relevant phenotype for both in vitro and in vivo applications. PMID:25683642

  14. Targeted B cell therapies in the treatment of adult and pediatric systemic lupus erythematosus.

    PubMed

    Hui-Yuen, J S; Nguyen, S C; Askanase, A D

    2016-09-01

    Belimumab (Benlysta) is a fully-humanized monoclonal antibody that inhibits B-lymphocyte stimulator (also known as B cell activating factor) and was approved by the U.S. Federal Drug Administration and European Medicines Evaluation Agency for treatment in adults with autoantibody-positive systemic lupus erythematosus (SLE). Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody targeting B lymphocytes. This review discusses the key findings of the phase III trials in adults with SLE and of real-world use of belimumab and rituximab in the care of both adult and pediatric SLE patients. It highlights the safety profile of belimumab and rituximab and gives insight into the consideration of these therapies for specific SLE disease states. It concludes with a discussion of the current clinical trials investigating B cell therapies in specific SLE disease states and a look to the future, with ongoing clinical trials. PMID:27497253

  15. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes.

    PubMed Central

    Overturf, K.; al-Dhalimy, M.; Ou, C. N.; Finegold, M.; Grompe, M.

    1997-01-01

    Previous work has shown that adult mouse hepatocytes can divide at least 18 times in vivo. To test whether this represents the upper limit of their regenerative capacity, we performed serial transplantation of hepatocytes in the fumarylacetoacetate hydrolase deficiency murine model of liver repopulation. Hepatocytes from adult donors were serially transplanted in limiting numbers six times and resulted in complete repopulation during each cycle. This corresponds to a minimal number of 69 cell doublings or a 7.3 x 10(20)-fold expansion. No evidence for abnormal liver function or altered hepatic architecture was found in repopulated animals. We conclude that a fraction of adult mouse hepatocytes have growth potential similar to that of hematopoietic stem cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9358753

  16. The spectrum of renal cell carcinoma in adults.

    PubMed

    Ananthakrishnan, Lakshmi; Kapur, Payal; Leyendecker, John R

    2016-06-01

    The spectrum of renal cell carcinoma (RCC) includes many neoplasms with distinct cytogenetics, biologic behaviors, and imaging appearances. The advent of molecular therapies targeting different tumor types, new insights into the relative roles of biopsy and surveillance for small incidental tumors, and a growing array of nephron-sparing interventions have altered management of RCC. Similarly, the role of the radiologist is changing, and it is becoming increasingly important for radiologists to familiarize themselves with the various types of RCC. This article introduces the reader to the common and uncommon recognized types of renal cell carcinoma and discusses how these neoplasms differ in imaging appearance and behavior. PMID:27108133

  17. Isolating Intestinal Stem Cells from Adult Drosophila Midguts by FACS to Study Stem Cell Behavior During Aging

    PubMed Central

    Pandur, Petra

    2014-01-01

    Aging tissue is characterized by a continuous decline in functional ability. Adult stem cells are crucial in maintaining tissue homeostasis particularly in tissues that have a high turnover rate such as the intestinal epithelium. However, adult stem cells are also subject to aging processes and the concomitant decline in function. The Drosophila midgut has emerged as an ideal model system to study molecular mechanisms that interfere with the intestinal stem cells’ (ISCs) ability to function in tissue homeostasis. Although adult ISCs can be easily identified and isolated from midguts of young flies, it has been a major challenge to study endogenous molecular changes of ISCs during aging. This is due to the lack of a combination of molecular markers suitable to isolate ISCs from aged intestines. Here we propose a method that allows for successful dissociation of midgut tissue into living cells that can subsequently be separated into distinct populations by FACS. By using dissociated cells from the esg-Gal4, UAS-GFP fly line, in which both ISCs and the enteroblast (EB) progenitor cells express GFP, two populations of cells are distinguished based on different GFP intensities. These differences in GFP expression correlate with differences in cell size and granularity and represent enriched populations of ISCs and EBs. Intriguingly, the two GFP-positive cell populations remain distinctly separated during aging, presenting a novel technique for identifying and isolating cell populations enriched for either ISCs or EBs at any time point during aging. The further analysis, for example transcriptome analysis, of these particular cell populations at various time points during aging is now possible and this will facilitate the examination of endogenous molecular changes that occur in these cells during aging. PMID:25548862

  18. Experimental allergic encephalomyelitis: effect of neonatal exposure to neuroantigen or neuroantigen immune cells on subsequent reactivity as adults.

    PubMed

    Willenborg, D O; Danta, G

    1985-01-01

    Neonatal Lewis rats are resistant to both active induction of EAE with neuroantigen and passive induction by transfer of immune cells. Actively sensitized neonates are, as adults, resistant to further active induction of disease, but are susceptible to passive induction with immune cells. Passively sensitized neonates are susceptible to active and passive disease as adults. In fact, actively sensitized adult animals which had received immune cells as neonates develop EAE much sooner than control animals, suggesting a memory response and the persistence of the transferred cells in the host. The cells persist for at least six months and these animals might be considered to be inapparent carriers of autoimmune disease. PMID:3843222

  19. Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins.

    PubMed

    Schuijers, Jurian; Clevers, Hans

    2012-06-13

    After its discovery as oncogen and morphogen, studies on Wnt focused initially on its role in animal development. With the finding that the colorectal tumour suppressor gene APC is a negative regulator of the Wnt pathway in (colorectal) cancer, attention gradually shifted to the study of the role of Wnt signalling in the adult. The first indication that adult Wnt signalling controls stem cells came from a Tcf4 knockout experiment: mutant mice failed to build crypt stem cell compartments. This observation was followed by similar findings in multiple other tissues. Recent studies have indicated that Wnt agonists of the R-spondin family provide potent growth stimuli for crypts in vivo and in vitro. Independently, Lgr5 was found as an exquisite marker for these crypt stem cells. The story has come full circle with the finding that the stem cell marker Lgr5 constitutes the receptor for R-spondins and occurs in complex with Frizzled/Lrp. PMID:22617424

  20. Otic Langerhans' Cell Histiocytosis in an Adult: A Case Report and Review of the Literature

    PubMed Central

    Gungadeen, Anil; Kullar, Peter; Yates, Philip

    2013-01-01

    Objective. To present a case of otic Langerhans' cell histiocytosis in an adult. Also included the diagnosis and management of the condition and a review of the relevant literature. Case Report. We report a case of a 41-year-old man with a history of persistent unilateral ear discharge associated with an aural polyp. Radiological imaging showed bony lesions of the skull and a soft-tissue mass within the middle ear. Histological analysis of the polyp demonstrated Langerhans' cell histiocytosis. His otological symptoms were completely resolved with the systemic therapy. Conclusions. Otic Langerhans' cell histiocytosis can present in adults. Persistent ear symptoms along with evidence of soft-tissue masses within the ear and bony lesions of the skull or elsewhere should prompt the otolaryngologists to include Langerhans' cell histiocytosis in their differential diagnosis. Management should be with systemic therapy rather than local surgical treatment. PMID:23762704

  1. Inverse relationship between adult hippocampal cell proliferation and synaptic rewiring in the dentate gyrus.

    PubMed

    Butz, Markus; Teuchert-Noodt, Gertraud; Grafen, Keren; van Ooyen, Arjen

    2008-01-01

    Adult neurogenesis is a key feature of the hippocampal dentate gyrus (DG). Neurogenesis is accompanied by synaptogenesis as new cells become integrated into the circuitry of the hippocampus. However, little is known to what extent the embedding of new neurons rewires the pre-existing network. Here we investigate synaptic rewiring in the DG of gerbils (Meriones unguiculatus) under different rates of adult cell proliferation caused by different rearing conditions as well as juvenile methamphetamine treatment. Surprisingly, we found that an increased cell proliferation reduced the amount of synaptic rewiring. To help explain this unexpected finding, we developed a novel model of dentate network formation incorporating neurogenesis and activity-dependent synapse formation and remodelling. In the model, we show that homeostasis of neuronal activity can account for the inverse relationship between cell proliferation and synaptic rewiring. PMID:18481284

  2. Genetic inactivation of Cdk7 leads to cell cycle arrest and induces premature aging due to adult stem cell exhaustion

    PubMed Central

    Ganuza, Miguel; Sáiz-Ladera, Cristina; Cañamero, Marta; Gómez, Gonzalo; Schneider, Ralph; Blasco, María A; Pisano, David; Paramio, Jesús M; Santamaría, David; Barbacid, Mariano

