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  1. SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes

    Liesenfeld, Melanie; Mosig, Sandy; Funke, Harald; Jansen, Lars; Runnebaum, Ingo B; Dürst, Matthias; Backsch, Claudia

    2013-01-01

    Genetic aberrations are required for the progression of HPV-induced cervical precancers. A prerequisite for clonal expansion of cancer cells is unlimited proliferative capacity. In a cell culture model for cervical carcinogenesis loss of genes located on chromosome 4q35→qter and chromosome 10p14-p15 were found to be associated with escape from senescence. Moreover, by LOH and I-FISH analyses a higher frequency of allele loss of these regions was also observed in cervical carcinomas as compared to CIN3. The aim of this study was to identify candidate senescence-related genes located on chromosome 4q35→qter and chromosome 10p14-p15 which may contribute to clonal expansion at the transition of CIN3 to cancer. Microarray expression analyses were used to identify candidate genes down-regulated in cervical carcinomas as compared to CIN3. In order to relate these genes with the process of senescence their respective cDNAs were overexpressed in HPV16-immortalized keratinocytes as well as in primary human fibroblasts and keratinocytes using lentivirus mediated gene transduction. Overall fifteen genes located on chromosome 4q35→qter and chromosome 10p14-p15 were identified. Ten of these genes could be validated in biopsies by RT-PCR. Of interest is the novel finding that SORBS2 and TLR3 can induce senescence in primary human fibroblasts and keratinocytes but not in HPV-immortalized cell lines. Intriguingly, the endogenous expression of both genes increases during finite passaging of primary keratinocytes in vitro. The relevance of the genes SORBS2 and TLR3 in the process of cellular senescence warrants further investigation. In ongoing experiments we are investigating whether this increase in gene expression is also characteristic of replicative senescence

  2. Alteration of keratinocyte differentiation and senescence by the tumor promoter dioxin

    Ray, Soma S.; Swanson, Hollie I.

    2003-01-01

    Exposure to the environmental contaminant dioxin, elicits a variety of responses, which includes tumor promotion, embryotoxicity/teratogenesis, and carcinogenesis in both animals and humans. Many of the effects of dioxin are mediated by the aryl hydrocarbon receptor (AHR), a ligand-activated bHLH (basic helix-loop-helix)/PAS transcription factor. We initiated this study to determine whether dioxin's tumor-promoting activities may lie in its ability to alter proliferation, differentiation, and/or senescence using normal human epidermal keratinocytes (HEKs). Here, we report that dioxin appears to accelerate differentiation as measured by flow cytometry and by increased expression of the differentiation markers involucrin and filaggrin. In addition, dioxin appears to increase proliferation as indicated by an increase in NADH/NADPH production and changes in cell cycle. Finally, dioxin decreases SA (senescence associated) β-galactosidase staining, an indicator of senescence, in the differentiating keratinocytes. These changes were accompanied by decreases in the expression levels of key cell cycle regulatory proteins p53, p16 INK4a , and p14 ARF . Our findings support the idea that dioxin may exert its tumor-promoting actions, in part, by downregulating the expression levels of key tumor suppressor proteins, which may impair the cell's ability to maintain its appropriate cellular status

  3. The effect of 648 nm diode laser irradiation on second messengers in senescent human keratinocytes

    Hawkins Evans, D.; Abrahamse, H.

    2009-02-01

    Background/purpose: Stress induced premature senescence (SIPS) is defined as the long-term effect of subcytotoxic stress on proliferative cell types. Cells in SIPS display differences at the level of protein expression which affect energy metabolism, defense systems, redox potential, cell morphology and transduction pathways. This study aimed to determine the effect of laser irradiation on second messengers in senescent cells and to establish if that effect can be directly linked to changes in cellular function such as cell viability or proliferation. Materials and Methods: Human keratinocyte cell cultures were modified to induce premature senescence using repeated sub-lethal stresses of 200 uM H2O2 or 5% OH every day for four days with two days recovery. SIPS was confirmed by senescence-associated β-galactosidase staining. Control conditions included normal, repeated stress of 500 uM H2O2 to induce apoptosis and 200 uM PBN as an anti-oxidant or free radical scavenger. Cells were irradiated with 1.5 J/cm2 on day 1 and 4 using a 648 nm diode laser (3.3 mW/cm2) and cellular responses were measured 1 h post irradiation. The affect on second messengers was assessed by measuring cAMP, cGMP, nitric oxide and intracellular calcium (Ca2+) while functional changes were assessed using cell morphology, ATP cell viability, LDH membrane integrity and WST-1 cell proliferation. Results: Results indicate an increase in NO and a decrease in cGMP and Ca2+ in 200 uM H2O2 irradiated cells while PBN irradiated cells showed a decrease in cAMP and an increase in ATP viability and cell proliferation. Conclusion: Laser irradiation influences cell signaling which ultimately changes the biological function of senescent cells. If laser therapy can stimulate the biological function of senescent cells it may be beneficial to conditions such as immune senescence, skin ageing, muscle atrophy, premature ageing of arteries in patients with advanced heart disease, neurodegenerative disorders and

  4. Resveratrol prevents oxidative stress-induced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes.

    Yasuo Ido

    Full Text Available The aging process is perceived as resulting from a combination of intrinsic factors such as changes in intracellular signaling and extrinsic factors, most notably environmental stressors. In skin, the relationship between intrinsic changes and keratinocyte function is not clearly understood. Previously, we found that increasing the activity of AMP-activated protein kinase (AMPK suppressed senescence in hydrogen peroxide (H2O2-treated human primary keratinocytes, a model of oxidative stress-induced cellular aging. Using this model in the present study, we observed that resveratrol, an agent that increases the activities of both AMPK and sirtuins, ameliorated two age-associated phenotypes: cellular senescence and proliferative dysfunction. In addition, we found that treatment of keratinocytes with Ex527, a specific inhibitor of sirtuin 1 (SIRT1, attenuated the ability of resveratrol to suppress senescence. In keeping with the latter observation, we noted that compared to non-senescent keratinocytes, senescent cells lacked SIRT1. In addition to these effects on H2O2-induced senescence, resveratrol also prevented the H2O2-induced decrease in proliferation (as indicated by 3H-thymidine incorporation in the presence of insulin. This effect was abrogated by inhibition of AMPK but not SIRT1. Compared to endothelium, we found that human keratinocytes expressed relatively high levels of Forkhead box O3 (FOXO3, a downstream target of both AMPK and SIRT1. Treatment of keratinocytes with resveratrol transactivated FOXO3 and increased the expression of its target genes including catalase. Resveratrol's effects on both senescence and proliferation disappeared when FOXO3 was knocked down. Finally, we performed an exploratory study which showed that skin from humans over 50 years old had lower AMPK activity than skin from individuals under age 20. Collectively, these findings suggest that the effects of resveratrol on keratinocyte senescence and proliferation

  5. Dysregulated ΔNp63α inhibits expression of Ink4a/arf, blocks senescence, and promotes malignant conversion of keratinocytes.

    Linan Ha

    Full Text Available p63 is critical for squamous epithelial development, and elevated levels of the ΔNp63α isoform are seen in squamous cell cancers of various organ sites. However, significant controversy exists regarding the role of p63 isoforms as oncoproteins or tumor suppressors. Here, lentiviruses were developed to drive long-term overexpression of ΔNp63α in primary keratinocytes. Elevated levels of ΔNp63α in vitro promote long-term survival and block both replicative and oncogene-induced senescence in primary keratinocytes, as evidenced by the expression of SA-β-gal and the presence of nuclear foci of heterochromatin protein 1γ. The contribution of ΔNp63α to cancer development was assessed using an in vivo grafting model of experimental skin tumorigenesis that allows distinction between benign and malignant tumors. Grafted lenti-ΔNp63α keratinocytes do not form tumors, whereas lenti-GFP/v-ras(Ha keratinocytes develop well-differentiated papillomas. Lenti-ΔNp63α/v-ras(Ha keratinocytes form undifferentiated carcinomas. The average volume of lenti-ΔNp63α/v-ras(Ha tumors was significantly higher than those in the lenti-GFP/v-ras(Ha group, consistent with increased BrdU incorporation detected by immunohistochemistry. The block in oncogene-induced senescence corresponds to sustained levels of E2F1 and phosphorylated AKT, and is associated with loss of induction of p16(ink4a/p19(arf. The relevance of p16(ink4a/p19(arf loss was demonstrated in grafting studies of p19(arf-null keratinocytes, which develop malignant carcinomas in the presence of v-ras(Ha similar to those arising in wildtype keratinocytes that express lenti-ΔNp63α and v-ras(Ha. Our findings establish that ΔNp63α has oncogenic activity and its overexpression in human squamous cell carcinomas contributes to the malignant phenotype, and implicate its ability to regulate p16(ink4a/p19(arf in the process.

  6. Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity.

    Maria V Chiantore

    Full Text Available Interferon (IFN-β inhibits cell proliferation and affects cell cycle in keratinocytes transformed by both mucosal high risk Human Papilloma Virus (HPV and cutaneous HPV E6 and E7 proteins. In particular, upon longer IFN-β treatments, cutaneous HPV38 expressing cells undergo senescence. IFN-β appears to induce senescence by upregulating the expression of the tumor suppressor PML, a well known IFN-induced gene. Indeed, experiments in gene silencing via specific siRNAs have shown that PML is essential in the execution of the senescence programme and that both p53 and p21 pathways are involved. IFN-β treatment leads to a modulation of p53 phosphorylation and acetylation status and a reduction in the expression of the p53 dominant negative ΔNp73. These effects allow the recovery of p53 transactivating activity of target genes involved in the control of cell proliferation. Taken together, these studies suggest that signaling through the IFN pathway might play an important role in cellular senescence. This additional understanding of IFN antitumor action and mechanisms influencing tumor responsiveness or resistance appears useful in aiding further promising development of biomolecular strategies in the IFN therapy of cancer.

  7. Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis

    Russell, Michael; Berardi, Philip; Gong Wei; Riabowol, Karl

    2006-01-01

    The INhibitor of Growth (ING) family of plant homeodomain (PHD) proteins induce apoptosis and regulate gene expression through stress-inducible binding of phospholipids with subsequent nuclear and nucleolar localization. Relocalization occurs concomitantly with interaction with a subset of nuclear proteins, including PCNA, p53 and several regulators of acetylation such as the p300/CBP and PCAF histone acetyltransferases (HATs), as well as the histone deacetylases HDAC1 and hSir2. These interactions alter the localized state of chromatin compaction, subsequently affecting the expression of subsets of genes, including those associated with the stress response (Hsp70), apoptosis (Bax, MDM2) and cell cycle regulation (p21 WAF1 , cyclin B) in a cell- and tissue-specific manner. The expression levels and subcellular localization of ING proteins are altered in a significant number of human cancer types, while the expression of ING isoforms changes during cellular aging, suggesting that ING proteins may play a role in linking cellular transformation and replicative senescence. The variety of functions attributed to ING proteins suggest that this tumor suppressor serves to link the disparate processes of cell cycle regulation, cell suicide and cellular aging through epigenetic regulation of gene expression. This review examines recent findings in the ING field with a focus on the functions of protein-protein interactions involving ING family members and the mechanisms by which these interactions facilitate the various roles that ING proteins play in tumorigenesis, apoptosis and senescence

  8. Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor.

    Véronique Bertrand-Vallery

    Full Text Available BACKGROUND: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. METHODOLOGY/PRINCIPAL FINDINGS: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29. Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta. CONCLUSIONS/SIGNIFICANCE: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.

  9. [Immunological theory of senescence].

    Drela, Nadzieja

    2014-01-01

    Senescence can result from decreased potential of the immune system to respond to foreign and self antigens. The most common effect is the inhibition to destroy dying and cancer cells and the decrease of the immune response to pathogens. Aging is closely related to inflammatory phenotype, which facilitate the development of age-related diseases. The mammal immune system is highly organized and adapted to react to a wide range of antigens. According to the immunological theory, the causative agents of senescence are multilevel changes of development and functions of immune cells. Some of changes can be beneficial for the maintenance of homeostasis and lifespan in continuously changing endogenous environment and immune history of the organism.

  10. Senescence is not inevitable

    Jones, Owen; Vaupel, James W.

    2017-01-01

    trajectories exists. These empirical observations support theoretical work indicating that a wide range of mortality and fertility trajectories is indeed possible, including senescence, negligible senescence and even negative senescence (improvement). Although many mysteries remain in the field...

  11. Octopus senescence: the beginning of the end.

    Anderson, Roland C; Wood, James B; Byrne, Ruth A

    2002-01-01

    Senescence is a normal stage of an octopus's life cycle that often occurs before death. Some of the following symptoms typify it: lack of feeding, retraction of skin around the eyes, uncoordinated movement, increased undirected activity, and white unhealing lesions on the body. There is inter- and intraspecific variability. Senescence is not a disease or a result of disease, although diseases can also be a symptom of it. Both males and females go through a senescent stage before dying-the males after mating, the females while brooding eggs and after the eggs hatch. There are many aspects of octopus senescence that have not yet been studied. This study discusses the ecological implications of senescence.

  12. Delayed Senescence

    2004-01-01

    Researcher Dr. Yi Li developed a technique to manipulate certain characteristics of plant growth such as anit-senescence. For example, the tobacco leaf was clipped from a transgenic plant (right), and a wildtype plant (left). During ground-based laboratory studies, both leaves were left in a darkened area for 4 months. When retrieved, the wildtype plant leaf was dried-out and the transgenic leaf remained fresh and green. A variation of this technology that involves manipulating plant hormones has been conducted in space-based studies on tomato plants through BioServe Space Technologies. The transport and distribution of auxin, an important plant hormone has shown to be influenced by microgravity, which could lead to improving the quality of fruits and vegetables grown on Earth.

  13. Senescence Meets Dedifferentiation

    Givaty Rapp, Yemima; Ransbotyn, Vanessa; Grafi, Gideon

    2015-01-01

    Senescence represents the final stage of leaf development but is often induced prematurely following exposure to biotic and abiotic stresses. Leaf senescence is manifested by color change from green to yellow (due to chlorophyll degradation) or to red (due to de novo synthesis of anthocyanins coupled with chlorophyll degradation) and frequently culminates in programmed death of leaves. However, the breakdown of chlorophyll and macromolecules such as proteins and RNAs that occurs during leaf senescence does not necessarily represent a one-way road to death but rather a reversible process whereby senescing leaves can, under certain conditions, re-green and regain their photosynthetic capacity. This phenomenon essentially distinguishes senescence from programmed cell death, leading researchers to hypothesize that changes occurring during senescence might represent a process of trans-differentiation, that is the conversion of one cell type to another. In this review, we highlight attributes common to senescence and dedifferentiation including chromatin structure and activation of transposable elements and provide further support to the notion that senescence is not merely a deterioration process leading to death but rather a unique developmental state resembling dedifferentiation. PMID:27135333

  14. PML, SUMOylation and senescence

    Hugues eDe Thé

    2013-07-01

    Full Text Available Since its discovery, 25 years ago, PML has been an enigma. Implicated in the oncogenic PML/RARA fusion, forming elusive intranuclear domains, triggering cell death or senescence, controlled by and perhaps controlling SUMOylation... there are multiple PML-related issues. Here we review the reciprocal interactions between PML, senescence and SUMOylation, notably in the context of cellular transformation.

  15. Evolution of plant senescence

    Young Mike

    2009-07-01

    Full Text Available Abstract Background Senescence is integral to the flowering plant life-cycle. Senescence-like processes occur also in non-angiosperm land plants, algae and photosynthetic prokaryotes. Increasing numbers of genes have been assigned functions in the regulation and execution of angiosperm senescence. At the same time there has been a large expansion in the number and taxonomic spread of plant sequences in the genome databases. The present paper uses these resources to make a study of the evolutionary origins of angiosperm senescence based on a survey of the distribution, across plant and microbial taxa, and expression of senescence-related genes. Results Phylogeny analyses were carried out on protein sequences corresponding to genes with demonstrated functions in angiosperm senescence. They include proteins involved in chlorophyll catabolism and its control, homeoprotein transcription factors, metabolite transporters, enzymes and regulators of carotenoid metabolism and of anthocyanin biosynthesis. Evolutionary timelines for the origins and functions of particular genes were inferred from the taxonomic distribution of sequences homologous to those of angiosperm senescence-related proteins. Turnover of the light energy transduction apparatus is the most ancient element in the senescence syndrome. By contrast, the association of phenylpropanoid metabolism with senescence, and integration of senescence with development and adaptation mediated by transcription factors, are relatively recent innovations of land plants. An extended range of senescence-related genes of Arabidopsis was profiled for coexpression patterns and developmental relationships and revealed a clear carotenoid metabolism grouping, coordinated expression of genes for anthocyanin and flavonoid enzymes and regulators and a cluster pattern of genes for chlorophyll catabolism consistent with functional and evolutionary features of the pathway. Conclusion The expression and phylogenetic

  16. The Immortal Senescence.

    Bianchi-Smiraglia, Anna; Lipchick, Brittany C; Nikiforov, Mikhail A

    2017-01-01

    Activation of oncogenic signaling paradoxically results in the permanent withdrawal from cell cycle and induction of senescence (oncogene-induced senescence (OIS)). OIS is a fail-safe mechanism used by the cells to prevent uncontrolled tumor growth, and, as such, it is considered as the first barrier against cancer. In order to progress, tumor cells thus need to first overcome the senescent phenotype. Despite the increasing attention gained by OIS in the past 20 years, this field is still rather young due to continuous emergence of novel pathways and processes involved in OIS. Among the many factors contributing to incomplete understanding of OIS are the lack of unequivocal markers for senescence and the complexity of the phenotypes revealed by senescent cells in vivo and in vitro. OIS has been shown to play major roles at both the cellular and organismal levels in biological processes ranging from embryonic development to barrier to cancer progression. Here we will briefly outline major advances in methodologies that are being utilized for induction, identification, and characterization of molecular processes in cells undergoing oncogene-induced senescence. The full description of such methodologies is provided in the corresponding chapters of the book.

  17. die rol van die unieverdedigingsmag in die onderdrukking van die

    agv regeringsoptrede nie.39. Siotsom. In die geskiedenis van die Unieverdedigings- mag word die gebeure random die 1914-staking oorskadu deur die Rebellie en Suid-Afrika se deelname aan die Eerste Wereldoorlog. Tog was dit 'n belangrike mylpaal in die geskiedenis van die organisasie, omdat dit sy eerste optrede ...

  18. Interaction Mortality: Senescence May Have Evolved because It Increases Lifespan

    Wensink, M. J.; Wrycza, T. F.; Baudisch, A.

    2014-01-01

    Given an extrinsic challenge, an organism may die or not depending on how the threat interacts with the organism's physiological state. To date, such interaction mortality has been only a minor factor in theoretical modeling of senescence. We describe a model of interaction mortality that does...... not involve specific functions, making only modest assumptions. Our model distinguishes explicitly between the physiological state of an organism and potential extrinsic, age-independent threats. The resulting mortality may change with age, depending on whether the organism's state changes with age. We find...... that depending on the physiological constraints, any outcome, be it 'no senescence' or 'high rate of senescence', can be found in any environment; that the highest optimal rate of senescence emerges for an intermediate physiological constraint, i.e. intermediate strength of trade-off; and that the optimal rate...

  19. Aging and senescence of skin cells in culture

    Rattan, Suresh

    2015-01-01

    Studying age-related changes in the physiology, biochemistry, and molecular biology of isolated skin cell populations in culture has greatly expanded the understanding of the fundamental aspects of skin aging. The three main cell types that have been studied extensively with respect to cellular...... aging in vitro are dermal fibroblasts, epidermal keratinocytes, and melanocytes. Serial subcultivation of normal diploid skin cells can be performed only a limited number of times, and the emerging senescent phenotype can be categorized into structural, physiological, biochemical, and molecular...... phenotypes, which can be used as biomarkers of cellular aging in vitro. The rate and phenotype of aging are different in different cell types. There are both common features and specific features of aging of skin fibroblasts, keratinocytes, melanocytes, and other cell types. A progressive accumulation...

  20. Die binding van die konfessie

    P. J. Coetzee

    1970-05-01

    Full Text Available Ons moet waak teen twee uiterstes. Aan die een kant het die dogma as onversoenlike vyand die dogmatisme en aan die ander kant die antidogmatisme — dit hou enersyds die gevaar in van verabsolutering (oorskatting, en ander- syds die gevaar van relativisme (onderskatting.

  1. Die Region braucht die Kultur - die Kultur braucht die Region

    Klemm, Ulrich

    1995-01-01

    Die Region braucht die Kultur - die Kultur braucht die Region. - In: Region in Aktion - oder: Region im Abseits? - Boxberg-Wölchingen : Eigenständige Regionalentwicklung Baden-Württemberg, 1995. - S. 25 f.

  2. Cytokine loops driving senescence

    Bartek, Jiří; Hodný, Zdeněk; Lukáš, Jan

    2008-01-01

    Roč. 10, č. 8 (2008), s. 887-889 ISSN 1465-7392 Institutional research plan: CEZ:AV0Z50520514 Keywords : cellular senescence * cytokines * autocrine feedback loop Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 17.774, year: 2008

  3. Possible role of ginsenoside Rb1 in skin wound healing via regulating senescent skin dermal fibroblast.

    Hou, Jingang; Kim, Sunchang

    2018-05-05

    Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H 2 O 2 exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP). The induction of SASP was regulated by p38MAPK/MSK2/NF-κB pathway. Interestingly, inhibition of p38MAPK activation only partially suppressed SASP. However, SASP was significantly inhibited by SB747651A, a specific MSK inhibitor. Additionally, we demonstrate that SASP stimulates migration of keratinocytes and myofibroblast transition of fibroblast, through fold-increased secretion of growth factors, platelet-derived growth factor AA (PDGF-AA) and AB (PDGF-AB), transforming growth factor beta 1 (TGF-β1) and beta 2 (TGF-β2), vascular endothelial growth factor A (VEGF-A) and D (VEGF-D), vascular endothelial growth factor receptor 2 (VEGFR2) and 3 (VEGFR3). Importantly, we also confirmed ginsenoside Rb1 promoted SASP-mediated healing process via p38MAPK/MSK2/NF-κB pathway. The results pointed to senescent fibroblast as a potential mechanism of wound healing control in human skin. Further, it provided a candidate targeted for wound therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...

  5. Cellular Senescence: A Translational Perspective

    James L. Kirkland

    2017-07-01

    Full Text Available Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP. Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.

  6. Die nabyheid van die Koninkryk

    W.J. Snyman

    1963-03-01

    Full Text Available Vanweë die belangrikheid daarvan volg hier ’n breër bespreking van die proefskrif van dr. Tjaart van der Walt oor die nabyheid van die Koninkryk as wat in ’n gewone resensie kan geskied. Die vraagstuk wat onder oë gesien word is so oud as die kerk en die teologie, soms minder en soms meer op die voorgrond. Tans kan gesê word, staan dit in die middelpunt. Daarby is dit nie maar ’n akademiese vraagstuk nie, maar ’n vraagstuk waarvoor elke nadenkende leser van die Skrif te staan kom.

  7. Cellular senescence and organismal aging.

    Jeyapalan, Jessie C; Sedivy, John M

    2008-01-01

    Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

  8. Die topkwark

    R. Tegen

    1998-07-01

    Full Text Available ’n Oorsig van die belangrikheid van die onlangs ontdekte topkwark by Fermilab in Chicago word gegee. Daar word aangetnon dat die topkwark belangrik is in fisika van die Oerknal, oftewel "Big Bang", en in die Standaard Model van Elementêredeeltjie-fisika. Toepaslike literatuur vir verdere studie kan van die lys van verwysings in hierdie kort, nietegniese artikel, nagegaan word.

  9. Senescence-Derived Extracellular Molecules as Modulators of Oral Cancer Development: A Mini-Review.

    Parkinson, Eric Kenneth; James, Emma L; Prime, Stephen S

    2016-01-01

    Oral cancers are predominantly oral squamous cell carcinomas (OSCCs) derived from keratinocytes, and there is now very detailed knowledge of the genetics and molecular biology of the epithelial tumourigenic component of these cancers, including the identification of cancer stem or tumour-initiating cells. Several key genetic alterations have been identified including the near ubiquitous loss of the CDKN2A/p16INK4A and p53 pathways and telomerase activation, together with frequent inactivation of the NOTCH1 canonical pathway either by somatic genetic alterations or by the presence of human papilloma virus. There is also evidence that OSCCs arise from a 'field' of altered cells and that malignant conversion takes place pre-dominantly at the microscopic level. However, in the last decade, it has been realised that tumour development and progression are influenced by the cells of the microenvironment with cross-talk between the epithelial (tumour) and mesenchymal components. OSCCs, especially those that have bypassed cellular senescence, produce an array of proteins and metabolites that induce cellular senescence in the normal surrounding cells; indeed, senescence is a common property of cancer-associated fibroblasts (CAFs). Cellular senescence is defined as an irreversible cell cycle arrest and is associated with the release of molecules known as the senescence-associated secretory phenotype that can selectively promote the growth of pre-neoplastic keratinocytes (osteopontin) and cancer invasion (transforming growth factor β, matrix metalloproteinases, interleukin 6 and lactate). In addition, both old and new work has shown that keratinocytes harbouring NOTCH loss-of-function mutations that lead to defective keratinocyte differentiation and loss of squamous epithelial barrier function may act as a tumour-promoting stimulus for initiated cells harbouring RAS pathway mutations by activating a wound response in the tumour mesenchyme. Thus, not all keratinocytes in the

  10. Biomarkers of replicative senescence revisited

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  11. Plant senescence and crop productivity

    Gregersen, Per L.; Culetic, Andrea; Boschian, Luca

    2013-01-01

    Senescence is a developmental process which in annual crop plants overlaps with the reproductive phase. Senescence might reduce crop yield when it is induced prematurely under adverse environmental conditions. This review covers the role of senescence for the productivity of crop plants....... With the aim to enhance productivity, a number of functional stay-green cultivars have been selected by conventional breeding, in particular of sorghum and maize. In many cases, a positive correlation between leaf area duration and yield has been observed, although in a number of other cases, stay...... plants, the expression of the IPT gene under control of senescence-associated promoters has been the most successful. The promoters employed for senescence-regulated expression contain cis-elements for binding of WRKY transcription factors and factors controlled by abscisic acid. In most crops...

  12. Androgen receptor drives cellular senescence.

    Yelena Mirochnik

    Full Text Available The accepted androgen receptor (AR role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.

  13. Die funksie van die belydenis in die struktuur van die kerk en die ...

    Ter wille van die argument wat in hierdie voordrag na vore gebring word, word vier sodanige konstituerende elemente van die kerklike struktuur onderskei, te wete die belydenis, die teologie, die verkondi- ging (meer bepaald die prediking) en die kerkorde (kerkwet volgens ons terminologie). Ons gaan nou elkeen hiervan ...

  14. Thalidomide increases human keratinocyte migration and proliferation.

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  15. Die posisie van die Helper in die sending

    I. J. van der Walt

    1972-05-01

    Full Text Available Gedurende die aanvangsjare van die sending het die helper ’n onmisbare funksie vervul. Hulle het die onherbergsame binnelande geken, waardevolle kontakpunte vir die sendelinge geopen en hulle mense geestelik help voorlig en voorberei.

  16. DIE GESKIEDENIS VAN DIE PERSONEELFUNKSIE IN DIE SA ...

    stel (kortdiensstelsel). Met die uitbreek van die oorlog in 1939 het die. Unieverdedigingsmag uit 40% Staandemag en. 60% aktiewe Burgermag bestaan. Op 22 Sept. 1939 is magtiging aan die Aktiewe Burgermag- eenhede verleen om vrywilligers vir die duur van die oorlog te aanvaar. Agv beswaar dat die Verdedigingswet.

  17. Die Formatestadt

    Günter Trojan

    2013-01-01

    Zu Zeiten von DV oder VHS (wer kennt das eigentlich noch?) war die Welt noch in Ordnung: Da hatte man eine Kassette in der Hand und wenn das passende Gerät gefunden wurde konnte man das Video auch abspielen. Günter Trojan diskutiert die Geschichte und Gegenwart unterschiedlicher Videoformate ...

  18. Die Formatestadt

    Günter Trojan

    2013-06-01

    Full Text Available Zu Zeiten von DV oder VHS (wer kennt das eigentlich noch? war die Welt noch in Ordnung: Da hatte man eine Kassette in der Hand und wenn das passende Gerät gefunden wurde konnte man das Video auch abspielen. Günter Trojan diskutiert die Geschichte und Gegenwart unterschiedlicher Videoformate ...

  19. Predatory senescence in ageing wolves.

    MacNulty, Daniel R; Smith, Douglas W; Vucetich, John A; Mech, L David; Stahler, Daniel R; Packer, Craig

    2009-12-01

    It is well established that ageing handicaps the ability of prey to escape predators, yet surprisingly little is known about how ageing affects the ability of predators to catch prey. Research into long-lived predators has assumed that adults have uniform impacts on prey regardless of age. Here we use longitudinal data from repeated observations of individually-known wolves (Canis lupus) hunting elk (Cervus elaphus) in Yellowstone National Park to demonstrate that adult predatory performance declines with age and that an increasing ratio of senescent individuals in the wolf population depresses the rate of prey offtake. Because this ratio fluctuates independently of population size, predatory senescence may cause wolf populations of equal size but different age structure to have different impacts on prey populations. These findings suggest that predatory senescence is an important, though overlooked, factor affecting predator-prey dynamics.

  20. Predatory senescence in aging wolves

    MacNulty, Daniel R.; Smith, Douglas W.; Vucetich, John A.; Mech, L. David; Stahler, Daniel R.; Packer, Craig

    2009-01-01

    It is well established that ageing handicaps the ability of prey to escape predators, yet surprisingly little is known about how ageing affects the ability of predators to catch prey. Research into long-lived predators has assumed that adults have uniform impacts on prey regardless of age. Here we use longitudinal data from repeated observations of individually-known wolves (Canis lupus) hunting elk (Cervus elaphus) in Yellowstone National Park to demonstrate that adult predatory performance declines with age and that an increasing ratio of senescent individuals in the wolf population depresses the rate of prey offtake. Because this ratio fluctuates independently of population size, predatory senescence may cause wolf populations of equal size but different age structure to have different impacts on prey populations. These findings suggest that predatory senescence is an important, though overlooked, factor affecting predator-prey dynamics.

  1. Predatory senescence in ageing wolves

    MacNulty, D.R.; Smith, D.W.; Vucetich, J.A.; Mech, L.D.; Stahler, D.R.; Packer, C.

    2009-01-01

    It is well established that ageing handicaps the ability of prey to escape predators, yet surprisingly little is known about how ageing affects the ability of predators to catch prey. Research into long-lived predators has assumed that adults have uniform impacts on prey regardless of age. Here we use longitudinal data from repeated observations of individually-known wolves (Canis lupus) hunting elk (Cervus elaphus) in Yellowstone National Park to demonstrate that adult predatory performance declines with age and that an increasing ratio of senescent individuals in the wolf population depresses the rate of prey offtake. Because this ratio fluctuates independently of population size, predatory senescence may cause wolf populations of equal size but different age structure to have different impacts on prey populations. These findings suggest that predatory senescence is an important, though overlooked, factor affecting predator-prey dynamics. ?? 2009 Blackwell Publishing Ltd/CNRS.

  2. Treatment of burn injuries with keratinocyte cultures

    Syring, C.; Maenig, H.J.; Von Versen, R.; Bruck, J.

    1999-01-01

    The German Institute for Cell and Tissue Replacement (DIZG) provides burned patients with skin and amnion for a temporary wound closure. Severely burned patients (>60% BSA for adults, >40% BSA for children) were supplied with autologous and allogenic grafts from cultured keratinocytes. The keratinocyte culture is done under GMP-conditions using the method of Rheinwald and Green. The 3T3 fibroblasts were irradiated with 60 Gy and used as feeder cells to produce keratinocyte sheets within 3 weeks. In this time up to 6.000 cm are available. The sheets were harvested by detachment with dispase (1,2 U/ml), fixed to gauze and transported to the hospital. The DIZG has a 3 years experience in the treatment of burns with keratinocyte sheets. The sheets were transplanted to patients in different hospitals, the total transplanted area is about 30.000 cm. This paper describes the experiences with ten severely burned patients treated with keratinocyte sheet

  3. Selective insulin resistance in hepatocyte senescence

    Aravinthan, Aloysious; Challis, Benjamin; Shannon, Nicholas; Hoare, Matthew; Heaney, Judith; Alexander, Graeme J.M.

    2015-01-01

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance

  4. Selective insulin resistance in hepatocyte senescence

    Aravinthan, Aloysious [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Challis, Benjamin [Institute of Metabolic Sciences, University of Cambridge, Cambridge (United Kingdom); Shannon, Nicholas [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Hoare, Matthew [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Heaney, Judith [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Foundation for Liver Research, Institute of Hepatology, London (United Kingdom); Alexander, Graeme J.M., E-mail: gja1000@doctors.org.uk [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom)

    2015-02-01

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance.

  5. Transgenic plants with altered senescence characteristics

    Amasino, Richard M.; Gan, Susheng; Noh, Yoo-Sun

    2002-03-19

    The identification of senescence-specific promoters from plants is described. Using information from the first senescence-specific promoter, SAG12 from Arabidopsis, other homologous promoters from another plant have been identified. Such promoters may be used to delay senescence in commercially important plants.

  6. NAC transcription factors in senescence

    Podzimska-Sroka, Dagmara; O'Shea, Charlotte; Gregersen, Per L.

    2015-01-01

    involving the hormone abscisic acid, Arabidopsis NAP promotes chlorophyll degradation, a hallmark of senescence. Furthermore, studies of the functional rice ortholog, OsNAP, suggest that NAC genes can be targeted to obtain specific changes in lifespan control and nutrient remobilization in crop plants...

  7. Die funksie van die skeppingstradisie in die boek Jeremia

    gedeeites voor wat sterk ooreenkomste toon met die beskrywings van die skep pingsgebeure in die boek Jeremia. • Volgpns Von Rad (1957:144-146) het daar wel 'n groep bestaan wat belange ge- had liet by die oorlewering van die skeppingstradisies. Dit was waarskynlik die. Sadokitiese priesters wat om twee redes aan ...

  8. Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro

    Siemes, Christina; Quast, Thomas; Kummer, Christiane; Wehner, Sven; Kirfel, Gregor; Mueller, Ulrike; Herzog, Volker

    2006-01-01

    Growing evidence shows that the soluble N-terminal form (sAPPα) of the amyloid precursor protein (APP) represents an epidermal growth factor fostering keratinocyte proliferation, migration and adhesion. APP is a member of a protein family including the two mammalian amyloid precursor-like proteins APLP1 and APLP2. In the mammalian epidermis, only APP and APLP2 are expressed. APP and APLP2-deficient mice die shortly after birth but do not display a specific epidermal phenotype. In this report, we investigated the epidermis of APP and/or APLP2 knockout mice. Basal keratinocytes showed reduced proliferation in vivo by about 40%. Likewise, isolated keratinocytes exhibited reduced proliferation rates in vitro, which could be completely rescued by either exogenously added recombinant sAPPα, or by co-culture with dermal fibroblasts derived from APP knockout mice. Moreover, APP-knockout keratinocytes revealed reduced migration velocity resulting from severely compromised cell substrate adhesion. Keratinocytes from double knockout mice died within the first week of culture, indicating essential functions of APP-family members for survival in vitro. Our data indicate that sAPPα has to be considered as an essential epidermal growth factor which, however, in vivo can be functionally compensated to a certain extent by other growth factors, e.g., factors released from dermal fibroblasts

  9. Die regsposisie van die gemolesteerde kind 1

    P.J. Schabort

    1991-03-01

    Full Text Available Hoe reik die reg uit na die seksueel gemolesteerde kind? As na die reg in wye verband gekyk word, sou dit alie wetgewing en alle gemeneregsbeginsels en alle regsprosedures insluit waardeur die Staat poog om molestering te voorkom en die gemolesteerde kind in beskerming te neem. Dit le baie wyd en sou byvoorbeeld die maatreels insluit van die Kindenvet 33 van 1960; die Wet op Egskeiding 70 van 1979; die Wet op Kindersorg 74 van 1983; die Wet op die Status van Kinders 82 van 1987 en die Wet op Bemiddeling in Sekere Egskeidingsaangeleenthede 24 van 1987. Eersdaags sal dit moontlik ook ’n Manifes vir die Regte van Kinders insluit wat vermoedelik geskoei sal wees op die W O se Konvensie vir die Regte van die Kind (1989 w a arv an die RSA tan s nog nie ’n ondertekenaar is nie.

  10. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  11. Identification of novel senescence-associated genes in ionizing radiation-induced senescent carcinoma cells

    Lee, Jae Seon; Kim, Bong Cho; Han, Na Kyung; Hong, Mi Na; Park, Su Min; Yoo, Hee Jung; Chu, In Sun; Lee, Sun Hee

    2009-01-01

    Cellular senescence is considered as a defense mechanism to prevent tumorigenesis. Ionizing radiation (IR) induces stress-induced premature senescence as well as apoptosis in various cancer cells. Senescent cells undergo functional and morphological changes including large and flattened cell shape, senescence-associated β-galactosidase (SA-βGal) activity, and altered gene expressions. Even with the recent findings of several gene expression profiles and supporting functional data, it is obscure that mechanism of IR-induced premature senescence in cancer cells. We performed microarray analysis to identify the common regulated genes in ionizing radiation-induced prematurely senescent human carcinoma cell lines

  12. Fibroblast Senescence and Squamous Cell Carcinoma: How wounding therapies could be protective

    Travers, Jeffrey B.; Spandau, Dan F; Lewis, Davina A.; Machado, Christiane; Kingsley, Melanie; Mousdicas, Nico; Somani, Ally-Khan

    2014-01-01

    Background Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age-dependent disease as the majority of these cancers are diagnosed in people over 70 years of age. Recent findings have led to a new hypothesis on the pathogenesis of SCC. Objectives To evaluate the potential of preventive therapies to reduce the incidence of SCC in at-risk geriatric patients. Materials and Methods Survey of current literature on wounding therapies to prevent SCCs. Results This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in geriatric dermis resulting in a reduction in dermal insulin-like growth factor-1 (IGF-1) expression. This lack of IGF-1 expression sensitizes epidermal keratinocytes to fail to suppress UVB-induced mutations leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF-1 expression, and correct the inappropriate UVB response found in geriatric skin, thus protecting geriatric keratinocytes from UVB-induced SCC initiation. Conclusions In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC. PMID:23437969

  13. Upregulation of cathepsin S in psoriatic keratinocytes.

    Schönefuss, Alexander; Wendt, Wiebke; Schattling, Benjamin; Schulten, Roxane; Hoffmann, Klaus; Stuecker, Markus; Tigges, Christian; Lübbert, Hermann; Stichel, Christine

    2010-08-01

    Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease is a concomitant feature of several diseases. Given this importance we studied the localization and regulation of CATS expression in normal and pathological human/mouse skin. In normal human skin CATS-immunostaining is mainly present in the dermis and is localized in macrophages, Langerhans, T- and endothelial cells, but absent in keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic dermatitis, actinic keratosis and psoriasis, CATS staining is strongly increased in the dermis. But only in psoriasis, CATS-immunostaining is also detectable in keratinocytes. We show that cocultivation with T-cells as well as treatment with cytokines can trigger expression and secretion of CATS, which is involved in MHC II processing in keratinocytes. Our data provide first evidence that CATS expression (i) is selectively induced in psoriatic keratinocytes, (ii) is triggered by T-cells and (iii) might be involved in keratinocytic MHC class II expression, the processing of the MHC class II-associated invariant chain and remodeling of the extracellular matrix. This paper expands our knowledge on the important role of keratinocytes in dermatological disease.

  14. Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span.

    Movahednia, Mohammad Mehdi; Kidwai, Fahad Karim; Zou, Yu; Tong, Huei Jinn; Liu, Xiaochen; Islam, Intekhab; Toh, Wei Seong; Raghunath, Michael; Cao, Tong

    2015-04-01

    Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-Kert(ACC)) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-Kert(AFF) were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-Kert(AFF) showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during

  15. Ethylene regulates phosphorus remobilization and expression of a phosphate transporter (PhPT1) during petunia corolla senescence

    Chapin, Laura J.; Jones, Michelle L.

    2009-01-01

    The programmed degradation of macromolecules during petal senescence allows the plant to remobilize nutrients from dying to developing tissues. Ethylene is involved in regulating the timing of nucleic acid degradation in petunia, but it is not clear if ethylene has a role in the remobilization of phosphorus during petal senescence. To investigate ethylene's role in nutrient remobilization, the P content of petals (collectively called the corolla) during early development and senescence was compared in ethylene-sensitive wild type Petunia×hybrida ‘Mitchell Diploid’ (MD) and transgenic petunias with reduced sensitivity to ethylene (35S::etr1-1). When compared to the total P content of corollas on the day of flower opening (the early non-senescing stage), P in MD corollas had decreased 74% by the late stage of senescence (advanced wilting). By contrast, P levels were only reduced by an average of 32% during etr1-1 corolla (lines 44568 and Z00-35-10) senescence. A high-affinity phosphate transporter, PhPT1 (PhPht1;1), was cloned from senescing petunia corollas by RT-PCR. PhPT1 expression was up-regulated during MD corolla senescence and a much smaller increase was detected during the senescence of etr1-1 petunia corollas. PhPT1 mRNA levels showed a rapid increase in detached corollas (treated at 1 d after flower opening) following treatment with low levels of ethylene (0.1 μl l-1). Transcripts accumulated in the presence of the protein synthesis inhibitor, cycloheximide, indicating that PhPT1 is a primary ethylene response gene. PhPT1 is a putative phosphate transporter that may function in Pi translocation during senescence. PMID:19380421

  16. The oxidative hypothesis of senescence

    Gilca M

    2007-01-01

    Full Text Available The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g., those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc. This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal β -oxidation and respiratory burst of phagocytic cells, antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol, alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

  17. A comparison of oncogene-induced senescence and replicative senescence: implications for tumor suppression and aging.

    Nelson, David M; McBryan, Tony; Jeyapalan, Jessie C; Sedivy, John M; Adams, Peter D

    2014-06-01

    Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway, the senescence-associated secretory phenotype. However, cellular senescence is initiated by diverse molecular triggers, such as activated oncogenes and shortened telomeres, and is associated with varied and complex physiological endpoints, such as tumor suppression and tissue aging. The extent to which distinct triggers activate divergent modes of senescence that might be associated with different physiological endpoints is largely unknown. To begin to address this, we performed gene expression profiling to compare the senescence programs associated with two different modes of senescence, oncogene-induced senescence (OIS) and replicative senescence (RS [in part caused by shortened telomeres]). While both OIS and RS are associated with many common changes in gene expression compared to control proliferating cells, they also exhibit substantial differences. These results are discussed in light of potential physiological consequences, tumor suppression and aging.

  18. PPARgamma Deficiency Counteracts Thymic Senescence

    David Ernszt

    2017-11-01

    Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

  19. Forging a signature of in vivo senescence.

    Sharpless, Norman E; Sherr, Charles J

    2015-07-01

    'Cellular senescence', a term originally defining the characteristics of cultured cells that exceed their replicative limit, has been broadened to describe durable states of proliferative arrest induced by disparate stress factors. Proposed relationships between cellular senescence, tumour suppression, loss of tissue regenerative capacity and ageing suffer from lack of uniform definition and consistently applied criteria. Here, we highlight caveats in interpreting the importance of suboptimal senescence-associated biomarkers, expressed either alone or in combination. We advocate that more-specific descriptors be substituted for the now broadly applied umbrella term 'senescence' in defining the suite of diverse physiological responses to cellular stress.

  20. Senescence induction; a possible cancer therapy

    Kondoh Hiroshi

    2009-01-01

    Full Text Available Abstract Cellular immortalization is a crucial step during the development of human cancer. Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replicative senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological proliferation stimuli: they have altered cell morphology and gene expression patterns, although they remain viable with preserved metabolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign lesions. Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. During immortalization, cells acquire genetic alterations that override senescence. Tumor suppressor genes and oncogenes are closely involved in senescence, as their knockdown and ectopic expression confer immortality and senescence induction, respectively. By using high throughput genetic screening to search for genes involved in senescence, several candidate oncogenes and putative tumor suppressor genes have been recently isolated, including subtypes of micro-RNAs. These findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy.

  1. Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse

    Demaria, Marco; O'Leary, Monique N.; Chang, Jianhui; Shao, Lijian; Liu, Su; Alimirah, Fatouma; Koenig, Kristin; Le, Catherine; Mitin, Natalia; Deal, Allison M.; Alston, Shani; Academia, Emmeline C.; Kilmarx, Sumner; Valdovinos, Alexis; Wang, Boshi; de Bruin, Alain; Kennedy, Brian K.; Melov, Simon; Zhou, Daohong; Sharpless, Norman E.; Muss, Hyman; Campisi, Judith

    Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinfl ammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells nonspecifi cally, often with adverse reactions. In accord with prior

  2. Die rol van die blanke werker in die motivering van die swart werker

    G. J. Oosthuizen

    1980-11-01

    Opsomming Die motivering van die Swart werker kan nie in die huidige situasie in isolasie bestudeer word nie, omdat die Blanke werker steeds in die bestuursposisie is en daarom die motivering van die Swart werker kan beïnvloed. Hierdie ondersoek was daarop gerig om die rol van die Blanke werker in die motivering van die Swart werker nader te ondersoek. Die houding en die leierskapsbenadering van die Blanke werker teenoor die Swart werker is gemeet, asook die behoeftes wat volgens die Blanke werker by die Swart werker bestaan, bevredig is, of nie bestaan nie. Die behoeftes van Swart werkers, soos deur hulleself gesien, is ook ondersoek. Ten opsigte van sekere aspekte is beduidende verskille gevind.

  3. Physiology and molecular biology of petal senescence

    Doorn, van W.G.; Woltering, E.J.

    2008-01-01

    Petal senescence is reviewed, with the main emphasis on gene expression in relation to physiological functions. Autophagy seems to be the major mechanism for large-scale degradation of macromolecules, but it is still unclear if it contributes to cell death. Depending on the species, petal senescence

  4. Targeting senescence cells in pancreatic cancer | IDRC ...

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  5. Oncogenic senescence: a multi-functional perspective

    Baker, D.J.; Alimirah, F.; Deursen, J.M.A. van; Campisi, J.; Hildesheim, J.

    2017-01-01

    Cellular senescence is defined as an irreversible growth arrest with the acquisition of a distinctive secretome. The growth arrest is a potent anticancer mechanism whereas the secretome facilitates wound healing, tissue repair, and development. The senescence response has also become increasingly

  6. Die hervertolking van die paradigma in verband met die ...

    Kerkorde van De Mist en die Algemene Reglement van 1816, wat onderskeidelik vir die Kaapse Kerk en die .... Een van die eerstes was Sam Freiherr von Pufendorf (1632-1694) wat in sy werk De habitu religionis ..... Koning was weer aan bewind (vgl Diepenhorst sj:74w; De Visser 1926/1927 lll:202w). 43.1 JD Janssen ...

  7. die heidelbergse kategismus en die kategesemateriaal van die ned

    subjek, objek, leerstof en die metodiek van die senior kategese. Bloemfontein: Algemene Jeugkommissie Sondagskoolboekhandel. de rAAd oer ned ger kerken in Zuid AfrikA. 1921. De zevende vergadering: handelinge. 1925. De negende vergadering: handelinge. de villierS, d. W. 1957. Die Kategese in die Ned. Geref.

  8. die sinodale verband van die nederduitse gereformeerde kerk in die

    Liezel

    Strauss. Die sinodale verband van die Nederduitse Gereformeerde Kerk. 122 die Vrystaatse Sinode anti-veranderingsgesind of eerder gesond-behoudend of gereformeerd-gematig? Veral as dit .... howe) in moeilike omstandighede gebring is (NG Kerk in die OVS 1865-1912:5). In 'n brief op 8 Augustus 1864 ontken Ds.

  9. Die kerkregtelike posisie van die ouderling en diaken in die ...

    ... drie dekades die Kerkreg gevestig as 'n selfstandige vak in die teologiese curriculum, maar ook 'n baie groot rol gespeel daarin dat die beginsels van die kerk like reg beter begryp word. Naas sy wetenskaplike bydrae word met eweveel genoegdoening gedink aan sy bcsondere persoonlikheid, sy werkvermoe, sy humor-.

  10. Possible Roles of Strigolactones during Leaf Senescence

    Yusuke Yamada

    2015-09-01

    Full Text Available Leaf senescence is a complicated developmental process that involves degenerative changes and nutrient recycling. The progress of leaf senescence is controlled by various environmental cues and plant hormones, including ethylene, jasmonic acid, salicylic acid, abscisic acid, cytokinins, and strigolactones. The production of strigolactones is induced in response to nitrogen and phosphorous deficiency. Strigolactones also accelerate leaf senescence and regulate shoot branching and root architecture. Leaf senescence is actively promoted in a nutrient-poor soil environment, and nutrients are transported from old leaves to young tissues and seeds. Strigolactones might act as important signals in response to nutrient levels in the rhizosphere. In this review, we discuss the possible roles of strigolactones during leaf senescence.

  11. Riglyne vir die onderwys.

    J. L. du Plooy

    1960-03-01

    Full Text Available In die afgelope vyftig jaar sedert die Unie tot stand gekom het, is veel op die gebied van onderwys tot stand gebring. Dit is heel natuurlik dat ’n mens sou vra: Wat van die toekoms?

  12. Piper betle L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts

    Lina Wati Durani

    2017-01-01

    Full Text Available Piper betle (PB is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%, presenescent (127.3%, and senescent (157.3% HDFs. Increased expressions of PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of SOD1 increased, whereas GPX1, PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.

  13. Piper betle L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts.

    Durani, Lina Wati; Khor, Shy Cian; Tan, Jen Kit; Chua, Kien Hui; Mohd Yusof, Yasmin Anum; Makpol, Suzana

    2017-01-01

    Piper betle (PB) is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs) was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%), presenescent (127.3%), and senescent (157.3%) HDFs. Increased expressions of PRDX6 , TP53 , CDKN2A , PAK2 , and MAPK14 were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of SOD1 increased, whereas GPX1 , PRDX6 , TP53 , CDKN2A , PAK2 , and MAPK14 were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.

  14. Vanillin protects human keratinocyte stem cells against ultraviolet B irradiation.

    Lee, Jienny; Cho, Jae Youl; Lee, Sang Yeol; Lee, Kyung-Woo; Lee, Jongsung; Song, Jae-Young

    2014-01-01

    Ultraviolet-B (UVB) irradiation is one of major factors which induce cellular damages in the epidermis. We investigated protective effects and mechanisms of vanillin, a main constituent of vanilla beans, against UVB-induced cellular damages in keratinocyte stem cells (KSC). Here, vanillin significantly attenuated UVB irradiation-induced cytotoxicity. The vanillin effects were also demonstrated by the results of the senescence-associated β-galactosidase and alkaline comet assays. In addition, vanillin induced production of pro-inflammatory cytokines. Attempts to elucidate a possible mechanism underlying the vanillin-mediated effects revealed that vanillin significantly reduced UVB-induced phosphorylation of ataxia telangiectasia mutated (ATM), serine threonine kinase checkpoint kinase 2 (Chk2), tumor suppressor protein 53 (p53), p38/mitogen-activated protein kinase (p38), c-Jun N-terminal kinase/stress-activated protein kinase (JNK), S6 ribosomal protein (S6RP), and histone 2A family member X (H2A.X). UVB-induced activation of p53 luciferase reporter was also significantly inhibited by vanillin. In addition, while ATM inhibitor had no effect on the vanillin effects, mouse double minute 2 homolog (MDM2) inhibitor significantly attenuated suppressive effects of vanillin on UVB-induced activation of p53 reporter in KSC. Taken together, these findings suggest that vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing

    Hoke, Glenn D.; Ramos, Corrine; Hoke, Nicholas N.; Crossland, Mary C.; Shawler, Lisa G.

    2016-01-01

    Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer. PMID:27840833

  16. Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing.

    Hoke, Glenn D; Ramos, Corrine; Hoke, Nicholas N; Crossland, Mary C; Shawler, Lisa G; Boykin, Joseph V

    2016-01-01

    Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer.

  17. Die partypolitiek en die toekoms van die Afrikaanse volkskultuur

    A.P. Treurnicht

    1970-03-01

    Full Text Available Reeds in 1853 het die Zuid Afrikaan hom soos volg uitgelaat: „Dis ’n dwaling wat ons reeds meermale bestry het dat ons as Britse onderdane verplig sou wees, om die Britse nasionaliteit ons s’n te maak. Die Kolonis van Hollandse oorsprong kan geen Engelsman word nie, en moet ook geen Nederlander wil wees nie. Wanneer hy weet om sy standpunt te waardeer, dan sal hy as verligte kolonis die grondtrekke van die Engelse volkskarakter met dié van die Nederlandse harmonies leer verenig en daardeur word wat hy as Kapenaar moet word.”

  18. Autocrine IL-6 mediates pituitary tumor senescence

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

    2017-01-01

    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  19. Die Voortrekker-Monument

    Gerard Moerdyk

    1938-03-01

    Full Text Available Die Eeufeesjaar is vir die Afrikaner ’n tydperk van besieling. Nog nooit sedert die ontstaan van ons volk het een enkele gebeurtenis soveel nasietrots gewek as die honderdjarige herdenking van die Groot Trek. Vir die eerste keer in ons geskiedenis voel ons ons nie meer Kapenaars, Vrystaters, Natalers, en Transvalers nie, maar Afrikaners, saamgesnoer deur die tradisies van ’n selfstandige kultuurvolk. Wanneer die klimaks van die Ossewatrek met die hocksteenlegging van die Voortrekker-Monument bereik word, sal die besieling nie uitsterf nie, die krag wat geskep is sal bly voortgroei tot ’n onweerstaanbare mag. Die Afrikaner sal homself vind, en as die Monument na sowat vyf jaar onthul word, sal die saad wat in hierdie jaar gesaai is, tot voile rypheid gekom het. Dan sal die Monument self tot die volk spreek; intussen egter, is dit wenslik, nee noodsaaklik selfs, om die Monument aan die Afrikaners te verklaar, om ‘n uiteensetting te gee van die noodsaaklikheid van so ’n Monument, sowel as om die motief te verduidelik wat as inspirasie gedien het vir die ontwerpdaar van.

  20. Die Britse owerheid en die onderwys op Heidelberg gedurende die ...

    The establishment of Christian National Education (CNE) Schools stimulated the concept of mother tongue education. Oor die klaskamerpraktyk en die werklike gehalte van onderrig tydens die kampskooltydperk is daar min bekend. Heidelberg wat na 1902 in 'n belangrike onderwyssentrum in Transvaal ontwikkel het, het ...

  1. Die belangrikste kenmerk van die diereproduksie- bedrywe oor die ...

    digdhede teen 1980 uit 'n kudde van 30 rnilj.skape ge- produseer moet word. Tweedens sal die faktore ... die Republiek van Suid-Mrika teen 1980 in totaal 28 milj. sal wees. Indien die produsente dit as 'n ..... Appendix Table 4 in Digestive Physiology and nutrition of ruminants Vol. 3 Ed. and Publ. D.C. Church, Oregon State ...

  2. DIE ROL VAN DIE TAALWETENSKAP IN DIE ONTWIKKELING VAN ...

    aanslag op die sogenaamde "Intentional Fallacy", heelwat verder. n. Mens sou hier eintlik ook op die invloed van Lacan se toepassing van. De Sacs sure op Freud moet wys, en op Macherey se Theory of Literary. Production. Barthes is naamlik besig om repressie teen te werk, en die teks as produksieproses in stede van ...

  3. Quantitative identification of senescent cells in aging and disease.

    Biran, Anat; Zada, Lior; Abou Karam, Paula; Vadai, Ezra; Roitman, Lior; Ovadya, Yossi; Porat, Ziv; Krizhanovsky, Valery

    2017-08-01

    Senescent cells are present in premalignant lesions and sites of tissue damage and accumulate in tissues with age. In vivo identification, quantification and characterization of senescent cells are challenging tasks that limit our understanding of the role of senescent cells in diseases and aging. Here, we present a new way to precisely quantify and identify senescent cells in tissues on a single-cell basis. The method combines a senescence-associated beta-galactosidase assay with staining of molecular markers for cellular senescence and of cellular identity. By utilizing technology that combines flow cytometry with high-content image analysis, we were able to quantify senescent cells in tumors, fibrotic tissues, and tissues of aged mice. Our approach also yielded the finding that senescent cells in tissues of aged mice are larger than nonsenescent cells. Thus, this method provides a basis for quantitative assessment of senescent cells and it offers proof of principle for combination of different markers of senescence. It paves the way for screening of senescent cells for identification of new senescence biomarkers, genes that bypass senescence or senolytic compounds that eliminate senescent cells, thus enabling a deeper understanding of the senescent state in vivo. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  4. Wêreldmededingendheid en die tegnologie

    C. W. I. Pistorius

    1996-07-01

    Full Text Available Afgesien van die interne uitdagings wat die Heropbou- en Ontwikkelingsprogram (HOP aan Suid-Afrika bied, moet die land ook tred hou met die veranderende globale omgewing, spesifiek die toenemende belangrikheid van ekonomiese sekuriteit as komponent van nasionale sekuriteit. Die konsep van mededingendheid vergestalt die doelwit wat nagestreef moet word ten einde die ontluikende globale ekonomiese stryd aan te durf. As ’n belangrike drywer van ekonomiese welvaart is tegnologie een van die belangrikste sleutels tot internasionale mededingendheid. Tegnologiese innovasie is die proses wat as hefboom hiervoor gebruik moet word. Dit is egter nodig dat tegnologie, en spesifiek die proses van tegnologiese innovasie, formeel en gestruktureerd bestuur moet word, sowel op nasionale as firmavlak. Op nasionale vlak is die voorsiene Nasionale Innovasiestelsel beslis ’n stap in die regte rigting.

  5. die ontstaan en die ontwikkeling van die skoolkadette-stelsel in die rsa

    toe algemene diensplig ingestel is. Die diens- plig het intussen sy volle beslag gekry en in. Weermagkringe het die gedagte posgevat dat skoolkadette. 'n deeglike ondersoek vereis ten einde die skoolgaande seun vir sy komende nasionale diensplig te orienteer. Tydens kadetopleldlng leer die seuns al die fynere kunsles ...

  6. Van die Gasredakteur

    cherish and teach.'1. Die Fakulteit Geneeskunde van die Universiteit van die Oranje-Vrystaat het pragtig gegroei ge- durende die eerste 21 jaar van sy bestaan. Die entoesiasme, doelgerigtheid, harde werk en inisia- tiewe van 'n groot aantal persone was hiervoor verantwoordelik. 'If we see a bit more clearly than they, it is ...

  7. Halfkrone vir die Nagmaal

    Owner

    die omgewing van Velddrif en Laaiplek, ook noordwaarts verby Lambertsbaai tot by. Doringbaai en Strandfontein. “Haar seeverhale is Sussie (Kotze) se belangrikste bydrae tot die Afrikaanse letterkunde”, sê Kotzé-Myburgh in die voorwoord van die versamelbundel. Die leser word herinner aan Kotze se debuutroman, ...

  8. Die teologie in gesprek met die ekonomie

    (1723-1790) sy vertrekpunt neem, ontwikkel, as oorwinnaars uit die Franse Revolu .... Die onmiddellike sukses van Adam Smith se 'Wealth of Nations' was .... alle vorme van sosialisme niks anders as 'kommunisme' (Wassenaar 1977:12) nie.

  9. Death penalty for keratinocytes: apoptosis versus cornification.

    Lippens, S; Denecker, G; Ovaere, P; Vandenabeele, P; Declercq, W

    2005-11-01

    Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a specific function such as formation of the skin barrier provided by corneocytes, also known as terminally differentiated keratinocytes. In this case, programmed cell death results in accumulation of functional cell corpses. Previously, this process has been associated with apoptotic cell death. In this overview, we discuss differences and similarities in the molecular regulation of epidermal programmed cell death and apoptosis. We conclude that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.

  10. Culture technique of rabbit primary epidermal keratinocytes

    Marini M

    2012-10-01

    Full Text Available The epidermis is the protective covering outer layer of the mammalian skin. The epidermal cells are stratified squamous epithelia which undergo continuous differentiation of loss and replacement of cells. Ninety per cent of epidermal cells consist of keratinocytes that are found in the basal layer of the stratified epithelium called epidermis. Keratinocytes are responsible for forming tight junctions with the nerves of the skin as well as in the process of wound healing. This article highlights the method of isolation and culture of rabbit primary epidermal keratinocytes in vitro. Approximately 2cm x 2cm oval shaped line was drawn on the dorsum of the rabbit to mark the surgical area. Then, the skin was carefully excised using a surgical blade and the target skin specimens harvested from the rabbits were placed in transport medium comprising of Dulbecco’s Modified Eagle Medium (DMEM and 1% of antibiotic-antimycotic solution. The specimens were transferred into a petri dish containing 70% ethanol and washed for 5 min followed by a wash in 1 x Dulbecco’s Phosphate Buffered Saline (DBPS. Then, the skin specimens were placed in DMEM and minced into small pieces using a scalpel. The minced pieces were placed in a centrifuge tube containing 0.6% Dispase and 1% antibiotic-antimycotic solution overnight at 4°C in a horizontal orientation. The epidermis layer (whitish, semi-transparent was separated from the dermis (pink, opaque, gooey with the aid of curved forceps by fixing the dermis with one pair of forceps while detaching the epidermis with the second pair. The cells were cultured at a density of 4 x 104 cells/cm2 in culture flask at 37°C and 5% CO2. The cell morphology of the keratinocytes was analyzed using inverted microscope.

  11. Die dogmatiese binding van die prediking

    genoemde probleemstelling wat ons homileties na riglyne wil soek, sonder die pretensie dat finale oplossings gevind sal word. Om hierdie probleem te ontleed is dit nodig om eers kortliks 'n begripsbepaling van die begrippe dogma, binding en prediking te maak. Vanuit die begripsbepaling kan ons dan probeer vasstel wat ...

  12. DIE PERSOON VAN VREDE IN DIE SENDING

    aan dat 'n lewe onder die gesag van God tot volle vrede lei: “In coming under the rule of Yahweh, moreover, life was made whole and safe.” Dit is spesifiek in die tempel waar die volheid van God se vrede ondervind word (1997:662):. The temple is indeed the place where Israel entered into Yahweh's full zone of shalom.

  13. Human keratinocyte sensitivity towards inflammatory cytokines varies with culture time

    G. Elliott

    1992-01-01

    Full Text Available Proliferating keratinocyte cultures have been reported to synthesize higher concentrations of prostaglandin (PG E than confluent ones. As interleukin-1 (IL-1 stimulates keratinocyte PGE synthesis we investigated whether the degree of confluency of the keratinocyte culture modified the response of the cells to IL-1. It was found that IL-1α (100 U/ml stimulated PGE2 synthesis by proliferating (7 days in culture but not differentiating (14 days in culture keratinocytes. Similar effects were observed using tumour necrosis factor-α. Both arachidonic acid (AA and the calcium ionophore A23187 stimulated PGE2 synthesis by 7 and 14 day cultures although the increase was greatest when 7 day cultures were used. Our data indicate that there is a specific down-regulation of the mechanism(s by which some inflammatory cytokines stimulate keratinocyte eicosanoid synthesis as cultured keratinocytes begin to differentiate.

  14. n Oorsig van die huidige stand van navorsing oor die

    Test

    7 Jun 2011 ... Die eerste maal wat dit as deel van die teks van 1 Johannes aangehaal word, is in die. 4de eeu in 'n Latynse teks, Liber Apologeticus (hf 4). Eers aan die einde van die 16de eeu is dit in 'n amptelike Katolieke uitgawe van die Vulgaat ingesluit. Die doel van die Johannesbriewe. Waarom is die Briewe ...

  15. Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis.

    Nakrieko, Kerry-Ann; Welch, Ian; Dupuis, Holly; Bryce, Dawn; Pajak, Agnieszka; St Arnaud, René; Dedhar, Shoukat; D'Souza, Sudhir J A; Dagnino, Lina

    2008-04-01

    Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function.

  16. Die Ware Buch und die Philologie

    Bernhard Hurch

    2017-10-01

    Full Text Available Die im 19. Jahrhundert sich verändernden Produktionsbedingungen für Druckwerke (Buchdruck, Satz, Papier, Bindung wirkten katalysierend auf die Fachkonstitution und Institutionalisierung der Philologien. Hier steht der tatsächliche Buchmarkt im Vordergrund der Darstellung, das Käuferpublikum und die Voraussetzungen des Vertriebs. Dazu gehören auch die Rezension als entstehende Textsorte und die rasch arbeitenden Rezensionsorgane. F.-R. Hausmann wurde in den letzten Jahren unentbehrlicher Mitarbeiter dieses im Rahmen des Grazer Schuchardt-Projekts "Netzwerk des Wissens" angesiedelten Ansatzes.

  17. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

    Lewinska, Anna; Wnuk, Maciej

    2017-04-01

    Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

  18. Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

    Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

    2013-11-01

    In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral

  19. Transcriptional analyses of natural leaf senescence in maize.

    Wei Yang Zhang

    Full Text Available Leaf senescence is an important biological process that contributes to grain yield in crops. To study the molecular mechanisms underlying natural leaf senescence, we harvested three different developmental ear leaves of maize, mature leaves (ML, early senescent leaves (ESL, and later senescent leaves (LSL, and analyzed transcriptional changes using RNA-sequencing. Three sets of data, ESL vs. ML, LSL vs. ML, and LSL vs. ESL, were compared, respectively. In total, 4,552 genes were identified as differentially expressed. Functional classification placed these genes into 18 categories including protein metabolism, transporters, and signal transduction. At the early stage of leaf senescence, genes involved in aromatic amino acids (AAAs biosynthetic process and transport, cellular polysaccharide biosynthetic process, and the cell wall macromolecule catabolic process, were up-regulated. Whereas, genes involved in amino acid metabolism, transport, apoptosis, and response to stimulus were up-regulated at the late stage of leaf senescence. Further analyses reveals that the transport-related genes at the early stage of leaf senescence potentially take part in enzyme and amino acid transport and the genes upregulated at the late stage are involved in sugar transport, indicating nutrient recycling mainly takes place at the late stage of leaf senescence. Comparison between the data of natural leaf senescence in this study and previously reported data for Arabidopsis implies that the mechanisms of leaf senescence in maize are basically similar to those in Arabidopsis. A comparison of natural and induced leaf senescence in maize was performed. Athough many basic biological processes involved in senescence occur in both types of leaf senescence, 78.07% of differentially expressed genes in natural leaf senescence were not identifiable in induced leaf senescence, suggesting that differences in gene regulatory network may exist between these two leaf senescence

  20. Senescence from glioma stem cell differentiation promotes tumor growth

    Ouchi, Rie; Okabe, Sachiko; Migita, Toshiro; Nakano, Ichiro; Seimiya, Hiroyuki

    2016-01-01

    Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.

  1. Senescence from glioma stem cell differentiation promotes tumor growth

    Ouchi, Rie [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Okabe, Sachiko; Migita, Toshiro [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakano, Ichiro [Department of Neurosurgery, Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, AL 35233 (United States); Seimiya, Hiroyuki, E-mail: hseimiya@jfcr.or.jp [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan)

    2016-02-05

    Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.

  2. Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

    Huey-Min Hwang

    2005-04-01

    Full Text Available Over the past several years, a great deal of interest has been focused on the harmful effects of ultraviolet (UV radiation to human skin. UV light has been implicated in aging, sunburn and skin cancer. Few studies, however, have been done to determine the effects that UV light, in conjunction with other environmental contaminants, may have on human skin. Polycyclic Aromatic Hydrocarbons (PAHs are a class of compounds that have been reported to be toxic, mutagenic and carcinogenic to many eukaryotic organisms. UV light is also known to increase the toxicity of PAHs through photo-activation and photo-modification. The purpose of this study was to assess the effects of UV-A irradiated pyrene (Pyr, 1-aminopyrene (1-AP and 1-hydroxypyrene (1-HP on human keratinocytes, the skin primary site of UV irradiated PAH exposure. Our findings indicate that simultaneous treatment of human keratinocyte cell line, HaCaT, with 1.0μg/ml pyrene, 1-AP or 1-HP and 3.9 J/cm2/min UV-A light resulted in significant inhibition of cell proliferation. Approximately 100% of the cells died in the case of UV-A irradiated 1-AP and 1-HP. In the case of UV-A irradiated pyrene, more than 70% of the cells died, indicating that UV-A is able to transform these PAHs into more harmful intermediates.

  3. CIRCADIAN CLOCK-ASSOCIATED 1 Inhibits Leaf Senescence in Arabidopsis

    Yi Song

    2018-03-01

    Full Text Available Leaf senescence is an integral part of plant development, and the timing and progressing rate of senescence could substantially affect the yield and quality of crops. It has been known that a circadian rhythm synchronized with external environmental cues is critical for the optimal coordination of various physiological and metabolic processes. However, the reciprocal interactions between the circadian clock and leaf senescence in plants remain unknown. Here, through measuring the physiological and molecular senescence related markers of several circadian components mutants, we found that CIRCADIAN CLOCK-ASSOCIATED 1 inhibits leaf senescence. Further molecular and genetic studies revealed that CCA1 directly activates GLK2 and suppresses ORE1 expression to counteract leaf senescence. As plants age, the expression and periodic amplitude of CCA1 declines and thus weakens the inhibition of senescence. Our findings reveal an age-dependent circadian clock component of the process of leaf senescence.

  4. Die vrede van Münster / Westfale en die betekenis daarvan vir die ...

    In die Suid-Afrikaanse kerkgeskiedenis egter is die Vrede van Münster as epogmakende gebeure tot dusver nie net in die algemeen verwaarloos nie, maar boonop is die direkte verband tussen hierdie sentrale historiese baken aan die een kant en aan die ander kant die vestiging van die VOC se verversingspos aan die ...

  5. Tegnologie en die mens

    omgewingsbesoedeling, volgend op industrialisasie en verstedeliking, gee uit- ing tot krete van wanhoop en frustrasie. Die maatskaplike ontwrigting agv outomatisasie het die begrippe van vervreemding en naam- loosheid op die voorgrond van sosiale be- wustheid geplaas. • Die Neutrale Siening. Tegnologie was nag. 34.

  6. GODSBEELDE IN DIE LITURGIE

    15 Mei 2010 ... Biezeveld, de Boer, Brümmer, Muis. 2001; Brown 2006; Durand 2007). ... Wanneer sal hy weer in God se teenwoordigheid verskyn (vers 3)? Dié vraag is vol onsekerheid. (Schuman 2004:8). Sy onsekerheid ... God se volk en die enkeling in die geskiedenis het al die trou van God ervaar waarop die digter ...

  7. Die ontwikkeling van die bestuursmotiveringsvraelys (BMV

    A. S. Engelbrecht

    1991-06-01

    Full Text Available The development of the Managerial Motivation Questionnaire (MMQ: Several criticisms of the psychometric suitability of existing measures of managerial motivation are reported in the literature. This study aimed at developing a new psychometrically sound instrument, the Managerial Motivation Questionnaire (MMQ. This was done on the basis of a comprehensive study of the literature on managerial motivation and the role-motivation theory. The preliminary MMQ was systematically shortened and refined until the final MMQ of 98 items was composed. This was based on social desirability and semantic appraisal, item analysis and factor analysis of the questionnaire. The results indicate that it was possible to develop a final MMQ that was relatively free of social desirability. It further demonstrated satsifactory internal consistencies on two samples (a = 0/90, N = 360; a = 0/91, N = 535, where all subscale items were found to be relatively pure measures of the isolated factors. Although some evidence was found providing support for the reliability of the MMQ, a need for further research on the construct validity of managerial motivation still exists. Opsomming In die literatuur word verskeie punte van kritiek teen die psigometriese geskiktheid van bestaande meetinstrumente van bestuursmotivering gerapporteer. Die doelstelling van hierdie studie was dus om aan die hand van die konseptuele omiyning van bestuursmotivering, en die rolmotiveringsteorie as algemene verwysingsraamwerk, 'n nuwe psigometries aanvaarbare meetinstrument, die Bestuursmotiveringsvraelys (BMV, te ontwikkel. Op grond van sosiale wenslikheids- en semantiese beoordeling, itemontleding en faktorontleding van die voorlopige BMV is die vraelys stelselmatig verkort en verfyn totdat die finale BMV van 98 items saamgestel is. Die resultate dui daarop dat hierdie studie wel daarin geslaag het om 'n finale BMV te ontwikkel wat relatief vry van sosiale wenslikheid is, bevredigende interne

  8. In vitro senescence of immune cells.

    Effros, Rita B; Dagarag, Mirabelle; Valenzuela, Hector F

    2003-01-01

    Immune cells are eminently suitable model systems in which to address the possible role of replicative senescence during in vivo aging. Since there are more than 10(8) unique antigen specificities present within the total T lymphocyte population of each individual, the immune response to any single antigen requires massive clonal expansion of the small proportion of T cells whose receptors recognize that antigen. The Hayflick Limit may, therefore, constitute a barrier to effective immune function, at least for those T cells that encounter their specific antigen more than once over the life course. Application of the fibroblast replicative senescence model to the so-called cytotoxic or CD8 T cell, the class of T cells that controls viral infection and cancer, has revealed certain features in common with other cell types as well as several characteristics that are unique to T cells. One senescence-associated change that is T cell-specific is the complete loss of expression of the activation signaling surface molecule, CD28, an alteration that enabled the documentation of high proportions of senescent T cells in vivo. The T cell model has also provided the unique opportunity to analyze telomere dynamics in a cell type that has the ability to upregulate telomerase yet nevertheless undergoes senescence. The intimate involvement of the immune system in the control of pathogens and cancer as well as in modulation of bone homeostasis suggests that more extensive analysis of the full range of characteristics of senescent T cells may help elucidate a broad spectrum of age-associated physiological changes.

  9. Varswateralge en die ekonomie

    W. E. Scott

    1988-03-01

    Full Text Available Die artikel bespreek die ekonomiese belong wat varswateralge alreeds het en hul moontlike verdere ontginning in die toekoms. Sowel gewenste as ongewenste aspekte word oorweeg en hoofsaaklik met voorbeelde uit Suid-Afrika geïllustreer. Die oormatige ontwikkeling van ongewenste alge in varswater verlaag die watergehalte dear verskeie chemiese veranderinge, wat kan wissel van smake en geure tot die produksie van verbindings wat gesondheidsgevare vir mens of dier inhou. Verwydering van ongewenste alge dra aansienlik by tot die koste van waterbehandeling. Oormatige alggroei belemmer ontspanningsgebruike en kan eiendomswaardes langs rivier- en damoewers beïnvloed.

  10. Prediking aan die hand van die metafoor van fiksieskryf

    p1243322

    HTS 64(3) 2008 siening van die self en waarheid. In die pre-moderne paradigma kan die dominante metafoor verstaan word aan die hand van 'n spieël wat die lig uit 'n transendente oorsprong weerkaats, terwyl die moderne paradigma uitgedruk word met die metafoor van 'n lamp wat 'n eie, oorspronklike lig binne die self.

  11. e .Kuraioriufn. DIE W ETENSKAPLIKE BETEKENIS VAN DIE W ERK

    Test

    ENGELBRECHT ver antwoordelik vir die Ou-Testamentiese vakke en Hebreeus. Die aan stelling van 'n derde professor het noodsaaklik geword, want dit sou. 85 .... De .Spreuken ran 5a/o?no omvat die nuwe vertaling en die ekse gese van die eerste 24 hoofstukke van die Spreukeboek. Die geskoold- heid in die Semitiese ...

  12. Drying without senescence in resurrection plants

    Griffiths, Cara A.; Gaff, Donald F.; Neale, Alan D.

    2014-01-01

    Research into extreme drought tolerance in resurrection plants using species such as Craterostigma plantagineum, C. wilmsii, Xerophyta humilis, Tortula ruralis, and Sporobolus stapfianus has provided some insight into the desiccation tolerance mechanisms utilized by these plants to allow them to persist under extremely adverse environmental conditions. Some of the mechanisms used to ensure cellular preservation during severe dehydration appear to be peculiar to resurrection plants. Apart from the ability to preserve vital cellular components during drying and rehydration, such mechanisms include the ability to down-regulate growth-related metabolism rapidly in response to changes in water availability, and the ability to inhibit dehydration-induced senescence programs enabling reconstitution of photosynthetic capacity quickly following a rainfall event. Extensive research on the molecular mechanism of leaf senescence in non-resurrection plants has revealed a multi-layered regulatory network operates to control programed cell death pathways. However, very little is known about the molecular mechanisms that resurrection plants employ to avoid undergoing drought-related senescence during the desiccation process. To survive desiccation, dehydration in the perennial resurrection grass S. stapfianus must proceed slowly over a period of 7 days or more. Leaves detached from the plant before 60% relative water content (RWC) is attained are desiccation-sensitive indicating that desiccation tolerance is conferred in vegetative tissue of S. stapfianus when the leaf RWC has declined to 60%. Whilst some older leaves remaining attached to the plant during dehydration will senesce, suggesting dehydration-induced senescence may be influenced by leaf age or the rate of dehydration in individual leaves, the majority of leaves do not senesce. Rather these leaves dehydrate to air-dryness and revive fully following rehydration. Hence it seems likely that there are genes expressed in

  13. Die dialogiese prinsipe

    J. J. de Klerk

    1981-08-01

    Full Text Available Met die dialogiese prinsipe word daardie beginsel bedoel, waarin die tweerigtingverkeer of kommunikasie onder, of met, of deur die mense op 'n heel besondere gesprekmatige wyse gere�l word. Tot die wese van die dialogiese prinsipe behoort "als Grundvoraussetzung das Ernstnehmen des Gesprachspartners und das darin enthaltene zuhoren-konnen. Dialog ist also etwas anderes als Disput oder Diskussion. Er setzt gegenseitiges Vertrauen und Hochachtung voraus."

  14. Emerging roles of lncRNAs in senescence

    Montes Resano, Marta; Lund, Anders H

    2016-01-01

    Cellular senescence is a complex stress response that leads to an irreversible state of cell growth arrest. Senescence may be induced by different stimuli such as telomere shortening, DNA damage or oncogenic insult among others. Senescent cells are metabolically highly active producing a wealth...

  15. Senescence rates in patients with end-stage renal disease

    Koopman, J J E; Rozing, M P; Kramer, Ada

    2011-01-01

    function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional...

  16. Die sestienpersoonlikheidsfaktorvraelys as hulpmiddel by die takseersentrum

    J. C. D. Augustyn

    1988-05-01

    Full Text Available The 16PF Personality Test as an aid to the assessment centre Assessment centres still remains costly and thime consuming. This study investigates the reduction of time and costs by the use of the 16 PF Personality Test as a method for measuring management dimensions. Promising results were obtained with a relatively small sample for the prediction of initiative and perseverance. Significant multiple correlations were also found for three criteria of management success. Further research may establish the use of the 16 PF as an aid to management assessment and thereby reduce the costs and time involved in assessment centres. Opsomming Takseersentrums se grootste probleem is gelee in die koste en tyd wat dit behels. Hierdie studie ondersoek die moontlikheid om beide te verminder deur die aanwending van die 16 PF Persoonlikheidsvraelys vir die meting van bestuursdimensies. Belowende resultate is met 'n relatiewe klein steekproef bevind ten opsigte van die voorspelling van inisiatiefen deursettingsvermoe. Beduidende meervoudige korrelasies is ook ten opsigte van drie kriteria van bestuursukses bevind. Verdere navorsing kan die gebruik van die 16 PF as hulpmiddel by bestuursevaluering vestig en sodoende die tydsduur en koste van takseersentrums verminder.

  17. DIE GESKIEDENIS VAN AFDELING LOGISTIEK

    1 Aug 1978 ... dan ook aangebied, Agv die probleem wat ont- staan het met die gebrek aan goedgekeurde poste vir die Afdeling en as gevolg van die ver- wagte vertraging met die ondersoek van die. DOS-span, het die Afdeling Logistiek en Afde- ling Personeel oorleg gepleeg en laasgenoemde het ingestem dat die ...

  18. Decorin gene expression and its regulation in human keratinocytes

    Velez-DelValle, Cristina; Marsch-Moreno, Meytha; Castro-Munozledo, Federico [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico); Kuri-Harcuch, Walid, E-mail: walidkuri@gmail.com [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico)

    2011-07-22

    Highlights: {yields} We showed that cultured human diploid epidermal keratinocytes express and synthesize decorin. {yields} Decorin is found intracytoplasmic in suprabasal cells of cultures and in human epidermis. {yields} Decorin mRNA expression in cHEK is regulated by pro-inflammatory and proliferative cytokines. {yields} Decorin immunostaining of psoriatic lesions showed a lower intensity and altered intracytoplasmic arrangements. -- Abstract: In various cell types, including cancer cells, decorin is involved in regulation of cell attachment, migration and proliferation. In skin, decorin is seen in dermis, but not in keratinocytes. We show that decorin gene (DCN) is expressed in the cultured keratinocytes, and the protein is found in the cytoplasm of differentiating keratinocytes and in suprabasal layers of human epidermis. RT-PCR experiments showed that DCN expression is regulated by pro-inflammatory and proliferative cytokines. Our data suggest that decorin should play a significant role in keratinocyte terminal differentiation, cutaneous homeostasis and dermatological diseases.

  19. Differentiation of human scalp hair follicle keratinocytes in culture.

    Weterings, P J; Verhagen, H; Wirtz, P; Vermorken, A J

    1984-01-01

    The morphology of human scalp hair follicle keratinocytes, cultured on the bovine eye lens capsule, is studied by light and electron microscopy. The hair follicle keratinocytes in the stratified cultures are characterized by the presence of numerous tonofilaments, desmosomes and lysosomes and by the presence of glycogen accumulations. The cells in the upper layers develop a cornified envelope. Moreover, an incomplete basal lamina is found between the capsule and the basal cells. However, some features of epidermal keratinocytes in vivo, such as keratohyalin granules and stratum corneum formation, are absent. Analysis of the polypeptides by sodium dodecylsulfate polyacrylamide gel electrophoresis also reveals differences between the cultured hair follicle cells and epidermis, whilst the patterns of cultured cells and hair follicle sheaths are similar. The morphological and protein biosynthetic aspects of terminal differentiation of the keratinocytes in vitro are correlated. These results are discussed in the light of the findings with cultured epidermal keratinocytes, reported in the literature.

  20. Planarians as a model of aging to study the interaction between stem cells and senescent cells in vivo

    Patrick M. Perrigue

    2015-12-01

    Full Text Available The depletion of stem cell pools and the accumulation of senescent cells in animal tissues are linked to aging. Planarians are invertebrate flatworms and are unusual in that their stem cells, called neoblasts, are constantly replacing old and dying cells. By eliminating neoblasts in worms via irradiation, the biological principles of aging are exposed in the absence of wound healing and regeneration, making planaria a powerful tool for aging research.

  1. Effects of UVB irradiation on keratinocyte growth factor (KGF) and receptor (KGFR) expression in cultured human keratinocytes

    Zhou, Y.; Lee, H.S.T.; Kooshesh, F.; Fujisawa, H.; Sauder, D.N.; Kondo, S. [Univ. of Toronto, Sunnybrook Health Science Centre, Div. of Dermatology, Toronto (Canada)

    1996-06-01

    Keratinocyte growth factor (KGF) and its receptor (KGFR) are thought to play important roles in normal keratinocyte growth and differentiation. Since UVB radiation is known to influence keratinocyte growth, we sought to determine whether UVB would alter the expression of KGF and KGFR. Using a reverse-transcription coupled polymerase chain reaction (RT-PCR), the present study examined the expression of KGF and KGFR mRNA in cultured normal human keratinocytes exposed to UVB irradiation. Total cellular RNA was extracted from cultured keratinocytes at various time points after irradiation, reverse transcribed and used for PCR amplification using primers specific for KGF and KGFR. Constitutive expression of KGFR mRNA, but not KGF mRNA, was detected in normal cultured human keratinocytes. After UVB irradiation at 300 J/m{sup 2}, the KGF mRNA remained undetectable while the KGFR mRNA level was significantly decreased. The down-regulation of KGFR mRNA expression was also confirmed by Northern blot analysis. Immunohistochemical studies demonstrated a decreased positive signal of KGFR in human keratinocytes after UVB irradiation. Our results suggest a possible role for the KGF-KGFR signalling pathway in the skin after exposure to UVB, and that UVB-induced growth inhibition of keratinocytes in hyperproliferative skin disorders may be related to downregulation of KGFR. (au) 39 refs.

  2. Die relevansie van die boek Prediker

    ook in die dogmatiek te bespeur is nie. 'n Vinnige oorsig oor die teksverwysings van. 'n paar wydgelese dogmatiekhandboeke kan dit bevestig. In Karl Barth se omvang- ryke Kirchliche Dogmatik word Prediker slegs vyf en dertig maal aangehaal en slegs sewe maal word teksgedeeltes bespreek. Emil Brunner haal Prediker ...

  3. Senescence and the pro-tumorigenic stroma.

    Alspach, Elise; Fu, Yujie; Stewart, Sheila A

    2013-01-01

    Hayflick and Moorhead first described senescence in the late 1960's as a permanent growth arrest that primary cells underwent after a defined number of cellular divisions in culture. This observation gave rise to the hypothesis that cells contained an internal counting mechanism that limited cellular division and that this limit was an important barrier to cellular transformation. What began as an in vitro observation has led to an immense body of work that reaches into all fields of biology and is of particular interest in the areas of aging, tissue regeneration, and tumorigenesis. The initially simplistic view that senescence limits cellular division and contributes to aging while stymying tumorigenesis has now evolved into an important and complex biological process that has numerous caveats and often opposing effects on tumorigenesis. In this review, we limit our discussion to the complex role senescence plays in tumorigenesis. Throughout the review we attempt to draw many parallels to other systems including the role senescent cells play in the tumor microenvironment and their significant molecular and phenotypic similarities to cancer associated fibroblasts (CAFs).

  4. biomedical challenges of human senescence: a review

    2002-12-12

    Dec 12, 2002 ... generation per mitochondrion. Understanding the role of cellular ageing in vivo is another major challenge for integrative study. The in vitro model of cell replicative senescence pioneered by. Sith and Pereira has elucidated the mechanisms limiting cell proliferation(30). Until recently the link between in.

  5. Senescence in the aging process [version 1; referees: 3 approved

    Richard GA Faragher

    2017-07-01

    Full Text Available The accumulation of ‘senescent’ cells has long been proposed to act as an ageing mechanism. These cells display a radically altered transcriptome and degenerative phenotype compared with their growing counterparts. Tremendous progress has been made in recent years both in understanding the molecular mechanisms controlling entry into the senescent state and in the direct demonstration that senescent cells act as causal agents of mammalian ageing. The challenges now are to gain a better understanding of how the senescent cell phenotype varies between different individuals and tissues, discover how senescence predisposes to organismal frailty, and develop mechanisms by which the deleterious effects of senescent cells can be ameliorated.

  6. Sirtuins, Cell Senescence, and Vascular Aging.

    Kida, Yujiro; Goligorsky, Michael S

    2016-05-01

    The sirtuins (SIRTs) constitute a class of proteins with nicotinamide adenine dinucleotide-dependent deacetylase or adenosine diphosphate-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition; and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, and contribute to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and nicotinamide adenine dinucleotide stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  7. Molecular bases of cellular senescence: Hayflick phenomenon 50 years later

    Patrycja Sosińska

    2016-03-01

    Full Text Available Normal human somatic cells have strictly limited proliferative capacity and reach a state of senescence when it becomes exhausted. It is believed that senescence is a response to extensive and irreparable DNA injury, localized in telomeric and/or non-telomeric regions of the genome. Main cause of this damage is oxidative stress, increasing due to deteriorated function of mitochondria. Senescent cells accumulate in tissues during aging, which is causatively linked with the development of various pathologies in elderly individuals, including cancer. This paper, prepared exactly 50 years after Leonard Hayflick’s discovery of the relationship between cellular senescence and organismal aging is aimed at presenting the current knowledge about molecular determinants of senescence, with particular emphasis paid to the role of oxidative stress, effectors of senescence at the level of cell cycle, markers of this phenomenon, and the effect of senescent cells on the development of certain age-related diseases.

  8. Use of NAP gene to manipulate leaf senescence in plants

    Gan, Susheng; Guo, Yongfeng

    2013-04-16

    The present invention discloses transgenic plants having an altered level of NAP protein compared to that of a non-transgenic plant, where the transgenic plants display an altered leaf senescence phenotype relative to a non-transgenic plant, as well as mutant plants comprising an inactivated NAP gene, where mutant plants display a delayed leaf senescence phenotype compared to that of a non-mutant plant. The present invention also discloses methods for delaying leaf senescence in a plant, as well as methods of making a mutant plant having a decreased level of NAP protein compared to that of a non-mutant plant, where the mutant plant displays a delayed leaf senescence phenotype relative to a non-mutant plant. Methods for causing precocious leaf senescence or promoting leaf senescence in a plant are also disclosed. Also disclosed are methods of identifying a candidate plant suitable for breeding that displays a delayed leaf senescence and/or enhanced yield phenotype.

  9. P. J. N. Smal, Die Universalisme in die Psalms. Academisch ...

    Test

    dat die historiese element in Israel se Godsopenbaring en daarmee die insig in sy betekenis te kort gedoen word. Die betekenis van die studie vir die historia revelationis is daardeur gering; as duidelike „tydlose” sistematisering van Outestamentiese gegewens oor die betrokke onder- werpe, soos die laaste hoofstuk, bl.

  10. DIE ONTVC'ERP VAN 'N SENDINGBELEID IN DIE HUIDIGE ...

    Test

    DIE ONTVC'ERP VAN 'N SENDINGBELEID IN DIE. HUIDIGE SITUASIE. Sending is 'n deel van die vervulling van die apostoliese opdrag van die kerk. Dit geskied op grond van en in gehoorsaamheid aan Gods. \\C'oord. Teologiese besinning is daarom die eerste en grondliggende vereiste by die ontwerp van 'n ...

  11. DIE PLEK VAN SANG EN MUSIEK IN DIE PROTESTANTSE ...

    Test

    Sy moet hierdie opdrag uitvoer deur mid del van die Prediking d.w.s. deur middel van die Woord-vorm, maar ook deur die bediening van die sakramente, dws. deur middel van die vorm van die Daad. Maar nou wil God nie hê dat die Kerk slegs één maal die Evangelie sal predik en die mense sal doop om hulle daarna.

  12. Packaged die heater

    Spielberger, Richard; Ohme, Bruce Walker; Jensen, Ronald J.

    2011-06-21

    A heater for heating packaged die for burn-in and heat testing is described. The heater may be a ceramic-type heater with a metal filament. The heater may be incorporated into the integrated circuit package as an additional ceramic layer of the package, or may be an external heater placed in contact with the package to heat the die. Many different types of integrated circuit packages may be accommodated. The method provides increased energy efficiency for heating the die while reducing temperature stresses on testing equipment. The method allows the use of multiple heaters to heat die to different temperatures. Faulty die may be heated to weaken die attach material to facilitate removal of the die. The heater filament or a separate temperature thermistor located in the package may be used to accurately measure die temperature.

  13. Die radio in Afrika

    S. de Villiers

    1966-03-01

    Full Text Available Omvang van radio-uitsendings in en na Afrika. — Redes vir die versnelde tempo van uitbreiding. — Radio as die geskikste massa-kommunikasiemiddel vir Afrika. — Faktore wat die verspreiding bemoeilik. — Skouspelagtige toename in luistertalle.Toe Plinius, wat in die jaar 79 oorlede is, in sy „Historia Naturalis” verklaar het dat daar altyd iets nuuts uit Afrika afkomstig is, kon hy nouliks voorsien het dat die „iets" negentien eeue later in die lug sou setel wat hierdie reuse-vasteland oorspan — ’n Babelse spraakverwarring en ’n ongekende, verbete woorde-oorlog in die etergolwe, onder meer daarop bereken om die harte en hoofde van derduisendes te verower.

  14. Die Erfindung des Manuskripts

    Benne, Christian

    Die Entstehung der literarischen Moderne ging seit dem 18. Jahrhundert damit einher, dass die Anzahl literarischer Manuskripte ebenso wuchs wie deren Bedeutung. Der Buchdruck hatte die Handschrift keineswegs überflüssig gemacht, sondern provozierte im Gegenteil einen neuen, am Autographen...

  15. Die begrafnisdíens

    Num 20: 1; Jos 24: 30; Hand 5: 5 - 11). Selfs van die ... Gebruike rondom die begrafnis het van geslag tot geslag gewissel. De Vaux ... der geskied deur die hoorders 'te onderrig, te vermaan, te vertroos en te bestraf, soos dit in elke geval ..... gehandhaaf hoef te word, veral in die lig van die feit dat die predikant die kerklike.

  16. Die gebruik van parallelplaatreologie vir die bepaling van die intrinsieke viskositeit van poli-etileentereftalaat

    O. C. Vorster

    2005-09-01

    Full Text Available Die bepaling van die intrinsieke viskositeit van poli-etileentereftalaat word bemoeilik deur die feit dat daar tans slegs twee metodes in gebruik is. In die eerste metode word die bepaling deur middel van oplossingsviskometrie gedoen, maar die toksisiteit van die oplosmiddel, asook die tydperk wat dit neem om die bepaling te doen, is ’n probleem. Die tweede metode word beperk deur die kompleksiteit en beskikbaarheid van die apparatuur in Suid-Afrika. In hierdie studie word ’n alternatiewe metode, gebaseer op parallelplaatreologie, voorgestel wat albei hierdie probleme oorkom en die resultate sodoende verkry, word vergelyk met dié wat met bestaande metodes verkry is.

  17. Stereotyped distribution of proliferating keratinocytes in disorders affecting the epidermis

    Pierard-Franchimont, C.; Pierard, G.E.