    2012-01-01

    Cyclin-dependent kinase (Cdk)7, the catalytic subunit of the Cdk-activating kinase (CAK) complex has been implicated in the control of cell cycle progression and of RNA polymerase II (RNA pol II)-mediated transcription. Genetic inactivation of the Cdk7 locus revealed that whereas Cdk7 is completely dispensable for global transcription, is essential for the cell cycle via phosphorylation of Cdk1 and Cdk2. In vivo, Cdk7 is also indispensable for cell proliferation except during the initial stages of embryonic development. Interestingly, widespread elimination of Cdk7 in adult tissues with low proliferative indexes had no phenotypic consequences. However, ablation of conditional Cdk7 alleles in tissues with elevated cellular turnover led to the efficient repopulation of these tissues with Cdk7-expressing cells most likely derived from adult stem cells that may have escaped the inactivation of their targeted Cdk7 alleles. This process, a physiological attempt to maintain tissue homeostasis, led to the attrition of adult stem cell pools and to the appearance of age-related phenotypes, including telomere shortening and early death. PMID:22505032

  3. Targeted Therapies in Adult B-Cell Malignancies

    PubMed Central

    Rossi, Jean-François

    2015-01-01

    B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted or common surface markers, activation of cellular pathways that regulate cell cycle, metabolism, proteasome activity, and protein synthesis. All molecules involved in these different cellular mechanisms are potent therapeutic targets. Nowadays, due to the progress of the biology, more and more targeted drugs are identified, a situation that is correlated with an extended field of the targeted therapy. The full knowledge of the cellular machinery and cell-cell communication allows making the best choice to treat patients, in the context of personalized medicine. Also, focus should not be restricted to the immediate effects observed as clinical endpoints, that is, response rate, survival markers with conventional statistical methods, but it should consider the prediction of different clinical consequences due to other collateral drug targets, based on new methodologies. This means that new reflection and new bioclinical follow-up have to be monitored, particularly with the new drugs used with success in B-cell malignancies. This review discussed the principal aspects of such evident bioclinical progress. PMID:26425544

  4. Ion-molecule reactions with CF3 radical

    NASA Astrophysics Data System (ADS)

    Miller, Thomas M.; Shuman, Nicholas S.; Wiens, Justin P.; Sawyer, Jordan C.; Martinez, Oscar, Jr.; Ard, Shaun G.; Viggiano, Albert A.

    2015-09-01

    The first measurements of reaction rate coefficients and products are reported for reactions of the radical CF3 with Ar+, Xe+, O2+,NO+, CO2+,and C2F5+,at 300 K. The work was carried out in a fast flow of typically 1.5 Torr helium buffer gas (4% argon) using the variable electron and neutral density attachment mass spectrometry (VENDAMS) technique. CF3 was produced via dissociative electron attachment to CF3I, resulting in CF3 concentrations that were well-quantified because the plasma diffusion rate, the electron concentration, and the rate coefficient for attachment to CF3I were separately measured in the experiment. The Ar+ + CF3 reaction was found to proceed at nearly the calculated collisional rate coefficient, yielding 90% CF2+along with CF3+.Reaction of CF3 with C2F5+is slower and yields 75% C2F4+along with CF3+.CF3 undergoes charge transfer reaction with Xe+, O2+,NO+, and CO2+,yielding CF3+.Arguments will be made regarding reaction mechanisms, including the role of spin conservation. Comparisons with Ar+ and O2+reaction with CH3 will be made. Supported by Air Force Office of Scientific Research, AFOSR-2303EP.

  5. Functions of an Adult Sickle Cell Group: Education, Task Orientation, and Support.

    ERIC Educational Resources Information Center

    Butler, Dennis J.; Beltran, Lou R.

    1993-01-01

    Reports on development of adult sickle cell support group and provides description of psychosocial factors most prevalent in patients' lives (anxiety about death, disruption of social support network, disability, dependence on pain medication, conflicts with health care providers). Notes that support group enhanced participants' knowledge about…

  6. Stress, Coping, and Psychological Adjustment of Adults with Sickle Cell Disease.

    ERIC Educational Resources Information Center

    Thompson, Robert J., Jr.; And Others

    1992-01-01

    Examined psychological adjustment to sickle cell disease (SCD) among 109 African-American adults. Good psychological adjustment was associated with lower levels of perceived daily stress and stress regarding SCD illness tasks, higher efficacy expectations, less use of palliative coping methods and negative thinking/passive adherence pain-coping…

  7. β1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells.

    PubMed

    Brooker, Sarah M; Bond, Allison M; Peng, Chian-Yu; Kessler, John A

    2016-07-01

    Integrins are transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions. The β1-integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that β1-integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny. Although NSCs in the hippocampal subgranular zone (SGZ) normally only infrequently differentiate into astrocytes, deletion of β1-integrin significantly enhanced astrocyte differentiation. Ablation of β1-integrin also led to reduced neurogenesis as well as depletion of the radial NSC population. Activation of integrin-linked kinase (ILK) in cultured adult NSCs from β1-integrin knockout mice reduced astrocyte differentiation, suggesting that at least some of the inhibitory effects of β1-integrin on astrocytic differentiation are mediated through ILK. In addition, β1-integrin conditional knockout also resulted in extensive cellular disorganization of the SGZ as well as non-neurogenic regions of the DG. The effects of β1-integrin ablation on DG structure and astrogliogenesis show sex-specific differences, with the effects following a substantially slower time-course in males. β1-integrin thus plays a dual role in maintaining the adult hippocampal NSC population by supporting the structural integrity of the NSC niche and by inhibiting astrocytic lineage commitment. GLIA 2016;64:1235-1251. PMID:27145730

  8. Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells.

    PubMed

    Chen, Yinyin; Huang, Kevin; Nakatsu, Martin N; Xue, Zhigang; Deng, Sophie X; Fan, Guoping

    2013-04-01

    The corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs), which is essential for maintaining corneal transparency. To better characterize CECs in different developmental stages, we profiled mRNA transcriptomes in human fetal and adult corneal endothelium with the goal to identify novel molecular markers in these cells. By comparing CECs with 12 other tissue types, we identified 245 and 284 signature genes that are highly expressed in fetal and adult CECs, respectively. Functionally, these genes are enriched in pathways characteristic of CECs, including inorganic anion transmembrane transporter, extracellular matrix structural constituent and cyclin-dependent protein kinase inhibitor activity. Importantly, several of these genes are disease target genes in hereditary corneal dystrophies, consistent with their functional significance in CEC physiology. We also identified stage-specific markers associated with CEC development, such as specific members in the transforming growth factor beta and Wnt signaling pathways only expressed in fetal, but not in adult CECs. Lastly, by the immunohistochemistry of ocular tissues, we demonstrated the unique protein localization for Wnt5a, S100A4, S100A6 and IER3, the four novel markers for fetal and adult CECs. The identification of a new panel of stage-specific markers for CECs would be very useful for characterizing CECs derived from stem cells or ex vivo expansion for cell replacement therapy. PMID:23257286

  9. Quiescent adult neural stem cells are exceptionally sensitive to cosmic radiation

    PubMed Central

    Encinas, Juan M.; Vazquez, Marcelo E.; Switzer, Robert C.; Chamberland, Dennis W.; Nick, Harry; Levine, Howard G.; Scarpa, Philip J.; Enikolopov, Grigori; Steindler, Dennis A.

    2012-01-01

    Generation of new neurons in the adult brain, a process that is likely to be essential for learning, memory, and mood regulation, is impaired by radiation. Therefore, radiation exposure might have not only such previously expected consequences as increased probability of developing cancer, but might also impair cognitive function and emotional stability. Radiation exposure is encountered in settings ranging from cancer therapy to space travel; evaluating the neurogenic risks of radiation requires identifying the at-risk populations of stem and progenitor cells in the adult brain. Here we have used a novel reporter mouse line to find that early neural progenitors are selectively affected by conditions simulating the space radiation environment. This is reflected both in a decrease in the number of these progenitors in the neurogenic regions and in an increase in the number of dying cells in these regions. Unexpectedly, we found that quiescent neural stem cells, rather than their rapidly dividing progeny, are most sensitive to radiation. Since these stem cells are responsible for adult neurogenesis, their death would have a profound impact on the production of new neurons in the irradiated adult brain. Our finding raises an important concern about cognitive and emotional risks associated with radiation exposure. PMID:18076878

  10. CF102 an A3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

    PubMed Central

    COHEN, S.; STEMMER, S.M.; ZOZULYA, G.; OCHAION, A.; PATOKA, R.; BARER, F.; BAR-YEHUDA, S.; RATH-WOLFSON, L.; JACOBSON, K.A.; FISHMAN, P.

    2012-01-01

    The Gi protein-associated A3 adenosine receptor (A3AR) is a member of the adenosine receptor family. Selective agonists at the A3AR, such as CF101 and CF102 were found to induce anti-inflammatory and anti-cancer effects. In this study, we examined the differential effect of CF102 in pathological conditions of the liver. The anti-inflammatory protective effect of CF101 was tested in a model of liver inflammation induced by Concanavalin A (Con. A) and the anti-cancer effect of CF102 was examined in vitro and in a xenograft animal model utilizing Hep-3B hepatocellular carcinoma (HCC) cells. The mechanism of action was explored by following the expression levels of key signaling proteins in the inflamed and tumor liver tissues, utilizing Western blot (WB) analysis. In the liver inflammation model, CF102 (100 μg/kg) markedly reduced the secretion of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase in comparison to the vehicle-treated group. Mechanistically, CF102 treatment decreased the expression level of phosphorylated glycogen synthase kinase-3β, NF-κB, and TNF-α and prevented apoptosis in the liver. This was demonstrated by decreased expression levels of Fas receptor (FasR) and of the pro-apoptotic proteins Bax and Bad in liver tissues. In addition, CF102-induced apoptosis of Hep-3B cells both in vitro and in vivo via de-regulation of the PI3K-NF-κB signaling pathway, resulting in up-regulation of pro-apoptotic proteins. Taken together, CF102 acts as a protective agent in liver inflammation and inhibits HCC tumor growth. These results suggest that CF102 through its differential effect is a potential drug candidate to treat various pathological liver conditions. PMID:21660967

  11. CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver.

    PubMed

    Cohen, S; Stemmer, S M; Zozulya, G; Ochaion, A; Patoka, R; Barer, F; Bar-Yehuda, S; Rath-Wolfson, L; Jacobson, K A; Fishman, P

    2011-09-01

    The Gi protein-associated A(3) adenosine receptor (A(3) AR) is a member of the adenosine receptor family. Selective agonists at the A(3) AR, such as CF101 and CF102 were found to induce anti-inflammatory and anti-cancer effects. In this study, we examined the differential effect of CF102 in pathological conditions of the liver. The anti-inflammatory protective effect of CF101 was tested in a model of liver inflammation induced by Concanavalin A (Con. A) and the anti-cancer effect of CF102 was examined in vitro and in a xenograft animal model utilizing Hep-3B hepatocellular carcinoma (HCC) cells. The mechanism of action was explored by following the expression levels of key signaling proteins in the inflamed and tumor liver tissues, utilizing Western blot (WB) analysis. In the liver inflammation model, CF102 (100 µg/kg) markedly reduced the secretion of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase in comparison to the vehicle-treated group. Mechanistically, CF102 treatment decreased the expression level of phosphorylated glycogen synthase kinase-3β, NF-κB, and TNF-α and prevented apoptosis in the liver. This was demonstrated by decreased expression levels of Fas receptor (FasR) and of the pro-apoptotic proteins Bax and Bad in liver tissues. In addition, CF102-induced apoptosis of Hep-3B cells both in vitro and in vivo via de-regulation of the PI3K-NF-κB signaling pathway, resulting in up-regulation of pro-apoptotic proteins. Taken together, CF102 acts as a protective agent in liver inflammation and inhibits HCC tumor growth. These results suggest that CF102 through its differential effect is a potential drug candidate to treat various pathological liver conditions. PMID:21660967

  12. Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone.

    PubMed

    Calzolari, Filippo; Michel, Julia; Baumgart, Emily Violette; Theis, Fabian; Götz, Magdalena; Ninkovic, Jovica

    2015-04-01

    We analyzed the progeny of individual neural stem cells (NSCs) of the mouse adult subependymal zone (SEZ) in vivo and found a markedly fast lineage amplification, as well as limited NSC self-renewal and exhaustion in a few weeks. We further unraveled the mechanisms of neuronal subtype generation, finding that a higher proportion of NSCs were dedicated to generate deep granule cells in the olfactory bulb and that larger clones were produced by these NSCs. PMID:25730673

  13. Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro

    PubMed Central

    Sintov, Elad; Nathan, Gili; Knoller, Sarah; Pasmanik-Chor, Metsada; Russ, Holger A.; Efrat, Shimon

    2015-01-01

    In-vitro expansion of functional adult human β-cells is an attractive approach for generating insulin-producing cells for transplantation. However, human islet cell expansion in culture results in loss of β-cell phenotype and epithelial-mesenchymal transition (EMT). This process activates expression of ZEB1 and ZEB2, two members of the zinc-finger homeobox family of E-cadherin repressors, which play key roles in EMT. Downregulation of ZEB1 using shRNA in expanded β-cell-derived (BCD) cells induced mesenchymal-epithelial transition (MET), β-cell gene expression, and proliferation attenuation. In addition, inhibition of ZEB1 expression potentiated redifferentiation induced by a combination of soluble factors, as judged by an improved response to glucose stimulation and a 3-fold increase in the fraction of C-peptide-positive cells to 60% of BCD cells. Furthermore, ZEB1 shRNA led to increased insulin secretion in cells transplanted in vivo. Our findings suggest that the effects of ZEB1 inhibition are mediated by attenuation of the miR-200c target genes SOX6 and SOX2. These findings, which were reproducible in cells derived from multiple human donors, emphasize the key role of ZEB1 in EMT in cultured BCD cells and support the value of ZEB1 inhibition for BCD cell redifferentiation and generation of functional human β-like cells for cell therapy of diabetes. PMID:26264186

  14. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    PubMed

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. PMID:26851220

  15. Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis.

    PubMed

    Shin, Jaehoon; Berg, Daniel A; Zhu, Yunhua; Shin, Joseph Y; Song, Juan; Bonaguidi, Michael A; Enikolopov, Grigori; Nauen, David W; Christian, Kimberly M; Ming, Guo-li; Song, Hongjun

    2015-09-01

    Somatic stem cells contribute to tissue ontogenesis, homeostasis, and regeneration through sequential processes. Systematic molecular analysis of stem cell behavior is challenging because classic approaches cannot resolve cellular heterogeneity or capture developmental dynamics. Here we provide a comprehensive resource of single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny. We further developed Waterfall, a bioinformatic pipeline, to statistically quantify singe-cell gene expression along a de novo reconstructed continuous developmental trajectory. Our study reveals molecular signatures of adult qNSCs, characterized by active niche signaling integration and low protein translation capacity. Our analyses further delineate molecular cascades underlying qNSC activation and neurogenesis initiation, exemplified by decreased extrinsic signaling capacity, primed translational machinery, and regulatory switches in transcription factors, metabolism, and energy sources. Our study reveals the molecular continuum underlying adult neurogenesis and illustrates how Waterfall can be used for single-cell omics analyses of various continuous biological processes. PMID:26299571

  16. Ternary Fission of {sup 249}Cf(n,f) and {sup 250}Cf(SF)

    SciTech Connect

    University of Gent, B-9000 Gent, Belgium; CEA Cadarache, F-13108 Saint-Paul-lez-Durance, France; Institute Laue-Langevin, F-38042 Grenoble, France; EC-JRC Institute for Reference Materials and Measurements, B-2440 Geel, Belgium; Wadsworth Center, New York State Department of Health, Albany NY 12201, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Vermote, S.; Wagemans, C.; Serot, O.; Soldner, T.; Geltenbort, P.; Gils, J. Van; Almahamid, I.; Tian, G.; Rao, L.

    2011-09-01

    During the last years, several Cm and Cf isotopes have been studied by our research group in the frame of a systematic investigation of gas emission characteristics in ternary fission. Here we report on new results on the energy distribution and the emission probability of {sup 3}H, {sup 4}He and {sup 6}He particles emitted in the spontaneous ternary fission of {sup 250}Cf (E{sub exc} = 0 MeV) and in the neutron induced ternary fission of {sup 249}Cf (E{sub exc} = 6.625 MeV). Both measurements were performed using suited and well-calibrated ΔE-E telescope detectors, at the IRMM (Geel, Belgium) for the spontaneous fission and at the very intense neutron beam PF1b at the Institute Laue-Langevin (Grenoble, France) for the neutron induced fission measurement. In this way, the existing database can be enlarged with new results for Z=98 isotopes, which is important for the systematic investigation. Moreover, the investigation of the 'isotope couple' {sup 249}Cf(n,f) - {sup 250}Cf(SF), together with corresponding data for other isotopes, will yield valuable information on the influence of the excitation energy on the particle emission probabilities.