    1989-01-01

    We used the technique of autoradiography after incorporation of tritiated thymidine ( 3 H-TdR) to evaluate keratinocyte proliferation in basal, epibasal, and other epidermal layers in 30 diseases affecting the epidermis. The number and proportion of 3 H-TdR-labeled keratinocytes were counted in the different layers of the epidermis. Significant correlations were found between the proliferative indices of the different epidermal layers. Such links indicate that the epidermis responds in a rather stereotyped way to various pathological conditions. There exists some regulation in the distribution, number, and proportion of 3 H-TdR-labeled keratinocytes in the various layers of the epidermis

  18. Die invloed van die neo-marxistiese kultuuranalise op die Wêreldraad van Kerke en die Gereformeerde Kerke van Nederland

    J. M. Vorster

    1979-05-01

    Full Text Available Toe die studente dwarsoor die VSA en Europa in die laat sestigerjare ’n plotselinge en radikale verset openbaar het teen die bestaande orde, het hulle die deur geopen vir ’n nuwe mededinger om die hart van die Westerse kultuur. Dit is die nou reeds bekende neo-Marxisme. Sedertdien het hierdie jongeling sy voetspore op vele vlakke van die Westerse kultuur gelaat.

  19. Molecular genetic approaches to the study of cellular senescence.

    Goletz, T J; Smith, J R; Pereira-Smith, O M

    1994-01-01

    Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Scanning Ion Conductance Microscopy of Live Keratinocytes

    Hegde, V; Mason, A; Saliev, T; Smith, F J D; McLean, W H I; Campbell, P A

    2012-01-01

    Scanning ion conductance microscopy (SICM) is perhaps the least well known technique from the scanning probe microscopy (SPM) family of instruments. As with its more familiar counterpart, atomic force microscopy (AFM), the technique provides high-resolution topographic imaging, with the caveat that target structures must be immersed in a conducting solution so that a controllable ion current may be utilised as the basis for feedback. In operation, this non-contact characteristic of SICM makes it ideal for the study of delicate structures, such as live cells. Moreover, the intrinsic architecture of the instrument, incorporating as it does, a scanned micropipette, lends itself to combination approaches with complementary techniques such as patch-clamp electrophysiology: SICM therefore boasts the capability for both structural and functional imaging. For the present observations, an ICnano S system (Ionscope Ltd., Melbourn, UK) operating in 'hopping mode' was used, with the objective of assessing the instrument's utility for imaging live keratinocytes under physiological buffers. In scans employing cultured HaCaT cells (spontaneously immortalised, human keratinocytes), we compared the qualitative differences of live cells imaged with SICM and AFM, and also with their respective counterparts after chemical fixation in 4% paraformaldehyde. Characteristic surface microvilli were particularly prominent in live cell imaging by SICM. Moreover, time lapse SICM imaging on live cells revealed that changes in the pattern of microvilli could be tracked over time. By comparison, AFM imaging on live cells, even at very low contact forces (< nN), could not routinely image microvilli: rather, an apparently convolved image of the underlying cytoskeleton was instead prevalent. We note that the present incarnation of the commercial instrument falls some way behind the market leading SPMs in terms of technical prowess and scanning speed, however, the intrinsic non-obtrusive nature of

  1. die pers as bron oor die geskiedenis van die eerste vrydeidsoorlog

    dood agv wonde wat hy tydens die slag opgedoen het. Dit was vir die Britse volk onaanvaarbaar dat slegs twee Boere gedood is nadat daar tussen. 20 000 en 30 000 rondtes op die Boere afgevuur is. Die pers kon net nie die ware syfers publiseer nie, want dit sou na 'n onwaarheid Iyk. Het die. Britse volk egter die Boere ...

  2. die impak van metodologie op die verstaan van die nuwe testament

    voorbeeld eers een maal deur die bril van die vorm- en redaksiekritiek na die Evangelies gekyk het, dink jy vir altyd anders oor hulle tot- standkoming. Inderdaad, nuwe metodes lei tot nuwe perspektiewe! Dit is dan ook waar die fokus van hierdie artikel val: die impak van metodologie op die verstaan van die Nuwe ...

  3. Verskuiwing in die moraal?

    S.P. van der Walt

    1974-03-01

    Full Text Available Modewoorde het ons deesdae oorgenoeg in die Christelike sedeleer en hulle kan nogal verwarring stig. U moet my vergun om met u te spreek oor een so ’n modewoord nl „verskuiwing’’ in die moraal. Dis nogal ’n mooi woord, wat so dikwels gebruik word op baie terreine en tog meer wil aandui as maar net ’n veranderde sienswyse, ’n wysiging in opvattinge of nuwe riglyne wat al gangbaar geword het in die praktyk. Die begrip wil eintlik die ewolusionêre gang beklemtoon, want dit is dan eintlik net die ou norme wat effens anders bekyk word of nie meer so nou geneem of dik onderstreep word nie. Die verskuiwing beteken dan dat alles nog dieselfde bly, net die posisie of plek het verander. Verskuiwing beteken tog plekverandering of plekwisseling en dan sekerlik nie in die sin dat die plekke ver uitmekaar lê nie. Verskuiwing beteken net maar vlak langs die vorige te staan kom. As dit dan ’n beter plek is, is dit ewolusie, ontwikkeling, verbetering.

  4. In Vitro Toxicity of Aluminum Nanoparticles in Human Keratinocytes

    McCormack-Brown, Stephanie

    2008-01-01

    .... There is no published data on AL NP toxicity effects on human skin. This research used in vitro techniques to determine the cytotoxicity of AL NPs, sized 50, 80, and 120 nm, on human keratinocytes...

  5. Serial cultivation of human scalp hair follicle keratinocytes.

    Weterings, P J; Roelofs, H M; Vermorken, A J; Bloemendal, H

    1983-01-01

    A method is described for the serial cultivation of adult human hair follicle keratinocytes. Plucked scalp hair follicles, placed on bovine eye lens capsules as a growth substrate, give rise to quickly expanding colonies within a few days. After trypsinization, the cells are replated with irradiated 3T3 cells as 'feeders'. Using this combination of techniques the keratinocytes can be subcultured up to four times. In this way about 10(7) keratinocytes can be generated from one single hair follicle. Moreover, the technique enables cryogenic storage of the cells, allowing for instance, convenient transportation. Subcultured hair follicle keratinocytes can be plated on glass coverslips. This allows immunofluorescence studies. The keratin cytoskeletons visualized using an antiserum against human keratin.

  6. Establishment of primary keratinocyte culture from horse tissue biopsates

    Jernej OGOREVC

    2015-12-01

    Full Text Available Primary cell lines established from skin tissue can be used in immunological, proteomic and genomic studies as in vitro skin models. The goal of our study was to establish a primary keratinocyte cell culture from tissue biopsates of two horses. The primary keratinocyte cell culture was obtained by mechanical and enzymatic dissociation and with explant culture method. The result was a heterogeneous primary culture comprised of keratinocytes and fibroblasts. To distinguish epithelial and mesenchymal cells immunofluorescent characterisation was performed, using antibodies against cytokeratin 14 and vimentin. We successfully at attained a primary cell line of keratinocytes, which could potentially be used to study equine skin diseases, as an animal model for human diseases, and for cosmetic and therapeutic product testing.

  7. Markers of T Cell Senescence in Humans

    Weili Xu

    2017-08-01

    Full Text Available Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as “immunosenescence” can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers.

  8. oor die inhoud en boodskap van die heidelbergse kategismus

    Smit. Oor die Inhoud en Boodskap van die Heidelbergse Kategismus. 52. Uiteraard sal dié tema saamhang met die bedoelinge agter die opstel van die Kategismus. Ook die vraag na moontlike bedoelinge of motiewe is egter 'n ingewikkelder vraag as wat miskien gedink mag word. Uiteraard was daar agter elke kategismus ...

  9. Thomas Erastus oor die struktuur van die gemeenskap'^

    óók aansprake en regte het, is die opvatting dat sowel die burgerlike gemeenskap as die kerk 'n perfecta societas sibi sufficiens is, nié werklik aanvaar nie. Die Middeleeuse gemeenskap was die corpus christianum,. 'n gemeenskap wat nie deur fisiese of politieke grense beperk was nie. Sy grense het gelê waar die grense ...

  10. die doel en wese van opvoedende onderwys en die implikasies

    Oaar moet onderskei word tussen die doelstellings van opvoedende onderwys en die einddoel wat bereik word deur die nastrewing van hierdie doelstellings. Gunter praat van die naderliggende doelstellings (1981, b1.105). \\/at die enddoel van opvoedende onderwys bet ref, gaan die meeste opvoedkundi ges akkoord dat ...

  11. Irradiation With Carbon Ion Beams Induces Apoptosis, Autophagy, and Cellular Senescence in a Human Glioma-Derived Cell Line

    Jinno-Oue, Atsushi; Shimizu, Nobuaki; Hamada, Nobuyuki; Wada, Seiichi; Tanaka, Atsushi; Shinagawa, Masahiko; Ohtsuki, Takahiro; Mori, Takahisa; Saha, Manujendra N.; Hoque, Ariful S.; Islam, Salequl; Kogure, Kimitaka; Funayama, Tomoo; Kobayashi, Yasuhiko

    2010-01-01

    Purpose: We examined biological responses of human glioma cells to irradiation with carbon ion beams (C-ions). Methods and Materials: A human glioma-derived cell line, NP-2, was irradiated with C-ions. Apoptotic cell nuclei were stained with Hoechst 33342. Induction of autophagy was examined either by staining cells with monodansylcadaverine (MDC) or by Western blotting to detect conversion of microtuble-associated protein light chain 3 (MAP-LC3) (LC3-I) to the membrane-bound form (LC3-II). Cellular senescence markers including induction of senescence-associated β-galactosidase (SA-β-gal) were examined. The mean telomere length of irradiated cells was determined by Southern blot hybridization. Expression of tumor suppressor p53 and cyclin/cyclin-dependent kinase inhibitor p21 WAF1/CIP1 in the irradiated cells was analyzed by Western blotting. Results: When NP-2 cells were irradiated with C-ions at 6 Gy, the major population of the cells died of apoptosis and autophagy. The residual fraction of attached cells ( WAF1/CIP1 was induced in NP-2 cells after irradiation. Furthermore, we found that irradiation with C-ions induced cellular senescence in a human glioma cell line lacking functional p53. Conclusions: Irradiation with C-ions induced apoptosis, autophagy, and cellular senescence in human glioma cells.

  12. Shining a Light on Black Holes in Keratinocytes.

    Bowman, Shanna L; Marks, Michael S

    2018-03-01

    The mechanisms by which melanins are transferred from melanocytes and stored within keratinocytes to generate skin pigmentation are hotly debated. Correia et al. and Hurbain et al. provide evidence that melanin cores of melanosomes are secreted from melanocytes and taken up and stored within non-degradative membranous organelles in keratinocytes in the basal epidermis of human skin. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Leaf senescence and nutrient remobilisation in barley and wheat

    Gregersen, P L; Holm, P B; Krupinska, K

    2008-01-01

    Extensive studies have been undertaken on senescence processes in barley and wheat and their importance for the nitrogen use efficiency of these crop plants. During the senescence processes, proteins are degraded and nutrients are re-mobilised from senescing leaves to other organs, especially...... of chloroplasts is summarised. Rubisco is thought to be released from chloroplasts into vesicles containing stroma material (RCB = Rubisco-containing bodies). These vesicles may then take different routes for their degradation. Transcriptome analyses on barley and wheat senescence have identified genes involved...... in degradative, metabolic and regulatory processes that could be used in future strategies aimed at modifying the senescence process. The breeding of crops for characters related to senescence processes, e.g. higher yields and better nutrient use efficiency, is complex. Such breeding has to cope with the dilemma...

  14. Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest.

    Sapieha, Przemyslaw; Mallette, Frédérick A

    2018-04-25

    In mitotic cells, cellular senescence is a permanent state of G1 arrest, that may have evolved in parallel to apoptosis, to limit proliferation of damaged cells and oncogenesis. Recent studies have suggested that postmitotic cells are also capable of entering a state of senescence, although the repercussions of postmitotic cellular senescence (PoMiCS) on tissue health and function are currently ill-defined. In tissues made largely of post-mitotic cells, it is evolutionary advantageous to preserve cellular integrity and cellular senescence of post-mitotic cells may prevent stressor-induced tissue degeneration and promote tissue repair. Paradoxically, PoMiCS may also contribute to disease progression through the generation of inflammatory mediators, termed the senescence-associated secretory phenotype. Here, we discuss the potential roles of PoMiCS and propose to enlarge the current definition of cellular senescence to postmitotic terminally differentiated cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Die tug oor ampsdraers tydens die doleansie van 1886

    J. Visser

    1986-06-01

    Full Text Available In art 29 van die Nederlandse Geloofsbelydenis word bely: “Die merktekens om die ware Kerk te ken is die volgende: As die Kerk die suiwere prediking van die evangelie uitoefen, as dit die suiwer bediening van die sakramente gebruik soos Christus dit ingestel het, as die kerklike tug gebruik word om die sondes te straf.” Dit spreek vanself dat wanneer ampsdraers, aan wie Christus sy kudde toevertrou het (Hand 20 : 28, met leer en /of lewenswandel in sonde volhard en nie daarin met tug gestuit word nie, word die ware kerk nie gebou nie maar afgebreek. 0ns sal later in hierdie artikel aantoon hoedanig die suiwer tug oor ampsdraers, veral leertug, tydens die Doleansie tot skade van die kerk van Christus agterweë gebly het.

  16. The WRKY transcription factor family and senescence in switchgrass.

    Rinerson, Charles I; Scully, Erin D; Palmer, Nathan A; Donze-Reiner, Teresa; Rabara, Roel C; Tripathi, Prateek; Shen, Qingxi J; Sattler, Scott E; Rohila, Jai S; Sarath, Gautam; Rushton, Paul J

    2015-11-09

    Early aerial senescence in switchgrass (Panicum virgatum) can significantly limit biomass yields. WRKY transcription factors that can regulate senescence could be used to reprogram senescence and enhance biomass yields. All potential WRKY genes present in the version 1.0 of the switchgrass genome were identified and curated using manual and bioinformatic methods. Expression profiles of WRKY genes in switchgrass flag leaf RNA-Seq datasets were analyzed using clustering and network analyses tools to identify both WRKY and WRKY-associated gene co-expression networks during leaf development and senescence onset. We identified 240 switchgrass WRKY genes including members of the RW5 and RW6 families of resistance proteins. Weighted gene co-expression network analysis of the flag leaf transcriptomes across development readily separated clusters of co-expressed genes into thirteen modules. A visualization highlighted separation of modules associated with the early and senescence-onset phases of flag leaf growth. The senescence-associated module contained 3000 genes including 23 WRKYs. Putative promoter regions of senescence-associated WRKY genes contained several cis-element-like sequences suggestive of responsiveness to both senescence and stress signaling pathways. A phylogenetic comparison of senescence-associated WRKY genes from switchgrass flag leaf with senescence-associated WRKY genes from other plants revealed notable hotspots in Group I, IIb, and IIe of the phylogenetic tree. We have identified and named 240 WRKY genes in the switchgrass genome. Twenty three of these genes show elevated mRNA levels during the onset of flag leaf senescence. Eleven of the WRKY genes were found in hotspots of related senescence-associated genes from multiple species and thus represent promising targets for future switchgrass genetic improvement. Overall, individual WRKY gene expression profiles could be readily linked to developmental stages of flag leaves.

  17. The disparity between human cell senescence in vitro and lifelong replication in vivo.

    Rubin, Harry

    2002-07-01

    Cultured human fibroblasts undergo senescence (a loss of replicative capacity) after a uniform, fixed number of approximately 50 population doublings, commonly termed the Hayflick limit. It has been long known from clonal and other quantitative studies, however, that cells decline in replicative capacity from the time of explantation and do so in a stochastic manner, with a half-life of only approximately 8 doublings. The apparent 50-cell doubling limit reflects the expansive propagation of the last surviving clone. The relevance of either figure to survival of cells in the body is questionable, given that stem cells in some renewing tissues undergo >1,000 divisions in a lifetime with no morphological sign of senescence. Oddly enough, these observations have had little if any effect on general acceptance of the Hayflick limit in its original form. The absence of telomerase in cultured human cells and the shortening of telomeres at each population doubling have suggested that telomere length acts as a mitotic clock that accounts for their limited lifespan. This concept assumed an iconic character with the report that ectopic expression of telomerase by a vector greatly extended the lifespan of human cells. That something similar might occur in vivo seemed consistent with initial reports that most human somatic tissues lack telomerase activity. More careful study, however, has revealed telomerase activity in stem cells and some dividing transit cells of many renewing tissues and even in dividing myocytes of repairing cardiac muscle. It now seems likely that telomerase is active in vivo where and when it is needed to maintain tissue integrity. Caution is recommended in applying telomerase inhibition to kill telomerase-expressing cancer cells, because it would probably damage stem cells in essential organs and even increase the likelihood of secondary cancers. The risk may be especially high in sun-exposed skin, where there are usually thousands of p53-mutant clones of

  18. The evolution of senescence in the tree of life

    Salguero-Gómez, Roberto

    The existing theories on the evolution of senescence assume that senescence is inevitable in all organisms. However, recent studies have shown that this is not necessarily true. A better understanding of senescence and its underlying mechanisms could have far-reaching consequences for conservation...... and eco-evolutionary research. This book is the first to offer interdisciplinary perspectives on the evolution of senescence in many species, setting the stage for further developments. It brings together new insights from a wide range of scientific fields and cutting-edge research done on a multitude...

  19. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  20. Die metafoor by Breyten Breytenbach

    Owner

    23 Jun 2009 ... metafories, of spesifiek verwysend, te werk gegaan is. Tyd sou mens die hoofmotief van die bundel noem, tyd en geheue wat verbygaan: 1 en 2; en die einde van die storie wat gekom het: “fluit-fluit my storie is uit”. (Die tema van verbygaan word weer opgeneem in 8 en 9: die stories wat nooit meer gehoor ...

  1. IRAN IN DIE INTERNASIONALE MAGSTRYD

    In die verband kan genoem word dat die Russe nog grotendeels gebruik maak van 'n metode waarvolgens water in die oliestratum gepomp word om 'n opwaartse druk van ru-olie te verseker; een nadeel hiervan is dat die water mettertyd deur die oliehoudende laag ontsnap en agv die drukverlies isvoortgesette ontginning.

  2. Die singulation method

    Swiler, Thomas P.; Garcia, Ernest J.; Francis, Kathryn M.

    2013-06-11

    A method is disclosed for singulating die from a semiconductor substrate (e.g. a semiconductor-on-insulator substrate or a bulk silicon substrate) containing an oxide layer (e.g. silicon dioxide or a silicate glass) and one or more semiconductor layers (e.g. monocrystalline or polycrystalline silicon) located above the oxide layer. The method etches trenches through the substrate and through each semiconductor layer about the die being singulated, with the trenches being offset from each other around at least a part of the die so that the oxide layer between the trenches holds the substrate and die together. The trenches can be anisotropically etched using a Deep Reactive Ion Etching (DRIE) process. After the trenches are etched, the oxide layer between the trenches can be etched away with an HF etchant to singulate the die. A release fixture can be located near one side of the substrate to receive the singulated die.

  3. Ontsporing van die regstaatsbegrip en sy konsekwensies vir die afrikanervolk

    N. G.S. Van der Walt

    1966-03-01

    Full Text Available Die opvatting van die suiwere regstaat bring sy vraagstukke mee wanneer dit in verband gebring word met die leer van die soewereiniteit in eie kring. Laasgenoemde leer wortel in die geloof dat God die mens roep tot diens aan Hom, en dat die mens vry moet wees om ten opsigte van alle lewensaspekte God na die hoogste mate te kan dien. Hierdie verskeidenheid van aspekte is deur dr. A. Kuyper en sy volgelinge gesistemati- seer tot menslike verbande en lewenskringe, elk met ’n be- paalde sfeer waarin ander kringe nie mag inmeng nie. Elkeen is dan soewerein binne sy eie kring. Met verwysing na die staat is dan gespreek van die staatstaak as synde die hand- hawing van die reg, en omdat die staat in toenemende mate hom veral in die latere tyd ook besig gehou het met bedrywig- hede wat nouliks as van juridiese aard beskou kan word, is daar die onderskeid gemaak tussen die primêre en sekundêre taak van die staat. Die sistematiek van die wetsidee, deur prof. Dooyeweerd ontwikkel, waar die staat sy bestemmingsfunksie in die regsaspek vind, het vanselfsprekend geen plek vir so 'n dualistiese staatstaak nie, en die oplossing is deur sommige daarin gesoek om sulke staatsoptrede te vertolk as hebbende wel betrekking op die regsgemeenskap of die regsverkeer. Staatsondernemings soos paaie, spoorweë, spellingreëling, ens. word dan beskou as noodsaaklik vir die instandhouding van die regsgemeenskap en regsverkeer. Tereg wys A. M. Donner1 daarop dat so ’n vertolking eintlik neerkom op ’n oorspanning van die regsbegrip. Hy self sien dan die staatstaak in vrede- of orde-handhawing, wat in die eerste plaas wel regshandha- wing veronderstel. Onder orde word dan alles verstaan wat noodsaaklik is vir die gladde verkeer in die ontwikkelingsgang van die regsgemeenskap. Die wese van die staat het dan vol- gens hom te doen met reg, maar sy taak is meer as suiwere regshandhawing. Wat onrus verwek en die orde versteur, moet uit die openbare lewe verwyder word, en die

  4. Die sterwende kindjie

    J.T. De Jongh van Arkel

    1983-09-01

    Full Text Available The thought of a child dying appears as an antithesis and thus the feelings evoked by the dying child are stronger than when older persons are dying. Around the child’s death bed there is no place for detached spectators and all become involved in caring for and supporting him. Caregivers also have a supporting responsibility towards the members of the child’s family.

  5. Analise van die Tswanaraaisel

    S. A. Swanepoel

    1984-05-01

    Full Text Available ’n Strukturele, stilistiese en funksionele bcskrywing van die Twanaraaisel bring mee dat daar aan die volgende aspekte aandag gegee moet word: •\tWat is ’n raaisel en lioe word dit in Tswana genoem. •\tTot watter studiegebied en literere genre hoort die raaisel en watter subvorme kan vir Tswana onderskei word. •\tHoe sien die struktuur van Tswanaraaisels daar uit. •\tDeur wie, waar, wanneer en hoe word Tswanaraaisels voorgedra. •\tWatter stilistiese kenmcrke kan in Tswanaraaisels onderskei word. •\tWatter funksies vervul raaisels in ’n Tswanagcmeenskap.

  6. The Angry Dying Patient.

    Houston, Robert E.

    1999-02-01

    Over 25 years ago, Kubler-Ross identified anger as a predictable part of the dying process. When the dying patient becomes angry in the clinical setting, all types of communication become strained. Physicians can help the angry dying patient through this difficult time by using 10 rules of engagement. When physicians engage and empathize with these patients, they improve the patient's response to pain and they reduce patient suffering. When physicians educate patients on their normal responses to dying and enlist them in the process of family reconciliation, they can impact the end-of-life experience in a positive way.

  7. Die brein soos beskou deur die Grieke en Romeine

    Francois P. Retief

    2015-02-01

    Full Text Available In Ou Egipte is mummifikasie met uitgebreide reseksie of uitsnyding van organe geassosieer, maar geen kennis is geneem van die morfologie van die brein nie. Griekse skrywers van die sesde en vyfde eeue v.C. het die brein aanvanklik gesien as die setel van intelligensie, die orgaan van sensoriese waarneming en gedeeltelik die oorsprong van sperma. Pneuma het ’n belangrike rol in breinfunksie gespeel. Hippokrates was die eerste om die brein te beskryf as ’n dubbele orgaan, wat met harsingvlies (meninges bedek, funksioneel van pneuma afhanklik en vertolker van begrip is. Tydgenote soos Plato, Aristoteles en Diokles het tot die beskrywing bygedra, maar laasgenoemde twee het beweer dat die hart die middelpunt van intelligensie is en nie die brein nie. Gedurende die laaste helfte van die vierde eeu v.C. is disseksie van die menslike liggaam tydelik aan die mediese skool van Alexandrië toegelaat en het dit tot merkwaardige vooruitgang in die begrip van die menslike anatomie en fisiologie gelei. Herofilus en Erasistratus het uitstekende beskrywings van die struktuur en funksie van die brein gegee wat eers in die tweede eeu n.C. deur Galenus geëwenaar is.

  8. DIE SUID-AFRIKAANSE JEUG IN VOORTREKKERTYDPERK

    dien. Die planke en velie moes keer dat die assegaaie die mense tref. Voor die geveg het die vrouens en groter dogters koeels gegiet. Tydens die geveg het die seuns gehelp skiet terwyl die vrouens en dogters die gewere vir die mans gelaai het. Van die dogters soos Nellie. Botha (11 jaar oud) en haar sussie Fya (15 jaar.

  9. Die uitbouing van die Bybelse kanon in antieke Judaïsme en die ...

    31 Jul 2015 ... die oer-Christelike boodskap tot by sy Ou Testamentiese wortels, die geskrifte van Israel wat cum grano salis die 'Bybel' van die oer-Christendom geword het en die blywende verwysingspunt van die Christelike boodskap is. Erkenning. Hierdie artikel is vertaal na Afrikaans deur Prof. Jan G. van der Watt.

  10. Die opleiding van bedryfsielkundiges aan die universiteit van Fort Hare

    W. Botha

    1977-11-01

    Full Text Available Die Departement Bedryfsielkunde aan die Universiteit van Fort Hare is 'n relatiewe jong departement en het eers in 1965 tot stand gekom. Voor hierdie datum is Bedryfsielkunde as 'n kort kursus deur die departement van suiwer Sielkunde aangebied en een van die destydse dosente, Dr. W. Backer, het die inisiatief geneem om 'n selfstandige departement van Bedryfsielkunde in die Fakulteit van Ekonomiese Wetenskappe op die been te bring.

  11. Oor die Bybel in die Afrikaanse digkuns

    another. As a matter of fact, the development of Afri kaans, the instrument of the poet, has been significantly influenced the Afrikaans translation of the Bible. Belie ... ook gesê het: Saam met ons literatuur, so oud as hy is. Die eerste Afrikaanse digter by wie ons omvattende Bybelse invloed kry, is. Totius, een van ons vroegste ...

  12. Strigolactone Regulates Leaf Senescence in Concert with Ethylene in Arabidopsis.

    Ueda, Hiroaki; Kusaba, Makoto

    2015-09-01

    Leaf senescence is not a passive degenerative process; it represents a process of nutrient relocation, in which materials are salvaged for growth at a later stage or to produce the next generation. Leaf senescence is regulated by various factors, such as darkness, stress, aging, and phytohormones. Strigolactone is a recently identified phytohormone, and it has multiple functions in plant development, including repression of branching. Although strigolactone is implicated in the regulation of leaf senescence, little is known about its molecular mechanism of action. In this study, strigolactone biosynthesis mutant strains of Arabidopsis (Arabidopsis thaliana) showed a delayed senescence phenotype during dark incubation. The strigolactone biosynthesis genes MORE AXIALLY GROWTH3 (MAX3) and MAX4 were drastically induced during dark incubation and treatment with the senescence-promoting phytohormone ethylene, suggesting that strigolactone is synthesized in the leaf during leaf senescence. This hypothesis was confirmed by a grafting experiment using max4 as the stock and Columbia-0 as the scion, in which the leaves from the Columbia-0 scion senesced earlier than max4 stock leaves. Dark incubation induced the synthesis of ethylene independent of strigolactone. Strigolactone biosynthesis mutants showed a delayed senescence phenotype during ethylene treatment in the light. Furthermore, leaf senescence was strongly accelerated by the application of strigolactone in the presence of ethylene and not by strigolactone alone. These observations suggest that strigolactone promotes leaf senescence by enhancing the action of ethylene. Thus, dark-induced senescence is regulated by a two-step mechanism: induction of ethylene synthesis and consequent induction of strigolactone synthesis in the leaf. © 2015 American Society of Plant Biologists. All Rights Reserved.

  13. Human Keratinocytes Radioprotection with Mentha Longifolia

    Rizzo, Angela Maria; Berselli, P.; Zava, S.; Negroni, M.; Corsetto, P.; Montorfano, G.; Bertolotti, A.; Ranza, E.; Ottolenghi, A.; Berra, B.

    Antioxidants are suggested to act as radioprotectors, and dietary supplements based on antiox-idants have been proposed for astronauts involved in long-term space missions. Plant extracts with antioxidant properties may be used in dietetic supplements for astronauts; in fact recent nutritional guidelines suggest that "fruits and vegetables may become as important on space-going vessels as limes were on the sea-going vessels of old". Mint presents a large variety of biological properties, such as antiallergenic, antibacterial, anti-inflammatory, antitumor, an-tiviral, gastrointestinal protective, hepatoprotective, chemopreventive activities, most of which are attributable to its antioxidant activity. The aim of the present study is to evaluate the antioxidant properties and protective bio-efficacy of a phenol enriched Mentha longifolia ex-tract on gamma rays stressed human keratinocytes (NCTC2544). We assessed first the in vitro antioxidant activity (ABTS and DPPH), and then evaluated different stress markers in order to investigate various oxidative stress targets: cell viability (MTT); retained proliferating ca-pability (CA); DNA damage (histone H2AX) and protein damage (HSP70 induction). Results indicate that this Mint extract has a higher antioxidant activity respect to fresh extracts, that could be responsible of its really interesting radio-protective effects.

  14. AMPK regulation of the growth of cultured human keratinocytes

    Saha, Asish K.; Persons, Kelly; Safer, Joshua D.; Luo Zhijun; Holick, Michael F.; Ruderman, Neil B.

    2006-01-01

    AMP kinase (AMPK) is a fuel sensing enzyme that responds to cellular energy depletion by increasing processes that generate ATP and inhibiting others that require ATP but are not acutely necessary for survival. In the present study, we examined the relationship between AMPK activation and the growth (proliferation) of cultured human keratinocytes and assessed whether the inhibition of keratinocyte growth by vitamin D involves AMPK activation. In addition, we explored whether the inhibition of keratinocyte proliferation as they approach confluence could be AMPK-related. Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). At concentrations of 10 -4 and 10 -3 M, AICAR inhibited keratinocyte growth by 50% and 95%, respectively, based on measurements of thymidine incorporation into DNA. It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK activation had occurred. Incubation with the thiazolidinedione, troglitazone (10 -6 M) caused similar alterations in P-AMPK, P-ACC, and cell growth. In contrast, the well known inhibition of keratinocyte growth by 1,25-dihydroxyvitamin D 3 (10 -7 and 10 -6 M) was not associated with changes in P-AMPK or P-ACC. Like most cells, the growth of keratinocytes diminished as they approached confluence. Thus, it was of note that we found a progressive increase in P-AMPK (1.5- to 2-fold, p 3 is AMPK-independent

  15. calvyn oor die leiding van die heilige gees in die verklaring van die

    Mittel alters, bis er zur Ruhe kommt bei den kanonischen Schriften der. Urzeit der christlichen Ära (Barth ... (ego tamen dimoveri non possum ab amore compendii, CO 10, 403). Deur die boodskap van die .... Idem ergo spiritus qui per os prophetarum loquutus est, in corda nostra penetret necesse est, ut persuadeat fideliter ...

  16. KERKWEES IN DIE

    Acta Theologica is an accredited South. African journal publishing ... SciELO South Africa. REDAKSIE/ ... 'n persoon belydenis van geloof af wat instemming met die betrokke kerk se ...... Ek was na my ongeluk buite aksie en op Clarens. 'n Mede-lid ...... Die “formation of new confessions, change to current confessions, and.

  17. Dying with dignity

    S P Kalantri

    2003-01-01

    The concept of dignity has beeen one of the ambiguous concepts in biomedical ethics. Thus the ambiguous nature of this concept has been extended to what it means to die with dignity. This research work is an investigation into the complexity in the understanding of "dying with dignity" in Applied Ethics.

  18. The day Madiba died

    8 Apr 2016 ... shibien en ma is nie happy nie. Susan Gaigher se allegoriese fanta- sie- oftewel wetenskapsfiksieverhale. “Martine se teepot” (46–55) en “Maslow”. (56–67) is verfrissend. Gaigher is een van die min skrywers in die bundel wat 'n kenmerkende en oorspronklike stem laat klink. 'n Mens sal 'n Gaigher-verhaal.

  19. Die entwicklung, die metamorphose, die entstehung: Die konzepte des organismus von Aristoteles bis Darwin

    Kamerer Eva

    2009-01-01

    Full Text Available (nemački In diesem Aufsatz versuche ich, die Elemente verschiedener Konzepte des Organismus in der Philosophie und in der Wissenschaft zu analysieren. Die Deutungen des Organismus und der Einheit der Natur bei Aristoteles, Kant und Goethe werden als ein Beispiel der Bewegung von einem finalistischen zum antifinalistischen Bild der Natur verstanden.

  20. Paradigmas en progressie in die teologie: *n Perspektief op die ...

    Die metodologie as besinningsterrein word egter al belangriker. Gedurende die tweede week van April 1988 het teoloë van dwarsoor Suid-. Afrika by die nuwe gebou van die Raad vir Geesteswetenskaplike Navorsing in. Pretoria byeen gekom vir 'n kongres van amper drie dae met die tema Paradigma.'> 476. ISSN 0259 ...

  1. die korrelasie tussen die gemiddelde daaglikse toename van ...

    'n Regressielyn is uit die gegewens bereken deur 'n beswaarde regressieanaliese en die 80 persent-voorspellings- bande is bepaal. Die punte wat ver buite die normale ver- spreidingsband geval hetkon almal met goeie rede as abnor- maal beskou word (sien tabel 1) en is nie ingesluit by die statistiese berekenings nie.

  2. amp' van die ouderling in die Nuwe Testament

    Jesus self het geen kerk gestig nie en daarom, veral omdat die Jesus-beweging inter mums ten opsigte van die Joodse godsdiens van sy tyd tot stand gekom het, het ...... Die klem val dus nie op die npoTCTT0fievo<; se rang of outoriteit nie, maar op sy pastorale funksie in die huishouding of huisgemeente (kyk Reicke.

  3. Polyamines, peroxidase and proteins involved in the senescence ...

    Senescence is the natural aging process at the cellular level or range of phenomena associated with this process. The objective of this review was to show the involvement of substances that may be related to senescence in plants, such as polyamines, peroxidase and proteins. These substances were related with the ...

  4. CLCA2 as a p53-Inducible Senescence Mediator

    Chizu Tanikawa

    2012-02-01

    Full Text Available p53 is a tumor suppressor gene that is frequently mutated in multiple cancer tissues. Activated p53 protein regulates its downstream genes and subsequently inhibits malignant transformation by inducing cell cycle arrest, apoptosis, DNA repair, and senescence. However, genes involved in the p53-mediated senescence pathway are not yet fully elucidated. Through the screening of two genome-wide expression profile data sets, one for cells in which exogenous p53 was introduced and the other for senescent fibroblasts, we have identified chloride channel accessory 2 (CLCA2 as a p53-inducible senescence-associated gene. CLCA2 was remarkably induced by replicative senescence as well as oxidative stress in a p53-dependent manner. We also found that ectopically expressed CLCA2 induced cellular senescence, and the down-regulation of CLCA2 by small interfering RNA caused inhibition of oxidative stress-induced senescence. Interestingly, the reduced expression of CLCA2 was frequently observed in various kinds of cancers including prostate cancer, whereas its expression was not affected in precancerous prostatic intraepithelial neoplasia. Thus, our findings suggest a crucial role of p53/CLCA2-mediated senescence induction as a barrier for malignant transformation.

  5. Cellular and molecular aspects of quinoa leaf senescence.

    López-Fernández, María Paula; Burrieza, Hernán Pablo; Rizzo, Axel Joel; Martínez-Tosar, Leandro Julián; Maldonado, Sara

    2015-09-01

    During leaf senescence, degradation of chloroplasts precede to changes in nuclei and other cytoplasmic organelles, RuBisCO stability is progressively lost, grana lose their structure, plastidial DNA becomes distorted and degraded, the number of plastoglobuli increases and abundant senescence-associated vesicles containing electronically dense particles emerge from chloroplasts pouring their content into the central vacuole. This study examines quinoa leaf tissues during development and senescence using a range of well-established markers of programmed cell death (PCD), including: morphological changes in nuclei and chloroplasts, degradation of RuBisCO, changes in chlorophyll content, DNA degradation, variations in ploidy levels, and changes in nuclease profiles. TUNEL reaction and DNA electrophoresis demonstrated that DNA fragmentation in nuclei occurs at early senescence, which correlates with induction of specific nucleases. During senescence, metabolic activity is high and nuclei endoreduplicate, peaking at 4C. At this time, TEM images showed some healthy nuclei with condensed chromatin and nucleoli. We have found that DNA fragmentation, induction of senescence-associated nucleases and endoreduplication take place during leaf senescence. This provides a starting point for further research aiming to identify key genes involved in the senescence of quinoa leaves. Published by Elsevier Ireland Ltd.

  6. Delay of Iris flower senescence by protease inhibitors

    Pak, C.; Doorn, van W.G.

    2005-01-01

    asterisk inside a circle sign Visible senescence of the flag tepals in Iris x hollandica (cv. Blue Magic) was preceded by a large increase in endoprotease activity. Just before visible senescence about half of total endoprotease activity was apparently due to cysteine proteases, somewhat less than

  7. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue

    Schafer, M.J.; White, T.A.; Evans, G.; Tonne, J.M.; Verzosa, G.C.; Stout, M.B.; Mazula, D.L.; Palmer, A.K.; Baker, D.J.; Jensen, M.D.; Torbenson, M.S.; Miller, J.D.; Ikeda, Y.; Tchkonia, T.; Deursen, J.M.A. van; Kirkland, J.L.; LeBrasseur, N.K.

    2016-01-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the

  8. Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

    Tohidnezhad, Mersedeh; Lammel, Justus; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

    2017-01-01

    Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo. PMID:28808357

  9. Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers.

    Salerno, Simona; Morelli, Sabrina; Giordano, Francesca; Gordano, Amalia; Bartolo, Loredana De

    2016-10-01

    In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Chemosensory Information Processing between Keratinocytes and Trigeminal Neurons

    Sondersorg, Anna Christina; Busse, Daniela; Kyereme, Jessica; Rothermel, Markus; Neufang, Gitta; Gisselmann, Günter; Hatt, Hanns; Conrad, Heike

    2014-01-01

    Trigeminal fibers terminate within the facial mucosa and skin and transmit tactile, proprioceptive, chemical, and nociceptive sensations. Trigeminal sensations can arise from the direct stimulation of intraepithelial free nerve endings or indirectly through information transmission from adjacent cells at the peripheral innervation area. For mechanical and thermal cues, communication processes between skin cells and somatosensory neurons have already been suggested. High concentrations of most odors typically provoke trigeminal sensations in vivo but surprisingly fail to activate trigeminal neuron monocultures. This fact favors the hypothesis that epithelial cells may participate in chemodetection and subsequently transmit signals to neighboring trigeminal fibers. Keratinocytes, the major cell type of the epidermis, express various receptors that enable reactions to multiple environmental stimuli. Here, using a co-culture approach, we show for the first time that exposure to the odorant chemicals induces a chemical communication between human HaCaT keratinocytes and mouse trigeminal neurons. Moreover, a supernatant analysis of stimulated keratinocytes and subsequent blocking experiments with pyrodoxalphosphate-6-azophenyl-2′,4′-disulfonate revealed that ATP serves as the mediating transmitter molecule released from skin cells after odor stimulation. We show that the ATP release resulting from Javanol® stimulation of keratinocytes was mediated by pannexins. Consequently, keratinocytes act as chemosensors linking the environment and the trigeminal system via ATP signaling. PMID:24790106

  11. Kinetics of growth and differentiation of cultured human epidermal keratinocytes

    Albers, K.M.

    1985-01-01

    A study was made of the interrelationship between replication and differentiation in cultures of human epidermal keratinocytes. Measures of both parameters were made using newly developed methods to quantify the rate at which keratinocytes replicate and the rate at which they withdraw from the cell cycle. Keratinocyte replication was measured by determining the cell doubling time, labeling index, and cell cycle duration. Cell cycle length was measured using a double label assay that determines the length of time between two successive phases of DNA synthesis. The first DNA synthesis phase was marked by labeling keratinocytes with 14 C-thymidine. At the next round of DNA synthesis, cells were labeled with bromodeoxyuridine, a heavy analog of thymidine. The cell cycle length is given by the time required for the 14 C-labeled DNA to become double labeled. To measure keratinocyte differentiation, the rate at which cells withdraw from the cell cycle was determined. To measure withdrawal, the percentage of cells labeled by a pulse of 14 C-thymidine that failed to undergo a second cycle of DNA synthesis, as measured by bromodeoxyuridine incorporation, was determined. Cells which failed to undergo a second cycle of synthesis were considered to have differentiated and withdrawn from the cell cycle

  12. Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

    Andreas Bayer

    2017-01-01

    Full Text Available Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs or their clinically related formulations (e.g., Vivostat PRF® came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10 and late (transglutaminase-1 and involucrin differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR- dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.

  13. Life History Trade-Offs Modulate the Speed of Senescence

    Salguero-Gómez, Roberto; Jones, Owen

    2017-01-01

    that the speed of senescence varies dramatically across the Tree of Life and that it has a moderate phylogenetic signal when considering both plants and animals but that this signal is stronger in animals than in plants, indicating that the strength of selection on the trait may differ between kingdoms. We next...... examined the speed of senescence at two taxonomic levels: comparing kingdoms, with plants more likely to postpone senescence than animals, and, when the data allowed for it, comparing taxonomic classes, where we found that pine trees are particularly slow to senesce, followed by reptiles and sponges. Most...... puzzling and worthy of investigation in itself. We used two open-data repositories of high-quality demographic information for animals and plants to present a novel overview of the degree of variation in life-history strategies and their component life-history traits, including the speed of senescence...

  14. Senescence gives insights into the morphogenetic evolution of anamniotes

    Éric Villiard

    2017-06-01

    Full Text Available Senescence represents a mechanism to avoid undesired cell proliferation that plays a role in tumor suppression, wound healing and embryonic development. In order to gain insight on the evolution of senescence, we looked at its presence in developing axolotls (urodele amphibians and in zebrafish (teleost fish, which are both anamniotes. Our data indicate that cellular senescence is present in various developing structures in axolotls (pronephros, olfactory epithelium of nerve fascicles, lateral organs, gums and in zebrafish (epithelium of the yolk sac and in the lower part of the gut. Senescence was particularly associated with transient structures (pronephros in axolotls and yolk sac in zebrafish suggesting that it may play a role in the elimination of these tissues. Our data supports the notion that cellular senescence evolved early in vertebrate evolution to influence embryonic development.

  15. Evasion of Cell Senescence Leads to Medulloblastoma Progression

    Lukas Tamayo-Orrego

    2016-03-01

    Full Text Available How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1+/− mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors.

  16. Die toekoms en ons roeping

    S. du Toit

    1954-03-01

    Full Text Available Om te weet wat ons roeping in die toekoms sal wees, moet ons eers besef wat in ons eie tyd aan die gang is en langs watter lyne die dinge beweeg. Dit is ons plig om te let op die tekens van die tye in die lig van die profetiese Woord. En dan wil ons dadelik beklemtoon dat ons in Suid-Afrika nie in die waan moet lewe dat ons hier onbekommerd en onaangetas deur die wêreldgebeure ons roeping en bestemming kan uitwerk nie.

  17. Die Hervormde Teologiese Studies na vyftig jaar

    INLEIDEND. In die tweede helfte van die jaar 1943 het die Hervormde Teologiese Studies die eerste maal verskyn. Dit was die produk van lang besinning en beplanning. Die dryfkrag agter die totstandkoming was prof dr S P Engeibrecht, 'n man wie se idealisme en toewyding aan die kerk groot dinge vir die kerk en ook die ...

  18. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    Schafer, Marissa J; White, Thomas A; Evans, Glenda; Tonne, Jason M; Verzosa, Grace C; Stout, Michael B; Mazula, Daniel L; Palmer, Allyson K; Baker, Darren J; Jensen, Michael D; Torbenson, Michael S; Miller, Jordan D; Ikeda, Yasuhiro; Tchkonia, Tamara; van Deursen, Jan M; Kirkland, James L; LeBrasseur, Nathan K

    2016-06-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  19. Die owerheidsinmenging met betrekking tot kerklike tughandelinge.

    L. Roeleveld

    1982-06-01

    Full Text Available Volgens art 29 NGB is die merktekens van die ware kerk die suiwere prediking van die Evangelie, die suiwere bediening van die Sakramente en die gebruik van die kerklike tug. Art. 32 NGB spreek uit dat die Kerkorde nie mag afwyk van wat Christus ingestel het nie. Menslike vindinge en wette om die gewetens te bind en te dwing, moet daarom verwerp word. Die ekskommunikasie of die ban moet toegepas word volgens die Woord van God.

  20. Pentateugtradisies in die boek Hosea

    om te bepaal of die verwysing na 'n gebeure te doen het met die verre verlede of met die .... Hosea 2:1-2 JHWH se trou aan sy beloftes. ... dat huile na Egipte sal terugkeer. Die presiese bedoeiing van die woorde 'huile sal terugkeer na Egipte' is omstre- de. Kommentatore soos Rudolph meen dat dit verstaan moet word as ...

  1. Die begrafnisdíens

    (De Vaux 1961:108). Was die begrafnis 'n familie of 'n kerklike aangeleentheid? Hierdie vraag word nie in die Bybel beantwoord nie. Abraham het sy vrou begrawe (Gen 23: 19-. 20). Isak en Ismael ..... ver gekom om die begrafnis 'n kerklike aangeleentheid te maak nie. Hierdie stap .... trou aan die sorg van God. * Die kerk ...

  2. Metodes in die Christelike etiek

    The basic question in Christian ethics is not primarily. 'What should I do?' The basic question is rather ' ... should therefore be accepted as being part of the method used in Christian ethics. 1. INLEIDEND ..... aan die kant van die onderdrukte' verkondig word, word die Christen opgeroep om horn te skaar aan die kant van die ...

  3. Arabidopsis CPR5 is a senescence-regulatory gene with pleiotropic functions as predicted by the evolutionary theory of senescence

    Jing, Hai-Chun; Anderson, Lisa; Sturre, Marcel J. G.; Hille, Jacques; Dijkwel, Paul P.

    2007-01-01

    Arabidopsis CPR5 is a senescence-regulatory gene with pleiotropic functions as predicted by the evolutionary theory of senescence Hai-Chun Jing1,2, Lisa Anderson3, Marcel J.G. Sturre1, Jacques Hille1 and Paul P. Dijkwel1,* 1Molecular Biology of Plants, Groningen Biomolecular Sciences and

  4. Micronucleus formation in cultured human keratinocytes: Involvement of intercellular bioactivation.

    van Pelt, F N; Haring, R M; Weterings, P J

    1991-01-01

    Micronucleus formation in cultured human keratinocytes was studied after exposure to benzo[a]pyrene, cyclophosphamide and 12-O-tetradecanoylphorbol-13-acetate without the addition of an exogenous metabolizing system. The first two agents need bioactivation by specific isoenzymes of cytochrome P-450 to form genotoxic intermediates. Benzo[a]pyrene induced the micronucleus formation in both uninduced and Aroclor 1254-pretreated cultures. Clastogenic effects of cyclophosphamide were observed only in Aroclor 1254-pretreated cells. The tumour promotor 12-O-tetradecanoylphorbol-13-acetate did not affect the frequency of micronuclei in human keratinocytes. The data indicate that cultured human keratinocytes can be used to study the tissue-specific response to genotoxic agents as well as interindividual variation in biotransformation capacity.

  5. Die teologiese skool in die P.U.K vir C.H.O.: met die betekenis van die teologiese skool vir die Christelike wetenskap

    F. Postma

    1944-03-01

    Full Text Available Die Teologiese Skool van die Gereformeerde Kerk gedink op 29 November 1944 sy vyf-en-sewentigjarige bestaan.Die Raad en Senaat van die P.U.K. vir C.H.O. wil ook langs hierdie weg die Teologiese Skool van harte gelukwens en die versekering gee dat daar by die outoriteite van die P.U.K. ’n diepgevoelde dankbaarheid heers dat hierdie inrigting sovele jare deur onse God en Vader gedra en gespaar is.

  6. The incidence and multiplicity rates of keratinocyte cancers in Australia.

    Pandeya, Nirmala; Olsen, Catherine M; Whiteman, David C

    2017-10-16

    To assess the incidence and multiplicity of keratinocyte cancers (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) excised in Australia, and to examine variations by age, sex, state, and prior skin cancer history. Analysis of individual-level Medicare data for keratinocyte cancer treatments (identified by eight specific MBS item codes) during 2011-2014. Histological data from the QSkin prospective cohort study were analysed to estimate BCC and SCC incidence. A 10% systematic random sample of all people registered with Medicare during 1997-2014. People aged at least 20 years in 2011 who made at least one claim for any MBS medical service during 2011-2014 (1 704 193 individuals). Age-standardised incidence rates (ASRs) and standardised incidence ratios (SIRs). The person-based incidence of keratinocyte cancer excisions in Australia was 1531 per 100 000 person-years; incidence increased with age, and was higher for men than women (SIR, 1.43; 95% CI, 1.42-1.45). Lesion-based incidence was 3154 per 100 000 person-years. The estimated ASRs for BCC and SCC were 770 per 100 000 and 270 per 100 000 person-years respectively. During 2011-2014, 3.9% of Australians had one keratinocyte cancer excised, 2.7% had more than one excised; 74% of skin cancers were excised from patients who had two or more lesions removed. Multiplicity was strongly correlated with age; most male patients over 70 were treated for multiple lesions. Keratinocyte cancer incidence was eight times as high among people with a prior history of excisions as among those without. The incidence and multiplicity of keratinocyte cancer in Australia are very high, causing a large disease burden that has not previously been quantified.

  7. Intermittent pressure decreases human keratinocyte proliferation in vitro.

    Nasca, Maria R; Shih, Alan T; West, Dennis P; Martinez, Wanda M; Micali, Giuseppe; Landsman, Adam S

    2007-01-01

    The aim of this study was to investigate the correlation between pressure changes and keratinocyte proliferation by determining whether keratinocytes exposed to altered mechanical pressures would proliferate at different rates compared to control cells not subjected to pressure changes. Tissue culture flasks of human keratinocytes plated at an approximate density of 15,000 cells/cm(2) undergoing an intermittent cyclic pressure of 362 mm Hg at a frequency of 2.28 or 5.16 cycles/min (0.038 or 0.086 Hz) for 8 h were compared to control flasks grown at ambient room pressure. An in-line pressure transducer was used to monitor and adjust pressure within the cell chambers, using a solenoid valve. A thymidine incorporation assay assessed the amount of cell proliferation in each set of experiments. Differences in proliferation between keratinocytes subjected to cyclic pressure changes and control cells were found to be statistically significant (p < 0.05) in 4 out of 5 proliferation assays. Also, a higher frequency of pressure changes consistently generated a reduced proliferation rate compared to that seen in cells exposed to a lower frequency of pressure changes. These data indicate that keratinocytes undergoing intermittent pressure changes exhibit decreased proliferation rates compared to controls. Furthermore, an increased frequency rate seems to have a greater effect on proliferation than low-frequency rate pressure changes, suggesting that the stress caused by frequently changed pressure may play a greater role in reducing keratinocyte proliferation than the actual magnitude of load applied to the cells. Our results support the current treatment protocol of reducing speed and duration of walking on the site of the wound to promote healing of foot ulcers. (c) 2007 S. Karger AG, Basel.

  8. Senescent mouse cells fail to overtly regulate the HIRA histone chaperone and do not form robust Senescence Associated Heterochromatin Foci

    Enders Greg H

    2010-06-01

    Full Text Available Abstract Background Cellular senescence is a permanent growth arrest that occurs in response to cellular stressors, such as telomere shortening or activation of oncogenes. Although the process of senescence growth arrest is somewhat conserved between mouse and human cells, there are some critical differences in the molecular pathways of senescence between these two species. Recent studies in human fibroblasts have defined a cell signaling pathway that is initiated by repression of a specific Wnt ligand, Wnt2. This, in turn, activates a histone chaperone HIRA, and culminates in formation of specialized punctate domains of facultative heterochromatin, called Senescence-Associated Heterochromatin Foci (SAHF, that are enriched in the histone variant, macroH2A. SAHF are thought to repress expression of proliferation-promoting genes, thereby contributing to senescence-associated proliferation arrest. We asked whether this Wnt2-HIRA-SAHF pathway is conserved in mouse fibroblasts. Results We show that mouse embryo fibroblasts (MEFs and mouse skin fibroblasts, do not form robust punctate SAHF in response to an activated Ras oncogene or shortened telomeres. However, senescent MEFs do exhibit elevated levels of macroH2A staining throughout the nucleus as a whole. Consistent with their failure to fully activate the SAHF assembly pathway, the Wnt2-HIRA signaling axis is not overtly regulated between proliferating and senescent mouse cells. Conclusions In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types to become immortalized and transformed, compared to human cells.

  9. Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.

    Costarelli, Laura; Giacconi, Robertina; Malavolta, Marco; Basso, Andrea; Piacenza, Francesco; Provinciali, Mauro; Maggio, Marcello G; Corsonello, Andrea; Lattanzio, Fabrizia

    2017-04-01

    Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.

  10. Die Frage nach Gerechtigkeit.

    Martin Jäggle

    2014-07-01

    Full Text Available ENGLISH: In the first part six stages in the author’s path of life are described, which have influenced his engagement with justice. The second part gives an insight into his religious educational work, in which the issue of justice was especially significant on the example of ‘religion in the context of migration’ and of the ecumenic initiative ‘lebens.werte.schule’ (school worth living. The vision of the Kingdom of God and the necessity of participation become apparent. DEUTSCH: Im ersten Teil werden sechs Stationen am Lebensweg des Autors beschrieben, die seine Auseinandersetzung mit Gerechtigkeit geprägt haben. Der zweite Teil gibt Einblick in seine religionspädagogische Arbeit, in der die Frage nach Gerechtigkeit besonders bedeutsam war am Beispiel ‚Religion im Kontext Migration‘ und der ökumenischen Initiative ‚lebens.werte.schule‘. Die Vision vom Reich Gottes und die Notwendigkeit von Partizipation werden dabei deutlich.

  11. Die EG-Kabotageverordnung

    Basedow, Jürgen

    1990-01-01

    Die EG-Kabotageverordnung : e. Schritt zur Verwirklichung d. Dienstleistungsfreiheit im Straßengüterverkehr / Jürgen Basedow ; Ansgar Held. - In: Europäische Zeitschrift für Wirtschaftsrecht. 1. 1990. S. 305-308

  12. Die Bibliothek des Bezirksmuseums Josefstadt

    Maria Ettl

    2015-01-01

    Josefstadt in Wien werden die Herkunft der Bibliotheksbestände und die beengte Raumsituation beschrieben. Abschließend wird auf die Erfassung der Medien mittels der Bibliothekssoftware „Biblioweb“ eingegangen.

  13. Aldefluor protocol to sort keratinocytes stem cells from skin

    Noronha, Samuel Marcos Ribeiro; Gragnani, Alfredo; Pereira, Thiago Antônio Calado; Correa, Silvana Aparecida Alves; Bonucci, Jessica; Ferreira, Lydia Masako

    2017-01-01

    Abstract Purpose: To investigate the use Aldefluor® and N, N - Dimethylaminobenzaldehyde (DEAB) to design a protocol to sort keratinocyte stem cells from cultured keratinocytes from burned patients. Methods: Activated Aldefluor® aliquots were prepared and maintained at temperature between 2 to 8°C, or stored at -20°C. Next, the cells were collected following the standard protocol of sample preparation. Results: Best results were obtained with Aldefluor® 1.5µl and DEAB 15 µl for 1 x 106 c...

  14. Die verband tussen die sielkundige kontrak en organisasieverbondenheid

    K. J. Stanz

    1999-06-01

    Full Text Available The relationship between the psychological contract and organisational commitment. The aim of this study is to design a measuring instrument with acceptable metric characteristics for the strength of the psychological contract within the South African context, and to determine empirically the relation between the strength of the psychological contract and organisational commitment. The Dhammanungune Model served as foundation for the design of the Strength of the Psychological Contract Questionnaire which consists of two scales namely, a needs expectation scale and a needs fulfilment expectation scale. The items of each scale have been formulated in the manner that ensures that the respondent reacts consecutively to two instructions namely, (a the level of the expectation and (b the importance of the expectation. This questionnaire was administered together with the Organisational Commitment Questionnaire to two population groups within the military environment. The Pearson Product Moment Correlation was calculated between the strength of the psychological contract and organisational commitment and the significance of the correlations was evaluated. Opsomming Die doel van die studie is om 'n meetinstrument met aanvaarbare metriese eienskappe vir die sterkte van die sielkundige kontrak vir Suid-Afrikaanse omstandighede te ontwerp en om empirics die verband tussen die sterkte van die sielkundige kontrak en organisasieverbondenheid te bepaal. Die sterkte van die sielkundige kontrak vraelys is op grond van die Dhammanungune-model ontwerp en het uit twee skale naamlik, die behoefteverwagting- en vervullingsverwagtingskale bestaan. Items vir eike skaal is sodanig geformuleer dat die respondent agteropeenvolgens op twee instruksies naamlik (a die vlak van die verwagting en (b die belangrikheid van die verwagting moet reageer. Die vraelys is saam met die organisasieverbondenheidsvraelys op twee populasies uit 'n militere omgewing toegepas. Die Pearson

  15. Die postpolitische Stadt

    Erik Swyngedouw

    2013-12-01

    Full Text Available Die Polis ist tot, es lebe die kreative Stadt! Während die Stadt, zumindest in Teilen des städtischen Raums, blüht und gedeiht, scheint die Polis im idealisierten griechischen Sinn dem Untergang geweiht; in diesem Verständnis ist sie der Ort der öffentlichen politischen Auseinandersetzung und demokratischen Unterhandlung und somit eine Stätte (oft radikaler Abweichung und Unstimmigkeit, an der die politische Subjektivierung buchstäblich ihren Platz hat. Diese Figur einer entpolitisierten (oder postpolitischen und postdemokratischen Stadt im Spätkapitalismus bildet das Leitmotiv des vorliegenden Beitrags. Ich lehne mich dabei an Jacques Rancière, Slavoj Žižek, Chantal Mouffe, Mustafa Dikeç, Alain Badiou und andere Kritiker jenes zynischen Radikalismus an, der dafür gesorgt hat, dass eine kritische Theorie und eine radikale politische Praxis ohnmächtig und unfruchtbar vor jenen entpolitisierenden Gesten stehen, die in der polizeilichen Ordnung des zeitgenössischen neoliberalen Spätkapitalismus als Stadtentwicklungspolitik [urban policy] und städtische Politik [urban politics] gelten. Ziel meiner Intervention ist es, das Politische wieder in den Mittelpunkt der zeitgenössischen Debatten über das Urbane zu stellen. [...

  16. Senescent phenotypes of skin fibroblasts from patients with Tangier disease

    Matsuura, Fumihiko; Hirano, Ken-ichi; Ikegami, Chiaki; Sandoval, Jose C.; Oku, Hiroyuki; Yuasa-Kawase, Miyako; Tsubakio-Yamamoto, Kazumi; Koseki, Masahiro; Masuda, Daisaku; Tsujii, Ken-ichi; Ishigami, Masato; Nishida, Makoto; Shimomura, Iichiro; Hori, Masatsugu; Yamashita, Shizuya

    2007-01-01

    Tangier disease (TD) is characterized by a deficiency of high density lipoprotein (HDL) in plasma and patients with TD have an increased risk for coronary artery disease (CAD). Recently, we reported that fibroblasts from TD exhibited large and flattened morphology, which is often observed in senescent cells. On the other hand, data have accumulated to show the relationship between cellular senescence and development of atherosclerotic CAD. The aim of the present study was to investigate whether TD fibroblasts exhibited cellular senescence. The proliferation of TD fibroblasts was gradually decreased at population doubling level (PDL) ∼10 compared with control cells. TD cells practically ceased proliferation at PDL ∼30. DNA synthesis was markedly decreased in TD fibroblasts. TD cells exhibited a higher positive rate for senescence-associated β-galactosidase (SA-β-gal), which is one of the biomarkers of cellular senescence in vitro. These data showed that TD cells reached cellular senescence at an earlier PDL compared with controls. Although, there was no difference in the telomere length of fibroblasts between TD and controls at the earlier passage (PDL 6), the telomere length of TD cells was shorter than that of controls at the late passage (PDL 25). Taken together, the current study demonstrates that the late-passaged TD fibroblasts showed senescent phenotype in vitro, which might be related to the increased cardiovascular manifestations in TD patients

  17. Die histologie en ultrastruktuur van die hepatopankreas van die bloukurper Oreochromis mossambicus

    M. M. Nel

    1990-07-01

    Full Text Available Die histologie en ultrastruktuur van die hepatopankreas van die bloukurper Oreochromis mossambicus word beskryf. ’n Dun bindweefselkapsel omring die lewer. Die hepatosietrangskikking vertoon as lobules, met die koorde van hepatosiete wat vanaf ’n sentrale vene uitradieer en met mekaar anastomaseer. Indiwiduele lewerlohules vertoon nie duidelike grense nie, maar enkele duidelike triades word wel in die lewer van O. mossambicus aangetref. Die hepatosiete bevat ’n enkele ronde kern met ’n duidelike nukleolus en die growwe endoplasmiese retikula kom in twee of meer rye om die kerne en teen die selgrense van die hepatosiete voor. Die ander sitoplasmiese organelle kom verspreid in die hepatosietsitoplasma voor. Die eksokriene pankreasselle is om die portale venes gesetel. Die kerne van hierdie selle is rond en is hasaal in die kubies- tot silindervormige selle gelee. ’n Goedontwikkelde growwe endoplasmiese retikulum — vesikulêr, tubulêr en sirkulêr in vorm — en sektretoriese granules wat apikaal in die sel gelee is, kom voor.

  18. Contrasting patterns of cytokinins between years in senescing aspen leaves

    Edlund, E.; Novák, Ondřej; Karady, M.; Ljung, K.; Jansson, S.

    2017-01-01

    Roč. 40, č. 5 (2017), s. 622-634 ISSN 0140-7791 R&D Projects: GA ČR GA14-34792S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : leaf senescence * arabidopsis-thaliana * autumn senescence * gene-expression * populus-trichocarpa * mass-spectrometry * tobacco plants * translocation * biosynthesis * identification * autumn senescence * gene expression * metabolism * Populus tremula * profiling Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Plant sciences, botany Impact factor: 6.173, year: 2016

  19. Die teologiese arbeid van Antonius HJ Gunneweg

    En dis 'n klein treetjie van klagte na aanklag en na protes teen die gode, die heersers wat die mens vernietig deur hom oor sy ware lewe te bedrieg. Die ideologie eis dan ook dienooreenkomstig die bevryding en emansipasie van die mens van die gode en van God (1983: 118—119). Volgens die Jahwis is dit die slang wat, ...

  20. The commitment of human cells to senescence.

    Holliday, Robin

    2014-01-01

    Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid fibroblasts grown in culture have a finite lifespan. Since that time, innumerable experiments have been published to discover the mechanism(s) that are responsible for this 'Hayflick limit' to continuous growth. Much new information has been gained, but there are certain features of this experimental system which have not been fully understood. One is the fact that different populations of the foetal lung strains WI-38 and MRC-5 have a range in division potential of at least a millionfold. The commitment theory of cellular aging, published more than 30 years ago, is able to explain this, but it has been consistently ignored. The theory predicts that bottlenecks, which are transient reductions in population size, can significantly reduce lifespan, or increase variability of lifespans. Computer simulations specify the effects of bottlenecks on longevity, and these were confirmed in two series of experiments. Commitment to senescence may be the loss of telomerase, which leads to the erosion of telomeres and the inability to grow indefinitely. Many experiments have been done with skin fibroblasts from human donors of different age, and it was originally thought that in vitro lifespan was inversely correlated with donor age. In these experiments, a single skin biopsy produces a population of cells that are grown to senescence. However, there is no reason to believe that skin fibroblasts are less variable in their in vitro lifespan than foetal lung strains, in which case the data points with skin cells are so variable that they may completely obscure any inverse correlation between culture lifespans and donor age.

  1. Rescuing loading induced bone formation at senescence.

    Sundar Srinivasan

    2010-09-01

    Full Text Available The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca(2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential.

  2. Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

    De Marco Federico

    2010-03-01

    Full Text Available Abstract Background The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS, which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. Results The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. Conclusions Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

  3. Die benutting van vraelyste met die oog op meer effektiewe ...

    UPuser

    effektiewe stresbeheer as een van die temas te hanteer. Op grond van die navorsing deur onder andere Lawson (1985) en Taylor (1999) sou ek graag die proses van differensiasie2 ook by genoemde lys voeg as tema vir bespreking tydens huweliksvoorbereiding. 2 Differensiasie kan beskryf word as die losmaakproses ...

  4. die aard van wetgewende diskresies by die suid-afrikaanse ...

    Administrator

    In enige moderne demokrasie is daar een of ander vorm van skeiding van magte tussen die wetgewende, uitvoerende en regsprekende gesag. Hierdie skeiding van magte, die sogenaamde trias politica, kan sover teruggevoer word as 1215, met die ondertekening van die Magna Carta deur Koning John van Engeland.

  5. die doeltreffendheid van die afrikaanse woordelys en spelreels

    sluiting by die reel vir die verdubbeling van medeklinkers na 'n kort, be- klemtoonde klinker, woorde soos ballet, ballon, terras, terrein, dissipel en dissipline slegs met een konsonant na die eerste vokaal gespel moes word, omdat daardie voorafgaande vokaal onbeklemtoon is. Ook hierdie uit- sondering op die reel word ...

  6. Die aanspraak op Goddelike steun in 'n konfliksituasie volgens die ...

    laws, and ethical or political principles. A synchronic investigation of relevant Old ... die toneel gebring met die vraag: 'aan wie se kant is God' (vgl bv The road to. Damascus 1979:6)? Volgens .... betrekking tot die Ou Testament: Hoe moet ons vasstel wie se kant God nou regtig kies, of wie veg aan die kant van God en wie ...

  7. FOXO1 expression in keratinocytes promotes connective tissue healing

    Zhang, Chenying; Lim, Jason; Liu, Jian; Ponugoti, Bhaskar; Alsadun, Sarah; Tian, Chen; Vafa, Rameen; Graves, Dana T.

    2017-01-01

    Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome. PMID:28220813

  8. Photodynamic toxicity of hematoporphyrin derivatives to human keratinocytes in culture.

    Kappus, H; Reinhold, C; Artuc, M

    Human keratinocytes in culture were able to take up hematoporphyrin derivatives (HPDs) used during photodynamic chemotherapy of tumors. In the absence of light, HPDs showed no cytotoxic effects to keratinocytes. However, after irradiation with visible light, HPDs induced immediate cytotoxicity as measured by the neutral red uptake assay. On the other hand, cell attachment as measured by protein estimation was not affected. When the cells treated with HPDs and irradiated with light were cultured for a further 72 h, they partially lost their ability to attach to the collagen surface. Most of the cells remaining attached after 72 h were no longer viable following treatment with HPDs and light. All parameters measured depended on the intracellular concentration of HPDs used (7-50 ng/10(5) cells) and the time of irradiation (0-30 min). These results suggest that human keratinocytes are a good model to study cytotoxic effects of photodynamically active drugs. Further, keratinocytes were unable to recover after damage caused by HPDs and light.

  9. Hyaluronan minimizes effects of UV irradiation on human keratinocytes

    Hašová, M.; Crhák, Tomáš; Šafaříková, Barbora; Dvořáková, J.; Muthný, T.; Velebný, V.; Kubala, Lukáš

    2011-01-01

    Roč. 303, č. 4 (2011), s. 277-284 ISSN 0340-3696 R&D Projects: GA ČR(CZ) GA305/08/1704 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hyaluronan * keratinocyte * ultraviolet light Subject RIV: BO - Biophysics Impact factor: 2.279, year: 2011

  10. Exploratory Study on the Stability Characteristics of Commercial Human Keratinocytes

    1990-04-01

    Invest. Dermatol. 75:176- 182; 1980. 16. Hayflick , L. The limited in vitro lifetime of huiran diploid strains. Exp. Cell Res. 37:614-636; 1965. 17...culture keratinocytes were considered by some investigators to have limited proliferative potential, so they used third and fourth passage commercial

  11. The peanut lectin-binding glycoproteins of human epidermal keratinocytes

    Morrison, A.I.; Keeble, S.; Watt, F.M.

    1988-01-01

    The peanut lectin (PNA) is known to bind more strongly to keratinocytes that are undergoing terminal differentiation than to proliferating keratinocytes. In order to investigate the significance of this change in cell-surface carbohydrate authors have identified the PNA-binding glycoproteins of cultured human keratinocytes and antibodies against them. Two heavily glycosylated bands of 110 and 250 kDa were resolved by PAGE of [ 14 C]galactose- or [ 14 C]mannose- and [ 14 C]glucosamine-labeled cell extracts eluted with galactose from PNA affinity columns. The higher molecular weight band was also detected on PNA blots of unlabeled cell extracts transferred to nitrocellulose. Both bands were sensitive to pronase digestion, but only the 250-kDa band was digested with trypsin. A rabbit antiserum that we prepared (anti-PNA-gp) immunoprecipitated both bands from cell extracts. In contrast to PNA, anti-PNA-gp bound equally to proliferating and terminally differentiating cells, indicating that some epitope(s) of the PNA-binding glycoproteins is present on the cell surface prior to terminal differentiation. When keratinocytes grown as a monolayer in low-calcium medium were switched to medium containing 2 mM calcium ions in order to induce desmosome formation and stratification, there was a dramatic redistribution of the PNA-binding glycoproteins, which became concentrated at the boundaries between cells. This may suggest a role for the glycoproteins in cell-cell interactions during stratification

  12. Integrin β4 Regulates Migratory Behavior of Keratinocytes by Determining Laminin-332 Organization*s

    Sehgal, Bernd U.; DeBiase, Phillip J.; Matzno, Sumio; Chew, Teng-Leong; Claiborne, Jessica N.; Hopkinson, Susan B.; Russell, Alan; Marinkovich, M. Peter; Jones, Jonathan C. R.

    2010-01-01

    Whether α6β4 integrin regulates migration remains controversial. β4 integrin-deficient (JEB) keratinocytes display aberrant migration in that they move in circles, a behavior that mirrors the circular arrays of laminin (LM)-332 in their matrix. In contrast, wild-type keratinocytes and JEB keratinocytes, induced to express β4 integrin, assemble laminin-332 in linear tracks over which they migrate. Moreover, laminin-332-dependent migration of JEB keratinocytes along linear tracks is restored when cells are plated on wild-type keratinocyte matrix, whereas wild-type keratinocytes show rotation over circular arrays of laminn-332 in JEB keratinocyte matrix. The activities of Rac1 and the actin cytoskeleton-severing protein cofilin are low in JEB keratinocytes compared with wild-type cells but are rescued following expression of wild-type β4 integrin in JEB cells. Additionally, in wild-type keratinocytes Rac1 is complexed with α6β4 integrin. Moreover, Rac1 or cofilin inactivation induces wild-type keratinocytes to move in circles over rings of laminin-332 in their matrix. Together these data indicate that laminin-332 matrix organization is determined by the α6β4 integrin/actin cytoskeleton via Rac1/cofilin signaling. Furthermore, our results imply that the organizational state of laminin-332 is a key determinant of the motility behavior of keratinocytes, an essential element of skin wound healing and the successful invasion of epidermal-derived tumor cells. PMID:16973601

  13. Spatial and temporal transcriptome changes occurring during flower opening and senescence of the ephemeral hibiscus flower, Hibiscus rosa-sinensis.

    Trivellini, Alice; Cocetta, Giacomo; Hunter, Donald A; Vernieri, Paolo; Ferrante, Antonio

    2016-10-01

    Flowers are complex systems whose vegetative and sexual structures initiate and die in a synchronous manner. The rapidity of this process varies widely in flowers, with some lasting for months while others such as Hibiscus rosa-sinensis survive for only a day. The genetic regulation underlying these differences is unclear. To identify key genes and pathways that coordinate floral organ senescence of ephemeral flowers, we identified transcripts in H. rosa-sinensis floral organs by 454 sequencing. During development, 2053 transcripts increased and 2135 decreased significantly in abundance. The senescence of the flower was associated with increased abundance of many hydrolytic genes, including aspartic and cysteine proteases, vacuolar processing enzymes, and nucleases. Pathway analysis suggested that transcripts altering significantly in abundance were enriched in functions related to cell wall-, aquaporin-, light/circadian clock-, autophagy-, and calcium-related genes. Finding enrichment in light/circadian clock-related genes fits well with the observation that hibiscus floral development is highly synchronized with light and the hypothesis that ageing/senescence of the flower is orchestrated by a molecular clock. Further study of these genes will provide novel insight into how the molecular clock is able to regulate the timing of programmed cell death in tissues. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. Transcriptional profile of genes involved in ascorbate glutathione cycle in senescing leaves for an early senescence leaf (esl) rice mutant.

    Li, Zhaowei; Su, Da; Lei, Bingting; Wang, Fubiao; Geng, Wei; Pan, Gang; Cheng, Fangmin

    2015-03-15

    To clarify the complex relationship between ascorbate-glutathione (AsA-GSH) cycle and H2O2-induced leaf senescence, the genotype-dependent difference in some senescence-related physiological parameters and the transcript levels and the temporal patterns of genes involved in the AsA-GSH cycle during leaf senescence were investigated using two rice genotypes, namely, the early senescence leaf (esl) mutant and its wild type. Meanwhile, the triggering effect of exogenous H2O2 on the expression of OsAPX genes was examined using detached leaves. The results showed that the esl mutant had higher H2O2 level than its wild type at the initial stage of leaf senescence. At transcriptional level, the association of expression of various genes involved in the AsA-GSH cycle with leaf senescence was isoform dependent. For OsAPXs, the transcripts of two cytosolic OsAPX genes (OsAPX1 and OsAPX2), thylakoid-bound OsAPX8, chloroplastic OsAPX7 and peroxisomal OsAPX4 exhibited remarkable genotype-dependent variation in their expression levels and temporal patterns during leaf senescence, there were significantly increasing transcripts of OsAXP1 and OsAPX7, severely repressed transcripts of OsAPX4 and OsAPX8 for the esl rice at the initial leaf senescence. In contrast, the repressing transcript of OsAPX8 was highly sensitive to the increasing H2O2 level in the senescing rice leaves, while higher H2O2 concentration resulted in the enhancing transcripts of two cytosolic OsAPX genes, OsAPX7 transcript was greatly variable with different H2O2 concentrations and incubating duration, suggesting that the different OsAPXs isoforms played a complementary role in perceiving and scavenging H2O2 accumulation at various H2O2 concentrations during leaf senescence. Higher H2O2 level, increased AsA level, higher activities of APX and glutathione reductase (GR), and relatively stable GSH content during the entire sampling period in the leaves of esl mutant implied that a close interrelationship existed

  15. Die huwelik as identiteitsmerker in die Ou Testament

    p1243322

    Gen 2:18). Uit die woorde van Genesis 2:24 dat man en vrou een sal wees, lei die derde formulier af dat dit “getuig dat die huwelik 'n allesinsluitende gemeenskap is ..... die formule gebruik word: “Hier volg die vertelling oor X se nageslag.” (Gen ..... verwys daarna as “intertwining the principal value concepts of tradition”.

  16. IFN-β antiproliferative effect and miRNA regulation in Human Papilloma Virus E6- and E7-transformed keratinocytes.

    Chiantore, Maria Vincenza; Mangino, Giorgio; Iuliano, Marco; Zangrillo, Maria Simona; De Lillis, Ilaria; Vaccari, Gabriele; Accardi, Rosita; Tommasino, Massimo; Fiorucci, Gianna; Romeo, Giovanna

    2017-01-01

    Human Papilloma Viruses (HPVs) are the causative agents of cervical cancer although other types of cancers are associated with HPV infection. Type I Interferons can interfere with HPV E6- and/or E7-dependent transformation and can affect microRNA (miRNA) expression. Cancer cells show a specific pattern of miRNA expression and HPVs are able to modulate miRNAs expressed in infected cells. Keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38) were studied to analyze the involvement of HPV oncoproteins in the anti-proliferative activity of IFN-β. In view of our previous data showing senescence induction by the cytokine in K38 cells, we observe that IFN-β treatment leads to p53-indipendent apoptosis in K16 cells whereas induces senescence in K16 cells if E6 is silenced and p53 expression is restored. The levels of selected miRNAs, deregulated in K16 and K38 cells, can be modulated by IFN-β when E6 and E7 proteins of HPV-16, but not HPV-38, are expressed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Re-appraisal of keratinocytes' role in vitiligo pathogenesis

    Ola Ahmed Bakry

    2018-01-01

    Full Text Available Background: Vitiligo is a common pigmentary disorder. Studies on its pathogenesis extensively investigated melanocytes' abnormalities and few studies searched for keratinocytes' role in disease development. Liver X receptor-α (LXR-α is a member of nuclear hormone receptors that acts as a transcription factor. Its target genes are the main regulators of melanocyte functions. Aim: The aim of this study is to investigate keratinocytes' role in vitiligo pathogenesis through immunohistochemical expression of LXR-α in lesional, perilesional, and distant nonlesional vitiligo skin. Materials and Methods: This case–control study was carried out on 44 participants. These included 24 patients with vitiligo and 20 age- and sex-matched normal individuals as a control group. Biopsies, from cases, were taken from lesional, perilesional, and distant nonlesional areas. Evaluation was done using immunohistochemical technique. Results: Keratinocyte LXR-α expression was upregulated in the lesional and perilesional skin (follicular and interfollicular epidermis compared with control skin (P<0.001 for all. There was significant association between higher histoscore (H-score in lesional epidermis (P<0.001 and in hair follicle (P=0.001 and the presence of angiogenesis. There was significant association between higher H-score in lesional epidermis and suprabasal vacuolization (P=0.02. No significant association was found between H-score or expression percentage and clinical data of selected cases. Conclusion: LXR-α upregulation is associated with keratinocyte damage in vitiligo lesional skin that leads to decreased keratinocyte-derived mediators and growth factors supporting the growth and/or melanization of surrounding melanocytes. Therefore, melanocyte function and survival are affected.

  18. Narratiwiteit en die Ou Testament

    INLEIDING. Die literêre benadering tot die Ou-Testamentiese narratiewe word algemeen as 'n alternatiewe paradigma in die Bybelwetenskappe aanvaar. Oor die filosofiese uit- gangspunte wat hierdie nuwe paradigma ten grondslag lê, bestaan daar egter nog weinig eenstemmigheid. Heelwat probleme van filosofiese en ...

  19. Eksistensialisme in die Franse letterkunde

    A. A. Teurlinckx

    1966-03-01

    Full Text Available Nooit sou die Franse jeug — en die van Europa en verder — in dié mate deur die eksistensialisme be'invloed gewees het nie, indien hierdie filosofie in wysgerige traktate sou begrawe gelê het. Die eksistensialiste het die koning van die filosofiese verhaal, Voltaire, met sukses op sy Candide- en Zadig-pad gevolg en hulle teorieë in letterkundige werke, ver- hale, romans en ook toneelstukke kwytgeraak, wat baie gelees is en waaruit ook ander literatore kragte en inspirasie geput het. Omrede daarvan is daar inderdaad baie eksistensialisme in die Franse letterkunde, maar ’n eintlike eksistensialistiese letterkunde was daar nie, en ’n Eksistensialistiese Letterkun­ dige skool het nooit bestaan nie. Ook sit hierdie eksistensialiste nie langs dieselfde vuur nie. Die Christelike eksistensialis Gabriel Marcel het op 21 April van hierdie jaar uitgevaar teen die „Sartriane” na aanleiding van die opvoering van Les Paravents, Die W indskerms van Jean Genêt in ’n Paryse staatsondersteunde teater. „Mens mag seker wees”, skryf Marcel in Les Nouvelles Littéraires, „dat die hele sartriaanse parogie sal skreeu: groot meesterwerk”. Voortgaande op sy distansiëring kan die literêre eksistensialiste in drie groepe ingedeel word: 1. Die Sartriane; 2. Die Christelike Eksistensialiste; 3. Die Onafhanklikes.

  20. Telomeres and replicative senescence: Is it only length that counts?

    von Zglinicki, T

    2001-07-26

    Telomeres are well established as a major 'replicometer', counting the population doublings in primary human cell cultures and ultimately triggering replicative senescence. However, neither is the pace of this biological clock inert, nor is there a fixed threshold telomere length acting as the universal trigger of replicative senescence. The available data suggest that opening of the telomeric loop and unscheduled exposure of the single-stranded G-rich telomeric overhang might act like a semaphore to signal senescent cell cycle arrest. Short telomere length, telomeric single-strand breaks, low levels of loop-stabilizing proteins, or other factors may trigger this opening of the loop. Thus, both telomere shortening and the ultimate signalling into senescence are able to integrate different environmental and genetic factors, especially oxidative stress-mediated damage, which might otherwise become a thread to genomic stability.

  1. Assessing senescence patterns in populations of large mammals

    Gaillard, J.-M.

    2004-06-01

    Full Text Available Theoretical models such as those of Gompertz and Weibull are commonly used to study senescence in survival for humans and laboratory or captive animals. For wild populations of vertebrates, senescence in survival has more commonly been assessed by fitting simple linear or quadratic relationships between survival and age. By using appropriate constraints on survival parameters in Capture-Mark-Recapture (CMR models, we propose a first analysis of the suitability of the Gompertz and the two-parameter Weibull models for describing aging-related mortality in free-ranging populations of ungulates. We first show how to handle the Gompertz and the two-parameter Weibull models in the context of CMR analyses. Then we perform a comparative analysis of senescence patterns in both sexes of two ungulate species highly contrasted according to the intensity of sexual selection. Our analyses provide support to the Gompertz model for describing senescence patterns in ungulates. Evolutionary implications of our results are discussed

  2. Role of P53 in Mammary Epithelial Cell Senescence

    Dimri, Goberdhan P

    2006-01-01

    .... We also chose several other targets of p53 that are induced by DNA damage. The RT PCR analysis aws carried out using mRNA prepared from young growing early passage and senescent late passage HMECs...

  3. Senescent vs. non-senescent cells in the human annulus in vivo: Cell harvest with laser capture microdissection and gene expression studies with microarray analysis

    Ingram Jane A

    2010-01-01

    Full Text Available Abstract Background Senescent cells are well-recognized in the aging/degenerating human disc. Senescent cells are viable, cannot divide, remain metabolically active and accumulate within the disc over time. Molecular analysis of senescent cells in tissue offers a special challenge since there are no cell surface markers for senescence which would let one use fluorescence-activated cell sorting as a method for separating out senescent cells. Methods We employed a novel laser capture microdissection (LCM design to selectively harvest senescent and non-senescent annulus cells in paraffin-embedded tissue, and compared their gene expression with microarray analysis. LCM was used to separately harvest senescent and non-senescent cells from 11 human annulus specimens. Results Microarray analysis revealed significant differences in expression levels in senescent cells vs non-senescent cells: 292 genes were upregulated, and 321 downregulated. Genes with established relationships to senescence were found to be significantly upregulated in senescent cells vs. non-senescent cells: p38 (MPAK14, RB-Associated KRAB zinc finger, Discoidin, CUB and LCCL domain, growth arrest and DNA-damage inducible beta, p28ING5, sphingosine-1-phosphate receptor 2 and somatostatin receptor 3; cyclin-dependent kinase 8 showed significant downregulation in senescent cells. Nitric oxidase synthase 1, and heat shock 70 kDa protein 6, both of which were significantly down-regulated in senescent cells, also showed significant changes. Additional genes related to cytokines, cell proliferation, and other processes were also identified. Conclusions Our LCM-microarray analyses identified a set of genes associated with senescence which were significantly upregulated in senescent vs non-senescent cells in the human annulus. These genes include p38 MAP kinase, discoidin, inhibitor of growth family member 5, and growth arrest and DNA-damage-inducible beta. Other genes, including genes

  4. Assisted Dying in Canada.

    Schuklenk, Udo

    This paper makes an affirmative ethical case in favour of the decriminalization of assisted dying in Canada. It then proceeds to defending the affirmative case against various slippery-slope arguments that are typically deployed by opponents of assisted dying. Finally, a recent case of questionable professional conduct by anti-euthanasia campaigners cum academics is flagged as a warning to all of us not to permit the quality of the professional debate to deteriorate unacceptably, despite the personal emotional investments involved on all sides of the debate.

  5. Calculating the Rate of Senescence From Mortality Data

    Koopman, Jacob J E; Rozing, Maarten P; Kramer, Anneke

    2016-01-01

    , they do not fit mortality rates at young and old ages. Therefore, we developed a method to calculate senescence rates from the acceleration of mortality directly without modeling the mortality rates. We applied the different methods to age group-specific mortality data from the European Renal Association......, the rate of senescence can be calculated directly from non-modeled mortality rates, overcoming the disadvantages of an indirect estimation based on modeled mortality rates....

  6. Accumulation of senescent cells in mitotic tissue of aging primates.

    Jeyapalan, Jessie C; Ferreira, Mark; Sedivy, John M; Herbig, Utz

    2007-01-01

    Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over 40 years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event.

  7. Gene pathways that delay Caenorhabditis elegans reproductive senescence.

    Meng C Wang

    2014-12-01

    Full Text Available Reproductive senescence is a hallmark of aging. The molecular mechanisms regulating reproductive senescence and its association with the aging of somatic cells remain poorly understood. From a full genome RNA interference (RNAi screen, we identified 32 Caenorhabditis elegans gene inactivations that delay reproductive senescence and extend reproductive lifespan. We found that many of these gene inactivations interact with insulin/IGF-1 and/or TGF-β endocrine signaling pathways to regulate reproductive senescence, except nhx-2 and sgk-1 that modulate sodium reabsorption. Of these 32 gene inactivations, we also found that 19 increase reproductive lifespan through their effects on oocyte activities, 8 of them coordinate oocyte and sperm functions to extend reproductive lifespan, and 5 of them can induce sperm humoral response to promote reproductive longevity. Furthermore, we examined the effects of these reproductive aging regulators on somatic aging. We found that 5 of these gene inactivations prolong organismal lifespan, and 20 of them increase healthy life expectancy of an organism without altering total life span. These studies provide a systemic view on the genetic regulation of reproductive senescence and its intersection with organism longevity. The majority of these newly identified genes are conserved, and may provide new insights into age-associated reproductive senescence during human aging.

  8. Density dependence triggers runaway selection of reduced senescence.

    Robert M Seymour

    2007-12-01

    Full Text Available In the presence of exogenous mortality risks, future reproduction by an individual is worth less than present reproduction to its fitness. Senescent aging thus results inevitably from transferring net fertility into younger ages. Some long-lived organisms appear to defy theory, however, presenting negligible senescence (e.g., hydra and extended lifespans (e.g., Bristlecone Pine. Here, we investigate the possibility that the onset of vitality loss can be delayed indefinitely, even accepting the abundant evidence that reproduction is intrinsically costly to survival. For an environment with constant hazard, we establish that natural selection itself contributes to increasing density-dependent recruitment losses. We then develop a generalized model of accelerating vitality loss for analyzing fitness optima as a tradeoff between compression and spread in the age profile of net fertility. Across a realistic spectrum of senescent age profiles, density regulation of recruitment can trigger runaway selection for ever-reducing senescence. This novel prediction applies without requirement for special life-history characteristics such as indeterminate somatic growth or increasing fecundity with age. The evolution of nonsenescence from senescence is robust to the presence of exogenous adult mortality, which tends instead to increase the age-independent component of vitality loss. We simulate examples of runaway selection leading to negligible senescence and even intrinsic immortality.

  9. Die afrikaner en sy pers*

    G. D. Scholtz

    1963-03-01

    Full Text Available Die versoek w at van u inrigting tot my gekom het om buitengewone professor in die Persw etenskap te word, was vir my deels vererend, m aar deels het dit my in 'n moeilike posisie gestel. Dit was vir my vererend, om dat dit gekom het van 'n universiteit m et wie se Christelik- Nasionale koers ek my ten voile kan vereenselwig. Dit was dan ook vir my vererend, om dat ek daardeur in staat gestel kan w ord om die volk w aartoe ek behoort, op 'n vir my nuwe terrein te dien. As sodanig is dit vir my im m ers m oontlik om ook ’n beskeie bydrae te lewer tot die geestelike vorm ing van die jeug van ons volk. Dit het my m oeilik geval om, w aar ek reeds die m iddeljarige leeftyd bereik het, nou vir die eerste maal as dosent op te tree, aangesien ek daarvan in die verlede nie die m inste kennis en ervaring opgedoen het nie. As joernalis rig ek my im m ers tot die breë publiek deur middel van die pen. As dosent m oet ek my deur middel van die mond tot die studente rig. Dit lê voor die hand dat die eise w at so aan my gestel word, totaal anders is as dié waar- aan ek oor 'n tydperk van m eer as 'n kw arteeu as joer­ nalis gewoond geraak het.

  10. Die vestiging van die Kerk in Natal, die Vrystaat en Transvaal na ...

    as eerste predikant van die Voortrekkers laat orden en bevestig. Daama het verskeie kerksake van tyd tot tyd aandag geniet. Met betrekking tot die bevestiging van huwelike stel Retief 'n meer ordelike reëling daar, naamlik dat die gebooie van voomemende egpa- re van nou af drie maal in die kerk afgekondig moes wrord ...

  11. Die skool en die onderwyser as faktore in die geestesgesondheid van die kind*

    B. C. Schutte

    1961-03-01

    Full Text Available Ons hou geestesgesondheidsweke, stig beroepsentrums, samel geld in om mense wat geestelik siek is te genees, klae oor die tekort aan psigiaters, kliniese sielkundiges, bedryfsielkundiges, voorligters, skoolpsigoloë,ens. ’n Karige kwarteeu gelede het ons aan al hierdie dinge slegs akademiese aandag gewy. In hierdie kursus wordverskeie tipes kinders bespreek en geleer hoe om hulle probleme te benader.

  12. When Somebody Dies

    ... bottle became useless. The container is gone, but what's inside — the water — remains. The part of a person that's left after the body dies is often called the "soul" or "spirit." Some people believe the soul is the part ...

  13. Die Kunst des Scheiterns

    Juul, Jesper

    2014-01-01

    Menschen haben von Kindesbeinen an das Verlangen, Erfolge zu erzielen und Kompetenz zu erreichen. Computerspieler entscheiden sich jedoch fortlaufend für eine Aktivität, die oft und wiederholt zum Verlieren führen muss und ein taubes Gefühl der Unfähigkeit erzeugt. Im Kino, im Theatersaal und bei...

  14. Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions?

    Toussaint, Olivier; Dumont, Patrick; Remacle, Jose; Dierick, Jean-Francois; Pascal, Thierry; Frippiat, Christophe; Magalhaes, Joao Pedro; Zdanov, Stephanie; Chainiaux, Florence

    2002-01-01

    No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in...

  15. Modelle in die onderrig van fisika

    J. J. A. Smit

    1998-07-01

    Full Text Available Die rol van modelle in die onderrig van fisika is sedert die vroeë tagtigerjare erken. In die onderrig word die absent op die kwantitaiewe aspekte van die vak geplaas, terwyl die kwatitatiewe aspekte min aandag kry.

  16. DIE SAGD - SY ONTSTAAN EN ONTWIKKELING

    31 Okt 1977 ... stelling van 'n higiene afdeling het in 'n belang- rike behoefte voorsien. Die pligte van die SAGO het dus op hierdie stadium die ondersoek van soldate, die sanita- sie van kampe, die verpleging van pasiente in militere hospitale en die opleiding van lede be- hels. 'n Hoogtepunt was die opening van die.

  17. Dimensional control of die castings

    Karve, Aniruddha Ajit

    The demand for net shape die castings, which require little or no machining, is steadily increasing. Stringent customer requirements are forcing die casters to deliver high quality castings in increasingly short lead times. Dimensional conformance to customer specifications is an inherent part of die casting quality. The dimensional attributes of a die casting are essentially dependent upon many factors--the quality of the die and the degree of control over the process variables being the two major sources of dimensional error in die castings. This study focused on investigating the nature and the causes of dimensional error in die castings. The two major components of dimensional error i.e., dimensional variability and die allowance were studied. The major effort of this study was to qualitatively and quantitatively study the effects of casting geometry and process variables on die casting dimensional variability and die allowance. This was accomplished by detailed dimensional data collection at production die casting sites. Robust feature characterization schemes were developed to describe complex casting geometry in quantitative terms. Empirical modeling was utilized to quantify the effects of the casting variables on dimensional variability and die allowance for die casting features. A number of casting geometry and process variables were found to affect dimensional variability in die castings. The dimensional variability was evaluated by comparisons with current published dimensional tolerance standards. The casting geometry was found to play a significant role in influencing the die allowance of the features measured. The predictive models developed for dimensional variability and die allowance were evaluated to test their effectiveness. Finally, the relative impact of all the components of dimensional error in die castings was put into perspective, and general guidelines for effective dimensional control in the die casting plant were laid out. The results of

  18. Die transvaalse ontwerp-ordonnansie oor die onderwys

    J. C. Coetzee

    1952-03-01

    Full Text Available In ’n Buitengewone Provinsiale Koerant van die Provinsie Transvaal is onder datum 25 Junie 1952 gepubliseer ’n „Ontwerp-Ordonnansie tot samevatting en wysiging van die Wette betreffende die Sentrale Beheer van die Onderwys, die Plaaslike Beheer van Skole, Godsdiensonderrig in Openbare Skole, Taal en die Onderwys, Onderwyspersoneel, Verpligte Onderwys, Toelating van Leerlinge tot Skole, Klasse of Inrigtings, Openbare Onderwys, Private Skole, Onderwys vir Kleurlinge en Asiate en Onderwys vir Naturelle, en om vir sake in verband daarmee voorsiening te maak” .