  17. Constitutive properties of adult mammalian cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

    1998-01-01

    BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

  18. Rh2(CF3CONH)4: The First Biological Assays of a Rhodium (II) Amidate

    PubMed Central

    Zyngier, Szulim Ber; de Souza, Aparecido Ribeiro; Najjar, Renato

    1997-01-01

    The rhodium (II) complexes Rh2(tfa)4.2(tfac) and Rh2(tfacam)4 (tfacam = CF3CONH-,tfa = CF3COO-,tfac = CF3CONH2) were synthesized and characterized by microanalysis and electronic and vibrational spectroscopies. Rh2(tfacam)4 was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra-amidate to have its biological activity evaluated. The LD50 value for Rh2(tfacam)4 is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects. PMID:18475814

  19. Quantitative analysis of signaling mechanisms controlling adult neural progenitor cell proliferation.

    PubMed

    Schaffer, David V; O'Neill, Analeah; Hochrein, Lisa; McGranahan, Tresa

    2004-01-01

    Tools of systems engineering and signal dynamics were employed to develop a quantitative model of the intracellular signaling systems involved in adult neural stem cell proliferation, based on pathways elucidated in our experimental systems. Neural progenitors isolated from the adult rat hippocampus are dependent on the basic fibroblast growth factor (FGF-2) and extracellular matrix (ECM) proteins. However, the intracellular effects of these stimuli were previously undetermined. We employed chemical inhibitors of known signal transduction molecules to identify important players in the FGF-2/ECM signal cascade, such as the cyclic AMP responsive element binding protein (CREB), protein kinase B/Akt, and several related molecules. Genetic mutants of these proteins were used to confirm their role in adult neural progenitor proliferation. Proliferation was assayed using the incorporation of a thymidine analog to determine cell doubling rate under various stimuli. Such assays have also uncovered novel synergistic signaling between FGF-2 and ECM components. This research is, to our knowledge, the first to elucidate intracellular signaling pathways for adult neural stem cell proliferation. Upon determination of the pertinent intracellular signaling pathways, quantitative immunoblots were employed to examine the dynamics of these systems. These data, as well as enzyme kinetics information from the literature, are being used to parameterize a dynamic mathematical model of progenitor proliferation events induced by FGF-2. This computational model will be used to predict the biochemical and mechanical signaling inputs necessary to achieve a desired proliferative output from the cells, based on specific extracellular stimuli. It is our hope that this essential quantitative understanding will facilitate the use of adult neural stem cells in medical applications. PMID:17271428

  20. Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review of the literature

    PubMed Central

    Majchrzak, Ewa; Szybiak, Bartosz; Wegner, Anna; Pienkowski, Piotr; Pazdrowski, Jakub; Luczewski, Lukasz; Sowka, Marcin; Golusinski, Pawel; Malicki, Julian; Golusinski, Wojciech

    2014-01-01

    Background Head and neck squamous cell carcinoma (HNSCC) is a disease of middle-aged to elderly adults. However, an increased incidence of HNSCC in young people under 45 years of age has been reported recently. In the present review, we focused on the epidemiology and aetiology of HNSCC in adults under 45 years of age. Methods We reviewed literature related to HNSCC in adult patients less than 45 years of age and discussed current treatment options and prognosis. Results HNSCC in young adults is associated with a higher incidence rate in nonsmokers, lower female-to-male ratio, a higher percentage of oral cavity and oropharynx tumours, and fewer second primary tumours. However, aside from traditional risk factors of tobacco and alcohol exposure, the causes of these cancers in young adults remain unclear. Agents that might contribute to risk include infection with high-risk human papillomavirus subtypes as well as genetic factors or immunodeficiency status. The expected increase in incidence and mortality of the young with HNSCC may become a major public health concern if current trends persist, particularly lifestyle habits that may contribute to this disease. Conclusions Given the younger age and potential long-term adverse sequelae of traditional HNSCC treatments, young adults should be treated on a case-by-case basis and post-therapy quality of life must be considered in any treatment-decision making process. PMID:24587773

  1. A Biopsychosocial-Spiritual Model of Chronic Pain in Adults with Sickle Cell Disease

    PubMed Central

    Taylor, Lou Ella V.; Stotts, Nancy A.; Humphreys, Janice; Treadwell, Marsha J.; Miaskowski, Christine

    2011-01-01

    Chronic pain in adults with sickle cell disease (SCD) is a complex multidimensional experience that includes biological, psychological, sociological, and spiritual factors. To date, three models of pain associated with SCD (i.e., biomedical model; biopsychosocial model for SCD pain; Health Belief Model) are published. The biopsychosocial (BPS) multidimensional approach to chronic pain developed by Turk and Gatchel is a widely used model of chronic pain. However, this model has not been applied to chronic pain associated with SCD. In addition, a spiritual/religious dimension is not included in this model. Because spirituality/religion is central to persons affected by SCD, this dimension needs to be added to any model of chronic pain in adults with SCD. In fact, data from one study suggest that spirituality/religiosity is associated with decreased pain intensity in adults with chronic pain from SCD. A BPS-Spiritual model is proposed for adults with chronic pain from SCD since it embraces the whole person. This model includes the biological, psychological, sociological, and spiritual factors relevant to adults with SCD based on past and current research. The purpose of this paper is to describe an adaptation of Turk and Gatchel’s model of chronic pain for adults with SCD and to summarize research findings that support each component of the revised model (i.e., biological, psychological, sociological, spiritual). The paper concludes with a discussion of implications for the use of this model in research. PMID:24315252

  2. Process of allogeneic hematopoietic cell transplantation decision making for older adults.

    PubMed

    Randall, J; Keven, K; Atli, T; Ustun, C

    2016-05-01

    Allogeneic hematopoietic cell transplantation (alloHCT) may be the only curative option for some older adults with hematologic malignancies, and its associated risks of significant morbidity and mortality warrant a clear, informed decision-making process. As older adults have not been transplanted routinely until recent years, younger people have been the prototypical group around whom the current process has developed. Yet, this process is applied to older adults who have different considerations than younger patients when making their transplant decision. Older adults do not have the open-ended lives of younger patients and are entitled to consider how to spend their remaining time. They also possess maturity and experience, and with proper knowledge, they can make informed choices rather than moving forward in the transplant process unaware. Notably, older patients face similar problems with the informed decision-making process in nephrology. Strategies such as providing education about alloHCT gradually and repeatedly during induction, presenting recent knowledge from the literature in plain language, and utilizing a team approach to patient education may help older adults make the best decision about transplant in light of their situation and values. Understanding when and how older adults decide on alloHCT is an important first step to further exploring this problem. PMID:26457910

  3. BDNF increases BrdU-IR cells in the injured adult zebra finch hippocampus.

    PubMed

    Lucas, Nikola N; Lee, Diane W

    2009-08-01

    Steroid-mediated cell proliferation, differentiation, and survival can be triggered by learning, experience, and brain injury. In the uninjured canary song system, testosterone induces cell proliferation that is blocked by an antibody to brain-derived neurotrophic factor (BDNF). However, little is known with regard to the effects of neurotrophic factors on injury-induced cell proliferation and incorporation. To address this, adult male zebra finches received bilateral hippocampal lesions by infusing saline into one hemisphere and BDNF into the other. BrdU (2-bromo-5-deoxyuridine) was then injected to label mitotic cells. A greater number of BrdU-immunoreactive (BrdU-IR) cells were observed in the BDNF-treated hemisphere in the hippocampus, but not in the septum or stem cell-rich subventricular zone, indicating that BDNF promoted localized cell proliferation and incorporation at the injury site only. PMID:19512953

  4. All the adult stem cells, where do they all come from? An external source for organ-specific stem cell pools.

    PubMed

    Nardi, N B

    2005-01-01

    Stem cells can self-renew and maintain the ability to differentiate into mature lineages. Whereas the "stemness" of embryonic stem cells is not discussed, the primitiveness of a stem cell type within adult organisms is not well determined. Data presently available are either inconclusive or controversial regarding two main topics: maintenance or senescente of the adult stem cell pool; and pluripotentiality of the cells. While programmed senescence or apoptosis following uncorrected mutations represent no problem for mature cells, the maintenance of the stem cell pool itself must be assured. Two different mechanisms can be envisaged for that. In the first mechanism, which is generally accepted, stem cells originate during ontogeny along with the organ which they are responsible for, and remain there during all the lifespan of the organism. Several observations derived from recent reports allow the suggestion of a second mechanism. These observations include: organ-specific stem cells are senescent; adult stem cells circulate in the organism; stem cell niches are essential for the existence and function of stem cells; adult stem cells can present lineage markers; embryo-like, pluripotent stem cells are present in adult organisms, as shown by the development of teratomas, tumors composed of derivatives of the three germ layers; and the fact that the gonads may be a reservoir of embryo-like, pluripotent stem cells in adult organisms. The second mechanism for the maintenance of adult stem cells compartments implies a source external to the organ they belong, consisting of pluripotent, embryo-like cells of unrestricted life span, presenting efficient mechanisms for avoiding or correcting mutations and capable to circulate in the organism. According to this model, primitive stem cells exist in a specific organ in adult organisms. They undergo asymmetrical divisions, which originate one "true" stem cell and another one which enters the pool of adult stem cells, circulating

  5. 75 FR 22693 - Airworthiness Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ...-7756; fax: (781) 238-7199. SUPPLEMENTARY INFORMATION: On January 8, 2010 (75 FR 1017), we published a final rule AD, FR Doc. E9-31274, in the Federal Register. That AD applies to GE CF34-1A, CF34-3A, and...; AD 2010-01-04] RIN 2120-AA64 Airworthiness Directives; General Electric Company (GE) CF34-1A,...