  19. DIE HEDENDAAGSE SIENING VAN DIE NORMERING VAN DUITS ...

    v a k t a a l k w a l i £ i k a s i e s ) neem d i e I n s t i t u t t a l l e take waar ter u i t b r e i d i n g van kennis van die Duitse taal in die buiteland. Sedert 1964 publiseer die. Institut die tydskrif Deutsch als Fremdsprache met die bylae Sprachpraxis, asook 'n handboek met die titel Deutsch - eln Lehrbuch Eur Auslander (Duits.

  20. Navigating "Assisted Dying".

    Schipper, Harvey

    2016-02-01

    Carter is a bellwether decision, an adjudication on a narrow point of law whose implications are vast across society, and whose impact may not be realized for years. Coupled with Quebec's Act Respecting End-of-life Care it has sharply changed the legal landscape with respect to actively ending a person's life. "Medically assisted dying" will be permitted under circumstances, and through processes, which have yet to be operationally defined. This decision carries with it moral assumptions, which mean that it will be difficult to reach a unifying consensus. For some, the decision and Act reflect a modern acknowledgement of individual autonomy. For others, allowing such acts is morally unspeakable. Having opened the Pandora's Box, the question becomes one of navigating a tolerable societal path. I believe it is possible to achieve a workable solution based on the core principle that "medically assisted dying" should be a very rarely employed last option, subject to transparent ongoing review, specifically as to why it was deemed necessary. My analysis is based on 1. The societal conditions in which have fostered demand for "assisted dying", 2. Actions in other jurisdictions, 3. Carter and Quebec Bill 52, 4. Political considerations, 5. Current medical practice. Leading to a series of recommendations regarding. 1. Legislation and regulation, 2. The role of professional regulatory agencies, 3. Medical professions education and practice, 4. Public education, 5. Health care delivery and palliative care. Given the burden of public opinion, and the legal steps already taken, a process for assisted-dying is required. However, those legal and regulatory steps should only be considered a necessary and defensive first step in a two stage process. The larger goal, the second step, is to drive the improvement of care, and thus minimize assisted-dying.

  1. Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

    Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

    1994-12-01

    To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

  2. Die historiese betroubaarheid van die aartsvadervertellinge. 'n Beknopte bespreking van die huidige debat na aanleiding van die jongste publikasie

    W. Vosloo

    1982-08-01

    Full Text Available Die afgelope twintig jaar was daar �n toenemende belangstelling in die aartsvadervertellinge in Genesis. Benewens die talle tydskrifartikels het skrywers soos die volgende ook boeke oor die onderwerp die lig laat sien: A. Parrot (1962, W. M. Clark (1964, R. Kilian (1966, R. E. Clements (1967, N. Lohfink (1967, H. Weidemann (1968, R. Martin-Achard (1969, T. L. Thompson (1974, J. van Seters (1975, J. P. Fokkelman (1975, C. Westermann (1976, R. Rendtorff (1977, J. Bright (1977, W. McKane (1979 en A. R. Millard en D. J. Wiseman (1980.

  3. 'n Kwalitatiewe ondersoek na die invloed van aspekte van die ...

    S Blignaut

    ISSN 0378-5254 Journal of Family Ecology and Consumer Sciences, Vol 26: No1, 1998. 15 ...... van byvoorbeeld die televisie en gedrukte media 'n invloed op die .... fashion promotion and advertising. New York. ... Consumer behaviour to-.

  4. PTTG1 attenuates drug-induced cellular senescence.

    Yunguang Tong

    Full Text Available As PTTG1 (pituitary tumor transforming gene abundance correlates with adverse outcomes in cancer treatment, we determined mechanisms underlying this observation by assessing the role of PTTG1 in regulating cell response to anti-neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1(-/- exhibited enhanced drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis, mitosis catastrophe or DNA damage were not detected, but features of senescence were observed using low doses of doxorubicin and TSA. The number of drug-induced PTTG1(-/- senescent cells increased ∼4 fold as compared to WT PTTG1-replete cells (p<0.001. p21, an important regulator of cell senescence, was induced ∼3 fold in HCT116 PTTG1(-/- cells upon doxorubicin or Trichostatin A treatment. Binding of Sp1, p53 and p300 to the p21 promoter was enhanced in PTTG1(-/- cells after treatment, suggesting transcriptional regulation of p21. p21 knock down abrogated the observed senescent effects of these drugs, indicating that PTTG1 likely suppresses p21 to regulate drug-induced senescence. PTTG1 also regulated SW620 colon cancer cells response to doxorubicin and TSA mediated by p21. Subcutaneously xenografted PTTG1(-/- HCT116 cells developed smaller tumors and exhibited enhanced responses to doxorubicin. PTTG1(-/- tumor tissue derived from excised tumors exhibited increased doxorubicin-induced senescence. As senescence is a determinant of cell responses to anti-neoplastic treatments, these findings suggest PTTG1 as a tumor cell marker to predict anti-neoplastic treatment outcomes.

  5. Toxicity of silver nanoparticles in monocytes and keratinocytes

    Orłowski, Piotr; Krzyzowska, Malgorzata; Winnicka, Anna

    2012-01-01

    Silver nanoparticles are of interest to be used as antimicrobial agents in wound dressings and coatings in medical devices, but potential adverse effects have been reported in the literature. The possible local inflammatory response to silver nanoparticles and the role of cell death in determining...... these effects are largely unknown. Effects of the mixture of silver nanoparticles of different sizes were compared in in vitro assays for cytotoxicity, caspase-1 and caspase-9 activity and bax expression. In all tested concentrations, silver nanoparticles were more toxic for RAW 264.7 monocytes than for 291.03C...... keratinocytes and induced significant caspase-1 activity and necrotic cell death. In keratinocytes, more significantly than in macrophages, silver nanoparticles led to increase of caspase-9 activity and apoptosis. These results indicate that effects of silver nanoparticles depend on the type of exposed cells...

  6. Modeling the Mechanical Performance of Die Casting Dies

    R. Allen Miller

    2004-02-27

    The following report covers work performed at Ohio State on modeling the mechanical performance of dies. The focus of the project was development and particularly verification of finite element techniques used to model and predict displacements and stresses in die casting dies. The work entails a major case study performed with and industrial partner on a production die and laboratory experiments performed at Ohio State.

  7. N HERSIENING VAN DIE AFRIKAANSE VERTALING VAN DIE ...

    Test

    vergewe. Dit sou in orde gewees het as daar gestaan het, ReMomë- j^onta^is hepta?ds. wat die grieks is vir sewentig maal sewe. Die uitdrukking. heMom&ontabis heptd sien hoogswaarskynlik op Gen. 4 : 24 (LXX) waar. Lameg meedeel dat hy sewe-en-sewentig-maal gewreek sal word. Daar sit die Afr. Vert, die uitdrukking ...

  8. The forms and fitness cost of senescence : Age-specific recapture, survival, reproduction, and reproductive value in a wild bird population

    Bouwhuis, Sandra; Choquet, Remi; Sheldon, Ben C.; Verhulst, Simon

    Longitudinal studies of senescence accumulate rapidly from natural populations. However, it is largely unknown whether different fitness components senesce in parallel, how reproductive and survival senescence contribute to declines in reproductive value, and how large the fitness cost of senescence

  9. Film Presentation: Die Urknallmaschine

    Carolyn Lee

    2010-01-01

    Die Urknallmaschine, an Austrian film by Gerd Baldauf, narrated by Norbert Frischauf (Alpha Österreich - ORF, 2009).  In CERN’s gigantic complex particles are accelerated to almost the speed of light, brought to collision and made to divide into even smaller particles. Public opinion of CERN’s research is also divided. Sceptics fear that black holes may be created. Might the goal to study the origin of the world lead to its destruction? The Austrian researcher Norbert Frischauf worked at CERN for many years. With his guidance it is possible to explore the world’s largest research centre, get a glimpse of the fascinating work the scientists do there and take a crash course in particle physics. Die Urknallmaschine will be presented on Friday, 25 June from 13:00 to 14:00 in the Main Auditorium. Language: German

  10. Dying for security

    Buchan, Bruce

    2011-01-01

    Full Text Available If political statements and media coverage are any guide, it seems Australians today are dying for security. At no other moment in our history has the spectre of war and terrorism so haunted popular, political and scholarly perceptions of Australia’s colonial past and of its geopolitical future. And yet, debates over colonial war or genocide and contemporary terrorism have been conducted in more or less complete isolation. In this article I argue that our contemporary obsession with ‘security’ is premised on the perennial threat of ‘insecurity’. This is the problem of in/security, and it has played a central role in the development of Western political thought. More importantly, its formulation in Western political thought provided a powerful justification for the violence of the early decades of Australia’s colonisation during which Indigenous Australians could also be said to have been dying for security.

  11. Dying for Security

    Bruce Buchan

    2011-03-01

    Full Text Available If political statements and media coverage are any guide, it seems Australians today are dying for security. At no other moment in our history has the spectre of war and terrorism so haunted popular, political and scholarly perceptions of Australia’s colonial past and of its geopolitical future. And yet, debates over colonial war or genocide and contemporary terrorism have been conducted in more or less complete isolation. In this article I argue that our contemporary obsession with ‘security’ is premised on the perennial threat of ‘insecurity’. This is the problem of in/security, and it has played a central role in the development of Western political thought. More importantly, its formulation in Western political thought provided a powerful justification for the violence of the early decades of Australia’s colonisation during which Indigenous Australians could also be said to have been dying for security.

  12. TIG3 - AN IMPORTANT REGULATOR OF KERATINOCYTE PROLIFERATION AND SURVIVAL

    Scharadin, Tiffany M.; Eckert, Richard L.

    2014-01-01

    Tazarotene induced gene 3 (TIG3) is a tumor suppressor protein. In normal human epidermis, TIG3 is present in the differentiated, suprabasal layers and regulates terminal differentiation. TIG3 level is reduced in hyperproliferative diseases, including psoriasis and skin cancer, suggesting that loss of TIG3 is associated with enhanced cell proliferation. Moreover, transient expression of TIG3 leads to terminal differentiation in normal keratinocytes and apoptosis in skin cancer cells. In both ...

  13. Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

    Bayer, Andreas; Tohidnezhad, Mersedeh; Lammel, Justus; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

    2017-01-01

    Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF?) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiatio...

  14. Sustainability of keratinocyte gene transfer and cell survival in vivo.

    Choate, K A; Khavari, P A

    1997-05-20

    The epidermis is an attractive site for therapeutic gene delivery because it is accessible and capable of delivering polypeptides to the systemic circulation. A number of difficulties, however, have emerged in attempts at cutaneous gene delivery, and central among these is an inability to sustain therapeutic gene production. We have examined two major potential contributing factors, viral vector stamina and involvement of long-lived epidermal progenitor cells. Human keratinocytes were either untreated or transduced with a retroviral vector for beta-galactosidase (beta-Gal) at > 99% efficiency and then grafted onto immunodeficient mice to regenerate human epidermis. Human epidermis was monitored in vivo after grafting for clinical and histologic appearance as well as for gene expression. Although integrated vector sequences persisted unchanged in engineered epidermis at 10 weeks post-grafting, retroviral long terminal repeat (LTR)-driven beta-Gal expression ceased in vivo after approximately 4 weeks. Endogenous cellular promoters, however, maintained consistently normal gene expression levels without evidence of time-dependent decline, as determined by immunostaining with species-specific antibodies for human involucrin, filaggrin, keratinocyte transglutaminase, keratin 10, type VII collagen, and Laminin 5 proteins out to week 14 post-grafting. Transduced human keratinocytes generated multilayer epidermis sustained through multiple epidermal turnover cycles; this epidermis demonstrated retention of a spatially appropriate pattern of basal and suprabasal epidermal marker gene expression. These results confirm previous findings suggesting that viral promoter-driven gene expression is not durable and demonstrate that keratinocytes passaged in vitro can regenerate and sustain normal epidermis for prolonged periods.

  15. Flow cytometry of human primary epidermal and follicular keratinocytes.

    Gragnani, Alfredo; Ipolito, Michelle Zampieri; Sobral, Christiane S; Brunialti, Milena Karina Coló; Salomão, Reinaldo; Ferreira, Lydia Masako

    2008-02-19

    The aim of this study was to characterize using flow cytometry cultured human primary keratinocytes isolated from the epidermis and hair follicles by different methods. Human keratinocytes derived from discarded fragments of total skin and scalp hair follicles from patients who underwent plastic surgery in the Plastic Surgery Division at UNIFESP were used. The epidermal keratinocytes were isolated by using 3 different methods: the standard method, upon exposure to trypsin for 30 minutes; the second, by treatment with dispase for 18 hours and with trypsin for 10 minutes; and the third, by treatment with dispase for 18 hours and with trypsin for 30 minutes. Follicular keratinocytes were isolated using the standard method. On comparing the group treated with dispase for 18 hours and with trypsin for 10 minutes with the group treated with dispase for 18 hours and with trypsin for 30 minutes, it was observed that the first group presented the largest number of viable cells, the smallest number of cells in late apoptosis and necrosis with statistical significance, and no difference in apoptosis. When we compared the group treated with dispase for 18 hours and with trypsin for 10 minutes with the group treated with trypsin, the first group presented the largest number of viable cells, the smallest number of cells in apoptosis with statistical significance, and no difference in late apoptosis and necrosis. When we compared the results of the group treated with dispase for 18 hours and with trypsin for 10 minutes with the results for follical isolation, there was a statistical difference in apoptosis and viable cells. The isolation method of treatment with dispase for 18 hours and with trypsin for 10 minutes produced the largest number of viable cells and the smallest number of cells in apoptosis/necrosis.

  16. N HERSIENING VAN DIE AFRIKAANSE VERTALING VAN DIE ...

    Test

    aangetoon het, 'n huis in Kapernaum gehad en hierdie geskiedenis speel in Kapernaum of daar digby af. Jesus en sy dissipele het namelik, volgens 6:35 geland by Gennesaret, net suid van Kapernaum Die gevolgtrekking word ondersteun deur Joh. 6:17 waarvolgens die dissi pele na die spysiging op Kapernaum gevaar ...

  17. 'n Verkenning van die soorte vennootskappe in die Amerikaanse reg ...

    In die Amerikaanse literatuur word talle verwysings gevind na die vennootskap in mynbou ("mining partnership"), familievennootskap ("family partnership", vennootskap in vaste eiendom ("partnership in real estate") en vennootskap vir boerdery ("farming partnership"). Hierdie onderskeiding is primer gebaseer op die tipe ...

  18. Geslagsverskille in die ouditiewe ontlokte potensiaal van die brein

    Anita D Stuart

    2006-10-01

    Full Text Available Gender differences in the auditory evoked potential of the brain. Based on literature indications of an association between temperament characteristics and the evoked potential of the brain, and indications of gender differences in certain temperament traits, the purpose of this study was to ascertain whether evoked responses also differentiated between the genders. A sample of 81 male and 210 female students was randomly selected. Two auditory evoked potential procedures were applied. The results indicated statistically significant differences in evoked potential responses between the genders. The results are interpreted against the background of sensory and neurological sources of the evoked potential responses and linked to the neurophysiological foundations of temperament. Opsomming: Gegrond op aanduidings in die literatuur van ’n assosiasie tussen temperamentskenmerke en die ontlokte potensiaal van die brein, sowel as aanduidings van geslagsverskille in sekere temperamentstrekke, was die doel van die huidige studie om te bepaal of ontloktepotensiaal-response ook tussen die geslagte onderskei. ’n Steekproef van 81 manlike en 210 vroulike studente is ewekansig geselekteer. Twee ouditiewe ontloktepotensiaal- prosedures is toegepas. Die resultate het op statisties beduidende verskille tussen die geslagte gedui. Die bevindinge word teen die agtergrond van die sensoriese en neurologiese oorsprong van ontloktepotensiaal–response geïnterpreteer en verbind aan die neurofisiologiese verankering van temperament.

  19. Die 'postmoderne' stempel in die Nuwe-Testamentiese hermeneutiek

    georiënteerde teorie en kritiek wat volgens Moore opbou tot 'n herhaling binne. Bybelnavorsing. Dit het reeds by Immanuel Kant begin. Sedert Kant is dit proble- maties cm die objek van kennis te beskou as iets wat kennis objektief in sigself bevat. Objektiwisme is prys gegee. Dialektiek het in die plek daarvan gekom. Die.

  20. duele verse sowel as die somtotaal die leser

    27 Jan 2006 ... selfs 'n landkaart afgedruk) terwyl dit ter- selfdertyd ver bo die lokale uitstyg. Die digter is sterk bewus van sy omgewing, geskiedenis en tradisies, maar veral van die algemene menslike kondisie wat binne hierdie referensiekader vergestalt word. Hy gebruik 'n bekende historiese slagveld as bundeltitel (en ...

  1. Die Leben Einsteins eine Reise durch die Geschichte der Physik

    Fiami

    2005-01-01

    Jeder kennt die Namen Einstein, Newton oder Galilei. aber was weiss man über sie? Hier ein Porträt Einsteins anhand von sechs Meilensteinen aus der Geschichte der Physik. Einstein tritt auf als Protagonist in verschiedenen Epochen und bei verschiedenen Entdeckungen, die die Welt verändert haben.

  2. DIE KONINGSBEDE AS ELEMENT IN DIE KRONINGSRITUEEL. By ...

    Test

    Die offerfees te Gibeon was 'n plegtigheid, waaraan geheel Israel deelgeneem het. Die duisend. "brandoffers" wat sowel Kon. as Kron. vermeld, sal wel opgevat moet word as „brandoffers en dankoffers", sodat daar vir die aanwesiges. *n groot feesmaaltyd aangerig is, vgl. I Kon. 3:15. n Sodanige maal- tyd verbind vors en ...

  3. Ruimtelike beplanning: die rol van die stads - en streeksbeplanner ...

    Ruimtelike beplanning: die rol van die stads - en streeksbeplanner in die saw. R Erasmus. Abstract. Since 1978 regional and town planners are employed in the SADF on a permanent basis as well as in the capacity of national service men. These men are all academically qualified and as such satisfy a need that developed ...

  4. n opinie oor die behaviouristiese siening versus die fenomenologie ...

    verband die eksperimente van Pavlov, Thorndike,. Skinner, Tolmann en Hull.) Fenomenologie. Die fenomenologie is 'n essensie-openbarende denkrigting. Dit impliseer'n denkende soektog na dit wat 'n besondere verskynsel of werklikheid maak juis dit wat dit is en nie iets anders nie. In die fenomenologiese antropologie ...

  5. Keratinocytes at the uppermost layer of epidermis might act as sensors of atmospheric pressure change.

    Denda, Mitsuhiro

    2016-01-01

    It has long been suggested that climate, especially atmospheric pressure change, can cause health problems ranging from migraine to myocardial infarction. Here, I hypothesize that the sensory system of epidermal keratinocytes mediates the influence of atmospheric pressure change on the human physiological condition. We previously demonstrated that even subtle changes of atmospheric pressure (5-20 hPa) induce elevation of intracellular calcium level in cultured human keratinocytes (excitation of keratinocytes). It is also established that communication occurs between epidermal keratinocytes and peripheral nerve systems. Moreover, various neurotransmitters and hormones that influence multiple systems (nervous, cardiovascular, endocrine, and immune systems) are generated and released from epidermal keratinocytes in response to various external stimuli. Thus, I suggest that pathophysiological phenomena induced by atmospheric pressure changes might be triggered by epidermal keratinocytes.

  6. Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients.

    Elango, Tamilselvi; Thirupathi, Anand; Subramanian, Swapna; Ethiraj, Purushoth; Dayalan, Haripriya; Gnanaraj, Pushpa

    2017-08-01

    Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p psoriasis by controlling the acanthosis.

  7. Response of human epidermal keratinocytes to UV light

    Kartasova, A.A.

    1987-01-01

    This thesis presents a study on the response of human epidermal keratinocytes to UV light as well as to other agents like 4-NQO and TPA. The effects of ultraviolet (UV) light on the protein synthesis in cultured keratinocytes are presented in ch. III. The next chapter describes the construction of a cDNA library using mRNA isolated from UV irradiated kernatinocytes. This library was differentially screened with cDNA probes synthesized on mRNA from either UV irradiated or nonirradiated cells. Several groups of cDNA clones corresponding to transcripts whose level in the cytoplasm seem to be affected by exposure to UV light have been isolated and characterized by cross-hybridization, sequencing and Northern blot analysis. More detailed analysis of some of the cDNA clones is presented in the two chapters following ch. IV. The complete cDNA sequence of the proteinase inhibitor cystatin A and the modulation of its expression by UV light and the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in keratinocytes are described in ch. V. Two other groups of cDNA clones have been isolated which do not cross-hybridize with each other on Southern blots. However, the primary structures of the proteins deduced from the nucleotide sequences of these two groups of cDNA clones are very similar. 212 refs.; 33 figs.; 2 tabs

  8. Neurohumoral mechanisms of keratinocytes regulation in diabetes mellitus

    Ekaterina Viktorovna Artemova

    2016-12-01

    Full Text Available The extent of damage to the nervous, vascular and microcirculatory systems in diabetic patients determine the regulation of physiological events that lead to the formation of chronic wounds, reduction of patient quality of life and increase of the financial value of medical care. Successful physiological repair is impossible without the successive phases of inflammation, proliferation and wound healing. Keratinocytes are the major cellular barrier components of the epidermis. These cells play an important role in physiological repair, as suggested by recent research, with many cells able to secrete steroid hormones de novo. Damage to the integrity of the skin leads to keratinocyte activation, triggering a cascade of reactions that contribute to changes in epidermal cell phenotype and lead to their proliferation and migration, analogous to changes in cellular adhesion and configuration of the cytoskeleton. An open question remains as to how the keratinocyte cell cycle, which is altered under conditions of hyperglycemia, and neurotransmitter metabolism during different stages of physiological repair are regulated. Understanding these processes will provide a scientific basis for the development of new targets for pharmacotherapies.

  9. UVA Irradiation of Dysplastic Keratinocytes: Oxidative Damage versus Antioxidant Defense

    Nechifor, Marina T.; Niculiţe, Cristina M.; Urs, Andreea O.; Regalia, Teodor; Mocanu, Mihaela; Popescu, Alexandra; Manda, Gina; Dinu, Diana; Leabu, Mircea

    2012-01-01

    UVA affects epidermal cell physiology in a complex manner, but the harmful effects have been studied mainly in terms of DNA damage, mutagenesis and carcinogenesis. We investigated UVA effects on membrane integrity and antioxidant defense of dysplastic keratinocytes after one and two hours of irradiation, both immediately after exposure, and 24 h post-irradiation. To determine the UVA oxidative stress on cell membrane, lipid peroxidation was correlated with changes in fatty acid levels. Membrane permeability and integrity were assessed by propidium iodide staining and lactate dehydrogenase release. The effects on keratinocyte antioxidant protection were investigated in terms of catalase activity and expression. Lipid peroxidation increased in an exposure time-dependent manner. UVA exposure decreased the level of polyunsaturated fatty acids, which gradually returned to its initial value. Lactate dehydrogenase release showed a dramatic loss in membrane integrity after 2 h minimum of exposure. The cell ability to restore membrane permeability was noted at 24 h post-irradiation (for one hour exposure). Catalase activity decreased in an exposure time-dependent manner. UVA-irradiated dysplastic keratinocytes developed mechanisms leading to cell protection and survival, following a non-lethal exposure. The surviving cells gained an increased resistance to apoptosis, suggesting that their pre-malignant status harbors an abnormal ability to control their fate. PMID:23222638

  10. Die Vier Typen von Projektmanagern

    Lund Pedersen, Carsten; Ritter, Thomas

    2018-01-01

    Bevor Sie einem Mitarbeiter die Leitung eines Projekts anvertrauen, sollten Sie sich über dessen Managementstil klar werden. Passt dieser nicht zur Art des Vorhabens, wird er scheitern. So treffen Sie die richtige Wahl....

  11. Die historiese Jesus as wondenverker

    Biblical Association, te wete 'The social sciences and second Testament exegesis'. John Pilch is die leier van die Society of Biblical Literature se 'Social sciences and ..... Hollenbach, P 1982. ... Stauffer, E 1982. Jesus ... London: Collins.

  12. Inactivation of AKT Induces Cellular Senescence in Uterine Leiomyoma

    Xu, Xiaofei; Lu, Zhenxiao; Qiang, Wenan; Vidimar, Vania; Kong, Beihua

    2014-01-01

    Uterine leiomyomas (fibroids) are a major public health problem. Current medical treatments with GnRH analogs do not provide long-term benefit. Thus, permanent shrinkage or inhibition of fibroid growth via medical means remains a challenge. The AKT pathway is a major growth and survival pathway for fibroids. We propose that AKT inhibition results in a transient regulation of specific mechanisms that ultimately drive cells into cellular senescence or cell death. In this study, we investigated specific mechanisms of AKT inhibition that resulted in senescence. We observed that administration of MK-2206, an allosteric AKT inhibitor, increased levels of reactive oxygen species, up-regulated the microRNA miR-182 and several senescence-associated genes (including p16, p53, p21, and β-galactosidase), and drove leiomyoma cells into stress-induced premature senescence (SIPS). Moreover, induction of SIPS was mediated by HMGA2, which colocalized to senescence-associated heterochromatin foci. This study provides a conceivable molecular mechanism of SIPS by AKT inhibition in fibroids. PMID:24476133

  13. Oxidative Stress Induces Senescence in Cultured RPE Cells.

    Aryan, Nona; Betts-Obregon, Brandi S; Perry, George; Tsin, Andrew T

    2016-01-01

    The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period [at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide]. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, cells with a high level of positive senescence-indicator SA-Beta-Gal-positive staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 MCM and at 800 MCM). Our data suggests that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence.

  14. Regulation of replicative senescence by NADP+ -dependent isocitrate dehydrogenase.

    Kil, In Sup; Huh, Tae Lin; Lee, Young Sup; Lee, You Mie; Park, Jeen-Woo

    2006-01-01

    The free radical hypothesis of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species that are produced as by-products of normal metabolic processes. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of cytosolic (IDPc) and mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In this paper, we demonstrate that modulation of IDPc or IDPm activity in IMR-90 cells regulates cellular redox status and replicative senescence. When we examined the regulatory role of IDPc and IDPm against the aging process with IMR-90 cells transfected with cDNA for IDPc or IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPc or IDPm expressed in target cells and their susceptibility to senescence, which was reflected by changes in replicative potential, cell cycle, senescence-associated beta-galactosidase activity, expression of p21 and p53, and morphology of cells. Furthermore, lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher and cellular redox status shifted to a prooxidant condition in the cell lines expressing the lower level of IDPc or IDPm. The results suggest that IDPc and IDPm play an important regulatory role in cellular defense against oxidative stress and in the senescence of IMR-90 cells.

  15. Plant senescence and proteolysis: two processes with one destiny.

    Diaz-Mendoza, Mercedes; Velasco-Arroyo, Blanca; Santamaria, M Estrella; González-Melendi, Pablo; Martinez, Manuel; Diaz, Isabel

    2016-01-01

    Senescence-associated proteolysis in plants is a complex and controlled process, essential for mobilization of nutrients from old or stressed tissues, mainly leaves, to growing or sink organs. Protein breakdown in senescing leaves involves many plastidial and nuclear proteases, regulators, different subcellular locations and dynamic protein traffic to ensure the complete transformation of proteins of high molecular weight into transportable and useful hydrolysed products. Protease activities are strictly regulated by specific inhibitors and through the activation of zymogens to develop their proteolytic activity at the right place and at the proper time. All these events associated with senescence have deep effects on the relocation of nutrients and as a consequence, on grain quality and crop yield. Thus, it can be considered that nutrient recycling is the common destiny of two processes, plant senescence and, proteolysis. This review article covers the most recent findings about leaf senescence features mediated by abiotic and biotic stresses as well as the participants and steps required in this physiological process, paying special attention to C1A cysteine proteases, their specific inhibitors, known as cystatins, and their potential targets, particularly the chloroplastic proteins as source for nitrogen recycling.

  16. Cultured allogenic keratinocytes for extensive burns: a retrospective study over 15 years.

    Auxenfans, Celine; Shipkov, Hristo; Bach, Christine; Catherine, Zulma; Lacroix, Pierre; Bertin-Maghit, Marc; Damour, Odile; Braye, Fabienne

    2014-02-01

    The aim was to review the use and indications of cultured allogenic keratinocytes (CAlloK) in extensive burns and their efficiency. This retrospective study comprised 15 years (1997-2012). all patients who received CAlloK. patients who died before complete healing. Evaluation criteria were clinical. Time and success of wound healing after CAlloK use were evaluated. The CAlloK were used for 2 indications - STSG donor sites and deep 2nd degree burns in extensively burned patients. A total of 70 patients were included with severity Baux score of 99.2 (from 51 to 144) and mean percentage of TBSA of 63.49% (from 21 to 96%). Fifty nine patients received CAlloK for STSG donor sites with a mean number of applications of 4 and mean surface of 3800 cm(2) per patient. Treated donor sites were re-harvested 2.5 times. The mean time of complete epithelialization was 7 days. In 11 patients, CAlloK were used for deep 2nd degree burns. The mean percentage of burned surface was 73.7%. The mean surface of CAlloK per patient was 2545 cm(2). Complete healing was achieved in 6.4 days. The CAlloK allow rapid healing of STSG donor-sites and deep 2nd second degree burns in extensively burned patients. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  17. Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation

    Grond, Susanne; Radner, Franz P.W.; Eichmann, Thomas O.; Kolb, Dagmar; Grabner, Gernot F.; Wolinski, Heimo; Gruber, Robert; Hofer, Peter; Heier, Christoph; Schauer, Silvia; Rülicke, Thomas; Hoefler, Gerald; Schmuth, Matthias; Elias, Peter M.; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2017-01-01

    Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism. PMID:27725204

  18. Precision die design by the die expansion method

    Ibhadode, A O Akii

    2009-01-01

    This book presents a new method for the design of the precision dies used in cold-forging, extrusion and drawing processes. The method is based upon die expansion, and attempts to provide a clear-cut theoretical basis for the selection of critical die dimensions for this group of precision dies when the tolerance on product diameter (or thickness) is specified. It also presents a procedure for selecting the minimum-production-cost die from among a set of design alternatives. The mathematical content of the book is relatively simple and will present no difficulty to those who have taken basic c

  19. Die Dokter-Pasient Rolverwantskap

    17 Aug 1974 ... en as sodanig 'n ral sped in die persoon se siektegedrag en uiteindelike patroon van hulpsoeke. SIEKEROL EN SOSIALISERING IN DIE. PASIENTROL ..... more cumulative, resulting in a more gradual social and professional maturation.' Vit die voorafgaande word dit duidelik dat Dewy se pragmatiese ...

  20. prosesseringsmetodes op die voedingswaarde van

    gebring is, kon geen betekenisvolle verskille tussen die drie monsters gevind word nie. Volgens Opstvedt (1976) kan ME waardes ook dien as 'n kriteria van proteien- kwaliteit, hoofsaaklik a.g.v. die verhoogde stikstofuit- skeiding in die urine wat sal plaasvind a.g.v. beskadiging van aminosure. De Groote (1968) het gevind ...

  1. Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

    Marchal Joëlle

    2005-10-01

    Full Text Available Abstract Background Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. Methods Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. Results Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. Conclusion The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers.

  2. Effect of Wnt3a on Keratinocytes Utilizing in Vitro and Bioinformatics Analysis

    Ju-Suk Nam

    2014-03-01

    Full Text Available Wingless-type (Wnt signaling proteins participate in various cell developmental processes. A suppressive role of Wnt5a on keratinocyte growth has already been observed. However, the role of other Wnt proteins in proliferation and differentiation of keratinocytes remains unknown. Here, we investigated the effects of the Wnt ligand, Wnt3a, on proliferation and differentiation of keratinocytes. Keratinocytes from normal human skin were cultured and treated with recombinant Wnt3a alone or in combination with the inflammatory cytokine, tumor necrosis factor α (TNFα. Furthermore, using bioinformatics, we analyzed the biochemical parameters, molecular evolution, and protein–protein interaction network for the Wnt family. Application of recombinant Wnt3a showed an anti-proliferative effect on keratinocytes in a dose-dependent manner. After treatment with TNFα, Wnt3a still demonstrated an anti-proliferative effect on human keratinocytes. Exogenous treatment of Wnt3a was unable to alter mRNA expression of differentiation markers of keratinocytes, whereas an altered expression was observed in TNFα-stimulated keratinocytes. In silico phylogenetic, biochemical, and protein–protein interaction analysis showed several close relationships among the family members of the Wnt family. Moreover, a close phylogenetic and biochemical similarity was observed between Wnt3a and Wnt5a. Finally, we proposed a hypothetical mechanism to illustrate how the Wnt3a protein may inhibit the process of proliferation in keratinocytes, which would be useful for future researchers.

  3. Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

    Sah, Shyam Kishor; Kim, Hae Young; Lee, Ji Hae; Lee, Seong-Wook; Kim, Hyung-Sik; Kim, Yeon-Soo; Kang, Kyung-Sun; Kim, Tae-Yoon

    2017-06-01

    The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca 2+ ) concentration. High Ca 2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca 2+ environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca 2+ -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca 2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602. © 2017 AlphaMed Press.

  4. DIE SAW SE ROL IN SWA

    wei die verdediging van die landsgrense teen 'n vyand wat die orde, gesag, vrede, stabiliteit en welvaart in Suidwes-Afrika en die Republiek van. Suid-Afrika wil vernietig. Hierdie oorlog moet nie ge'lsoleerd gesien word nie, maar in perspektief geplaas word teen die agtergrond van 'n nag groter konflik, naamlik die van die ...

  5. Die Subjektiewe en Objektiewe doelwitte van Arbeid

    T. H. Veldsman

    1982-11-01

    Die artikel gee aandag aan die subjektiewe en objektiewe doelwitte van arbeid. Hul plek en funksie binne 'n voorgestelde geïntegreerde motiveringsmodel word eerstens aangedui. Vervolgens word die verwantskap tussen die twee doelwitte uitgelig, gevolg deur 'n bespreking van die aard van die objektiewe doel. Laastens word die invloed van moderne arbeid op hierdie doelwitte uitgestippel.

  6. DIE EKSISTENSIEFILOSOFIE VAN KARL JASPERS. ENKELE ...

    Test

    Kierkegaard en Nietzsche, Max Weber en Dilthey, om maar enkeles te noem, en 5.) Jaspers se persoonlike beskouing oor die roe ping en die taak van die Filosofie, sy aanvoeling van die filosofiese problematiek en sy grondhouding teenoor die eksistensiële verbonden- hede. Die woord van Fichte, naamlik dat die Filosofie ...

  7. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  8. The Pace and Shape of Senescence in Angiosperms

    Baudisch, Annette; Salguero-Gómez, Roberto; Jones, Owen

    2013-01-01

    1. Demographic senescence, the decay in fertility and increase in the risk of mortality with age, is one of the most striking phenomena in ecology and evolution. Comparative studies of senescence patterns of plants are scarce, and consequently, little is known about senescence and its determinants...... (‘senescence’), decreases (‘negative senescence’) or remains constant over age (‘negligible senescence’). 3. We extract mortality trajectories from ComPADRe III, a data base that contains demographic information for several hundred plant species. We apply age-from-stage matrix decomposition methods to obtain...... age-specific trajectories from 290 angiosperm species of various growth forms distributed globally. From these trajectories, we survey pace and shape values and investigate how growth form and ecoregion influence these two aspects of mortality using a Bayesian regression analysis that accounts...

  9. The emerging role of alternative splicing in senescence and aging.

    Deschênes, Mathieu; Chabot, Benoit

    2017-10-01

    Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that changes in the activity of splicing factors and in the production of key splice variants can impact cellular senescence and the aging phenotype. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. Dying with dignity.

    Madan, T N

    1992-08-01

    Death is a theme of central importance in all cultures, but the manner in which it is interpreted varies from society to society. Even so, traditional cultures, including Christian, Hindu and Jain religious traditions, exhibited a positive attitude to death and did not look upon it in a dualistic framework of good vs bad, or desirable vs undesirable. Nor was pessimism the dominant mood in their thinking about death itself. A fundamental paradigm shift occurred in the West in the eighteenth century when death was desacralized and transformed into a secular event amenable to human manipulation. From those early beginnings, dying and death have been thoroughly medicalized and brought under the purview of high technology in the twentieth century. Once death is seen as a problem for professional management, the hospital displaces the home, and specialists with different kinds and degrees of expertise take over from the family. Everyday speech and the religious idiom yield place to medical jargon. The subject (an ageing, sick or dying person) becomes the object of this make-believe yet real world. As the object of others' professional control, he or she loses the freedom of self-assessment, expression and choice. Or, he or she may be expected to choose when no longer able to do so. Thus, not only freedom but dignity also is lost, and lawyers join doctors in crisis manipulation and perpetuation. Although the modern medical culture has originated in the West, it has gradually spread to all parts of the world, subjugating other kinds of medical knowledge and other attitudes to dying and death.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The nuclear receptor NR2E1/TLX controls senescence

    Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M.; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

    2014-01-01

    The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumours including glioblastomas. Despite NR2E1 regulating targets like p21CIP1 or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that Polycomb repressive complexes (PRC) also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the Polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16INK4a and direct repression of p21CIP1. In addition NR2E1 expression also counteracts oncogene-induced senescence (OIS). The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of Polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer. PMID:25328137

  12. The nuclear receptor NR2E1/TLX controls senescence.

    O'Loghlen, Ana; Martin, Nadine; Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

    2015-07-30

    The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumors including glioblastomas. Despite NR2E1 regulating targets like p21(CIP1) or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that polycomb repressive complexes also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16(INK4a) and direct repression of p21(CIP1). In addition NR2E1 expression also counteracts oncogene-induced senescence. The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer.

  13. Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

    Johannes Fessler

    2018-02-01

    Full Text Available ObjectiveT-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid arthritis (RA. Premature senescence of lymphocytes including the accumulation of senescent CD4+ T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far.MethodsThis includes a prospective study of consecutive patients with RA (n = 107, patients with primary osteopenia/-porosis (n = 75, and healthy individuals (n = 38. Bone mineral density (BMD was determined by dual-energy X-ray absorptiometry scan. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed to analyze the pro-osteoclastic phenotype and the function of senescent CD4+CD28− T-cells.ResultsPatients with osteopenia/-porosis yielded a higher prevalence of senescent CD4+CD28− T-cells than individuals with normal BMD, in the RA, as well as in the non-RA cohort. Receptor activator of nuclear factor kappa-B ligand (RANKL was expressed at higher levels on CD4+CD28− T-cells as compared to CD28+ T-cells. Stimulation with interleukin-15 led to an up-regulation of RANKL expression, particularly on CD28− T-cells. CD4+CD28− T-cells induced osteoclastogenesis more efficiently than CD28+ T-cells.ConclusionOur data indicate that senescent T-cells promote osteoclastogenesis more efficiently than conventional CD28+ T-cells, which might contribute to the pathogenesis of systemic bone loss in RA and primary osteoporosis.

  14. Sal die ‘ewolusie’ vanaf biologie na lewenswetenskappe ‘uitsterwing’ van die vakgebied voorkom?

    Johanna G. Ferreira

    2012-03-01

    Full Text Available In hierdie artikel word die wysiging van die skoolvak van ‘biologie’ na ‘lewenswetenskappe’ bespreek, asook die gepaardgaande en verwagte implikasies van die verandering. Die vraag word gestel of die beoogde wysiging wel noemenswaardig is en of dit enigsins ‘n verskil aan die dalende belangstelling in die lewenswetenskappe op tersiêre vlak sal maak. Die wysigings in die nuwe kurrikula verhoog die relevansie van die vakinhoud vir leerders en vir die gemeenskap, maar sekere kwessies kry nie aandag nie. Voorstelle word gemaak om die kurrikulum te wysig en onderrigmetodes aan te pas om die nodige vaardighede by leerders te vestig.

  15. enkele fasette van die problematiek van die akademikus by die skryf

    Om verskeie redes het dit van die allergrootste belong geword dot 'n his- tories korrekte, wetenskaplike weerga- we van bogenoemde gebeure opge- teken moet word. Die sluier, in sommige gevalle am logiese redes toegepas, moes eenvoudig gelig word am gebeure wat die gewone man op stroot in Suid-Afrika dikwels ...

  16. Die Defects and Die Corrections in Metal Extrusion

    Sayyad Zahid Qamar

    2018-05-01

    Full Text Available Extrusion is a very popular and multi-faceted manufacturing process. A large number of products for the automotive, aerospace, and construction sectors are produced through aluminum extrusion. Many defects in the extruded products occur because of the conditions of the dies and tooling. The problems in dies can be due to material issues, design and manufacturing, or severe usage. They can be avoided by maintaining the billet quality, by controlling the extrusion process parameters, and through routine maintenance. Die problems that occur on a day-to-day basis are mostly repairable and are rectified through various types of die correction operations. These defects and repair operations have not been reported in detail in the published literature. The current paper presents an in-depth description of repairable die defects and related die correction operations in metal extrusion. All major die defects are defined and classified, and their causes, preventive measures, and die correction operations are described. A brief frequency-based statistical study of die defects is also carried out to identify the most frequent die corrections. This work can be of direct benefit to plant engineers and operators and to researchers and academics in the field of metal extrusion.

  17. Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence.

    Wiley, Christopher D; Flynn, James M; Morrissey, Christapher; Lebofsky, Ronald; Shuga, Joe; Dong, Xiao; Unger, Marc A; Vijg, Jan; Melov, Simon; Campisi, Judith

    2017-10-01

    Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations. Individual senescent cells were surprisingly heterogeneous in their gene expression signatures. This cell-to-cell variability resulted in a loss of correlation among the expression of several senescence-associated genes. Many genes encoding senescence-associated secretory phenotype (SASP) factors, a major contributor to the effects of senescent cells in vivo, showed marked variability with a subset of highly induced genes accounting for the increases observed at the population level. Inflammatory genes in clustered genomic loci showed a greater correlation with senescence compared to nonclustered loci, suggesting that these genes are coregulated by genomic location. Together, these data offer new insights into how genes are regulated in senescent cells and suggest that single markers are inadequate to identify senescent cells in vivo. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA

    Demaria, Marco; Ohtani, Naoko; Youssef Hassan, Sameh|info:eu-repo/dai/nl/374027080; Rodier, Francis; Toussaint, Wendy; Mitchell, James R; Laberge, Remi-Martin; Vijg, Jan; Van Steeg, Harry; Dollé, Martijn E T; Hoeijmakers, Jan H J; de Bruin, Alain|info:eu-repo/dai/nl/304837261; Hara, Eiji; Campisi, Judith

    2014-01-01

    Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s)

  19. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

    Demaria, Marco; Ohtani, Naoko; Youssef, Sameh A; Rodier, Francis; Toussaint, Wendy; Mitchell, James R; Laberge, Remi-Martin; Vijg, Jan; Van Steeg, Harry; Dollé, Martijn E T; Hoeijmakers, Jan H J; de Bruin, Alain; Hara, Eiji; Campisi, Judith

    2014-01-01

    Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s)

  20. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

    M. Demaria (Marco); N. Ohtani (Naoko); S. Youssef (SamehA.); F. Rodier (Francis); W. Toussaint (Wendy); J. Mitchell (JamesR.); R.-M. Laberge (Remi-Martin); J. Vijg (Jan); H. VanSteeg (Harry); M. Dollé (MartijnE.T.); J. Hoeijmakers (JanH.J.); A. deBruin (Alain); E. Hara (Eiji); J. Campisi (Judith)

    2014-01-01

    textabstractCellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the

  1. Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts

    Micutkova, Lucia; Diener, Thomas; Li, Chen

    2011-01-01

    Cellular senescence can be induced by a variety of mechanisms, and recent data suggest a key role for cytokine networks to maintain the senescent state. Here, we have used a proteomic LC-MS/MS approach to identify new extracellular regulators of senescence in human fibroblasts. We identified 26 e...

  2. Targeting Senescent Cells : Possible Implications for Delaying Skin Aging: A Mini-Review

    Velarde, Michael C.; Demaria, Marco

    2016-01-01

    Senescent cells are induced by a wide variety of stimuli. They accumulate in several tissues during aging, including the skin. Senescent cells secrete proinflammatory cytokines, chemokines, growth factors, and proteases, a phenomenon called senescence-associated secretory phenotype (SASP), which are

  3. Die hermeneutiek van gereformeerde kerkreg

    Andries le Roux du Plooy

    2012-10-01

    Full Text Available Die artikel het op die belangrikheid en noodsaaklikheid van ‘n hermeneutiek vir die gereformeerde kerkreg gefokus. Die kerkregtelike dokument wat besonderlik ter sake was, is die kerkorde van die Gereformeerde kerke in Suid-Afrika, met sy besondere band met die Dordtse kerkorde van 1618 en 1619. Agtereenvolgens is aandag gegee aan die volgende aspekte soos (1 die eiesoortige aard van ‘n kerkorde as ‘n teologiese dokument en teks, in onderskeiding van regsdokumente; (2 die aard van die hermeneutiek van kerkreg; (3 enkele teorieë oor die interpretasie of uitleg van tekste, veral regstekste en (4 normatiewe vooronderstellings en reëls vir die interpretasie en verstaan van die teks en artikels van die kerkorde asook besluite van kerklike vergaderinge. Die gevolgtrekking was dat weinig indringende navorsing gedoen is oor die saak van hermeneutiek vir kerkreg, hoewel dit noodsaaklik is. Duidelike hermeneutiese reëls is gesuggereer en verduidelik, wat sou kon meehelp dat kerke en kerklike vergaderinge die artikels van die kerkorde asook besluite en reglemente wat daarop berus het, kan interpreteer en toepas. The hermeneutics of reformed church polity. The article focused on the importance and urgency of a design for reformed hermeneutics on church polity. The Church Order referred to in the article is the Church Order of the Reformed Churches in South Africa, which are closely related to the Church Order of Dordt of 1618 and 1619. The following aspects received attention namely (1  the unique character of a Church Order, in comparison to and distinguished from legal documents and statutes; (2 the character and nature of hermeneutics of church polity; (3 theories of interpretation in the common law tradition and their relevance to church polity and (4 normative presuppositions and marks for the interpretation and understanding of the text and articles of the Church Order, as well as the resolutions of church assemblies. It was found that

  4. Die verband tussen lokus van beheer en die werks prestasie van swart bemarkers in die lewensversekeringsbedryf

    E. L. Coetzer

    1997-06-01

    Full Text Available The relationship between locus of control and the work performance of black marketers in the life assurance industry. The aim of the study was to establish the relationship between locus of control and the work performance of black marketers in the life assurance industry. These constructs were selected by virtue of the lack of empirical research regarding the assumed relationship between them. The Locus of Control Scale of Schepers (1995 was used for measuring locus of control. Work performance was measured by the commission earned per month by the marketer, the number of policies generated by the marketer, as well as the percentage of lapsed policies. The relevant measurements were obtained in respect of a sample of 149 black marketing personnel. The results indicated a modest but statistically significant relationship between external locus of control and the work performance of black marketers. Opsomming Die doel van die studie was om die verband tussen lokus van beheer en die werksprestasie van swart bemarkers in die lewensversekeringsbedryf te bepaal. Hierdie konstrukte is gekies op grond van die gebrek aan empiriese navorsing rakende die veronderstelde verband tussen genoemde konstrukte. Die Lokus van Beheer-vraelys van Schepers (1995 is in die meting van lokus van beheer gebruik. Werksprestasie is aan die hand van kommissie per maand verdien, aantal polisse gegenereer deur 'n bemarker en die persentasie vervalde polisse, gemeet. Die tersaaklike metinge is verkry ten opsigte van 'n steekproef van 149 swart bemarkers. Die resultate toon 'n klein, dog statisties beduidende verband tussen eksterne lokus van beheer en die werksprestasie van swart bemarkers in die lewensversekeringsbedryf.