  6. Prenatal immune activation alters hippocampal place cell firing characteristics in adult animals.

    PubMed

    Wolff, Amy R; Bilkey, David K

    2015-08-01

    Prenatal maternal immune activation (MIA) is a risk factor for several developmental neuropsychiatric disorders, including autism, bipolar disorder and schizophrenia. Adults with these disorders display alterations in memory function that may result from changes in the structure and function of the hippocampus. In the present study we use an animal model to investigate the effect that a transient prenatal maternal immune activation episode has on the spatially-modulated firing activity of hippocampal neurons in adult animals. MIA was induced in pregnant rat dams with a single injection of the synthetic cytokine inducer polyinosinic:polycytidylic acid (poly I:C) on gestational day 15. Control dams were given a saline equivalent. Firing activity and local field potentials (LFPs) were recorded from the CA1 region of the adult male offspring of these dams as they moved freely in an open arena. Most neurons displayed characteristic spatially-modulated 'place cell' firing activity and while there was no between-group difference in mean firing rate between groups, place cells had smaller place fields in MIA-exposed animals when compared to control-group cells. Cells recorded in MIA-group animals also displayed an altered firing-phase synchrony relationship to simultaneously recorded LFPs. When the floor of the arena was rotated, the place fields of MIA-group cells were more likely to shift in the same direction as the floor rotation, suggesting that local cues may have been more salient for these animals. In contrast, place fields in control group cells were more likely to shift firing position to novel spatial locations suggesting an altered response to contextual cues. These findings show that a single MIA intervention is sufficient to change several important characteristics of hippocampal place cell activity in adult offspring. These changes could contribute to the memory dysfunction that is associated with MIA, by altering the encoding of spatial context and by

  7. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  8. A mystery unraveled: nontumorigenic pluripotent stem cells in human adult tissues

    PubMed Central

    Simerman, Ariel A; Perone, Marcelo J; Gimeno, María L; Dumesic, Daniel A; Chazenbalk, Gregorio D

    2014-01-01

    Introduction: Embryonic stem cells and induced pluripotent stem cells have emerged as the gold standard of pluripotent stem cells and the class of stem cell with the highest potential for contribution to regenerative and therapeutic application; however, their translational use is often impeded by teratoma formation, commonly associated with pluripotency. We discuss a population of nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress Enduring (Muse) cells, which offer an innovative and exciting avenue of exploration for the potential treatment of various human diseases. Areas covered: This review discusses the origin of Muse cells, describes in detail their various unique characteristics, and considers future avenues of their application and investigation with respect to what is currently known of adult pluripotent stem cells in scientific literature. We begin by defining cell potency, then discuss both mesenchymal and various reported populations of pluripotent stem cells, and finally delve into Muse cells and the characteristics that set them apart from their contemporaries. Expert opinion: Muse cells derived from adipose tissue (Muse-AT) are efficiently, routinely and painlessly isolated from human lipoaspirate material, exhibit tripoblastic differentiation both spontaneously and under media-specific induction, and do not form teratomas. We describe qualities specific to Muse-AT cells and their potential impact on the field of regenerative medicine and cell therapy. PMID:24745973

  9. Functional and Molecular Characterization of Rod-like Cells from Retinal Stem Cells Derived from the Adult Ciliary Epithelium

    PubMed Central

    Demontis, Gian Carlo; Aruta, Claudia; Comitato, Antonella; De Marzo, Anna; Marigo, Valeria

    2012-01-01

    In vitro generation of photoreceptors from stem cells is of great interest for the development of regenerative medicine approaches for patients affected by retinal degeneration and for high throughput drug screens for these diseases. In this study, we show unprecedented high percentages of rod-fated cells from retinal stem cells of the adult ciliary epithelium. Molecular characterization of rod-like cells demonstrates that they lose ciliary epithelial characteristics but acquire photoreceptor features. Rod maturation was evaluated at two levels: gene expression and electrophysiological functionality. Here we present a strong correlation between phototransduction protein expression and functionality of the cells in vitro. We demonstrate that in vitro generated rod-like cells express cGMP-gated channels that are gated by endogenous cGMP. We also identified voltage-gated channels necessary for rod maturation and viability. This level of analysis for the first time provides evidence that adult retinal stem cells can generate highly homogeneous rod-fated cells. PMID:22432014

  10. Nonlinear clustering in the CfA redshift survey

    SciTech Connect

    Alimi, J.; Blanchard, A.; Schaeffer, R. Ecole Polytechnique, Palaiseau Paris VII Universite CEA, Service de Physique Theorique de Saclay, Gif-sur-Yvette )

    1990-01-01

    The probability of finding a hole in a randomly placed sphere of volume V has been considered in the Cfa survey by numerous authors. The main emphasis of these studies has been on a scaling law derived from the assumption of hierarchical clustering. Here, the counts in cell statistics P(N) in the CfA redshift survey are analyzed. The results show that the general behavior of the P(N) can be predicted on the sole assumption of the hierarchical hypothesis. Scaling forms can then be predicted which appear to be verified to a fairly good extent in the Cfa redshift survey. This implies that the hypothesis of scale-invariant many-body correlations function provides for a satisfactory description of the count-in-cell statistics. 23 refs.

  11. TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

    PubMed Central

    Horlad, Hasita; Ohnishi, Koji; Ma, Chaoya; Fujiwara, Yukio; Niino, Daisuke; Ohshima, Koichi; Jinushi, Masahisa; Matsuoka, Masao; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples. It was found that direct co-culture with macrophages induced chemoresistance in the ATLL ATN-1 cell line, but not in other cell lines, including TL-Mor, ED and ATL-2S. It was also found that expression of the T cell Ig and mucin domain-containing molecule-3 (TIM-3) was induced in ATN-1 cells by their long-term co-culture with macrophages. TIM-3 gene transfection induced chemoresistance in the ATN-1 cells. Immunostaining of ATLL tissues showed TIM-3 expression in 25 out of 58 ATLL cases. Although TIM-3 expression was not associated with overall survival or T classification, it was associated with resistance to chemotherapy. TIM-3 expression is therefore considered to be a marker for predicting the efficacy of chemotherapy, and TIM-3-associated signals may be a therapeutic target for patients with ATLL. PMID:27446463

  12. Renal Cell Carcinoma in a Young Adult – Do We Need Further Investigations?

    PubMed Central

    Walter, Matthias; Wetterauer, Christian; Bruder, Elisabeth; Obermann, Ellen C.; Subotic, Svetozar; Wyler, Stephen

    2016-01-01

    Renal cell carcinomas (RCC), mostly occurring in adults aged 60–70 years, can result from well-known factors like cigarette smoking, obesity and hypertension. However, they have been associated with genetic alterations in children and young adults. A 28 year-old male patient with a confirmed RCC underwent biomolecular and immunohistochemical analyses due to his young age. A point mutation of the von Hippel-Lindau tumor suppressor gene was identified. Young patients under 40 years with diagnosed RCC should undergo additional diagnostic investigation, hence the discovery of an underlying cause. This could be important for further treatment and counseling of these young patients. PMID:27169022

  13. Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells.

    PubMed

    Jadhav, Unmesh; Nalapareddy, Kodandaramireddy; Saxena, Madhurima; O'Neill, Nicholas K; Pinello, Luca; Yuan, Guo-Cheng; Orkin, Stuart H; Shivdasani, Ramesh A

    2016-06-01

    Bivalent promoters in embryonic stem cells (ESCs) carry methylation marks on two lysine residues, K4 and K27, in histone3 (H3). K4me2/3 is generally considered to promote transcription, and Polycomb Repressive Complex 2 (PRC2) places K27me3, which is erased at lineage-restricted genes when ESCs differentiate in culture. Molecular defects in various PRC2 null adult tissues lack a unifying explanation. We found that epigenomes in adult mouse intestine and other self-renewing tissues show fewer and distinct bivalent promoters compared to ESCs. Groups of tissue-specific genes that carry bivalent marks are repressed, despite the presence of promoter H3K4me2/3. These are the predominant genes de-repressed in PRC2-deficient adult cells, where aberrant expression is proportional to the H3K4me2/3 levels observed at their promoters in wild-type cells. Thus, in adult animals, PRC2 specifically represses genes with acquired, tissue-restricted promoter bivalency. These findings provide new insights into specificity in chromatin-based gene regulation. PMID:27212235

  14. Cognitive deficits are associated with unemployment in adults with sickle cell anemia.

    PubMed

    Sanger, Maureen; Jordan, Lori; Pruthi, Sumit; Day, Matthew; Covert, Brittany; Merriweather, Brenda; Rodeghier, Mark; DeBaun, Michael; Kassim, Adetola

    2016-08-01

    An estimated 25-60% of adults with sickle cell disease (SCD) are unemployed. Factors contributing to the high unemployment rate in this population are not well studied. With the known risk of cognitive deficits associated with SCD, we tested the hypothesis that unemployment is related to decrements in intellectual functioning. We conducted a retrospective chart review of 50 adults with sickle cell anemia who completed cognitive testing, including the Wechsler Adult Intelligence Scale-IV, as part of standard care. Employment status was recorded at the time of testing. Medical variables examined as possible risk factors for unemployment included disease phenotype, cerebral infarction, and pain frequency. The mean age of the sample was 30.7 years (range = 19-59); 56% were women. Almost half of the cohort (44%) were unemployed. In a multivariate logistic regression model, lower IQ scores (odds ratio = 0.88; p = .002, 95% confidence interval, CI [0.82, 0.96]) and lower educational attainment (odds ratio = 0.13; p = .012, 95% CI [0.03, 0.65]) were associated with increasing odds of unemployment. The results suggest that cognitive impairment in adults with sickle cell anemia may contribute to the risk of unemployment. Helping these individuals access vocational rehabilitation services may be an important component of multidisciplinary care. PMID:27167865

  15. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    PubMed Central

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  16. Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats.

    PubMed

    Martí-Carbonell, Maria Assumpció; Garau, Adriana; Sala-Roca, Josefina; Balada, Ferran

    2012-01-01

    Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups. PMID:23093010

  17. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  18. Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps.

    PubMed

    Broughton, Kathleen M; Sussman, Mark A

    2016-03-01

    Much has changed since our survey of the landscape for myocardial regeneration powered by adult stem cells 4 years ago.(1) The intervening years since that first review has witnessed an explosive expansion of studies that advance both understanding and implementation of adult stem cells in promoting myocardial repair. Painstaking research from innumerable laboratories throughout the world is prying open doors that may lead to restoration of myocardial structure and function in the wake of pathological injury. This global effort has produced deeper mechanistic comprehension coupled with an evolving appreciation for the complexity of myocardial regeneration in the adult context. Undaunted by both known and (as yet) unknown challenges, pursuit of myocardial regenerative medicine mediated by adult stem cell therapy has gathered momentum fueled by tantalizing clues and visionary goals. This concise review takes a somewhat different perspective than our initial treatise, taking stock of the business sector that has become an integral part of the field while concurrently updating state of affairs in cutting edge research. Looking retrospectively at advancement over the years as all reviews eventually must, the fundamental lesson to be learned is best explained by Jonatan Mårtensson: "Success will never be a big step in the future. Success is a small step taken just now." PMID:26941423

  19. Differential Effects of Focused and Unfocused Written Correction on the Accurate Use of Grammatical Forms by Adult ESL Learners

    ERIC Educational Resources Information Center

    Sheen, Younghee; Wright, David; Moldawa, Anna

    2009-01-01

    Building on Sheen's (2007) study of the effects of written corrective feedback (CF) on the acquisition of English articles, this article investigated whether direct focused CF, direct unfocused CF and writing practice alone produced differential effects on the accurate use of grammatical forms by adult ESL learners. Using six intact adult ESL…

  20. Managing the acutely ill adult with sickle cell disease.

    PubMed

    Brown, Marvelle

    Sickle cell disease (SCD) is an autosomal recessively inherited condition, affecting the structure of the haemoglobin. SCD is a long-term chronic condition which is manifested by periods of acute painful sickling crisis, known as vaso-occlusive crisis (VOC) and is the cause of 90% of sickle cell-related hospital admissions. SCD is one of the most common genetic conditions worldwide and in the UK there are approximately 12,500 people living with it (Streetly et al,1997; Howard et al, 2008), making it more common than cystic fibrosis, yet there still remains many challenges in managing these patients when they become acutely ill. Lack of awareness and understanding of the illness, concerns regarding addiction and limited attention to the psycho-social implications of the illness, leads to less than effective care for this patient group when they are hospitalized. The aims of this article are to outline the pathophysiology of SCD, identify the causes of VOC and discuss the key principles of nursing management for patients experiencing a VOC. PMID:22306637

  1. Adult human neural crest-derived cells for articular cartilage repair.

    PubMed

    Pelttari, Karoliina; Pippenger, Benjamin; Mumme, Marcus; Feliciano, Sandra; Scotti, Celeste; Mainil-Varlet, Pierre; Procino, Alfredo; von Rechenberg, Brigitte; Schwamborn, Thomas; Jakob, Marcel; Cillo, Clemente; Barbero, Andrea; Martin, Ivan

    2014-08-27

    In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions. PMID:25163479

  2. Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas and other nonmuscle tissues.

    PubMed

    Di Rocco, Giuliana; Tritarelli, Alessandra; Toietta, Gabriele; Gatto, Ilaria; Iachininoto, Maria Grazia; Pagani, Francesca; Mangoni, Antonella; Straino, Stefania; Capogrossi, Maurizio C

    2008-02-01

    At the embryonic or fetal stages, autonomously myogenic cells (AMCs), i.e., cells able to spontaneously differentiate into skeletal myotubes, have been identified from several different sites other than skeletal muscle, including the vascular compartment. However, in the adult animal, AMCs from skeletal muscle-devoid tissues have been described in only two cases. One is represented by thymic myoid cells, a restricted population of committed myogenic progenitors of unknown derivation present in the thymic medulla; the other is represented by a small subset of adipose tissue-associated cells, which we recently identified. In the present study we report, for the first time, the presence of spontaneously differentiating myogenic precursors in the pancreas and in other skeletal muscle-devoid organs such as spleen and stomach, as well as in the periaortic tissue of adult mice. Immunomagnetic selection procedures indicate that AMCs derive from Flk-1(+) progenitors. Individual clones of myogenic cells from nonmuscle organs are morphologically and functionally indistinguishable from skeletal muscle-derived primary myoblasts. Moreover, they can be induced to proliferate in vitro and are able to participate in muscle regeneration in vivo. Thus, we provide evidence that fully competent myogenic progenitors can be derived from the Flk-1(+) compartment of several adult tissues that are embryologically unrelated to skeletal muscle. PMID:18094147

  3. zebraflash transgenic lines for in vivo bioluminescence imaging of stem cells and regeneration in adult zebrafish

    PubMed Central

    Chen, Chen-Hui; Durand, Ellen; Wang, Jinhu; Zon, Leonard I.; Poss, Kenneth D.

    2013-01-01

    The zebrafish has become a standard model system for stem cell and tissue regeneration research, based on powerful genetics, high tissue regenerative capacity and low maintenance costs. Yet, these studies can be challenged by current limitations of tissue visualization techniques in adult animals. Here we describe new imaging methodology and present several ubiquitous and tissue-specific luciferase-based transgenic lines, which we have termed zebraflash, that facilitate the assessment of regeneration and engraftment in freely moving adult zebrafish. We show that luciferase-based live imaging reliably estimates muscle quantity in an internal organ, the heart, and can longitudinally follow cardiac regeneration in individual animals after major injury. Furthermore, luciferase-based detection enables visualization and quantification of engraftment in live recipients of transplanted hematopoietic stem cell progeny, with advantages in sensitivity and gross spatial resolution over fluorescence detection. Our findings present a versatile resource for monitoring and dissecting vertebrate stem cell and regeneration biology. PMID:24198277

  4. The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus

    PubMed Central

    Li, Guangnan; Fang, Li; Fernández, Gloria; Pleasure, Samuel J.