  5. Is die ortodoksie se verstaan van die sondeval belemmerend vir die gesprek tussen teologie en natuurwetenskap?

    Johan Buitendag

    2012-11-01

    Full Text Available In hierdie artikel is betoog dat die Gereformeerde Ortodoksie se begrip van die sondeval ’n  belemmering  was  vir  die  gesprek  tussen  teologie  en  natuurwetenskap.  Die  rede hiervoor was dat dit ten eerste ’n bepaalde verstaan van liniêre tyd nahou en ten tweede dat dit ’n bonatuurlike ingryp veronderstel het. Albei hierdie aspekte het die debat onnodig problematiseer. Die argument is ontwikkel deur eerstens die probleem te definieer, gevolg deur ’n uiteensetting van die standpunte van Augustinus en Calvyn onderskeidelik oor die sondeval. As ’n heuristiese sleutel is die konsepte van infralapsarisme en supralapsarisme aangewend om die tema te ontleed. Die artikel is afgesluit met die oortuiging dat die imago Dei ’n beliggaamde menslike persoon is wat biologies in die geskiedenis in terme van selfbewussyn en morele verantwoordelikheid ontluik het. Is the Orthodoxy’s notion of the Fall inhibitory for the dialogue between theology and science? In this article it was argued that the Reformed Orthodoxy’s interpretation of the Fall had become an impediment in the dialogue between theology and science. The reason was that it assumed firstly a specific understanding of linear time and secondly a metaphysical intervention. Both events were unnecessarily problematising the debate. The argument was deployed by stating the problem, followed by an exposition of the views of Augustine and Calvin on the Fall. As a heuristic key, the concepts of infralapsarism and supralapsarism were applied respectively to analyse the topic. The article concluded with the conviction that the imago Dei is an embodied human person that had biologically emerged in history as a center of self-awareness, and moral responsibility.

  6. Sedimentêre omgewings van die Inhaca-eilandstelsel met spesiale verwysing na die petrografiese en geochemiese eienskappe van die sedimente spesiale verwysing na die petrografiese en geochemiese eienskappe van die sedimente

    Marieke Peché

    2011-09-01

    Full Text Available Die Inhaca-eilandstelsel is geleë langs die suidooskus van Mosambiek. Die oostekant van die stelsel grens aan die Indiese Oseaan en die westekant aan die Baai van Maputo. Hierdie eilandstelsel bestaan uit Inhaca- en Portugese eiland, asook ’n groep sandbanke wat van die noordlike punt van Inhaca na Portugese eiland strek. Die doel van hierdie studie is om die verskillende moderne en oer-sedimentêre omgewings op die eilandstelsel te identifiseer en te beskryf, die invloed van getye en golfaksie op die moderne sedimentêre omgewing vas te stel en die geochemiese en petrografiese samestelling van die geologiese eenhede te bepaal.

  7. Die vangnet van die woord: forensies-linguistiese getuienis in 'n ...

    Een van die redes daarvoor is waarskynlik die gepaardgaande sleurwerk verbonde aan die verwerking van die betrokke taaldata — iets wat egter deur die onlangse meteoriese vooruitgang in tegnologiese tegnieke op die agtergrond geskuif is en nuwe moontlikhede na vore laat kom het. In die lig van die kompleksiteit van ...

  8. het om die Woord van God aan die gemeente te bedien. A. D. P ont ...

    Test

    Sizoo vertel met die vlotheid van die ervare skrywer en die ver antwoordelikheid van die wetenskaplike ... Maar in stiptelike trou aan die feitelikheid, verlaat die skrywer hom uitsluitlik op die outentieke bronne om ... de leser; in sy rykdom van gegewens en wetenskaplike betroubaarheid kan dit met vrug gelees word deur die ...

  9. Die invloed van herbivorie en vuur op die oorlewing van sekere meerjarige kruide langs die Sabierivier, Kruger Nasionale Park

    H. Myburgh

    2012-03-01

    Full Text Available Die groot vloede wat in die jaar 2000 in die Kruger Nasionale Park plaasgevind het, het dierivieroewerplantegroei versteur. Dit het die geleentheid gebied om heinings op te rig langsdie Sabierivier om herbivore uit sekere gebiede uit te sluit en sodoende die herstel van die rivieroewerekosisteme te monitor.

  10. Die heelal en sy onstaan (II

    D. J. Van Rooy

    1952-03-01

    Full Text Available Ons kennis en wetenskap van die hemelliggame word volkome bepaal deur die lig wat ons van hulle ontvang, d.w.s. as ons die feite wat die Bybel daaromtrent meedeel, buite rekening laat.

  11. Versoening tussen leerders: Is parallelmediumskole die antwoord op die rassismeprobleem?

    Du Plessis, Elize; Marais, Petro

    2017-01-01

    Die Suid-Afrikaanse Grondwet stel dit duidelik dat enige vorm van diskriminasie nie toegelaat mag word nie. In ons skole beteken dit dat elke leerder ʼn reg het op goeie opvoeding en ʼn veilige skoolomgewing. Die fokus van hierdie navorsing is gerig op bestaande parallelmediumskole. Die uiteindelike vraagstuk is dus hoe multikulturele onderwys bevorder word en hoe rassisme aangespreek kan word? As teoretiese raamwerk is Kohlsberg se kognitiewe ontwikkelingsbenadering en Whitehouse se univerele ...

  12. Die ontmaskering van die bose: Eksegetiese perspektiewe op ...

    p1243322

    2 Yarbro Collins (1983) bied tans nog die beste agtergrond vir 'n besinning oor geweld in ..... John's grammatical howlers are intentionally designed to alert listerners ..... 26 In die Nuwe Testament word Paul se snydende opmerking teenoor die Korintiërs as ..... rnt g0r`m nh8 ldfhrs`}m du sg}u fg}u + n2sh d/m sg>}} e`ql`jdh.

  13. Accurate defect die placement and nuisance defect reduction for reticle die-to-die inspections

    Wen, Vincent; Huang, L. R.; Lin, C. J.; Tseng, Y. N.; Huang, W. H.; Tuo, Laurent C.; Wylie, Mark; Chen, Ellison; Wang, Elvik; Glasser, Joshua; Kelkar, Amrish; Wu, David

    2015-10-01

    Die-to-die reticle inspections are among the simplest and most sensitive reticle inspections because of the use of an identical-design neighboring-die for the reference image. However, this inspection mode can have two key disadvantages: (1) The location of the defect is indeterminate because it is unclear to the inspector whether the test or reference image is defective; and (2) nuisance and false defects from mask manufacturing noise and tool optical variation can limit the usable sensitivity. The use of a new sequencing approach for a die-to-die inspection can resolve these issues without any additional scan time, without sacrifice in sensitivity requirement, and with a manageable increase in computation load. In this paper we explore another approach for die-to-die inspections using a new method of defect processing and sequencing. Utilizing die-to-die double arbitration during defect detection has been proven through extensive testing to generate accurate placement of the defect in the correct die to ensure efficient defect disposition at the AIMS step. The use of this method maintained the required inspection sensitivity for mask quality as verified with programmed-defectmask qualification and then further validated with production masks comparing the current inspection approach to the new method. Furthermore, this approach can significantly reduce the total number of defects that need to be reviewed by essentially eliminating the nuisance and false defects that can result from a die-to-die inspection. This "double-win" will significantly reduce the effort in classifying a die-to-die inspection result and will lead to improved cycle times.

  14. Die pastorale sielkundige as diakonale pastor

    A. J. Smuts

    1985-08-01

    Full Text Available In die bedieningspatroon van die Ned. Geref. Kerk het die pastorale sielkundige die afgelope aantal jare steeds meer op die voorgrond begin tree. Hy is egter 'n problematiese figuur, wie se identiteit van meer as een kant onder bespreking is. In ander lande, selfs in die VSA waar die kerk veel gebruik maak van die sielkunde, is dit moeilik om 'n presiese parallel vir hom te vind. Sowel binne as buite die kerk word hy deur sommige bevraagteken. Daarom is dit noodsaaklik om vanuit die teologie te kyk na die werk wat hy doen.

  15. Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

    Bonnie H Y Yeung

    Full Text Available Stanniocalcin-1 (STC1, a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam formation, followed by cell migration. In this study, staurosporine (STS treatment induced human keratinocyte (HaCaT e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK, the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

  16. Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

    Yeung, Bonnie H Y; Wong, Chris K C

    2011-01-01

    Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

  17. Human keratinocytes produce the complement inhibitor factor H: synthesis is regulated by interferon-gamma

    Timár, Krisztina K.; Pasch, Marcel C.; van den Bosch, Norbert H. A.; Jarva, Hanna; Junnikkala, Sami; Meri, Seppo; Bos, Jan D.; Asghar, Syed S.

    2006-01-01

    Locally synthesized complement is believed to play an important role in host defense and inflammation at organ level. In the epidermis, keratinocytes have so far been shown to synthesize two complement components, C3 and factor B. Here, we studied the synthesis of factor H by human keratinocytes. We

  18. Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

    Dongyuan Lü

    Full Text Available Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.

  19. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Michael, Anthony E. [Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, 3rd Floor, Lanesborough Wing, St. George' s, University of London, Cranmer Terrace, Tooting, London SW17 0RE (United Kingdom); Jaulim, Adil [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Bhogal, Ranjit [Life Science, Unilever R and D Colworth House, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Burrin, Jacky M. [Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ (United Kingdom); Philpott, Michael P. [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom)

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  20. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-01

    Research highlights: → Primary keratinocytes express the steroid enzymes required for cortisol synthesis. → Normal primary human keratinocytes can synthesise cortisol. → Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. → StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7- 3 H]-pregnenolone through each steroid intermediate to [7- 3 H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra

  1. effect of farmyard manure on senescence, nitrogen and protein

    DR. AMINU

    treatment (manurex2) at the ratio of 5:1 soil to manure and the control (no manure added). Plastic pots of ... seasons, senescence started earlier rainy season than in dry season. On the other hand ... These changes, visible to the naked eye are.

  2. Alkaline protease from senesced leaves of invasive weed | Gaur ...

    step procedure involving ammonium sulfate precipitation and Sephadex G-250 gel permeation chromatography. The Sephadex-G-250 fraction of senesced leaves of Lantana camara showed 28.31 fold with a yield of 6.19%. The enzyme was ...

  3. Role of polyamines and ethylene as modulators of plant senescence

    Unknown

    Plant Biotechnology Division, Institute of Himalayan Bioresource Technology, Palampur 176 061, India ... Under optimal conditions of growth, senescence, a terminal phase of development, sets in after a certain physio- logical age. It is a dynamic ..... Escribano M I and Merodio C 1994 The relevance of polyamine levels in ...

  4. Testosterone supplementation restores vasopressin innervation in the senescent rat brain

    Goudsmit, E.; Fliers, E.; Swaab, D. F.

    1988-01-01

    The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

  5. Functional age as an indicator of reservoir senescence

    Miranda, Leandro E.; Krogman, R. M.

    2015-01-01

    It has been conjectured that reservoirs differ in the rate at which they manifest senescence, but no attempt has been made to find an indicator of senescence that performs better than chronological age. We assembled an indicator of functional age by creating a multimetric scale consisting of 10 metrics descriptive of reservoir environments that were expected to change directionally with reservoir senescence. In a sample of 1,022 U.S. reservoirs, chronological age was not correlated with functional age. Functional age was directly related to percentage of cultivated land in the catchment and inversely related to reservoir depth. Moreover, aspects of reservoir fishing quality and fish population characteristics were related to functional age. A multimetric scale to indicate reservoir functional age presents the possibility for management intervention from multiple angles. If a reservoir is functionally aging at an accelerated rate, action may be taken to remedy the conditions contributing most to functional age. Intervention to reduce scores of selected metrics in the scale can potentially reduce the rate of senescence and increase the life expectancy of the reservoir. This leads to the intriguing implication that steps can be taken to reduce functional age and actually make the reservoir grow younger.

  6. Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

    Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

  7. Digilanid C by die behandeling van hartlyers

    Snyman, Hendrik Willem

    1942-01-01

    In die voorafgaande word 'n literatuur studie oor die ontwikkeling en huidige stand van die chemie en farmakologie van die Digitalis purpurea en Digitalis lanata gegee, waarin spesiaal gelet word op die chemiese samestelling en farmakologiese aktiwiteit van die Digitalis lanata glikoside. Daarna

  8. HISTORIESE OORSIG VAN DIE ONTSTAAN EN ONTWIKKELING ...

    In 1933 belas Rykskanselier. Hitler vir. Goering, Minister van Lugvaart, in die geheim met die skepping van die Luftwaffe. Die basis in Rusland is gesluit en toekomstige vlieeniers is nou in die geheim na Italie waar hulle elke aspek van moderne oorlog- voering oefen en die Blitzkrieg-gedagte, deur op ondersteuning van 'n.

  9. EUNUG IN DIE ANTIEKE NABYE OOSTE

    rang. In Assiries beteken die woord “hoof-eunug”. Soos reeds vermeld (by 2), vorm die eunug 'n belangrike deel van die Assiriese burokrasie. Dokumente dui aan ... rang in die Babiloniese weermag, en so 'n amptenaar het saam met die rabsag ..... baie laat, in die inter-testamentêre periode, gebruik is vir 'n gekastreerde.

  10. Die Transition zur pflegenden Tochter

    Dagmar Dräger

    2004-11-01

    Full Text Available Das Buch aus der Reihe „Studien zur Gesundheits- und Pflegewissenschaft“ beschreibt den theoretischen Hintergrund, das methodische Vorgehen und die Ergebnisse einer biografischen Untersuchung, die sich dem Übergang von der Tochter zur pflegenden Tochter widmete. Grundlage der Publikation ist die Dissertation (2002 der Autorin. Mit der Berücksichtigung biographischer und familiärer Hintergründe wird eine neue Perspektive in der Forschung zu pflegenden Angehörigen eingenommen.

  11. Maintaining Low Voiding Solder Die Attach for Power Die While Minimizing Die Tilt

    Hamm, Randy; Peterson, Kenneth A.

    2015-10-01

    This paper addresses work to minimize voiding and die tilt in solder attachment of a large power die, measuring 9.0 mm X 6.5 mm X 0.1 mm (0.354” x 0.256” x 0.004”), to a heat spreader. As demands for larger high power die continue, minimizing voiding and die tilt is of interest for improved die functionality, yield, manufacturability, and reliability. High-power die generate considerable heat, which is important to dissipate effectively through control of voiding under high thermal load areas of the die while maintaining a consistent bondline (minimizing die tilt). Voiding was measured using acoustic imaging and die tilt was measured using two different optical measurement systems. 80Au-20Sn solder reflow was achieved using a batch vacuum solder system with optimized fixturing. Minimizing die tilt proved to be the more difficult of the two product requirements to meet. Process development variables included tooling, weight and solder preform thickness.

  12. F4/80+ Macrophages Contribute to Clearance of Senescent Cells in the Mouse Postpartum Uterus.

    Egashira, Mahiro; Hirota, Yasushi; Shimizu-Hirota, Ryoko; Saito-Fujita, Tomoko; Haraguchi, Hirofumi; Matsumoto, Leona; Matsuo, Mitsunori; Hiraoka, Takehiro; Tanaka, Tomoki; Akaeda, Shun; Takehisa, Chiaki; Saito-Kanatani, Mayuko; Maeda, Kei-Ichiro; Fujii, Tomoyuki; Osuga, Yutaka

    2017-07-01

    Cellular senescence, defined as an irreversible cell cycle arrest, exacerbates the tissue microenvironment. Our previous study demonstrated that mouse uterine senescent cells were physiologically increased according to gestational days and that their abnormal accumulation was linked to the onset of preterm delivery. We hypothesized that there is a mechanism for removal of senescent cells after parturition to maintain uterine function. In the current study, we noted abundant uterine senescent cells and their gradual disappearance in wild-type postpartum mice. F4/80+ macrophages were present specifically around the area rich in senescent cells. Depletion of macrophages in the postpartum mice using anti-F4/80 antibody enlarged the area of senescent cells in the uterus. We also found excessive uterine senescent cells and decreased second pregnancy success rate in a preterm birth model using uterine p53-deleted mice. Furthermore, a decrease in F4/80+ cells and an increase in CD11b+ cells with a senescence-associated inflammatory microenvironment were observed in the p53-deleted uterus, suggesting that uterine p53 deficiency affects distribution of the macrophage subpopulation, interferes with senescence clearance, and promotes senescence-induced inflammation. These findings indicate that the macrophage is a key player in the clearance of uterine senescent cells to maintain postpartum uterine function. Copyright © 2017 Endocrine Society.

  13. Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

    Ceccarelli, Simona; Cardinali, Giorgia; Aspite, Nicaela; Picardo, Mauro; Marchese, Cinzia; Torrisi, Maria Rosaria; Mancini, Patrizia

    2007-01-01

    Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10

  14. Effect of Nanodiamond and Nanoplatinum Liquid, DPV576, on Human Primary Keratinocytes.

    Ghoneum, Mamdooh H; Katano, Hideki; Agrawal, Sudhanshu; Ganguly, Sreerupa; Agrawal, Anshu

    2017-01-01

    Nanofabrics are now being used in a wide range of products that come into direct contact with skin, including carpet, clothing, and medical fabrics. In the current study, we examined the effect of a dispersed aqueous mixture of nanodiamond (ND) and nanoplatinum (NP) (DPV576) on human primary keratinocytes with respect to transient receptor potential vanilloid (TRPV) channel expression, secretion of cytokines and production of nerve growth factor (NGF). Keratinocytes were treated with DPV576 at concentrations of 1:10 and 1:100 dilutions for 24 hours in vitro, and their activation of was determined by production of cytokines TNF-α, IL-1β, and prostaglandin (PGE2), and by production of NGF. Inhibitor experiments were carried out by incubating keratinocytes with the TRPV4-selective antagonist HC-067047. TRPV receptor expression (TRPV1, TRPV3 and TRPV4) on keratinocytes as well as changes in Ca2+ potential were examined by flow cytometry. DPV576 treatment of keratinocytes resulted in the following effects: (1) stimulation of keratinocytes as indicated by the significant secretion of cytokines IL-1β, TNF-α, and PGE2, an effect noted only at higher concentration (1:10); (2) significant decrease in the expression of TRPV4 on keratinocytes with a spike in the calcium flux, but no change in the expression of TRPV1 and TRPV3; (3) induction of cytokine secretion independent of TRPV4, as the addition of TRPV4 inhibitor had no significant effect on the cytokine production from keratinocytes; (4) induction of NGF secretion by keratinocytes. These results demonstrate that DPV576 activates keratinocytes via multiple signaling pathways which may reduce stress associated with inflammation, pain, and circadian rhythms. ND/NP-coated fabrics that target the modulation of local inflammation, pain, and circadian rhythms could potentially be of benefit to humans.

  15. Neurokognitiewe integrasie en die leerproses

    Du Preez, Johan J.

    1991-12-01

    Full Text Available The purpose of this article, "Neuro-cognitive integration and the learning process'; is to find principles and strategies for the development of brain potential and the optimal integration of subject matter. Eight neuro-cognitive systems are identified and their importance to the integration of subject matter is emphasized. These systems are cortical energy, coding, planning and controlling, as well as the verbal sequential, non-verbal holistic, physical-motor, social effective and the subconscious. The relevant principles and strategies can serve as basis for mainstream and special education, guidance as well as psychotherapy. Die doe! met hierdie artikel is om beginsels en strategiee te vind om breinpotensiaal te ontsluit en leerstof optimaal te integreer. Aan die hand van 'n neurokognitiewe model word 'n aantal beginsels en strategiee bespreek en die verband met die leerproses word aangetoon. Agt neurokognitiewe sisteme is gei'dentifiseer en die belangrike rot wat dit speel ten opsigte van die integrasie van leerstof word beklemtoon. Genoemde sisteme sluit die volgende in: kortikale energie, kodering, beplanning en kontrolering, asook die verbaal-sekwensiele, nieverbaal-holistiese, fisiek-motoriese, sosio-affektiewe en die subbewuste. Genoemde beginsels en strategiee kan oak dien as grondslag vir hoofstroomonderwys, spesialiseringsonderwys, voorligting sowel as psigoterapie.

  16. Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2

    Hubackova, Sona; Davidova, Eliska; Rohlenova, Katerina

    2018-01-01

    and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent...... cells. In naturally aged mice treated with MitoTam for 4 weeks, we observed a significant decrease of senescence markers in all tested organs compared to non-treated animals. Mechanistically, we found that the susceptibility of senescent cells to MitoTam is linked to a very low expression level...... of adenine nucleotide translocase-2 (ANT2), inherent to the senescent phenotype. Restoration of ANT2 in senescent cells resulted in resistance to MitoTam, while its downregulation in non-senescent cells promoted their MitoTam-triggered elimination. Our study documents a novel, translationally intriguing role...

  17. HJURP regulates cellular senescence in human fibroblasts and endothelial cells via a p53-dependent pathway.

    Heo, Jong-Ik; Cho, Jung Hee; Kim, Jae-Ryong

    2013-08-01

    Holliday junction recognition protein (HJURP), a centromere protein-A (CENP-A) histone chaperone, mediates centromere-specific assembly of CENP-A nucleosome, contributing to high-fidelity chromosome segregation during cell division. However, the role of HJURP in cellular senescence of human primary cells remains unclear. We found that the expression levels of HJURP decreased in human dermal fibroblasts and umbilical vein endothelial cells in replicative or premature senescence. Ectopic expression of HJURP in senescent cells partially overcame cell senescence. Conversely, downregulation of HJURP in young cells led to premature senescence. p53 knockdown, but not p16 knockdown, abolished senescence phenotypes caused by HJURP reduction. These data suggest that HJURP plays an important role in the regulation of cellular senescence through a p53-dependent pathway and might contribute to tissue or organismal aging and protection of cellular transformation.

  18. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    Diepeningen, van A.D.; Debets, A.J.M.; Slakhorst-Wandel, S.M.; Hoekstra, R.F.

    2008-01-01

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with

  19. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    van Diepeningen, Anne D; Debets, Alfons J M; Slakhorst, S Marijke; Hoekstra, Rolf F

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with

  20. Numerical optimization of die geometry in open die forging

    Christiansen, Peter; Hattel, Jesper Henri; Bay, Niels

    2013-01-01

    This paper deals with numerical optimization of open die forging of large metallic ingots made by casting implying risk of defects, e.g. central pores. Different material hardening properties and die geometries are combined in order to investigate, which geometry gives rise to maximum closure...

  1. die geskiedenis van die saw gedenkteken te fort klapperkop militere ...

    As gevolg van enige optrede, op enige plek, te enige tyd, deur enige vyand van die RSA of deur enige terroris(te), insurgent(e) of ander persoon of persone wat die RSA en sy volkere kwaadgesind is. h. Binne twee jaar (vyfhondred-en-dertig dae) nadat hy/sy met 'n ongeskiktheids- pensioen uit diens getree het agv siekte,.

  2. Die adversatiewe stelsel van bewyslewering en die beste belang ...

    MJM Venter

    weeg. Hierdie vraag word teen die agtergrond daarvan beoordeel dat veral dispute ..... restructuring family into the highly polarized positions of court-based dispute resolution.16. Talle alternatiewe om tekortkominge in die adversatiewe proses te ..... De Jong M "Mediation and Other Appropriate Forms of Alternative Dispute.

  3. Die teologiese debat: Die waarde of betekenis daarvan

    Ego vero hoc libro non contuli sed asservi et assero, ac penes nullum vo- lo esse iudicium, sed omnibus suadeo, ut praestent obsequium. (M Luther, De servo arbitrio, 1525). 1. INLEIDING. In ons dae is dit hoe mode om oor alles debat te voer. Een van die towerwoorde van ons tyd, veral op die politiek-staatkundige terrein, ...

  4. Die konteks vir die keuse van geriefsvoedsel van bepaalde ...

    Seugnet

    70. Die konteks vir die keuse van geriefsvoedsel van bepaalde beroepsvroue *. Martha Kok en Priscilla Botha. ABSTRACT. The purpose of this research is to understand and describe the context in which career women choose, purchase and use convenience food (CF). A person is rarely isolated from or unaffected by.

  5. Die vlugtige taal van vergeet: Die metafoor by Breyten Breytenbach ...

    From his first book of poetry, die ysterkoei moet sweet (“the iron cow must sweat”, 1964), till his most recent one, die windvanger (“the windcatcher”, 2007), metaphor has been a central means towards the creation of meaning for Breytenbach. This article will investigate the use of metaphor particularly in this recent book.

  6. Selenoproteins are essential for proper keratinocyte function and skin development.

    Aniruddha Sengupta

    2010-08-01

    Full Text Available Dietary selenium is known to protect skin against UV-induced damage and cancer and its topical application improves skin surface parameters in humans, while selenium deficiency compromises protective antioxidant enzymes in skin. Furthermore, skin and hair abnormalities in humans and rodents may be caused by selenium deficiency, which are overcome by dietary selenium supplementation. Most important biological functions of selenium are attributed to selenoproteins, proteins containing selenium in the form of the amino acid, selenocysteine (Sec. Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA gene (Trsp ablates selenoprotein expression. We generated mice with targeted removal of selenoproteins in keratin 14 (K14 expressing cells and their differentiated descendents. The knockout progeny had a runt phenotype, developed skin abnormalities and experienced premature death. Lack of selenoproteins in epidermal cells led to the development of hyperplastic epidermis and aberrant hair follicle morphogenesis, accompanied by progressive alopecia after birth. Further analyses revealed that selenoproteins are essential antioxidants in skin and unveiled their role in keratinocyte growth and viability. This study links severe selenoprotein deficiency to abnormalities in skin and hair and provides genetic evidence for the role of these proteins in keratinocyte function and cutaneous development.

  7. Pylstertmotte (Lepidoptera: Sphingidae van die Nasionale Krugerwildtuin

    M. A. van den Berg

    1975-07-01

    Full Text Available 'n Totaal van 42 spesies van pylstertmotte is in die Nasionale Krugerwildtuin versamel. Die bekendste hiervan is die patatrusper (Herse convolvuli (L en die dood-skedelmot (Acherontia atropos (L. Die volgende spesies wat versamel is, se voorkoms is nog nie voorheen vir die Republiek van Suid-Afrika aangemeld nie nl. Pemba flavillacea (Walk., Praedora plagiata (R. &J., Leptoclanis basalis (Walk., Polyptychus calcareus (R. &J., Polyptychus compar (R. &J., Nephele aequivalens (Walk., Nephele peneus (Cram., Hippotion roseipennis (Butler en Xenosphingia jansei (Jord.. Die verspreiding van Oligographa juniperi (Bsd. wat langs die kusgebiede van Natal en die Oos-Kaap aangetrefword, is op verskeie plekke in die Krugerwildtuin versamel.

  8. RNA transcription in isolated chloroplasts during senescence and rejuvenation of intact cotyledons of CUCURBITA PEPO L. (ZUCCHINI)

    Mishev, K.; Ananiev, E.; Denev, L.; Radeva, G.

    2006-01-01

    RNA transcription was studied in intact chloroplasts isolated from cotyledons of Cucurbita pepoL. (zucchini) during their growth and development including natural senescence and rejuvenation. Rejuvenation of cotyledons was studied after decapitation of the epicotyl above the senescing yellow cotyledons. Maximal incorporation of [32P] UTP into overall chloroplast RNA was measured two days after exposure of seedlings to light (day 6 th after the onset of germination), followed by a gradual decrease reaching minimal values at the age of 25-28 days when cotyledons began to yellow and eventually die. Rejuvenation of cotyledons completely restored chloroplast RNA synthesis and fifteen days after decapitation (at the age of 40 days), the values of chloroplast transcription even exceeded that of the maximal transcriptional activity in young cotyledons. Inhibitory analysis with tagetitoxin (a specific inhibitor of plastid encoded chloroplast RNA polymerase (PEP)) showed that in young and rejuvenated cotyledons about 85% of chloroplast RNA polymerase activity was due to PEP and only 15% corresponded to the nuclear encoded plastid RNA polymerase (NEP). Definite regions of two chloroplast encoded genes were amplified by means of PCR technique using specific DNA primers for Rubisco large subunit gene (rbcL) and the housekeeping gene for chloroplast 16S rRNA as well as chloroplast DNA as a template. The appropriate lengths of the amplified DNA fragments were checked by restriction analysis

  9. Statues Also Die

    Pierre-Philippe Fraiture

    2016-10-01

    Full Text Available “African thinking,” “African thought,” and “African philosophy.” These phrases are often used indiscriminately to refer to intellectual activities in and/or about Africa. This large field, which sits at the crossroads between analytic philosophy, continental thought, political philosophy and even linguistics is apparently limitless in its ability to submit the object “Africa” to a multiplicity of disciplinary approaches. This absence of limits has far-reaching historical origins. Indeed it needs to be understood as a legacy of the period leading to African independence and to the context in which African philosophy emerged not so much as a discipline as a point of departure to think colonial strictures and the constraints of colonial modes of thinking. That the first (self-appointed exponents of African philosophy were Westerners speaks volumes. Placide Tempels but also some of his predecessors such as Paul Radin (Primitive Man as Philosopher, 1927 and Vernon Brelsford (Primitive Philosophy, 1935 were the first scholars to envisage this extension of philosophy into the realm of the African “primitive.” The material explored in this article – Statues Also Die (Marker, Resnais, and Cloquet, Bantu Philosophy (Tempels, The Cultural Unity of Negro Africa (Cheikh Anta Diop, and It For Others (Duncan Campbell - resonates with this initial gesture but also with the ambition on part of African philosophers such as VY Mudimbe to challenge the limits of a discipline shaped by late colonialism and then subsequently recaptured by ethnophilosophers. Statues Also Die is thus used here as a text to appraise the limitations of African philosophy at an early stage.  The term “stage,” however, is purely arbitrary and the work of African philosophers has since the 1950s often been absorbed by an effort to retrieve African philosophizing practices before, or away from, the colonial matrix. This activity has gained momentum and has been

  10. Die faktore gemeenskaplik aan die selfondersoekvraelys van Holland en die nuwe Suid-Afrikaanse beroepsbelangstellingsvraelys

    C. Swanevelder

    1992-06-01

    Full Text Available The factors common to the Self Directed Search of Holland (SDS and the new South African Vocational Interest Inventory (SAVII. The new South African Vocational Interest Inventory was locally developed with the purpose to create a single vocational interest inventory for all population groups in the RSA. In this study the common factors underlying the SDS and the SAVII were determined with the aid of interbattery factor analysis. The results indicate that there are six common factors underlying the two instruments for both the standard nine boys and girls, and that these factors agree with the six factors built into the SDS by Holland. Opsomming Die nuwe Suid-Afrikaanse Beroepsbelangstellingsvraelys (SABBV is plaaslik ontwikkel met die doel om 'n enkele beroepsbelangstellingsvraelys vir alle bevolkingsgroepe binne die RSA, daar te stel. In hierdie studie is daar ondersoek ingestel na die gemeenskaplike faktore onderliggend aan die SABBV en die Selfondersoekvraelys (SOV van Holland met behulp van 'n interbatteryfaktorontleding. Daar is bevind dat daar ses gemeenskaplike faktore onderliggend aan die twee instrumente is vir sowel standerd nege seuns as dogters, en dat hierdie faktore ooreenstem met die ses faktore wat deur Holland in die SOV ingebou is.

  11. Awareness of Dying Preface

    Barney G. Glaser, PhD, Hon. PhD

    2015-12-01

    Full Text Available Recently The New York Times reported: “VERY ILL CHILDREN TOLD OF DISEASE; Leukemia Patients at N.I.H. Not Shielded From Truth. . . . A child should always be told the truth, even when he has an incurable disease such as leukemia, according to two researchers who interviewed 51 children hospitalized at the National Cancer Institute, Bethesda, Maryland, for treat¬ment of leukemia.” This kind of news item reflects the growing concern among researchers and public about matters which touch on morality as much as on the technical aspects of medi¬cine. The rapidly increasing proportion of elderly people in the American population presents a range of personal and social questions; not the least is how they view their newly won longevity (often including anticipated years of chronic disease as well as their attitudes toward death. In consequence, many geriatric specialists are beginning to study American attitudes toward death, while others, spurred on by what seems a sense-less prolonging of life within hospital walls by medical tech¬nology run wild, are raising questions about death and dying in American life.

  12. Die Parlamentswahlen 2008 in Malaysia

    Reher, Stefanie; Knirsch, Thomas

    2008-01-01

    aus diversen Parteien bestehende Oppositionsbündnis erfuhr überraschend eine klare Stärkung. Während die aus der UMNO und 13 weiteren Koalitionären bestehende BN unter dem Motto „Sicherheit, Frieden, Wohlstand” für Premier Badawi warb, führten die Oppositionsparteien DAP, PAS und PRK – letztere unter...

  13. In diens van die Kompanjie

    was ook siektes WQl Jit onvoldoende of ondoel- treffende voeding, eentonige kos en ontoerei- kende geneesmiddels voortgespruit het, terwyl behoorlike versorging dikwels ontbreek he!. Doodsoorsake tydens die seereis het voartge- vloei uit ongelukke aan boord, beperkte ruimte vir die bemanning en geringe vars lug, ...

  14. Die Mythen von der Globalisierung

    Nell, Phillip; Schmitt, Jan; Decreton, Benoit

    2017-01-01

    Der Wissensstand über den Grad und die Art der Globalisierung ist viel niedriger als angenommen. Daraus entstehen Fehleinschätzungen.......Der Wissensstand über den Grad und die Art der Globalisierung ist viel niedriger als angenommen. Daraus entstehen Fehleinschätzungen....

  15. n hoofstuk in die (outo)biografie van die predikant (pastor?) 1 ...

    biografie van die dominee (pastor?), spreek om verskeie redes boekdele. Die gebruik van die onbepaalde lidwoord is eerstens 'n bevestiging dat die artikel slegs 'n verdere bydrae (hoofstuk) tot die bestaande en steeds voortgaande gesprek (boek) oor die biografie van die dominee is (Heitink 2001). Tweedens plaas ek ...

  16. die krag van simbole en rites in die liturgie 1. probleemstelling

    uitroepe vervang met die drie keer Kyrie eleison, die drie maal Christe eleison en die drie keer Kyrie eleison-uitroepe (Albrecht 1989:43). Op die lang duur het die uitroep dus heeltemal losgeraak van die gebede en het dit 'n selfstandige liturgiese element geword (Van Rongen. 1990:35). Die Reformasie met sy nadruk op ...

  17. Vanaf die Fermat-punte na die De Villiers-punte van ’n driehoek

    Michael de Villiers

    2010-01-01

    Full Text Available Hierdie artikel beskryf die ontdekking van die sogenaamde De Villiers-punte van ’n driehoek die bewyse wat betrokke is, en trek die historiese oorsprong terug na die Fermat-punte van ’n driehoek, die swaartepunt van ’n driehoek, en ’n nuttige veralgemening van die Fermat-punte van ’n driehoek.

  18. Montessori-skole: die ander kant

    Monica Viljoen

    1995-03-01

    Full Text Available Na aanleiding van die artikel “Die invloed van die New Age-beweging op die onderwysagenda van die toekoms” deur Lien van Niekerk en Corinne Meier van die Departement Historiese Opvoedkunde van Unisa (vgl. Koers, 59 (1 1994:69-84 wil ek graag ’n ander sy van Montessori-skole onder die aandag van Koers lesers bring.

  19. Mediamonitering in die bestuur van korporatiewe beeld

    2012-01-01

    M.Comm. Die waarde van hierdie ondersoek hou verband met die bemarking van 'n onderneming en die handhawing van 'n mededingende voordeel deur die projektering van 'n positiewe beeld (Anon., 1995a:92; Bateman & Zeithaml, 1993:75; Caminiti, 1992:50; Kotler & Armstrong, 1991:240). Hierdie aspek neem toe in belangrikheid soos wat die besigheidsmilieu in Suid-Afrika verander, veral wat betref die toetrede van buitelandse maatskappye tot die Suid-Afrikaanse mark.

  20. Chlorophyll loss associated with heat-induced senescence in bentgrass.

    Jespersen, David; Zhang, Jing; Huang, Bingru

    2016-08-01

    Heat stress-induced leaf senescence is characterized by the loss of chlorophyll from leaf tissues. The objectives of this study were to examine genetic variations in the level of heat-induced leaf senescence in hybrids of colonial (Agrostis capillaris)×creeping bentgrass (Agrostis stolonifera) contrasting in heat tolerance, and determine whether loss of leaf chlorophyll during heat-induced leaf senescence was due to suppressed chlorophyll synthesis and/or accelerated chlorophyll degradation in the cool-season perennial grass species. Plants of two hybrid backcross genotypes ('ColxCB169' and 'ColxCB190') were exposed to heat stress (38/33°C, day/night) for 28 d in growth chambers. The analysis of turf quality, membrane stability, photochemical efficiency, and chlorophyll content demonstrated significant variations in the level of leaf senescence induced by heat stress between the two genotypes, with ColXCB169 exhibiting a lesser degree of decline in chlorophyll content, photochemical efficiency and membrane stability than ColXCB190. The assays of enzymatic activity or gene expression of several major chlorophyll-synthesizing (porphobilinogen deaminase, Mg-chelatase, protochlorophyllide-reductase) and chlorophyll-degrading enzymes (chlorophyllase, pheophytinase, and chlorophyll-degrading peroxidase) indicated heat-induced decline in leaf chlorophyll content was mainly due to accelerated chlorophyll degradation, as manifested by increased gene expression levels of chlorophyllase and pheophytinase, and the activity of pheophytinase (PPH), while chlorophyll-synthesizing genes and enzymatic activities were not differentially altered by heat stress in the two genotypes. The analysis of heat-induced leaf senescence of pph mutants of Arabidopsis further confirmed that PPH could be one enzymes that plays key roles in regulating heat-accelerated chlorophyll degradation. Further research on enzymes responsible in part for the loss of chlorophyll during heat

  1. Filosofiese tendense in die wordinggeskiedenis van ons verstaan van die fisiese natuur

    D. F. M. Strauss

    2006-09-01

    Full Text Available Die ontstaan van ’n lang tradisie van natuurwetenskaplike denke is in antieke Griekeland te vind – die bakermat van die Westerse beskawing en die bron van geartikuleerde rasionele besinning. Die vroegste fases van die Griekse kultuur het reeds geboorte geskenk aan ’n teoretiese nadenke oor die heelal. Die Pythagoreërs is veral bekend vir hul klem op die verklaringskrag van getalsverhoudinge. In hul tese dat “alles getal is” het hulle egter slegs rasionale getalle (breuke erken en gevolglik uiteindelik vasgeloop in die ontdekking van irrasionale getalle wat tot die geometrisering van die Griekse wiskunde gelei het en tegelyk die bedding gevorm het van waaruit ’n magtige tradisie van ruimte-metafisika gegroei het wat die hele middeleeuse tydperk omspan het. Die vermeende statiese syn is in die mees ekstreme geval – die skool van Parmenides en die argumente van Zeno teen veelheid en beweging – tot in die uiteindelike antinomiese konsekwensies daarvan deurdink. Dit was egter eers die vroeg-moderne tyd – die voorgangers en nakomelinge van Galilei – wat naas getal en ruimte ’n waardering ontwikkel het vir die verklaringskrag van beweging (vergelyk die klassieke meganistiese wêreldbeeld van die heelal as ’n meganisme van stofdeeltjies in beweging. Maar ook hierdie meganistiese reduksie (waardeur alle fisiese verskynsels herlei is tot die beweging van al of niegelade massapunte sou uiteindelik misluk omdat dit nie van die onomkeerbaarheid van fisiese prosesse rekenskap kon gee nie. Gevolglik beliggaam eers die fisika van die 20ste eeu ’n erkenning van die deurslaggewend-stempelende rol van energie-werking (dus van die fisiese aspek in die aard van stoflike dinge en prosesse. Die artikel word afgesluit met ’n vlugtige verduideliking van die implikasies van die voorafgaande argumentasie vir ’n benadering van die misterie van die bestaan van materie.

  2. Die identifisering van maatstawwe vir die navorsingsprestasie van akademici

    H. A. Labuschagne

    1990-06-01

    Full Text Available Identification of criteria for academic research performance. At South African universities, the achievement of objectives is usually measured in terms of so-called "process criteria" (e.g. pass rates, instead of performance criteria which reflect the quality of academic personnel. Stimulated by the need to identify valid indices of research performance, as a component of academic performance, this study investigated the dimensionality of several criteria, identified from empirical and literature studies. It was found that various valid criteria could be represented by six constructs, viz.: the stature of the researcher as scientist; scientific contributions; enhancement of own profession; community development; participation in research projects; and giving advice to persons or institutions outside the university. Opsomming By Suid-Afrikaanse universiteite word doelwitbereiking gewoonlik aan die hand van sogenaamde "prosesmaat-stawwe" (bv. slaagsyfers in plaas van prestasiemaatstawwe wat die gehalte van akademiese personeel weerspieel, gemeet. Na aanleiding van 'n behoefte aan die identifisering van geldige rigtingwysers vir navorsingsprestasie as 'n komponent van akademiese prestasie, is daar ondersoek ingestel na die dimensionaliteit van verskillende maatstawwe wat vooraf deur middel van empiriese- en literatuurstudies geidentifiseer is. Daar is gevind dat verskeie geldige maatstawwe deur ses konstrukte verteenwoordig word, te wete: die statuur van die navorser as wetenskaplike, wetenskaplike bydraes, uitbouing van eie professie, gemeenskapsontwikkeling, deelname aan navorsingsprojekte en advieslewering aan persone of instellings buite die Universiteit.

  3. The protective effects of piceatannol from passion fruit (Passiflora edulis) seeds in UVB-irradiated keratinocytes.

    Maruki-Uchida, Hiroko; Kurita, Ikuko; Sugiyama, Kenkichi; Sai, Masahiko; Maeda, Kazuhisa; Ito, Tatsuhiko

    2013-01-01

    The use of naturally occurring botanicals with substantial antioxidant activity to prevent photoageing is receiving increasing attention. We have previously identified piceatannol and scirpusin B, which is a dimer of piceatannol, as strong antioxidants that are present in passion fruit (Passiflora edulis) seeds. In the present study, the effects of passion fruit seed extract, piceatannol, and scirpusin B on human keratinocytes were investigated. The passion fruit seed extract and piceatannol upregulated the glutathione (GSH) levels in keratinocytes in a dose-dependent manner, indicating that piceatannol is an active component of the passion fruit seed extract in keratinocytes. The pretreatment with piceatannol also suppressed the UVB-induced generation of reactive oxygen species (ROS) in the keratinocytes. In addition, the transfer of the medium from the UVB-irradiated keratinocytes to non-irradiated fibroblasts enhanced matrix-metalloproteinase (MMP)-1 activity, and this MMP-1 induction was reduced when the keratinocytes were pretreated with piceatannol. These results suggest that piceatannol attenuates the UVB-induced activity of MMP-1 along with a reduction of ROS generation in keratinocytes. Thus, piceatannol and passion fruit seed extract containing high amounts of piceatannol are potential anti-photoageing cosmetic ingredients.

  4. Exogenous hydrogen sulfide promotes cell proliferation and differentiation by modulating autophagy in human keratinocytes

    Xie, Xin; Dai, Hui; Zhuang, Binyu; Chai, Li; Xie, Yanguang; Li, Yuzhen

    2016-01-01

    The effects and the underlying mechanisms of hydrogen sulfide (H 2 S) on keratinocyte proliferation and differentiation are still less known. In the current study, we investigated the effects and the underlying mechanisms of exogenous H 2 S on keratinocyte proliferation and differentiation. Human keratinocytes (HaCaT cells) were treated with various concentrations (0.05, 0.25, 0.5 and 1 mM) of sodium hydrosulfide (NaHS, a donor of H 2 S) for 24 h. A CCK-8 assay was used to assess cell viability. Western blot analysis was performed to determine the expression levels of proteins associated with differentiation and autophagy. Transmission electron microscopy was performed to observe autophagic vacuoles, and flow cytometry was applied to evaluate apoptosis. NaHS promoted the viability, induced the differentiation, and enhanced autophagic activity in a dose-dependent manner in HaCaT cells but had no effect on cell apoptosis. Blockage of autophagy by ATG5 siRNA inhibited NaHS-induced cell proliferation and differentiation. The current study demonstrated that autophagy in response to exogenous H 2 S treatment promoted keratinocyte proliferation and differentiation. Our results provide additional insights into the potential role of autophagy in keratinocyte proliferation and differentiation. - Highlights: • Exogenous H 2 S promotes keratinocyte proliferation and differentiation. • The effects of H 2 S on proliferation and differentiation is modulated by autophagy. • Exogenous H 2 S has no effect on keratinocyte apoptosis.

  5. Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease.

    Scorza, Breanna M; Wacker, Mark A; Messingham, Kelly; Kim, Peter; Klingelhutz, Aloysius; Fairley, Janet; Wilson, Mary E

    2017-10-01

    All Leishmania species parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. Mouse studies suggest that early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. We hypothesized that Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection. Incubation of primary or immortalized human keratinocytes with Leishmania infantum or Leishmania major, which cause visceral or cutaneous leishmaniasis, respectively, elicited dramatically different responses. Keratinocytes incubated with L. infantum significantly increased expression of proinflammatory genes for IL-6, IL-8, tumor necrosis factor, and IL-1B, whereas keratinocytes exposed to several L. major isolates did not. Furthermore, keratinocyte-monocyte co-incubation studies across a 4 µM semipermeable membrane suggested that L. infantum-exposed keratinocytes release soluble factors that enhance monocyte control of intracellular L. infantum replication (P Leishmania species that may affect the course of disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Possible role of epidermal keratinocytes in the construction of acupuncture meridians.

    Denda, Mitsuhiro; Tsutsumi, Moe

    2014-04-01

    Acupuncture meridians consist of a network of acupuncture points on the skin, stimulation of which is well established to have a variety of physiological effects. We have previously demonstrated that epidermal keratinocytes contain multiple sensory systems for temperature, mechanical stimuli, electric potentials and other stimuli. These sensory systems generate changes in the calcium-ion concentration in the epidermis, so epidermal keratinocytes can generate spatially-localized electro-physiological patterns in the skin. We have previously demonstrated signaling between epidermal keratinocytes and peripheral nerve systems. Therefore, stimuli sensed by epidermal keratinocytes might be transferred to the unmyelinated nerve fibers that are known to exist in the epidermis and, thence, to the spinal cord and brain. We propose that epidermal keratinocytes form an information-gathering network in the skin and that this network plays a key role in whole-body homeostasis in response to the changing environment. We also hypothesize that this network corresponds to the acupuncture meridians. As supporting examples, we present some striking calcium propagation patterns observed in cultured human keratinocytes after adenosine-triphosphate (ATP) stimulation. These results support the ideas that keratinocytes can generate spatially-restricted signaling patterns after environmental stimulation and that the cultures might be in-vitro models of meridians as an information-gathering network in skin. Copyright © 2014. Published by Elsevier B.V.