    2013-01-01

    SUMMARY Adult neurogenesis represents a unique form of plasticity in the dentate gyrus requiring the presence of long-lived neural stem cells (LL-NSCs). However, the embryonic origin of these LL-NSCs remains unclear. The prevailing model assumes that the dentate neuroepithelium throughout the longitudinal axis of the hippocampus generates both the LL-NSCs and embryonically produced granule neurons. Here we show that the NSCs initially originate from the ventral hippocampus during late gestation and then relocate into the dorsal hippocampus. The descendants of these cells are the source for the LL-NSCs in the subgranular zone (SGZ). Furthermore, we show that the origin of these cells and their maintenance in the dentate are controlled by distinct sources of Sonic Hedgehog (Shh). The revelation of the complexity of both the embryonic origin of hippocampal LL-NSCs and the sources of Shh has important implications for the functions of LL-NSCs in the adult hippocampus. PMID:23643936

  5. A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages.

    PubMed

    Pearson, Bret J; Sánchez Alvarado, Alejandro

    2010-01-01

    The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus far. Planaria have a single p53 family member, Smed-p53, which is predominantly expressed in newly made stem cell progeny. When Smed-p53 is targeted by RNAi, the stem cell population increases at the expense of progeny, resulting in hyper-proliferation. However, ultimately the stem cell population fails to self-renew. Our results suggest that prior to the vertebrates, an ancestral p53-like molecule already had functions in stem cell proliferation control and self-renewal. PMID:20040488

  6. Adult human neural stem cell therapeutics: Current developmental status and prospect

    PubMed Central

    Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics. PMID:25621112

  7. Adult human arterial smooth muscle cells in primary culture. Modulation from contractile to synthetic phenotype.

    PubMed

    Thyberg, J; Nilsson, J; Palmberg, L; Sjölund, M

    1985-01-01

    Smooth muscle cells were isolated enzymatically from adult human arteries, grown in primary culture in medium containing 10% whole blood serum, and studied by transmission electron microscopy and [3H]thymidine autoradiography. In the intact arterial wall and directly after isolation, each smooth muscle cell had a nucleus with a wide peripheral zone of condensed chromatin and a cytoplasm dominated by myofilament bundles with associated dense bodies. After 1-2 days of culture, the cells had attached to the substrate and started to spread out. At the same time, a characteristic fine-structural modification took place. It included nuclear enlargement, dispersion of the chromatin and formation of large nucleoli. Moreover, myofilament bundles disappeared and an extensive rough endoplasmic reticulum and a large Golgi complex were organized in the cytoplasm. This morphological transformation of the cells was completed in 3-4 days. It was accompanied by initiation of DNA replication and mitosis. The observations demonstrate that adult human arterial smooth muscle cells, when cultivated in vitro, pass through a phenotypic modulation of the same type as arterial smooth muscle cells from experimental animals. This modulation gives the cells morphological and functional properties resembling those of the modified smooth muscle cells found in fibroproliferative lesions of atherosclerosis. Further studies of the regulation of smooth muscle phenotype and growth may provide important clues for a better understanding of the pathogenesis of atherosclerosis. PMID:3967287

  8. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    SciTech Connect

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal . E-mail: iahmad@unmc.edu

    2006-01-13

    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS.

  9. A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages

    PubMed Central

    Pearson, Bret J.; Alvarado, Alejandro Sánchez

    2010-01-01

    The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus far. Planaria have a single p53 family member, Smed-p53, which is predominantly expressed in newly made stem cell progeny. When Smed-p53 is targeted by RNAi, the stem cell population increases at the expense of progeny, resulting in hyper-proliferation. However, ultimately the stem cell population fails to self-renew. Our results suggest that prior to the vertebrates, an ancestral p53-like molecule already had functions in stem cell proliferation control and self-renewal. PMID:20040488

  10. Adult neural precursor cells form connexin-dependent networks that improve their survival.

    PubMed

    Ravella, Ajaya; Ringstedt, Thomas; Brion, Jean-Pierre; Pandolfo, Massimo; Herlenius, Eric

    2015-10-21

    Establishment of cellular networks and calcium homeostasis are essential for embryonic stem cell proliferation and differentiation. We also hypothesized that adult neural progenitor cells form functional cellular networks relevant for their development. We isolated neuronal progenitor cells from the subventricular zone of 5-week-old mice to investigate the role of gap junctions, calcium homeostasis, and cellular networks in cell differentiation and survival. Western blotting and reverse transcription-PCR showed that the cells expressed the gap junction components connexin 26, 36, 43, and 45, and that expression of connexin 43 increased in early (8 days) differentiated cells. Transmission electron microscopy and immunocytochemistry also indicated that gap junctions were present. Scrape-loading experiments showed dye transfer between cells that could be prevented by gapjunction blockers; thus, functional intercellular gap junctions had been established. However, dye transfer was four times stronger in differentiated cultures, correlating with the increased connexin 43 expression. During time-lapse calcium imaging, both differentiated and undifferentiated cultures showed spontaneous calcium activity that was reduced by gap junction blockers. Cross-correlation analysis of the calcium recordings showed that the cells were interconnected through gap junctions and that the early-differentiated cells were organized in small-world networks. Gap junction blockers did not affect proliferation and differentiation, but resulted in twice as many apoptotic cells. mRNAi knockdown of connexin 43 also doubled the number of apoptotic cells. We conclude that adult neural progenitor cells form networks in vitro that are strengthened during early differentiation by increased expression of connexin 43. The networks are functional and improve cell survival. PMID:26351758

  11. Diagnosis of Adult Patients with Cystic Fibrosis.

    PubMed

    Nick, Jerry A; Nichols, David P

    2016-03-01

    The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. PMID:26857767

  12. Designer Self-Assembling Peptide Nanofiber Scaffolds for Adult Mouse Neural Stem Cell 3-Dimensional Cultures

    PubMed Central

    Gelain, Fabrizio; Bottai, Daniele; Vescovi, Angleo; Zhang, Shuguang

    2006-01-01

    Biomedical researchers have become increasingly aware of the limitations of conventional 2-dimensional tissue cell culture systems, including coated Petri dishes, multi-well plates and slides, to fully address many critical issues in cell biology, cancer biology and neurobiology, such as the 3-D microenvironment, 3-D gradient diffusion, 3-D cell migration and 3-D cell-cell contact interactions. In order to fully understand how cells behave in the 3-D body, it is important to develop a well-controlled 3-D cell culture system where every single ingredient is known. Here we report the development of a 3-D cell culture system using a designer peptide nanofiber scaffold with mouse adult neural stem cells. We attached several functional motifs, including cell adhesion, differentiation and bone marrow homing motifs, to a self-assembling peptide RADA16 (Ac-RADARADARADARADA-COHN2). These functionalized peptides undergo self-assembly into a nanofiber structure similar to Matrigel. During cell culture, the cells were fully embedded in the 3-D environment of the scaffold. Two of the peptide scaffolds containing bone marrow homing motifs significantly enhanced the neural cell survival without extra soluble growth and neurotrophic factors to the routine cell culture media. In these designer scaffolds, the cell populations with β-Tubulin+, GFAP+ and Nestin+ markers are similar to those found in cell populations cultured on Matrigel. The gene expression profiling array experiments showed selective gene expression, possibly involved in neural stem cell adhesion and differentiation. Because the synthetic peptides are intrinsically pure and a number of desired function cellular motifs are easy to incorporate, these designer peptide nanofiber scaffolds provide a promising controlled 3-D culture system for diverse tissue cells, and are useful as well for general molecular and cell biology. PMID:17205123

  13. Anaplastic large cell lymphoma in paediatric and young adult patients.

    PubMed

    Turner, Suzanne D; Lamant, Laurence; Kenner, Lukas; Brugières, Laurence

    2016-05-01

    Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20-40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side-effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial. PMID:26913827

  14. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    SciTech Connect

    Khalifa, Shaden A.M.; Medina, Philippe de; Erlandsson, Anna; El-Seedi, Hesham R.; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-04-11

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

  15. Adult neural stem cells in distinct microdomains generate previously unknown interneuron types

    PubMed Central

    Merkle, Florian T.; Fuentealba, Luis C.; Sanders, Timothy A.; Magno, Lorenza; Kessaris, Nicoletta; Alvarez-Buylla, Arturo

    2014-01-01

    Throughout life, neural stem cells (NSCs) in different domains of the ventricular-subventricular zone (V-SVZ) of the adult rodent brain generate several subtypes of interneurons that regulate the function of the olfactory bulb (OB). The full extent of diversity among adult NSCs and their progeny is not known. Here, we report the generation of at least four previously unknown OB interneuron subtypes that are produced in finely patterned progenitor domains in the anterior ventral V-SVZ of both the neonatal and adult brain. Progenitors of these novel interneurons are responsive to sonic hedgehog (SHH) and are organized into microdomains that correlate with the expression domains of the Nkx6.2 and Zic family of transcription factors. This work reveals an unexpected degree of complexity in the specification and patterning of NSCs in the postnatal mouse brain. PMID:24362763

  16. The Effect of Sleep Continuity on Pain in Adults with Sickle Cell Disease

    PubMed Central

    Moscou-Jackson, Gyasi; Finan, Patrick H.; Campbell, Claudia M.; Smyth, Joshua M.; Haythornthwaite, Jennifer A.