  7. Lactobacillus rhamnosus GG Lysate Increases Re-Epithelialization of Keratinocyte Scratch Assays by Promoting Migration.

    Mohammedsaeed, Walaa; Cruickshank, Sheena; McBain, Andrew J; O'Neill, Catherine A

    2015-11-05

    A limited number of studies have investigated the potential of probiotics to promote wound healing in the digestive tract. The aim of the current investigation was to determine whether probiotic bacteria or their extracts could be beneficial in cutaneous wound healing. A keratinocyte monolayer scratch assay was used to assess re-epithelialization; which comprises keratinocyte proliferation and migration. Primary human keratinocyte monolayers were scratched then exposed to lysates of Lactobacillus (L) rhamnosus GG, L. reuteri, L. plantarum or L. fermentum. Re-epithelialization of treated monolayers was compared to that of untreated controls. Lysates of L. rhamnosus GG and L. reuteri significantly increased the rate of re-epithelialization, with L. rhamnosus GG being the most efficacious. L. reuteri increased keratinocyte proliferation while L. rhamnosus GG lysate significantly increased proliferation and migration. Microarray analysis of L. rhamnosus GG treated scratches showed increased expression of multiple genes including the chemokine CXCL2 and its receptor CXCR2. These are involved in normal wound healing where they stimulate keratinocyte proliferation and/or migration. Increased protein expression of both CXCL2 and CXCR2 were confirmed by ELISA and immunoblotting. These data demonstrate that L. rhamnosus GG lysate accelerates re-epithelialization of keratinocyte scratch assays, potentially via chemokine receptor pairs that induce keratinocyte migration.

  8. Gelatin for purification and proliferation of primary keratinocyte culture for use in chronic wounds and burns.

    Rahsaz, Marjan; Geramizadeh, Bita; Kaviani, Maryam; Marzban, Saeed

    2015-04-01

    Human epidermal keratinocytes are currently established as a treatment for burns and wounds and have laboratory applications. Keratinocyte culture contamination by unwanted cells and inhibition of cell proliferation are barriers in primary keratinocyte culture. According to the recent literature, these cells are hard to culture. The present study was conducted to evaluate the efficacy of gelatin-coated surfaces in keratinocyte cultures. After enzymatic isolation of keratinocytes from normal epidermis by trypsin, the cells were cultured on gelatin-coated flasks in serum-free medium. Another group of cells were cultured as a control group without gelatin coating. We showed positive effects of surface coating with gelatin on the primary culture of keratinocytes. Culture of these cells on a gelatincoated surface showed better proliferation with suitable morphology. By using gelatin, adhesion of these cells to the surface was more efficient and without contamination by small round cells. Successful primary culture of keratinocytes on a gelatin-coated surface may provide better yield and optimal number of cells for research and clinical applications.

  9. [Cultivated keratinocytes on micro-carriers: in vitro studies of a new carrier system].

    Hecht, J; Hoefter, E A; Hecht, J; Haraida, S; Nerlich, A; Hartinger, A; Mühlbauer, W; Dimoudis, N

    1997-03-01

    Epidermal grafts from confluently cultivated keratinocytes have been used since the early eighties for the treatment of severe burns, where the shortage of donor sites for split-thickness skin grafts did not allow for adequate wound coverage. The difficult handling of these grafts as well as the advanced differentiation of their epithelial cells into a multilayer sheet poses a problem for their clinical application. The aim of the study was to characterize cultivated keratinocytes, as well as to observe their migration and proliferation from the MC onto a surface. Keratinocytes were isolated from human foreskin and cultivated in serum-free and serum-containing medium according to a modified method by Rheinwald and Green. Collagen-coated Dextran beads were used as MC. The MC were colonized with keratinocytes using the Spinner culture technique. After seeding the colonized MC into culture flasks, their migration and proliferation was monitored regularly through immunohistochemical studies and measurement of the metabolic cell activity. Immunohistological staining proved that the cells isolated from human foreskin represent keratinocytes of the basal type. Keratinocytes, cultivated with serum-containing and serum free medium, both adhered to the surface of the MC, then migrated onto the surface of the flasks and proliferated to form a multilayer of epithelial cells. In the long-term, a flexible epithelial graft consisting of poorly differentiated keratinocytes should be available, which is simple to produce and easy to handle. This would be an alternative method for treating wounds, where the conventional multilayer epithelial graft (ET) is insufficient.

  10. The impact of cellular senescence in skin ageing: A notion of mosaic and therapeutic strategies.

    Toutfaire, Marie; Bauwens, Emilie; Debacq-Chainiaux, Florence

    2017-10-15

    Cellular senescence is now recognized as one of the nine hallmarks of ageing. Recent data show the involvement of senescent cells in tissue ageing and some age-related diseases. Skin represents an ideal model for the study of ageing. Indeed, skin ageing varies between individuals depending on their chronological age but also on their exposure to various exogenous factors (mainly ultraviolet rays). If senescence traits can be detected with ageing in the skin, the senescent phenotype varies among the various skin cell types. Moreover, the origin of cellular senescence in the skin is still unknown, and multiple origins are possible. This reflects the mosaic of skin ageing. Senescent cells can interfere with their microenvironment, either via the direct secretion of factors (the senescence-associated secretory phenotype) or via other methods of communication, such as extracellular vesicles. Knowledge regarding the impact of cellular senescence on skin ageing could be integrated into dermatology research, especially to limit the appearance of senescent cells after photo(chemo)therapy or in age-related skin diseases. Therapeutic approaches include the clearance of senescent cells via the use of senolytics or via the cooperation with the immune system. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells.

    Seno, Kotomi; Tanikawa, Nao; Takahashi, Hironori; Ohkuchi, Akihide; Suzuki, Hirotada; Matsubara, Shigeki; Iwata, Hisataka; Kuwayama, Takehito; Shirasuna, Koumei

    2018-02-15

    We investigated the effect of oxygen concentrations on cellular senescence and autophagy and examined the role of autophagy in human trophoblast cells. Human first-trimester trophoblast cells (Sw.71) were incubated under 21%, 5%, or 1% O 2 concentrations for 24 hours. We examined the extent of senescence caused using senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated secretory phenotype (SASP) as markers. Moreover, we examined the role of autophagy in causing cellular senescence using an autophagy inhibitor (3-methyladenine, 3MA). Physiological normoxia (5% O 2 ) decreased SA-β-Gal-positive cells and SASP including interleukin-6 (IL-6) and IL-8 compared with cultured cells in 21% O 2 . Pathophysiological hypoxia (1% O 2 ) caused cytotoxicity, including extracellular release of ATP and lactate dehydrogenase, and decreased senescence phenotypes. 3MA-treated trophoblast cells significantly suppressed senescence markers (SA-β-Gal-positive cells and SASP secretion) in O 2 -independent manner. We conclude that O 2 concentration modulates cellular senescence phenotypes regulating autophagy in the human trophoblast cells. Moreover, inhibiting autophagy suppresses cellular senescence, suggesting that autophagy contributes to oxygen stress-induced cellular senescence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. In vivo inhibition of cysteine proteases provides evidence for the involvement of 'senescence-associated vacuoles' in chloroplast protein degradation during dark-induced senescence of tobacco leaves.

    Carrión, Cristian A; Costa, María Lorenza; Martínez, Dana E; Mohr, Christina; Humbeck, Klaus; Guiamet, Juan J

    2013-11-01

    Breakdown of leaf proteins, particularly chloroplast proteins, is a massive process in senescing leaves. In spite of its importance in internal N recycling, the mechanism(s) and the enzymes involved are largely unknown. Senescence-associated vacuoles (SAVs) are small, acidic vacuoles with high cysteine peptidase activity. Chloroplast-targeted proteins re-localize to SAVs during senescence, suggesting that SAVs might be involved in chloroplast protein degradation. SAVs were undetectable in mature, non-senescent tobacco leaves. Their abundance, visualized either with the acidotropic marker Lysotracker Red or by green fluorescent protein (GFP) fluorescence in a line expressing the senescence-associated cysteine protease SAG12 fused to GFP, increased during senescence induction in darkness, and peaked after 2-4 d, when chloroplast dismantling was most intense. Increased abundance of SAVs correlated with higher levels of SAG12 mRNA. Activity labelling with a biotinylated derivative of the cysteine protease inhibitor E-64 was used to detect active cysteine proteases. The two apparently most abundant cysteine proteases of senescing leaves, of 40kDa and 33kDa were detected in isolated SAVs. Rubisco degradation in isolated SAVs was completely blocked by E-64. Treatment of leaf disks with E-64 in vivo substantially reduced degradation of Rubisco and leaf proteins. Overall, these results indicate that SAVs contain most of the cysteine protease activity of senescing cells, and that SAV cysteine proteases are at least partly responsible for the degradation of stromal proteins of the chloroplast.

  13. Filaggrin-dependent secretion of sphingomyelinase protects against staphylococcal α-toxin-induced keratinocyte death.

    Brauweiler, Anne M; Bin, Lianghua; Kim, Byung Eui; Oyoshi, Michiko K; Geha, Raif S; Goleva, Elena; Leung, Donald Y M

    2013-02-01

    The skin of patients with atopic dermatitis (AD) has defects in keratinocyte differentiation, particularly in expression of the epidermal barrier protein filaggrin. AD skin lesions are often exacerbated by Staphylococcus aureus-mediated secretion of the virulence factor α-toxin. It is unknown whether lack of keratinocyte differentiation predisposes to enhanced lethality from staphylococcal toxins. We investigated whether keratinocyte differentiation and filaggrin expression protect against cell death induced by staphylococcal α-toxin. Filaggrin-deficient primary keratinocytes were generated through small interfering RNA gene knockdown. RNA expression was determined by using real-time PCR. Cell death was determined by using the lactate dehydrogenase assay. Keratinocyte cell survival in filaggrin-deficient (ft/ft) mouse skin biopsies was determined based on Keratin 5 staining. α-Toxin heptamer formation and acid sphingomyelinase expression were determined by means of immunoblotting. We found that filaggrin expression, occurring as the result of keratinocyte differentiation, significantly inhibits staphylococcal α-toxin-mediated pathogenicity. Furthermore, filaggrin plays a crucial role in protecting cells by mediating the secretion of sphingomyelinase, an enzyme that reduces the number of α-toxin binding sites on the keratinocyte surface. Finally, we determined that sphingomyelinase enzymatic activity directly prevents α-toxin binding and protects keratinocytes against α-toxin-induced cytotoxicity. The current study introduces the novel concept that S aureus α-toxin preferentially targets and destroys filaggrin-deficient keratinocytes. It also provides a mechanism to explain the increased propensity for S aureus-mediated exacerbation of AD skin disease. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  14. Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes.

    Rasmussen, Cathy A; Allen-Hoffmann, B Lynn

    2012-04-01

    For patients suffering from catastrophic burns, few treatment options are available. Chimeric coculture of patient-derived autologous cells with a "carrier" cell source of allogeneic keratinocytes has been proposed as a means to address the complex clinical problem of severe skin loss. Currently, autologous keratinocytes are harvested, cultured, and expanded to form graftable epidermal sheets. However, epidermal sheets are thin, are extremely fragile, and do not possess barrier function, which only develops as skin stratifies and matures. Grafting is typically delayed for up to 4 weeks to propagate a sufficient quantity of the patient's cells for application to wound sites. Fully stratified chimeric bioengineered skin substitutes could not only provide immediate wound coverage and restore barrier function, but would simultaneously deliver autologous keratinocytes to wounds. The ideal allogeneic cell source for this application would be an abundant supply of clinically evaluated, nontumorigenic, pathogen-free, human keratinocytes. To evaluate this potential cell-based therapy, mixed populations of a green fluorescent protein-labeled neonatal human keratinocyte cell line (NIKS) and unlabeled primary keratinocytes were used to model the allogeneic and autologous components of chimeric monolayer and organotypic cultures. Relatively few autologous keratinocytes may be required to produce fully stratified chimeric skin substitute tissue substantially composed of autologous keratinocyte-derived regions. The need for few autologous cells interspersed within an allogeneic "carrier" cell population may decrease cell expansion time, reducing the time to patient application. This study provides proof of concept for utilizing NIKS keratinocytes as the allogeneic carrier for the generation of bioengineered chimeric skin substitute tissues capable of providing immediate wound coverage while simultaneously supplying autologous human cells for tissue regeneration.

  15. Die toepassing van die K3-model op die televisieteks Colour TV

    “OIL's approach to investigating the coloured market took place in the form of ethnographic research which ... communication strategies” (Botha 2010: 14). ... Op grond van die waarnemings, onderhoude en vraelyste het OIL tot die volgende ..... hold onto your nearest and dearest because this is going to be a kwaai mix bag.

  16. T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.

    Cécilia Brun

    Full Text Available Cutaneous wound healing requires keratinocyte proliferation, migration and differentiation to restore the barrier function of the skin. The calcineurin/nuclear factor of activated-T-cell (NFAT signaling pathway has been recently shown to be involved in keratinocyte growth, differentiation and migration. It is induced by an increased intracellular calcium rate and its inhibition results in decreased capacities of keratinocytes to migrate. Nevertheless, the link between calcineurin activation and keratinocyte migration remains unknown. Recently, Orai1, a pore subunit of a store-operated calcium channel that favors calcium influx, was shown to play a critical role to control proliferation and migration of basal keratinocytes. Of interest, the actin-bundling T-plastin is crucial in cell motility through cross-linking to actin filament and its synthesis was shown to be induced by calcium influx and regulated by the calcineurin/NFAT pathway in tumor Sezary cells. We investigated herein the role of the calcineurin/NFAT pathway-dependent T-plastin in keratinocyte migration, by quantifying T-plastin expression in keratinocytes and by analyzing their migration under calcineurin inhibition or knockdown of NFAT2 or T-plastin. We did confirm the role of the calcineurin/NFAT pathway in keratinocyte migration as shown by their decreased capacities to migrate after FK506 treatment or siNFAT2 transfection in both scratching and Boyden assays. The expression of NFAT2 and T-plastin in keratinocytes was decreased under FK506 treatment, suggesting that T-plastin plays a role in keratinocyte migration downstream to the calcineurin/NFAT pathway. Accordingly, siRNA knockdown of T-plastin expression also decreased their migration capacities. Actin lamellipodia formation as well as FAK and β6-integrin expression were also significantly decreased after treatment with FK506 or siRNA, reinforcing that NFAT2-dependent T-plastin expression plays a role in keratinocyte

  17. Members of the barley NAC transcription factor gene family show differential co-regulation with senescence-associated genes during senescence of flag leaves

    Christiansen, Michael W; Gregersen, Per L.

    2014-01-01

    -expressed with members of the NAC gene family. In conclusion, a list of up to 15 NAC genes from barley that are strong candidates for being regulatory factors of importance for senescence and biotic stress-related traits affecting the productivity of cereal crop plants has been generated. Furthermore, a list of 71...... in the NAC transcription factor family during senescence of barley flag leaves was studied. Several members of the NAC transcription factor gene family were up-regulated during senescence in a microarray experiment, together with a large range of senescence-associated genes, reflecting the coordinated...... activation of degradation processes in senescing barley leaf tissues. This picture was confirmed in a detailed quantitative reverse transcription–PCR (qRT–PCR) experiment, which also showed distinct gene expression patterns for different members of the NAC gene family, suggesting a group of ~15 out of the 47...

  18. The role of SUMOylation in ageing and senescent decline.

    Princz, Andrea; Tavernarakis, Nektarios

    2017-03-01

    Posttranslational protein modifications are playing crucial roles in essential cellular mechanisms. SUMOylation is a reversible posttranslational modification of specific target proteins by the attachment of a small ubiquitin-like protein. Although the mechanism of conjugation of SUMO to proteins is analogous to ubiquitination, it requires its own, specific set of enzymes. The consequences of SUMOylation are widely variable, depending on the physiological state of the cell and the attached SUMO isoform. Accumulating recent findings have revealed a prominent role of SUMOylation in molecular pathways that govern senescence and ageing. Here, we review the link between SUMO attachment events and cellular processes that influence senescence and ageing, including promyelocytic leukaemia (PML) nuclear body and telomere function, autophagy, reactive oxygen species (ROS) homeostasis and growth factor signalling. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Stress-induced premature senescence of endothelial cells.

    Chen, Jun; Patschan, Susann; Goligorsky, Michael S

    2008-01-01

    Stress-induced premature senescence (SIPS) is characterized by cell cycle arrest and curtailed Hayflick limit. Studies support a central role for Rb protein in controlling this process via signaling from the p53 and p16 pathways. Cellular senescence is considered an essential contributor to the aging process and has been shown to be an important tumor suppression mechanism. In addition, emerging evidence suggests that SIPS may be involved in the pathogenesis of chronic human diseases. Here, focusing on endothelial cells, we discuss recent advances in our understanding of SIPS and the pathways that trigger it, evaluate their correlation with the apoptotic response and examine their links to the development of chronic diseases, with the emphasis on vasculopathy. Emerging novel therapeutic interventions based on recent experimental findings are also reviewed.

  20. Inability of keratinocytes lacking their specific transglutaminase to form cross-linked envelopes: Absence of envelopes as a simple diagnostic test for lamellar ichthyosis

    Jeon, Saewha; Djian, Philippe; Green, Howard

    1998-01-01

    Epidermal keratinocytes, late in their terminal differentiation, form cross-linked envelopes resistant to ionic detergent and reducing agent. Because the cross-linking process is catalyzed by the keratinocyte transglutaminase, the absence of active transglutaminase should result in failure of the keratinocyte to form a cross-linked envelope. Three keratinocyte strains bearing mutations in the keratinocyte transglutaminase were examined: two contained no detectable transglutaminase mRNA and no...

  1. Die kliniese kindersielkundige as diagnostikus1

    D. J. W. Strümpfer

    1961-03-01

    Full Text Available Die benaming „Kliniese Kindersielkunde” is nog onbekend en gevolglik betreklik onbemind. Dit is in 1951 die eerste keer gebruik. Die werk van die Kliniese Kindersielkunde is egter so oud as die werk van die algemene Kliniese Sielkunde, waarvan die geskiedenis gewoonlik teruggevoer word tot die begin van sielkundige toetsing vroeg in die tagtigerjare. Tot ’n aansienlike mate is hierdie vroeë werk op kinders uitgevoer, bv. dié van Galton en later die van Binet en Simon. Witmer het in 1896 die eerste sielkundige kliniek geopen en het ook die term „Kliniese Sielkunde” ingevoer; die meerderheid van sy pasiënte was egter ook kinders. Tot voor die Tweede Wêreldoorlog was klinies-sielkundige werk hoofsaaklik op kinders toegespits. Sedertdien het die kliniese sielkundige tot ’n belangrike mate toegetree tot die gebied van die diagnose en terapie van psigiese afwykings by volwassenes, tot so ’n mate dat in die gedagtes en geskrifte van baie werkers die terrein van die Kliniese Sielkunde byna tot werk met volwassenes beperk word.

  2. James Henry Greathead en die Londense Moltrein

    Laurence Wright

    2017-07-01

    Full Text Available Die artikel ondersoek die oorsprong en vroeë geskiedenis van die toestel genaamd die ‘Greathead Skild’, ‘n belangrike nuwigheid in Viktoriaanse ingenieurwetenskap, wat van deurslaggewende belang was in die konstruksie van die Londense Moltrein. Die doel is om die basis te ontleed waarop, baie jare later, ‘n Suid-Afrikaanse ingenieur wye openbare erkenning in die vorm van ‘n standbeeld vir die ‘ontwerp’ van die Skild geniet het. Uit die perspektief van kulturele studies beskou, hoe moet ons uitvinding verstaan, gegewe dat ander briljante ingenieurs ook betrokke was? Hierdie vraag word ontleed met die gebruik van die konsep ‘extelligence’ (Stewart and Cohen 1997, in samehang met ander kontemporêre en geskiedkundige weergawes, insluitend Greathead se eie rekord van sy prestasies in die verrigtinge van die Instituut van Siviele Ingenieurs en voorgelê in The City and South London Railway (1896, onder redaksie van James Forrest. Hierdie artikel is die eerste keer as referaat aangebied by die konferensie oor ‘Nuuthede en Innovasie in die Negentiende Eeu’ aan die Noordwes-Universiteit, Mei 2016.

  3. DIE NAAM “NEDERDUITSE GEREFORMEERDE KERK”

    P.J. Strauss. DIE NAAM “NEDERDUITSE. GEREFORMEERDE KERK”. ABSTRACT. An investigation into the name of the Dutch Reformed Church (DRC) reveals that it is a reformed church in the ... P.J. Strauss, Fakulteit Teologie, Universiteit van die Vrystaat, Suid‑Afrika. ..... Dit is so omdat die staat en sy howe die reg in die ...

  4. Abstraksie en veralgemening in die Wiskunde

    B.C. Strydom

    1967-03-01

    Full Text Available Wanneer ek tot u spreek oor abstraksie en veralgemening in die Wiskunde, wil ek u aandag vestig op die belangrikheid daarvaan vir die Wiskunde, maar u terselfdertyd daarop wys dat die wiskundige hom nie langs hierdie weg heeltemal van die werklikheid kan losmaak nie.

  5. Immune senescence: relative contributions of age and cytomegalovirus infection.

    Andrea Mekker

    Full Text Available Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV infection with or without thymectomy (Tx alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8(+ T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any 'de novo' immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence.

  6. A continuum mathematical model of endothelial layer maintenance and senescence

    Friedman Avner

    2007-08-01

    Full Text Available Abstract Background The monolayer of endothelial cells (ECs lining the inner wall of blood vessels deteriorates as a person ages due to a complex interplay of a variety of causes including cell death arising from shear stress of blood flow and cellular oxidative stress, cellular senescence, and decreased rate of replacement of dead ECs by progenitor stem cells. Results A continuum mathematical model is developed to describe the dynamics of large EC populations of the endothelium using a system of differential equations for the number densities of cells of different generations starting from endothelial progenitors to senescent cells, as well as the densities of dead cells and the holes created upon clearing dead cells. Aging of cells is manifested in three ways, namely, losing the ability to divide when the Hayflick limit of 50 generations is reached, decreasing replication rate parameters and increasing death rate parameters as cells divide; due to the dependence of these rate parameters on cell generation, the model predicts a narrow distribution of cell densities peaking at a particular cell generation. As the chronological age of a person advances, the peak of the distribution – corresponding to the age of the endothelium – moves towards senescence correspondingly. However, computer simulations also demonstrate that sustained and enhanced stem cell homing can halt the aging process of the endothelium by maintaining a stationary cell density distribution that peaks well before the Hayflick limit. The healing rates of damaged endothelia for young, middle-aged, and old persons are compared and are found to be particularly sensitive to the stem cell homing parameter. Conclusion The proposed model describes the aging of the endothelium as being driven by cellular senescence, with a rate that does not necessarily correspond to the chronological aging of a person. It is shown that the age of the endothelium depends sensitively on the homing

  7. A continuum mathematical model of endothelial layer maintenance and senescence.

    Wang, Ying; Aguda, Baltazar D; Friedman, Avner

    2007-08-10

    The monolayer of endothelial cells (ECs) lining the inner wall of blood vessels deteriorates as a person ages due to a complex interplay of a variety of causes including cell death arising from shear stress of blood flow and cellular oxidative stress, cellular senescence, and decreased rate of replacement of dead ECs by progenitor stem cells. A continuum mathematical model is developed to describe the dynamics of large EC populations of the endothelium using a system of differential equations for the number densities of cells of different generations starting from endothelial progenitors to senescent cells, as well as the densities of dead cells and the holes created upon clearing dead cells. Aging of cells is manifested in three ways, namely, losing the ability to divide when the Hayflick limit of 50 generations is reached, decreasing replication rate parameters and increasing death rate parameters as cells divide; due to the dependence of these rate parameters on cell generation, the model predicts a narrow distribution of cell densities peaking at a particular cell generation. As the chronological age of a person advances, the peak of the distribution - corresponding to the age of the endothelium - moves towards senescence correspondingly. However, computer simulations also demonstrate that sustained and enhanced stem cell homing can halt the aging process of the endothelium by maintaining a stationary cell density distribution that peaks well before the Hayflick limit. The healing rates of damaged endothelia for young, middle-aged, and old persons are compared and are found to be particularly sensitive to the stem cell homing parameter. The proposed model describes the aging of the endothelium as being driven by cellular senescence, with a rate that does not necessarily correspond to the chronological aging of a person. It is shown that the age of the endothelium depends sensitively on the homing rates of EC progenitor cells.

  8. Cytokines shape chemotherapy-induced and 'bystander' senescence

    Hodný, Zdeněk; Hubáčková, Soňa; Bartek, Jiří

    2010-01-01

    Roč. 2, č. 2 (2010), s. 375-376 ISSN 1945-4589 R&D Projects: GA ČR GA204/08/1418; GA ČR GA301/08/0353 Institutional research plan: CEZ:AV0Z50520514 Keywords : bystander cellular senescence * cytokines * PML Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.964, year: 2010

  9. Die Dankesrede bei der Preisverleihung

    Elenmari Pletikos Olof

    2012-12-01

    Full Text Available Festliche Preisverleihungen sind Gelegenheiten, bei denen von den Preisträgerneine kurze Rede erwartet wird. Obwohl die Dankesrede eine kleinere Randgattung innerhalb des epideiktischen Genres ist, steht sie im Mittelpunkt des Ereignisses. Rhetorikhandbücher geben zahlreiche Ratschläge, wie eine gute Festrede vorbereitet werden soll, um zu unterhalten, zu bewegen und zu belehren. Ziel dieser Untersuchung ist es festzustellen, welche Eigenschaften der Dankesrede die Zuhörer als erwünscht oder unerwünscht wahrnehmen und welche Charakteristika am meisten zur Qualität festlicher Dankesreden beitragen. Das Korpus der gesprochenen Texte bilden 30 Dankesreden anlässlich kroatischer Preisverleihungen in den Bereichen Schauspiel, Sport, Musik, Fernsehen, Literatur und Wirtschaft. Die Audio-Aufnahmen der Dankesreden wurden einer Gruppe von Hörern zur Bewertung in folgenden Kategorien vorgelegt: interessant, geistreich, hoher Sprachstil, feierlich, emotiv, persönlich, originell, bescheiden, vorbereitet und spontan. Zusätzlich wurde zu jeder Rede die offene Frage gestellt, was dem Zuhörer an der Rede gefallen oder nicht gefallen habe. Die Resultate der Perzeptionsanalye lassen erkennen, dass die Interessantheit einer Rede mit der Eigenschaft des Geistreichen, des Originellen, des Emotionalen und des Persönlichen in Verbindung gebracht wird und die Eigenschaft des Festlichen im Wesentlichen nur mit dem hohen Sprachstil und der Vorbereitetheit des Textes korreliert. Einige Eigenschaften können sowohl erwünscht als auch unerwünscht sein, z. B. Dialekt, Persönliches und Kürze. Die besten Dankesreden haben Eigenschaften, die im Grunde schwer miteinander zu verbinden sind: Einerseits soll der Text vorbereitet sein (hoher Stil, Wortwahl, Figuren, Originalität der Geschichte, Humor, andererseits wird bei der Ausführung Spontaneität (Aufrichtigkeit, Emotionalität, Persönlichkeit erwartet.

  10. Author: T Bekker DIE MOONTLIKE REGSHERVORMING VAN DIE ...

    RV

    So ver terug as die vroeë twintigste eeu het die Appèlhof in Cassiem v Standard. Bank of SA Ltd,1 .... 838; Capital Building Society v De Jager 1963 3 SA 381 (T); Smit v Walles 1985 2 SA 189 (T). 196-198. 18 ...... moeilik kon regverdig.97. Ons howe het tot op hede gehuiwer om 'n algemene plig van goeie trou ten aansien.

  11. Cytoplasmic chromatin triggers inflammation in senescence and cancer.

    Dou, Zhixun; Ghosh, Kanad; Vizioli, Maria Grazia; Zhu, Jiajun; Sen, Payel; Wangensteen, Kirk J; Simithy, Johayra; Lan, Yemin; Lin, Yanping; Zhou, Zhuo; Capell, Brian C; Xu, Caiyue; Xu, Mingang; Kieckhaefer, Julia E; Jiang, Tianying; Shoshkes-Carmel, Michal; Tanim, K M Ahasan Al; Barber, Glen N; Seykora, John T; Millar, Sarah E; Kaestner, Klaus H; Garcia, Benjamin A; Adams, Peter D; Berger, Shelley L

    2017-10-19

    Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

  12. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  13. Oxidative stress induces senescence in human mesenchymal stem cells

    Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

    2011-07-01

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

  14. The thorny path linking cellular senescence to organismalaging

    Patil, Christopher K.; Mian, Saira; Campisi, Judith

    2005-08-09

    Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; Martin, 1993). How well have these hypotheses weathered the ensuing decades? Before answering this question, we first consider current insights into the causes and consequences of cellular senescence. Like Lorenzini et al., we limit our discussion to mammals. We also focus on fibroblasts, the cell type studied by Lorenzini et al., but consider other types as well. We suggest that replicative capacity in culture is not a straightforward assessment, and that it correlates poorly with both longevity and body mass. We speculate this is due to the malleable and variable nature of replicative capacity, which renders it an indirect metric of qualitative and quantitative differences among cells to undergo senescence, a response that directly alters cellular phenotype and might indirectly alter tissue structure and function.

  15. Ultraviolet radiation induction of ornithine decarboxylase in rat keratinocytes

    Rosen, C.F.; Gajic, D.; Drucker, D.J.

    1990-01-01

    UV radiation plays an important role in the induction of cutaneous malignancy, including basal cell and squamous cell carcinomas and malignant melanoma. In addition to its effects on DNA damage and repair mechanisms, UV radiation has been shown to modulate the expression of specific genes, altering the levels of their mRNAs and the synthesis of their corresponding proteins. In order to gain further information about the molecular effects of UV radiation, we have studied the regulation of ornithine decarboxylase (ODC) gene expression in response to UVB radiation. ODC is the rate-limiting enzyme in polyamine biosynthesis, is involved in growth and differentiation, and has been implicated in carcinogenesis. Keratinocytes grown in culture were either sham-irradiated or exposed to increasing doses of UVB (1-5 mJ/cm2). Northern blot analysis of keratinocyte RNA under basal conditions demonstrated the presence of two ODC mRNA transcripts. Increasing exposure to UVB resulted in a dose-dependent increase in the levels of both ODC mRNA transcripts. The induction of ODC gene expression following UVB was noted 2 h after UVB exposure, and ODC mRNA levels continued to increase up to 24 h after UVB exposure. The UVB-induced increase in ODC gene expression was not serum dependent, despite the ability of serum alone to induce ODC gene expression. The mRNA transcripts for actin and hexosaminidase A were not induced after UVB exposure. These studies show that the UVB-induced increase in ODC activity is due, at least in part, to an increase in ODC gene expression and they provide a useful model for the analysis of the molecular effects of UVB radiation

  16. Ultraviolet radiation induction of ornithine decarboxylase in rat keratinocytes

    Rosen, C.F.; Gajic, D.; Drucker, D.J. (Women' s College Hospital, Toronto, Ontario (Canada))

    1990-05-01

    UV radiation plays an important role in the induction of cutaneous malignancy, including basal cell and squamous cell carcinomas and malignant melanoma. In addition to its effects on DNA damage and repair mechanisms, UV radiation has been shown to modulate the expression of specific genes, altering the levels of their mRNAs and the synthesis of their corresponding proteins. In order to gain further information about the molecular effects of UV radiation, we have studied the regulation of ornithine decarboxylase (ODC) gene expression in response to UVB radiation. ODC is the rate-limiting enzyme in polyamine biosynthesis, is involved in growth and differentiation, and has been implicated in carcinogenesis. Keratinocytes grown in culture were either sham-irradiated or exposed to increasing doses of UVB (1-5 mJ/cm2). Northern blot analysis of keratinocyte RNA under basal conditions demonstrated the presence of two ODC mRNA transcripts. Increasing exposure to UVB resulted in a dose-dependent increase in the levels of both ODC mRNA transcripts. The induction of ODC gene expression following UVB was noted 2 h after UVB exposure, and ODC mRNA levels continued to increase up to 24 h after UVB exposure. The UVB-induced increase in ODC gene expression was not serum dependent, despite the ability of serum alone to induce ODC gene expression. The mRNA transcripts for actin and hexosaminidase A were not induced after UVB exposure. These studies show that the UVB-induced increase in ODC activity is due, at least in part, to an increase in ODC gene expression and they provide a useful model for the analysis of the molecular effects of UVB radiation.

  17. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi; Kotani, Eiji; Hirano, Tomoko; Nakajima, Yumiko; Matsumoto, Goichi; Mori, Hajime

    2014-01-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals

  18. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Kotani, Eiji [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan); Hirano, Tomoko [Venture Laboratory, Kyoto Institute of Technology, Kyoto (Japan); Nakajima, Yumiko [Functional Genomics Group, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa (Japan); Matsumoto, Goichi [Division of Oral Surgery, Yokohama Clinical Education Center of Kanagawa Dental University, Yokohama (Japan); Mori, Hajime, E-mail: hmori@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan)

    2014-09-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals.

  19. Quantenfische die Stringtheorie und die Suche nach Weltformel

    Lüst, Dieter

    2011-01-01

    Lässt sich das Verhalten aller Dinge, von den kleinsten Teilchen bis zum Universum, einheitlich beschreiben? Der heißeste Kandidat für die Entwicklung einer Weltformel, die alle physikalischen Phänomene erklären kann, ist die Stringtheorie. Sollte sie sich als richtig erweisen, so würde das unser Verständnis über den Ursprung der Naturgesetze dramatisch verändern. Denn das von uns beobachtete Universum wäre dann vermutlich eine winzige Blase in einem viel größeren Gebilde, dem Multiversum. Um die Stringtheorie und die Idee des Multiversums plausibel zu machen, greift der international bekannte theoretische Physiker Dieter Lüst auf ein Modell zurück: das Leben von Fischen in einem Teich. Eines Tages gelingt es den Fischen, die kleinsten Teilchen zu identifizieren, aus denen alles im Fischteich besteht - eingeschlossen sie selbst. Sie nennen diese Urbausteine Quantenfische, da ihr Verhalten nahelegt, dass sie auch eine Art von Lebewesen sind. Doch der ersten folgt eine weitere Entdeckung der Fisch...

  20. Die rol van persoonlikheidstrekke in die weerstand teen stres

    Sonja V. R. van Oudtshoorn

    1988-05-01

    Full Text Available The role of personality characteristics in resistance to stress: A study was conducted to establish whether certain personality characteristics contribute to resistance to stress. Rescue brigadesmen, performing dangerous rescue operations in the goldmining industry, served as basis for the study. The sample consisted of 63 current, 56 ex- and 50 non-brigadesmen. Results indicate that brigadesmen, on the basis of their personality structure, are better equipped to cope with stress. Scores on the 16PF show that they have a lower level of interpersonal anxiety (Factor Q4 and that they are more practical (Factor I, emotionally stable (Factor C, and conscientious (Factor G. These findings support existing knowledge of the 16PF. Opsomming Ten einde vas te stel ofdaar sekere persoonlikheidstrekke bestaan wat bydra tot weerstand teen stres, is 'n studie uitgevoer met reddingspanlede, wat lewensgevaarlike reddingsdiens in die goudmynbedryf verrig, as ondersoekgroep. Die streekproefhet uit 63 huidige, 56 oud-reddingspanlede en 50 amptenare, wat nog nooit aan die span behoort het nie, bestaan. Dit blyk dat reddingspanlede, op grond van hulle persoonlikheidstruktuur, beter toegerus is om stres te hanteer. Tellings op die 16PF toon dat hulle oor 'n laervlakvan interpersoonlike angs beskik, (Faktor Q4, dat hulle meer prakties (Faktor I, emosioneel stabiel (Faktor C en konsensieus is (Faktor G. Hierdie bevindinge sluit aan by die reeds bestaande kennis oor die 16PF.

  1. Nuwe patogene in die voedselbedryf

    M. M. Ehlers

    1996-07-01

    Full Text Available ’n “Nuwe generasie” voedselpatogene het die afgelope jare hul verskyning gemaak en kan 'n ernstige gevaar vir die voedselbedryf inhou. Hierdie organismes is uiters aanpasbaar en bestaande voedselprosesseringstegnieke, veral die verkoeling van voedsel, is nie altyd volkome effektief om hul groei te voorkom nie. Clostridium botulinum tipe E, enterotoksigeniese Eschsrichia coli. Listeria monocytogenes en Aeromonas hydrophila is in staat om in voedsel by 5 °C te groei. Campylobacter jejuni en Brucella kan weer by 5 °C oorleef en 'n derde groep organismes, naamlik Salmonella, Staphylococcus aureus, Vibrio parahaemolyticus en Vibrio vulnificus kan by temperature tussen 5 °C en 12 °C groei en hul teenwoordigheid is ’n aanduiding dat die koueketting verbreek is.

  2. Die Last mit der Lust

    Lutz Sauerteig

    2004-03-01

    Full Text Available Robert Jütte legt mit Lust ohne Last eine umfassende, allgemeinverständliche und spannend zu lesende Geschichte der Empfängnisverhütung von der Antike bis in die unmittelbare Gegenwart vor.

  3. Translational researches on leaf senescence for enhancing plant productivity and quality.

    Guo, Yongfeng; Gan, Su-Sheng

    2014-07-01

    Leaf senescence is a very important trait that limits yield and biomass accumulation of agronomic crops and reduces post-harvest performance and the nutritional value of horticultural crops. Significant advance in physiological and molecular understanding of leaf senescence has made it possible to devise ways of manipulating leaf senescence for agricultural improvement. There are three major strategies in this regard: (i) plant hormone biology-based leaf senescence manipulation technology, the senescence-specific gene promoter-directed IPT system in particular; (ii) leaf senescence-specific transcription factor biology-based technology; and (iii) translation initiation factor biology-based technology. Among the first strategy, the P SAG12 -IPT autoregulatory senescence inhibition system has been widely explored and successfully used in a variety of plant species for manipulating senescence. The vast majority of the related research articles (more than 2000) showed that crops harbouring the autoregulatory system displayed a significant delay in leaf senescence without any abnormalities in growth and development, a marked increase in grain yield and biomass, dramatic improvement in horticultural performance, and/or enhanced tolerance to drought stress. This technology is approaching commercialization. The transcription factor biology-based and translation initiation factor biology-based technologies have also been shown to be very promising and have great potentials for manipulating leaf senescence in crops. Finally, it is speculated that technologies based on the molecular understanding of nutrient recycling during leaf senescence are highly desirable and are expected to be developed in future translational leaf senescence research. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6

    Xu, Shun; Huang, Haijiao; Li, Nanhong; Zhang, Bing; Jia, Yubin; Yang, Yukun; Yuan, Yuan; Xiong, Xing-dong; Wang, Dengchuan; Zheng, Hui-ling [Institute of Aging Research, Guangdong Medical University, Dongguan (China); Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan (China); Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang (China); Liu, Xinguang, E-mail: xgliu64@126.com [Institute of Aging Research, Guangdong Medical University, Dongguan (China); Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan (China); Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang (China)

    2016-05-13

    MicroRNAs are a large class of tiny noncoding RNAs, which have emerged as critical regulators of gene expression, and thus are involved in multiple cellular processes, including cellular senescence. MicroRNA-33 has previously been established to exert crucial effect on cell proliferation, lipid metabolism and cholesterol metabolism. Nonetheless, the association between microRNA-33 and cellular senescence and its underlying molecular mechanism are far to be elucidated. The present study has attempted to probe into the effect of microRNA-33 on MEFs senescence. Our data unveiled that microRNA-33 was dramatically down-regulated in senescent MEFs compared to the young MEFs, and ectopic expression of microRNA-33 promoted MEFs senescence, while knock-down of microRNA-33 exhibited a protective effect against senescence phenotype. Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse. Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33. Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression. -- Highlights: •MicroRNA-33 was dramatically down-regulated in senescent MEF cells. •Altered expression of microRNA-33 exerted a critical role in MEFs senescence. •MicroRNA-33 promoted the replicative senescence of MEFs via targeting of CDK6.

  5. Senescence in the wild: Insights from a long-term study on Seychelles warblers.

    Hammers, Martijn; Kingma, Sjouke A; Bebbington, Kat; van de Crommenacker, Janske; Spurgin, Lewis G; Richardson, David S; Burke, Terry; Dugdale, Hannah L; Komdeur, Jan

    2015-11-01

    Senescence--the progressive age-dependent decline in performance--occurs in most organisms. There is considerable variation in the onset and rate of senescence between and within species. Yet the causes of this variation are still poorly understood, despite being central to understanding the evolution of senescence. Long-term longitudinal studies on wild animals are extremely well-suited to studying the impact of environmental and individual characteristics (and the interaction between the two) on senescence, and can help us to understand the mechanisms that shape the evolution of senescence. In this review, we summarize and discuss the insights gained from our comprehensive long-term individual-based study of the Seychelles warbler (Acrocephalus sechellensis). This species provides an excellent model system in which to investigate the evolution of senescence in the wild. We found that Seychelles warblers show senescent declines in survival and reproduction, and discuss how individual characteristics (body condition, body size) and environmental effects (low- versus high-quality environments) may affect the onset and rate of senescence. Further, we highlight the evidence for trade-offs between early-life investment and senescence. We describe how key cellular and physiological processes (oxidative stress and telomere shortening) underpinning senescence are affected by individual and environmental characteristics in the Seychelles warbler (e.g. food availability, reproductive investment, disease) and we discuss how such physiological variation may mediate the relationship between environmental characteristics and senescence. Based on our work using Seychelles warblers as a model system, we show how insights from long-term studies of wild animals may help unravel the causes of the remarkable variation in senescence observed in natural systems, and highlight areas for promising future research.

  6. MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6

    Xu, Shun; Huang, Haijiao; Li, Nanhong; Zhang, Bing; Jia, Yubin; Yang, Yukun; Yuan, Yuan; Xiong, Xing-dong; Wang, Dengchuan; Zheng, Hui-ling; Liu, Xinguang

    2016-01-01

    MicroRNAs are a large class of tiny noncoding RNAs, which have emerged as critical regulators of gene expression, and thus are involved in multiple cellular processes, including cellular senescence. MicroRNA-33 has previously been established to exert crucial effect on cell proliferation, lipid metabolism and cholesterol metabolism. Nonetheless, the association between microRNA-33 and cellular senescence and its underlying molecular mechanism are far to be elucidated. The present study has attempted to probe into the effect of microRNA-33 on MEFs senescence. Our data unveiled that microRNA-33 was dramatically down-regulated in senescent MEFs compared to the young MEFs, and ectopic expression of microRNA-33 promoted MEFs senescence, while knock-down of microRNA-33 exhibited a protective effect against senescence phenotype. Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse. Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33. Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression. -- Highlights: •MicroRNA-33 was dramatically down-regulated in senescent MEF cells. •Altered expression of microRNA-33 exerted a critical role in MEFs senescence. •MicroRNA-33 promoted the replicative senescence of MEFs via targeting of CDK6.

  7. Premature aging/senescence in cancer cells facing therapy: good or bad?

    Gonzalez, Llilians Calvo; Ghadaouia, Sabrina; Martinez, Aurélie; Rodier, Francis

    2016-02-01

    Normal and cancer cells facing their demise following exposure to radio-chemotherapy can actively participate in choosing their subsequent fate. These programmed cell fate decisions include true cell death (apoptosis-necroptosis) and therapy-induced cellular senescence (TIS), a permanent "proliferative arrest" commonly portrayed as premature cellular aging. Despite a permanent loss of proliferative potential, senescent cells remain viable and are highly bioactive at the microenvironment level, resulting in a prolonged impact on tissue architecture and functions. Cellular senescence is primarily documented as a tumor suppression mechanism that prevents cellular transformation. In the context of normal tissues, cellular senescence also plays important roles in tissue repair, but contributes to age-associated tissue dysfunction when senescent cells accumulate. Theoretically, in multi-step cancer progression models, cancer cells have already bypassed cellular senescence during their immortalization step (see hallmarks of cancer). It is then perhaps surprising to find that cancer cells often retain the ability to undergo TIS, or premature aging. This occurs because cellular senescence results from multiple signalling pathways, some retained in cancer cells, aiming to prevent cell cycle progression in damaged cells. Since senescent cancer cells persist after therapy and secrete an array of cytokines and growth factors that can modulate the tumor microenvironment, these cells may have beneficial and detrimental effects regarding immune modulation and survival of remaining proliferation-competent cancer cells. Similarly, while normal cells undergoing senescence are believed to remain indefinitely growth arrested, whether this is true for senescent cancer cells remains unclear, raising the possibility that these cells may represent a reservoir for cancer recurrence after treatment. This review discusses our current knowledge on cancer cell senescence and highlight questions

  8. pastorale begeleiding aan die persoon met dissosiatiewe ...

    psychological or pastoral by nature. Effective assistance to the person ... INLEIDING. Volgens die kriteria in die DSM-IV2 (Diagnostic and statistical manual of mental disorders, 4th edition) van die APA (American Psychiatric. Association 1995) ...

  9. Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

    Hahn, Hyung Jin; Youn, Hae Jeong; Cha, Hwa Jun; Kim, Karam; An, Sungkwan

    2016-01-01

    Background We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. Objective We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. Methods To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. Results Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. Conclusion These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation. PMID:27489424

  10. Prevention of burn wound conversion by allogeneic keratinocytes cultured on acellular xenodermis

    Matoušková, Eva; Brož, L.; Pokorná, Eva; Königová, R.