    2015-01-01

    This analysis examined the influence of quantifiable parameters of daily sleep continuity, primarily sleep duration and sleep fragmentation, on daily pain in adults with Sickle Cell Disease (SCD). Seventy-five adults with SCD completed baseline psychosocial measures and daily morning (sleep) and evening (pain) diaries over a three-month period. Mixed-effect modeling was used to examine daily between- and within-subjects effects of sleep continuity parameters on pain, as well as the synergistic effect of sleep fragmentation and sleep duration on pain. Results revealed nights of shorter sleep duration and time in bed, increased fragmentation, and less efficient sleep (relative to one’s own mean) were followed by days of greater pain severity. Further, the analgesic benefit of longer sleep duration was attenuated when sleep fragmentation was elevated. These results suggest that both the separate and combined effects of sleep duration and fragmentation should be considered in evaluating pain in adults with SCD. PMID:25842346

  17. Ceftriaxone-resistant Salmonella septicemia and osteomyelitis in sickle cell disease adults.

    PubMed

    Morgan, James S; Laber, Damian A

    2006-06-01

    The majority of data evaluating Salmonella infections in sickle cell anemia (SCD) comes from studies performed in children. We report a SCD adult who presented with ceftriaxone-resistant Salmonella bacteremia. After appropriate initial therapy, persistent back pain prompted evaluation by magnetic resonance imaging of the spine, which revealed osteomyelitis and a psoas abscess. The patient responded to percutaneous drainage and antibiotics. This report summarizes some of the findings of large SCD studies evaluating Salmonella bacteremia and osteomyelitis, focusing on adults. Our case exemplifies the need for antibiotic coverage for Salmonella species in adult SCD patients with septicemia. We argue that imaging studies looking for osteomyelitis should be done routinely in SCD patients with Salmonella bacteremia. PMID:16800421

  18. Environmental enrichment influences neuronal stem cells in the adult crayfish brain

    PubMed Central

    Ayub, Neishay; Benton, Jeanne L.; Zhang, Yi; Beltz, Barbara S.

    2011-01-01

    New neurons are incorporated throughout life into the brains of many vertebrate and non-vertebrate species. This process of adult neurogenesis is regulated by a variety of external and endogenous factors, including environmental enrichment, which increases the production of neurons in juvenile mice and crayfish. The primary goal of the present study was to exploit the spatial separation of the neuronal precursor cell lineage in crayfish to determine which generation(s) of precursors is altered by environmental conditions. Further, in crayfish, an intimate relationship between the 1st generation neuronal precursors (stem cells) and cells circulating in the hemolymph has been proposed (Zhang et al., 2009). Therefore, a second goal was to assess whether environmental enrichment alters the numbers or types of cells circulating in the hemolymph. We find that neurogenesis in the brains of sexually differentiated procambarid crayfish is enhanced by environmental enrichment as previously demonstrated by Sandeman and Sandeman (2000) in young, sexually undifferentiated Cherax destructor. We also show that environmental enrichment increases the cell cycle rate of neuronal stem cells. While there was no effect of environment on the overall numbers of cells circulating in the hemolymph, enrichment resulted in increased expression of glutamine synthetase, a marker of the neuronal stem cells, in a small percentage of circulating cells; there was little or no expression of this enzyme in hemolymph cells extracted from deprived animals. Thus, environmental enrichment influences the rate of neuronal stem cell division in adult crayfish, as well as the composition of cells circulating in the hemolymph. PMID:21485010

  19. Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice

    NASA Technical Reports Server (NTRS)

    Hayes, N. L.; Nowakowski, R. S.

    2002-01-01

    The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.

  20. Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes.

    PubMed

    Lee, Joon; Stagg, Mark A; Fukushima, Satsuki; Soppa, Gopal K R; Siedlecka, Urszula; Youssef, Samuel J; Suzuki, Ken; Yacoub, Magdi H; Terracciano, Cesare M N

    2009-04-01

    Adult progenitor cell transplantation has been proposed for the treatment of heart failure, but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction coupling of recipient cardiomyocytes are altered. Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After 3 wk, they received intramyocardial injections of either 10(7) green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10(6) GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. The contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca(2+) handling by indo-1 and fluo-4 fluorescence, and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time to peak of the Ca(2+) transient observed in failing cardiomyocytes. The smaller and slower L-type Ca(2+) current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca(2+) sparks suggested a normalization of sarcoplasmic reticulum Ca(2+) leak after skeletal myoblast transplantation. The increased Ca(2+) wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance, and excitation-contraction coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation. PMID:19181964

  1. Distribution and phenotype of TrkB oligodendrocyte lineage cells in the adult rat spinal cord.

    PubMed

    Coulibaly, Aminata P; Deer, Matthew R; Isaacson, Lori G

    2014-09-25

    The distribution and phenotype of a previously undescribed population of nonneuronal cells in the intact spinal cord that expresses TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4), were characterized by examining the extent of co-localization of TrkB with NG2, which identifies oligodendrocyte progenitors (OPCs) or CC1, a marker for mature oligodendrocytes (OLs). All TrkB nonneuronal cells expressed Olig2, confirming their role in the OL lineage. Similar to OPCs and OLs, TrkB cells resided in gray and white matter of the spinal cord in similar abundance. Less than 2% of TrkB cells expressed NG2, while over 80% of TrkB cells in the adult spinal cord co-expressed CC1. Most OPCs did not express detectable levels of TrkB, however a small OPC pool (~5%) showed TrkB immunoreactivity. The majority of mature OLs (~65%) expressed TrkB, but a population of mature OLs (~36%) did not express TrkB at detectable levels, and 17% of TrkB nonneuronal cells did not express NG2 or CC1. Approximately 20% of the TrkB nonneuronal population in the ventral horn resided in close proximity to motor neurons and were categorized as perineuronal. We conclude that TrkB is expressed by several pools of OL lineage cells in the adult spinal cord. These findings are important in understanding the neurotrophin regulation of OL lineage cells in the adult spinal cord. PMID:25072185

  2. Human amniotic epithelial cells are reprogrammed more efficiently by induced pluripotency than adult fibroblasts.

    PubMed

    Easley, Charles A; Miki, Toshio; Castro, Carlos A; Ozolek, John A; Minervini, Crescenzio F; Ben-Yehudah, Ahmi; Schatten, Gerald P

    2012-06-01

    Cellular reprogramming from adult somatic cells into an embryonic cell-like state, termed induced pluripotency, has been achieved in several cell types. However, the ability to reprogram human amniotic epithelial cells (hAECs), an abundant cell source derived from discarded placental tissue, has only recently been investigated. Here we show that not only are hAECs easily reprogrammed into induced pluripotent stem cells (AE-iPSCs), but hAECs reprogram faster and more efficiently than adult and neonatal somatic dermal fibroblasts. Furthermore, AE-iPSCs express higher levels of NANOG and OCT4 compared to human foreskin fibroblast iPSCs (HFF1-iPSCs) and express decreased levels of genes associated with differentiation, including NEUROD1 and SOX17, markers of neuronal differentiation. To elucidate the mechanism behind the higher reprogramming efficiency of hAECs, we analyzed global DNA methylation, global histone acetylation, and the mitochondrial DNA A3243G point mutation. Whereas hAECs show no differences in global histone acetylation or mitochondrial point mutation accumulation compared to adult and neonatal dermal fibroblasts, hAECs demonstrate a decreased global DNA methylation compared to dermal fibroblasts. Likewise, quantitative gene expression analyses show that hAECs endogenously express OCT4, SOX2, KLF4, and c-MYC, all four factors used in cellular reprogramming. Thus, hAECs represent an ideal cell type for testing novel approaches for generating clinically viable iPSCs and offer significant advantages over postnatal cells that more likely may be contaminated by environmental exposures and infectious agents. PMID:22686477

  3. Intensive care outcomes in adult hematopoietic stem cell transplantation patients

    PubMed Central

    Bayraktar, Ulas D; Nates, Joseph L

    2016-01-01

    Although outcomes of intensive care for patients undergoing hematopoietic stem cell transplantation (HSCT) have improved in the last two decades, the short-term mortality still remains above 50% among allogeneic HSCT patients. Better selection of HSCT patients for intensive care, and consequently reduction of non-beneficial care, may reduce financial costs and alleviate patient suffering. We reviewed the studies on intensive care outcomes of patients undergoing HSCT published since 2000. The risk factors for intensive care unit (ICU) admission identified in this report were primarily patient and transplant related: HSCT type (autologous vs allogeneic), conditioning intensity, HLA mismatch, and graft-versus-host disease (GVHD). At the same time, most of the factors associated with ICU outcomes reported were related to the patients’ functional status upon development of critical illness and interventions in ICU. Among the many possible interventions, the initiation of mechanical ve