    2002-01-01

    Roč. 3, č. 1 (2002), s. 29-35 ISSN 1389-9333 Institutional research plan: CEZ:AV0Z5052915 Keywords : human keratinocytes * tissue engineered skin * dried porcine dermis Subject RIV: EB - Genetics ; Molecular Biology

  11. Acellular porcine xenodermis as a temporary wound cover and substratum for cultured keratinocytes

    Matoušková, Eva; Stehlíček, P.; Veselý, Pavel

    2002-01-01

    Roč. 4, - (2002), s. 83-85 ISSN 1473-2262 Institutional research plan: CEZ:AV0Z5052915 Keywords : wound healing * cultured keratinocytes * dried porcine dermis Subject RIV: EB - Genetics ; Molecular Biology

  12. Keratinocyte-derived growth factors play a role in the formation of hypertrophic scars

    Niessen, FB; Andriessen, MP; Schalkwijk, J; Visser, L; Timens, W

    In predisposed individuals, wound healing can lead to hypertrophic scar or keloid formation, characterized by an overabundant extracellular matrix. It has recently been shown that hypertrophic scars are accompanied by abnormal keratinocyte differentiation and proliferation, and significantly

  13. Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product

    Zheng, Ruijin [Pharmacology and Toxicology and Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Environmental Health Science, New York Medical College, Valhalla, NY (United States); Mishin, Vladimir; Black, Adrienne T. [Pharmacology and Toxicology and Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Shakarjian, Michael P. [Environmental Health Science, New York Medical College, Valhalla, NY (United States); Kong, Ah-Ng Tony; Laskin, Debra L. [Pharmacology and Toxicology and Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2014-03-01

    4-Hydroxynonenal (4-HNE) is a lipid peroxidation end product generated in response to oxidative stress in the skin. Keratinocytes contain an array of antioxidant enzymes which protect against oxidative stress. In these studies, we characterized 4-HNE-induced changes in antioxidant expression in mouse keratinocytes. Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4. In both cell types, HO-1 was the most sensitive, increasing 86–98 fold within 6 h. Further characterization of the effects of 4-HNE on HO-1 demonstrated concentration- and time-dependent increases in mRNA and protein expression which were maximum after 6 h with 30 μM. 4-HNE stimulated keratinocyte Erk1/2, JNK and p38 MAP kinases, as well as PI3 kinase. Inhibition of these enzymes suppressed 4-HNE-induced HO-1 mRNA and protein expression. 4-HNE also activated Nrf2 by inducing its translocation to the nucleus. 4-HNE was markedly less effective in inducing HO-1 mRNA and protein in keratinocytes from Nrf2 −/− mice, when compared to wild type mice, indicating that Nrf2 also regulates 4-HNE-induced signaling. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that 4-HNE-induced HO-1 is localized in keratinocyte caveolae. Treatment of the cells with methyl-β-cyclodextrin, which disrupts caveolar structure, suppressed 4-HNE-induced HO-1. These findings indicate that 4-HNE modulates expression of antioxidant enzymes in keratinocytes, and that this can occur by different mechanisms. Changes in expression of keratinocyte antioxidants may be important in protecting the skin from oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a reactive aldehyde. • 4-HNE induces antioxidant proteins in mouse keratinocytes. • Induction of

  14. The efficient ones; Die Leistungsfaehigen

    Anon.

    2000-06-01

    The increase of output of a solar system where vacuum tube collectors replace flatbed collectors is difficult to calculate exactly. The formula for the calculation of efficiency is the basis of such calculations. Due to evacuation and better insulation the heat loss of vacuum tube collectors is smaller than that of flatbed collectors. This is also evident in the fact that the efficiency curve decreases less steeply as the temperature difference increases. Efficiency remains relatively high. Up to now vacuum tube collectors have been a niche product but more and more companies now sell these efficient collectors.(orig.). [German] Wie stark sich die Leistung der Solaranlage verbessert, wenn man Vakuumroehrenkollektoren (VRK) statt Flachkollektoren einsetzt, laesst sich nur schwer berechnen. Grundlage ist stets die Wirkungsgradformel. Aufgrund der Evakuierung und dadurch besseren Isolierung weisen die VRK deutlich geringere Waermeverluste auf als Flachkollektoren. Dies drueckt sich auch dadurch aus, dass die Wirkungsgradkurve mit wachsender Temperaturdifferenz {delta}{theta} deutlich flacher abfaellt. Der Wirkungsgrad bleibt relativ hoch. Als Hightech-Produkt hatte der Vakuumroehrenkollektor bisher eine typische Marktnische besetzt. Doch immer mehr Anbieter entscheiden sich fuer die Vermarktung dieser leistungsfaehigen Kollektoren. (orig.)

  15. Reparation of damaged forging dies

    Vukić Lazić

    2015-03-01

    Full Text Available The forging dies are in exploitation exposed to elevated temperatures and variable impact loads, both compressive and shear. Steels for manufacturing of these tools must endure those loads while maintaining mechanical properties and being resistant to wear and thermal fatigue. For those reasons, the alloyed steels are used for making the forging dies, though they have less weldability, because alloying increases proneness to hardening. Any reparatory hard facing (HF of the damaged dies would require the specially adjusted technology to the particular piece. In this paper reparatory hard facing of dies used for forging pieces in the automobile industry is considered. Prior to reparatory hard facing of the real tools, numerous experimental hard facings on models were performed. All the model hard facings were done on the same steels which were used for production of the real forging dies. To define the optimal hard facing technology one needs to derive the optimal combination of the adequate heat treatment(s, to select the proper filler metals and the welding procedure. The established optimal HF technology was applied to real forging dies whose service life was further monitored in conditions of exploitation

  16. Uitdagings in die onderrig van evolusie in die lewenswetenskappeklaskamer

    Josef J. de Beer

    2013-02-01

    Full Text Available In hierdie artikel skryf die outeurs oor navorsing wat hulle gedoen het oor onderwysers se siening van die onderrig van evolusie, wat in 2008 as ’n tema in lewenswetenskappe in Suid-Afrikaanse skole ingesluit is. Hierdie vernuwing in die kurrikulum is met gemengde reaksies begroet. Terwyl sommige onderwysers dit met entoesiasme onderrig, is baie gekant teen die onderrig van evolusie. Die artikel is gebaseer op ’n navorsingsprojek waarby 255 onderwysers betrek is. Vraelyste is gebruik om kwalitatiewe data, wat vir diskoers ontleed is, in te samel. Die diskoers van die onderwysers het getoon dat ’n groot getal van hulle nie hul onderrigopdrag kan versoen met hul geloof nie en konsepte oor evolusie as ‘feite’ verduidelik, maar seker maak dat evolusie as ’n teorie gediskrediteer word. Dit het verreikende implikasies vir sowel onderwyseropleiding as kurrikulumontwikkeling. Konseptuele veranderingsteorie word as ’n lens gebruik om na hierdie problematiek te kyk. Challenges in the teaching of evolution in the life sciences classroom. In this article the authors report on research that was conducted about teachers’ views on evolution, which was introduced as a theme in the school life sciences curriculum in 2008. This innovation in the curriculum has been met with mixed reactions. Whereas some teachers embrace this new theme, many teachers are opposed to the teaching of evolution. The article reports on an inquiry that was conducted amongst 255 teachers and in which survey questionnaires were used to collect qualitative data, which was analysed for its discourse. The discourse of the teachers shows that many of them cannot reconcile their religious faith with their teaching and that they may teach the ‘facts’ of evolution, but make sure that they discredit evolution as a theory. This raises serious concerns about teacher education and curriculum development. The authors examine these issues through the lens of conceptual change

  17. Redox regulation of peroxiredoxin and proteinases by ascorbate and thiols during pea root nodule senescence.

    Groten, Karin; Dutilleul, Christelle; van Heerden, Philippus D R; Vanacker, Hélène; Bernard, Stéphanie; Finkemeier, Iris; Dietz, Karl-Josef; Foyer, Christine H

    2006-02-20

    Redox factors contributing to nodule senescence were studied in pea. The abundance of the nodule cytosolic peroxiredoxin but not the mitochondrial peroxiredoxin protein was modulated by ascorbate. In contrast to redox-active antioxidants such as ascorbate and cytosolic peroxiredoxin that decreased during nodule development, maximal extractable nodule proteinase activity increased progressively as the nodules aged. Cathepsin-like activities were constant throughout development but serine and cysteine proteinase activities increased during senescence. Senescence-induced cysteine proteinase activity was inhibited by cysteine, dithiotreitol, or E-64. Senescence-dependent decreases in redox-active factors, particularly ascorbate and peroxiredoxin favour decreased redox-mediated inactivation of cysteine proteinases.

  18. The emerging role of senescent cells in tissue homeostasis and pathophysiology

    Kaoru Tominaga

    2015-05-01

    Full Text Available Cellular senescence is a state of permanent growth arrest and is thought to play a pivotal role in tumor suppression. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis in physiological conditions in vivo. However, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. Both p53/p21 and p16/RB pathways are important for irreversible growth arrest in senescent cells. Senescent cells secret numerous biologically active factors. This specific secretion phenotype by senescent cells may largely contribute to physiological and pathological consequences in organisms. Here I review the molecular basis of cell cycle arrest and the specific secretion phenotype in cellular senescence. I also summarize the current knowledge of the role of cellular senescence in vivo in physiological and pathological settings.

  19. Actuarial senescence in a long-lived orchid challenges our current understanding of ageing.

    Dahlgren, Johan Petter; Colchero, Fernando; Jones, Owen R; Øien, Dag-Inge; Moen, Asbjørn; Sletvold, Nina

    2016-11-16

    The dominant evolutionary theory of actuarial senescence-an increase in death rate with advancing age-is based on the concept of a germ cell line that is separated from the somatic cells early in life. However, such a separation is not clear in all organisms. This has been suggested to explain the paucity of evidence for actuarial senescence in plants. We used a 32 year study of Dactylorhiza lapponica that replaces its organs each growing season, to test whether individuals of this tuberous orchid senesce. We performed a Bayesian survival trajectory analysis accounting for reproductive investment, for individuals under two types of land use, in two climatic regions. The mortality trajectory was best approximated by a Weibull model, showing clear actuarial senescence. Rates of senescence in this model declined with advancing age, but were slightly higher in mown plots and in the more benign climatic region. At older ages, senescence was evident only when accounting for a positive effect of reproductive investment on mortality. Our results demonstrate actuarial senescence as well as a survival-reproduction trade-off in plants, and indicate that environmental context may influence senescence rates. This knowledge is crucial for understanding the evolution of demographic senescence and for models of plant population dynamics. © 2016 The Author(s).

  20. Identification and characterization of secretory proteins during ionizing radiation-induced premature senescence

    Han, Na Kyung; Hong, Mi Na; Jung, Seung Hee; Kang, Kyoung Ah; Lee, Jae Seon; Chi, Seong Gil

    2011-01-01

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated β alactosidase positivity. Recently a large number of molecular phenotypes such as changes in gene expression, protein processing and chromatin organization have been also described. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence. Here, we show that senescent human breast cancer MCF7 cells promote the proliferation, invasion and migration of neighboring cells

  1. Aberrant localization of lamin B receptor (LBR) in cellular senescence in human cells

    Arai, Rumi; En, Atsuki; Ukekawa, Ryo [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Miki, Kensuke [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama 231-0048 (Japan); Fujii, Michihiko, E-mail: mifuji@yokohama-cu.ac.jp [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Ayusawa, Dai [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama 231-0048 (Japan)

    2016-05-13

    5-Bromodeoxyuridine (BrdU), a thymidine analogue, induces cellular senescence in mammalian cells. BrdU induces cellular senescence probably through the regulation of chromatin because BrdU destabilizes or disrupts nucleosome positioning and decondenses heterochromatin. Since heterochromatin is tethered to the nuclear periphery through the interaction with the nuclear envelope proteins, we examined the localization of the several nuclear envelope proteins such as lamins, lamin-interacting proteins, nuclear pore complex proteins, and nuclear transport proteins in senescent cells. We have shown here that lamin B receptor (LBR) showed a change in localization in both BrdU-induced and replicative senescent cells.

  2. Physiological and biochemical aspects of flower development and senescence in Nicotiana plumbaginifolia Viv.

    Nisar Shaziya

    2017-06-01

    Full Text Available Healthy buds of Nicotiana plumbaginifolia growing in the Kashmir University Botanic Garden were selected for the present study. Flower development and senescence was divided into seven stages, viz., tight bud stage (I, mature bud stage (II, pencil stage (III, partially open stage (IV, open stage (V, partially senescent stage (VI and senescent stage (VII. Various physiological and biochemical changes were recorded at each stage of flower development and senescence. Floral diameter, fresh mass, dry mass and water content showed an increase up to flower opening (stage V and thereafter a significant decrease was recorded as the flower development progressed towards senescence through stages VI and VII. An increase in α-amino acids, total phenols and sugars was registered towards anthesis (stage V and a decrease in these parameters was recorded with senescence. Protease activity showed a significant increase towards senescence with a concomitant decrease in soluble proteins. Based on the quantitative analysis of various biochemical parameters, the flower opening in N. plumbaginifolia seems to be accompanied by an increase in the water content, soluble proteins, α‑amino acids and phenols. A decrease in these parameters, besides an increase in protease activity induces senescence in the beautiful flowers of N. plumbaginifolia. Understanding flower senescence may help in improving the postharvest performance of this beautiful ornamental flower to make it a potential material for the floriculture industry.

  3. Identification and characterization of secretory proteins during ionizing radiation-induced premature senescence

    Han, Na Kyung; Hong, Mi Na; Jung, Seung Hee; Kang, Kyoung Ah; Lee, Jae Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chi, Seong Gil [Korea University, Seoul (Korea, Republic of)

    2011-05-15

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated {beta} alactosidase positivity. Recently a large number of molecular phenotypes such as changes in gene expression, protein processing and chromatin organization have been also described. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence. Here, we show that senescent human breast cancer MCF7 cells promote the proliferation, invasion and migration of neighboring cells

  4. The Role of the S40 Gene Family in Leaf Senescence

    Muhammad Jehanzeb

    2017-10-01

    Full Text Available Senescence affect different traits of plants, such as the ripening of fruit, number, quality and timing of seed maturation. While senescence is induced by age, growth hormones and different environmental stresses, a highly organized genetic mechanism related to substantial changes in gene expression regulates the process. Only a few genes associated to senescence have been identified in crop plants despite the vital significance of senescence for crop yield. The S40 gene family has been shown to play a role in leaf senescence. The barley HvS40 gene is one of the senescence marker genes which shows expression during age-dependent as well as dark-induced senescence. Like barley HvS40, the Arabidopsis AtS40-3 gene is also induced during natural senescence as well as in response to treatment with abscisic acid, salicylic acid, darkness and pathogen attack. It is speculated that rice OsS40 has a similar function in the leaf senescence of rice.

  5. The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy

    Markus Schosserer

    2017-11-01

    Full Text Available Cellular senescence describes an irreversible growth arrest characterized by distinct morphology, gene expression pattern, and secretory phenotype. The final or intermediate stages of senescence can be reached by different genetic mechanisms and in answer to different external and internal stresses. It has been maintained in the literature but never proven by clearcut experiments that the induction of senescence serves the evolutionary purpose of protecting the individual from development and growth of cancers. This hypothesis was recently scrutinized by new experiments and found to be partly true, but part of the gene activities now known to happen in senescence are also needed for cancer growth, leading to the view that senescence is a double-edged sword in cancer development. In current cancer therapy, cellular senescence is, on the one hand, intended to occur in tumor cells, as thereby the therapeutic outcome is improved, but might, on the other hand, also be induced unintentionally in non-tumor cells, causing inflammation, secondary tumors, and cancer relapse. Importantly, organismic aging leads to accumulation of senescent cells in tissues and organs of aged individuals. Senescent cells can occur transiently, e.g., during embryogenesis or during wound healing, with beneficial effects on tissue homeostasis and regeneration or accumulate chronically in tissues, which detrimentally affects the microenvironment by de- or transdifferentiation of senescent cells and their neighboring stromal cells, loss of tissue specific functionality, and induction of the senescence-associated secretory phenotype, an increased secretory profile consisting of pro-inflammatory and tissue remodeling factors. These factors shape their surroundings toward a pro-carcinogenic microenvironment, which fuels the development of aging-associated cancers together with the accumulation of mutations over time. We are presenting an overview of well-documented stress

  6. die kasteel••de goede hoop" (1921.1923): die verhaal van in ...

    3. TWEE. KOMITEE-VERGADERINGS. BESLUITE a. Doel en samestelling van die komitee. Op 12 Desember 1921 stuur die Sekretans yap Verdediging uitnodigings aan sekere amptelike instansies en ander behingstd1endes waarin hy die redes vir die wenslikheid van 'n komitee en die werksaamhede uitecnsit en die ge-.

  7. Chrístologie: Die historiese Jesus en die kerugmatiese Christus by ...

    dige Here van sy kerk. Die Christelike teologie en die kerk het dus nie 'n ander oprsprong as wat die Christologiese belydenis van die oer-Christendom het nie, naamlik die paasgebeure. Schmithals (1972b:77) wil kerk en teologie aanmoedig om hierdie oorsprong in gedagte te hou en om goed te besef dat die Christus-.

  8. PROF DR FELIX V. lATEGAN: Die Boer se Roer. Die Groot ...

    PROF DR FELIX V. lATEGAN: Die Boer se. Roer. Die Groot Geweerboek van Suid-. Afrika. Tafelberg. Uitgewers. Kaapstad, pp. 209, bibliografie, register. Sonder die Boer en sy roer is die geskiede:lis van ons land feitlik ondenkbc:wr en dit is clan ook vo/kome juis gesien dat die skrywer van hierdie baanbrekerswerk die ...

  9. Die Energiesicherheit Europas in Bezug auf Erdgas und die Auswirkungen einer Kartellbildung im Gassektor

    Krämer, Luis-Martín

    2011-01-01

    Die Dissertation untersucht die aktuelle Sicherheit der europaeischen Erdgasversorgung. Sie beruecksichtigt zudem die moeglichen Auswirkungen einer Kartellbildung auf die europaeische Gasversorgungssicherheit. Die Arbeit besteht aus einer detaillierten empirischen Studie und darauf aufbauender Szenarioanalyse. Hierzu wird auf den Interdependenzansatz von Robert O. Keohane und Joseph Nye zurueckgegriffen. Zur Darstellung des komplexen Themenbereichs wird auf die Darstellungspraxis der Dichten ...

  10. Paulus as vredemaker. Oor die resepsie van die Brief aan Filemon ...

    7 Jul 2015 ... Inleiding. Die woord 'vrede' kom net een maal in die Filemonbrief voor, en wel in die aanhef van die brief. Kommentatore merk egter gereeld op dat 'n mens nie daaruit moet aflei dat dié begrip onbelangrik vir die verstaan van die brief is nie. Om een voorbeeld te noem: Barth en Blanke. (2002) skryf as volg:.

  11. Die berekening van vloeiing in ’n roterende annulus deur die metode van kunsmatige saamdrukbaarheid

    H. Grobler

    1987-03-01

    Full Text Available Die vloeiing van ’n onsaamdrukbare, viskeuse vloeier word ondersoek aan die hand van die numeriese oplossing van die gediskretiseerde Navier-Stokes- en kontinuiteitsbeheervergelykings. In die besonder word vloeiing in ’n annulus bestaande uit twee koaksiale silinders wat elk ten opsigte van die ander kan roteer, en met ’n voorgeskrewe drukval oor die lengte van die silinder, beskou. Die oplossings word bereken deur die toepassing van Chorin se metode van kunsmatige saamdrukbaarheid, waarin die tydonafhanklike beheervergelykings getransformeer word na tydafhanklike hulpvergelykings deur die invoering van ’n kunsmatige toestandsvergelyking. Die oplossing van die hulpvergelykings konvergeer na ’n stasionêre oplossing, wat ooreenstem met die oplossing van die oorspronklike tydonafhanklike beheervergelykings. Die gedrag van die vloeier, wanneer ten voile ontwikkelde laminêre vloeiing bereik word, is met sukses bereken. ’n Eenvoudige model vir die bepaling van ontwikkeling van vloeiing langs die annulus vir enige gegewe invloeisnelheidsprofiel word voorgestel. Die berekende resultate stem ooreen met die resultate wat uit die fisika van die probleem verwag word.

  12. Comparative studies of types 1 and 2 herpes simplex virus infection of cultured normal keratinocytes.

    Su, S J; Wu, H H; Lin, Y H; Lin, H Y

    1995-01-01

    AIMS--To investigate the differences in biological properties, multiplication patterns, and cytopathic effects between type 1 and type 2 herpes simplex virus (HSV) through the replication of HSV in cultured normal human keratinocytes. METHODS--Keratinocytes were obtained from surgical specimens of normal gingiva, cervix, trunk skin, and newborn foreskin. They were cultured in serum free, chemically defined, culture medium and infected with a pool of HSV collected from clinical specimens. RESU...

  13. Adherence of human oral keratinocytes and gingival fibroblasts to nano-structured titanium surfaces.

    Dorkhan, Marjan; Yücel-Lindberg, Tülay; Hall, Jan; Svensäter, Gunnel; Davies, Julia R

    2014-06-21

    A key element for long-term success of dental implants is integration of the implant surface with the surrounding host tissues. Modification of titanium implant surfaces can enhance osteoblast activity but their effects on soft-tissue cells are unclear. Adherence of human keratinocytes and gingival fibroblasts to control commercially pure titanium (CpTi) and two surfaces prepared by anodic oxidation was therefore investigated. Since implant abutments are exposed to a bacteria-rich environment in vivo, the effect of oral bacteria on keratinocyte adhesion was also evaluated. The surfaces were characterized using scanning electron microscopy (SEM). The number of adhered cells and binding strength, as well as vitality of fibroblasts and keratinocytes were evaluated using confocal scanning laser microscopy after staining with Live/Dead Baclight. To evaluate the effect of bacteria on adherence and vitality, keratinocytes were co-cultured with a four-species streptococcal consortium. SEM analysis showed the two anodically oxidized surfaces to be nano-structured with differing degrees of pore-density. Over 24 hours, both fibroblasts and keratinocytes adhered well to the nano-structured surfaces, although to a somewhat lesser degree than to CpTi (range 42-89% of the levels on CpTi). The strength of keratinocyte adhesion was greater than that of the fibroblasts but no differences in adhesion strength could be observed between the two nano-structured surfaces and the CpTi. The consortium of commensal streptococci markedly reduced keratinocyte adherence on all the surfaces as well as compromising membrane integrity of the adhered cells. Both the vitality and level of adherence of soft-tissue cells to the nano-structured surfaces was similar to that on CpTi. Co-culture with streptococci reduced the number of keratinocytes on all the surfaces to approximately the same level and caused cell damage, suggesting that commensal bacteria could affect adherence of soft-tissue cells to

  14. Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.

    McCoy, Sara S; Reed, Tamra J; Berthier, Celine C; Tsou, Pei-Suen; Liu, Jianhua; Gudjonsson, Johann E; Khanna, Dinesh; Kahlenberg, J Michelle

    2017-11-01

    SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  15. Influence of ion implantation on the adhesion and grow of human keratinocytes

    Walachova, K.; Svorcik, V.; Dvorakova, B.; Vogtova, D.

    1999-01-01

    Interaction of keratinocytes with polymer modified by ion implantation was studied with the possibility of cultivate these cells for regeneration of dermal cover, for example, heavy burned persons. The modification on polyethylene (PE) with 100 μm thickness was processed by implantation the Ar + ions with the energy 63 keV and Xe + ions with the energy 156 keV. Some characteristics of superficial modified layers and influence of ion implantation on the adhesion and proliferation of keratinocytes were studied

  16. Die kritiek van tradisie en die tradisie van kritiek in die Geesteswetenskappe. 'n Rekonstruksie van die debat tussen Habermas en Gadamer

    Duvenage, Pieter

    2013-01-01

    In hierdie bydrae word die bekende debat (1967-1971) tussen Jürgen Habermas en Hans-Georg Gadamer gerekonstrueer. Die debat word hier in noue samehang met die kwessie van die geesteswetenskappe gelees. Die bydrae val in vier dele uiteen. In die eerste afdeling word Habermas se opening tot die debat in vyf onderafdelings uiteengesit. Dit gaan hier oor Gadamer se verdediging van tradisie en Habermas se kritiek op die begrip (1.1). In antwoord op Gadamer se begrip van tradisie ontwerp Habermas s...

  17. Enkele opmerkings oor die intrinsieke waarde van die Latynse teks van Kodeks Bezae as herstelbron vir die Griekse teks van die Nuwe Testament

    G. J.C. Jordaan

    1985-05-01

    Full Text Available Een van die belangrikste oud-Latynse vertalings word gevind in Kodeks Bezae, ’n vyfde-eeuse manuskrip van die vier Evangelies. Kodeks Bezae bevat ’n Griekse teks (D en ’n Latynse teks (d van die Evangelies langs mekaar, die Latynse teks in ’n lettertipe wat baie aan die Griekse majuskelskrif herinner. Wat hierdie dokument so merkwaardig maak, is die feit dat dit die enigste manuskrip is wat ’n Griekse Evangelie-teks uit die Westerse teksfamilie bevat.

  18. Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis.

    Simon, Franck; Bergeron, Daniele; Larochelle, Sébastien; Lopez-Vallé, Carlos A; Genest, Hervé; Armour, Alexis; Moulin, Véronique J

    2012-05-01

    Hypertrophic scars are a pathological process characterized by an excessive deposition of extracellular matrix components. Using a tissue-engineered reconstructed human skin (RHS) method, we previously reported that pathological keratinocytes induce formation of a fibrotic dermal matrix. We further investigated keratinocyte action using conditioned media. Results showed that conditioned media induce a similar action on dermal thickness similar to when an epidermis is present. Using a two-dimensional electrophoresis technique, we then compared conditioned media from normal or hypertrophic scar keratinocytes and determined that TIMP-1 was increased in conditioned media from hypertrophic scar keratinocytes. This differential profile was confirmed using ELISA, assaying TIMP-1 presence on media from monolayer cultured keratinocytes and from RHS. The dermal matrix of these RHS was recreated using mesenchymal cells from three different origins (skin, wound and hypertrophic scar). The effect of increased TIMP-1 levels on dermal fibrosis was also validated independently from the mesenchymal cell origin. Immunodetection of TIMP-1 showed that this protein was increased in the epidermis of hypertrophic scar biopsies. The findings of this study represent an important advance in understanding the role of keratinocytes as a direct potent modulator for matrix degradation and scar tissue remodeling, possibly through inactivation of MMPs. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

  19. Fos and jun proteins are specifically expressed during differentiation of human keratinocytes.

    Mehic, Denis; Bakiri, Latifa; Ghannadan, Minoo; Wagner, Erwin F; Tschachler, Erwin

    2005-01-01

    Activator protein 1 (AP-1) proteins play key roles in the regulation of cell proliferation and differentiation. In this study we investigated the expression of Fos and Jun proteins in different models of terminal differentiation of human keratinocytes and in skin from psoriasis patients. All Jun and Fos proteins, with the exception of FosB, were efficiently expressed in keratinocytes in monolayer cultures. In contrast, in normal epidermis as well as in organotypic epidermal cultures, the expression pattern of AP-1 proteins was dependent on the differentiation stage. Fos proteins were readily detected in nuclei of keratinocytes of basal and suprabasal layers. JunB and JunD were expressed in all layers of normal epidermis. Interestingly, expression of c-Jun started suprabasally, then disappeared and became detectable again in distinct cells of the outermost granular layer directly at the transition zone to the stratum corneum. In psoriatic epidermis, c-Jun expression was prominent in both hyperproliferating basal and suprabasal keratinocytes, whereas c-Fos expression was unchanged. These data indicate that AP-1 proteins are expressed in a highly specific manner during terminal differentiation of keratinocytes and that the enhanced expression of c-Jun in basal and suprabasal keratinocytes might contribute to the pathogenesis of psoriasis.

  20. Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro.

    Bayer, Andreas; Tohidnezhad, Mersedeh; Berndt, Rouven; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Simanski, Maren; Gläser, Regine; Harder, Jürgen

    2018-01-01

    Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF ® ) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds. Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation. Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays. Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. AKT delays the early-activated apoptotic pathway in UVB-irradiated keratinocytes via BAD translocation.

    Claerhout, Sofie; Decraene, David; Van Laethem, An; Van Kelst, Sofie; Agostinis, Patrizia; Garmyn, Marjan

    2007-02-01

    Upon irradiation with a high dose of UVB, keratinocytes undergo apoptosis as a protective mechanism. In previous work, we demonstrated the existence of an early-activated UVB-induced apoptotic pathway in growth factor-depleted human keratinocytes, which can be substantially delayed by the exclusive supplementation of IGF-1. We now show that in human keratinocytes, IGF-1 inhibits the onset of UVB-triggered apoptosis through a transcriptional independent, AKT-mediated mechanism, involving BAD serine 136 phosphorylation. Our results show that the early UVB-induced apoptosis in growth factor-depleted human keratinocytes is exclusively triggered through the mitochondrial pathway. It is accompanied by BAX translocation, cytochrome c release, and procaspase-9 cleavage, but not by procaspase-8 or BID cleavage. In human keratinocytes, IGF-1 supplementation inhibits these events in a transcription-independent manner. Both IGF-1 supplementation and the transduction of a membrane-targeted form of AKT result in a shift of the BH3-only protein BAD from the mitochondria to the cytoplasm, paralleled by an increase of AKT-specific Ser136 phospho-BAD bound to 14-3-3zeta protein. These data indicate that AKT-induced BAD phosphorylation and its subsequent cytoplasmic sequestration by 14-3-3zeta is a major mechanism responsible for the postponement of UVB-induced apoptosis in human keratinocytes.

  2. Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor

    Matsumoto, K.; Hashimoto, K.; Yoshikawa, K.; Nakamura, T.

    1991-01-01

    Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes

  3. Smad4 disruption accelerates keratinocyte reepithelialization in murine cutaneous wound repair.

    Yang, Leilei; Li, Wenlong; Wang, Shaoxia; Wang, Lijuan; Li, Yang; Yang, Xiao; Peng, Ruiyun

    2012-10-01

    Keratinocyte reepithelialization is a rate-limiting event in cutaneous wound repair, which involves the migration and proliferation of keratinocytes to cover the denuded dermal surface. Transforming growth factor-β1 (TGF-β1) has the ability to induce epithelial cell migration while inhibiting proliferation, and controversial results have been generated regarding the effect of TGF-β signaling on reepithelialization. In this study, full-thickness skin wounds were made in keratinocyte-specific Smad4 knockout and the control mice. The wound closure, reepithelialization, keratinocyte proliferation, myofibroblast numbers and collagen deposition of were assessed. The results showed that the proliferation of keratinocytes increased, which accelerated the reepithelialization, and led to faster wound repair in the epidermis of Smad4 mutant mice. Upregulation of keratin 17, 14-3-3 sigma and phosphorylated AKT in the hyperproliferative epidermis may be correlated with the accelerated reepithelialization. We conclude that Smad4 plays an inhibitory role in the keratinocyte-mediated reepithelialization of wound healing.

  4. Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

    Kioka, Noriyuki; Ito, Takuya; Yamashita, Hiroshi; Uekawa, Natsuko; Umemoto, Tsutomu; Motoyoshi, Soh; Imai, Hiroshi; Takahashi, Kenzo; Watanabe, Hideto; Yamada, Masayasu; Ueda, Kazumitsu

    2010-01-01

    In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantially suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.

  5. Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes.

    Sayedyahossein, Samar; Nini, Lylia; Irvine, Timothy S; Dagnino, Lina

    2012-10-01

    Phagocytic melanosome uptake by epidermal keratinocytes is a central protective mechanism against damage induced by ultraviolet radiation. Phagocytosis requires formation of pseudopodia via actin cytoskeleton rearrangements. Integrin-linked kinase (ILK) is an important modulator of actin cytoskeletal dynamics. We have examined the role of ILK in regulation of phagocytosis, using epidermal keratinocytes isolated from mice with epidermis-restricted Ilk gene inactivation. ILK-deficient cells exhibited severely impaired capacity to engulf fluorescent microspheres in response to stimulation of the keratinocyte growth factor (KGF) receptor or the protease-activated receptor-2. KGF induced ERK phosphorylation in ILK-expressing and ILK-deficient cells, suggesting that ILK is not essential for KGF receptor signaling. In contrast, KGF promoted activation of Rac1 and formation of pseudopodia in ILK-expressing, but not in ILK-deficient cells. Rac1-deficient keratinocytes also showed substantially impaired phagocytic ability, underlining the importance of ILK-dependent Rac1 function for particle engulfment. Finally, cross-modulation of KGF receptors by integrins may be another important element, as integrin β1-deficient keratinocytes also fail to show significant phagocytosis in response to KGF. Thus, we have identified a novel signaling pathway essential for phagocytosis in keratinocytes, which involves ILK-dependent activation of Rac1 in response to KGF, resulting in the formation of pseudopodia and particle uptake.

  6. Ca2+-dependent localization of integrin-linked kinase to cell junctions in differentiating keratinocytes.

    Vespa, Alisa; Darmon, Alison J; Turner, Christopher E; D'Souza, Sudhir J A; Dagnino, Lina

    2003-03-28

    Integrin complexes are necessary for proper proliferation and differentiation of epidermal keratinocytes. Differentiation of these cells is accompanied by down-regulation of integrins and focal adhesions as well as formation of intercellular adherens junctions through E-cadherin homodimerization. A central component of integrin adhesion complexes is integrin-linked kinase (ILK), which can induce loss of E-cadherin expression and epithelial-mesenchymal transformation when ectopically expressed in intestinal and mammary epithelia. In cultured primary mouse keratinocytes, we find that ILK protein levels are independent of integrin expression and signaling, since they remain constant during Ca(2+)-induced differentiation. In contrast, keratinocyte differentiation is accompanied by marked reduction in kinase activity in ILK immunoprecipitates and altered ILK subcellular distribution. Specifically, ILK distributes in close apposition to actin fibers along intercellular junctions in differentiated but not in undifferentiated keratinocytes. ILK localization to cell-cell borders occurs independently of integrin signaling and requires Ca(2+) as well as an intact actin cytoskeleton. Further, and in contrast to what is observed in other epithelial cells, ILK overexpression in differentiated keratinocytes does not promote E-cadherin down-regulation and epithelial-mesenchymal transition. Thus, novel tissue-specific mechanisms control the formation of ILK complexes associated with cell-cell junctions in differentiating murine epidermal keratinocytes.

  7. Derivation of keratinocytes from chicken embryonic stem cells: Establishment and characterization of differentiated proliferative cell populations

    Mathilde Couteaudier

    2015-03-01

    Full Text Available A common challenge in avian cell biology is the generation of differentiated cell-lines, especially in the keratinocyte lineage. Only a few avian cell-lines are available and very few of them show an interesting differentiation profile. During the last decade, mammalian embryonic stem cell-lines were shown to differentiate into almost all lineages, including keratinocytes. Although chicken embryonic stem cells had been obtained in the 1990s, few differentiation studies toward the ectodermal lineage were reported. Consequently, we explored the differentiation of chicken embryonic stem cells toward the keratinocyte lineage by using a combination of stromal induction, ascorbic acid, BMP4 and chicken serum. During the induction period, we observed a downregulation of pluripotency markers and an upregulation of epidermal markers. Three homogenous cell populations were derived, which were morphologically similar to chicken primary keratinocytes, displaying intracellular lipid droplets in almost every pavimentous cell. These cells could be serially passaged without alteration of their morphology and showed gene and protein expression profiles of epidermal markers similar to chicken primary keratinocytes. These cells represent an alternative to the isolation of chicken primary keratinocytes, being less cumbersome to handle and reducing the number of experimental animals used for the preparation of primary cells.

  8. Die gebruik van die mite in Die werfbobbejaan van Alexander Strachan

    E. M.M. Klopper

    1996-05-01

    Full Text Available The use of myths in Die werfbobbejaan by Alexander Strachan This article focuses on the rote of Zulu myths in Alexander Strachan’s novel Die werfbobbejaan. It lakes as point of departure sources on mythology like Cuddon (1991, Baldick (1990, Grimal (1969, Levi-Strauss (1979 and Jung (1969. Die werfbobbejaan essentially recounts the story of a man (the adventurer, the academic, the writer, the hunter who also is the central character in Strachan's two preceding novels. Die werfbobbejaan focuses on the completion of an individuation process in the life of the central character, a process already begun in the preceding two novels and which in this novel finally culminates in the confrontation between hunter and baboon. The completion of this process is facilitated by the African milieu of Zululand where people give meaning to their existence by means of myths, and where no distinction is made between the mythic and rational modes of experiencing reality.

  9. Die rol van die onderwys in die handhawing en uitbouing van ons volkskultuur

    G.J. Jordaan

    1970-03-01

    Full Text Available Op die oog af lyk dit ’n baie maklike onderwerp, maar hoe meer 'n mens daaroor nadink hoe ingewikkelder en omvangryker word die implikasies wat verband hou. Dit is veral so omdat dit hier voor alles gaan om eerste fundamentele uitgangspunte, dit wil sê, om lewens- en wêreldbeskouing. Dit geld van albei komponente — van onderwys sowel as van kultuur.

  10. Die vraag na ’n nuwe belydenisskrif

    J. H. van Wyk

    1974-05-01

    Full Text Available Die mees bekende reformatoriese belydenisskrifte dateer uit die sestiende en sewentiende eeue (E 16—17 en is dus almal 300 tot 400 jaar oud: Die Galliese Konfessie 1559, die Nederlandse Geloofsbelydenis 1561, die Heidelbergse Kategismus 1563, die 39 Articles 1563, die Tweede Helvietiese Konfessie 1566, die Dordtse Leerreëls 1619, die Westminsterse Konfessie 1646.

  11. as by die huisbesoek. HP WOLMARANS. PROF. DR. SP ...

    Test

    van 'n evangeüedienaar wat alles fei! gehad het vir die werk en werk kring waartoe God hom geroep het. Hy is dan ook werklik die eerste grondlegger van die gemeente in Zoutpansberg en die man wat dit opgewerk het. Die geskiedenis van Hofmeyer is die geskiedenis van die kerk- vereniging en die redes waarom die ...

  12. Die krisis van ongeloof in Numeri 13-14

    Die ver- haal gebruik die aanloklikheid van die land as 'n submotief om 'n groter drama uit te beeld: die konflik tussen Israel en sy God. ISSN 0259 9422 ... In aansluiting by Eksodus 34 laat die liefde en trou van die Here aan Horn die ...... langs die weg van die tema van veertig jaar dat 'de hoofdstukken 13-14 een sleutel-.

  13. MicroRNA Regulation of Ionizing Radiation-Induced Premature Senescence

    Wang Yong; Scheiber, Melissa N.; Neumann, Carola; Calin, George A.; Zhou Daohong

    2011-01-01

    Purpose: MicroRNAs (miRNAs) have emerged as critical regulators of many cellular pathways. Ionizing radiation (IR) exposure causes DNA damage and induces premature senescence. However, the role of miRNAs in IR-induced senescence has not been well defined. Thus, the purpose of this study was to identify and characterize senescence-associated miRNAs (SA-miRNAs) and to investigate the role of SA-miRNAs in IR-induced senescence. Methods and Materials: In human lung (WI-38) fibroblasts, premature senescence was induced either by IR or busulfan (BU) treatment, and replicative senescence was accomplished by serial passaging. MiRNA microarray were used to identify SA-miRNAs, and real-time reverse transcription (RT)-PCR validated the expression profiles of SA-miRNAs in various senescent cells. The role of SA-miRNAs in IR-induced senescence was characterized by knockdown of miRNA expression, using anti-miRNA oligonucleotides or by miRNA overexpression through the transfection of pre-miRNA mimics. Results: We identified eight SA-miRNAs, four of which were up-regulated (miR-152, -410, -431, and -493) and four which were down-regulated (miR-155, -20a, -25, and -15a), that are differentially expressed in both prematurely senescent (induced by IR or BU) and replicatively senescent WI-38 cells. Validation of the expression of these SA-miRNAs indicated that down-regulation of miR-155, -20a, -25, and -15a is a characteristic miRNA expression signature of cellular senescence. Functional analyses revealed that knockdown of miR-155 or miR-20a, but not miR-25 or miR-15a, markedly enhanced IR-induced senescence, whereas ectopic overexpression of miR-155 or miR-20a significantly inhibited senescence induction. Furthermore, our studies indicate that miR-155 modulates IR-induced senescence by acting downstream of the p53 and p38 mitogen-activated protein kinase (MAPK) pathways and in part via regulating tumor protein 53-induced nuclear protein 1 (TP53INP1) expression. Conclusion: Our

  14. Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

    Gokhan Yildiz

    Full Text Available Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal" by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15

  15. Generation of organotypic raft cultures from primary human keratinocytes.

    Anacker, Daniel; Moody, Cary

    2012-02-22

    The development of organotypic epithelial raft cultures has provided researchers with an efficient in vitro system that faithfully recapitulates epithelial differentiation. There are many uses for this system. For instance, the ability to grow three-dimensional organotypic raft cultures of keratinocytes has been an important milestone in the study of human papillomavirus (HPV)(1). The life cycle of HPV is tightly linked to the differentiation of squamous epithelium(2). Organotypic epithelial raft cultures as demonstrated here reproduce the entire papillomavirus life cycle, including virus production(3,4,5). In addition, these raft cultures exhibit dysplastic lesions similar to those observed upon in vivo infection with HPV. Hence this system can also be used to study epithelial cell cancers, as well as the effect of drugs on epithelial cell differentiation in general. Originally developed by Asselineau and Prunieras(6) and modified by Kopan et al.(7), the organotypic epithelial raft culture system has matured into a general, relatively easy culture model, which involves the growth of cells on collagen plugs maintained at an air-liquid interface (Figure 1A). Over the course of 10-14 days, the cells stratify and differentiate, forming a full thickness epithelium that produces differentiation-specific cytokeratins. Harvested rafts can be examined histologically, as well as by standard molecular and biochemical techniques. In this article, we describe a method for the generation of raft cultures from primary human keratinocytes. The same technique can be used with established epithelial cell lines, and can easily be adapted for use with epithelial tissue from normal or diseased biopsies(8). Many viruses target either the cutaneous or mucosal epithelium as part of their replicative life cycle. Over the past several years, the feasibility of using organotypic raft cultures as a method of studying virus-host cell interactions has been shown for several herpesviruses, as

  16. Podoplanin expression in peritumoral keratinocytes predicts aggressive behavior in extramammary Paget's disease.

    Cho, Zaigen; Konishi, Eiichi; Kanemaru, Mai; Isohisa, Taro; Arita, Takahiro; Kawai, Minako; Tsutsumi, Miho; Mizutani, Hiromi; Takenaka, Hideya; Ozawa, Toshiyuki; Tsuruta, Daisuke; Katoh, Norito; Asai, Jun

    2017-07-01

    Recent studies have demonstrated podoplanin expression in several tumors, which has been associated with lymph node metastasis and poor prognosis. Podoplanin expression in peritumoral cells such as cancer-associated fibroblasts also correlates with tumor progression in several cancers. However, podoplanin expression and its association with extramammary Paget's disease (EMPD) remain unclear. In this study, we examined whether the presence of podoplanin expression in tumor cells or peritumoral basal keratinocytes correlated with aggressive behavior in patients with EMPD and investigated the mechanisms of podoplanin-mediated tumor invasion in this disorder. Skin samples of 37 patients with EMPD were investigated by immunohistochemical analysis. The functions of podoplanin in keratinocytes were examined in vitro by RT-PCR and with invadopodia gelatin-degradation assays using HaCaT cells. Podoplanin was not identified in tumor cells in all cases. Podoplanin expression in peritumoral basal keratinocytes was observed in 25 patients (67.6%). In in situ EMPD, 50% of cases (9 in 18) exhibited podoplanin-positive keratinocytes, whereas 84.2% (16 in 19) demonstrated positive staining in invasive EMPD (P<0.05). Podoplanin expression in peritumoral keratinocytes was also associated with tumor thickness (P<0.005). By immunohistochemical analysis, podoplanin-positive peritumoral keratinocytes were found to be negative for E-cadherin, one of the major adhesion molecules of keratinocytes, which might contribute to tumor invasion into the dermis through a crack in the basal cell layer induced by down-regulation of cell adhesion therein. We further found that podoplanin-positive keratinocytes exhibited invadopodia, which are thought to function in the migration of cancer cells through tissue barriers, indicating that podoplanin-positive peritumoral basal keratinocytes might assist tumor invasion by degrading the extracellular matrix. The presence of podoplanin expression in

  17. RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3-dependent control of STAT1

    Pedersen, Esben Ditlev Kølle; Wang, Zhipeng; Stanley, Alanna

    2012-01-01

    Crosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin, and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays...... hypersensitive to inflammatory stimuli both in vitro and in vivo, suggesting a major role for RAC1 in regulating the crosstalk between the epidermis and the immune system....

  18. Gene expression studies on human keratinocytes transduced with human growth hormone gene for a possible utilization in gene therapy

    Mathor, Monica Beatriz.

    1994-01-01

    Taking advantage of the recent progress in the DNA-recombinant techniques and of the potentiality of normal human keratinocytes primary culture to reconstitute the epidermis, it was decided to genetically transform these keratinocytes to produce human growth hormone under controllable conditions that would be used in gene therapy at this hormone deficient patients. The first step to achieve this goal was to standardize infection of keratinocytes with retrovirus producer cells containing a construct which included the gene of bacterial b-galactosidase. The best result was obtained cultivating the keratinocytes for 3 days in a 2:1 mixture of retrovirus producer cells and 3T3-J2 fibroblasts irradiated with 60 Gy, and splitting these infected keratinocytes on 3T3-J2 fibroblasts feeder layer. Another preliminary experiment was to infect normal human keratinocytes with interleukin-6 gene (hIL-6) that, in pathologic conditions, could be reproduced by keratinocytes and secreted to the blood stream. Thus, we verify that infected keratinocytes secrete an average amount of 500 ng/10 6 cell/day of cytokin during the in vitro life time, that certify the stable character of the injection. These keratinocytes, when grafted in mice, secrete hIL-6 to the blood stream reaching levels of 40 pg/ml of serum. After these preliminary experiments, we construct a retroviral vector with the human growth hormone gene (h GH) driven by human metallothionein promoter (h PMT), designated DChPMTGH. Normal human keratinocytes were infected with DChPMTGH producer cells, following previously standardized protocol, obtaining infected keratinocytes secreting to the culture media 340 ng h GH/10 6 cell/day without promoter activation. This is the highest level of h GH secreted in human keratinocytes primary culture described in literature. The h GH value increases approximately 10 times after activation with 100 μM Zn +2 for 8-12 hours. (author). 158 refs., 42 figs., 6 tabs

  19. H{sup +}/peptide transporter (PEPT2) is expressed in human epidermal keratinocytes and is involved in skin oligopeptide transport

    Kudo, Michiko; Katayoshi, Takeshi; Kobayashi-Nakamura, Kumiko [DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba 261-0025 (Japan); Akagawa, Mitsugu [Department of Biological Chemistry, Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531 (Japan); Tsuji-Naito, Kentaro, E-mail: knaito@dhc.co.jp [DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba 261-0025 (Japan)

    2016-07-08

    Peptide transporter 2 (PEPT2) is a member of the proton-coupled oligopeptide transporter family, which mediates the cellular uptake of oligopeptides and peptide-like drugs. Although PEPT2 is expressed in many tissues, its expression in epidermal keratinocytes remains unclear. We investigated PEPT2 expression profile and functional activity in keratinocytes. We confirmed PEPT2 mRNA expression in three keratinocyte lines (normal human epidermal keratinocytes (NHEKs), immortalized keratinocytes, and malignant keratinocytes) by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. In contrast to PEPT1, PEPT2 expression in the three keratinocytes was similar or higher than that in HepG2 cells, used as PEPT2-positive cells. Immunolocalization analysis using human skin showed epidermal PEPT2 localization. We studied keratinocyte transport function by measuring the oligopeptide content using liquid chromatography/tandem mass spectrometry. Glycylsarcosine uptake in NHEKs was pH-dependent, suggesting that keratinocytes could absorb small peptides in the presence of an inward H{sup +} gradient. We also performed a skin-permeability test of several oligopeptides using skin substitute, suggesting that di- and tripeptides pass actively through the epidermis. In conclusion, PEPT2 is expressed in keratinocytes and involved in skin oligopeptide uptake. -- Highlights: •PEPT2 is expressed in keratinocytes, which are more common than other skin cells. •Immunolocalization analysis using human skin revealed epidermal PEPT2 localization. •Keratinocytes could absorb small peptides in the presence of an inward H{sup +} gradient. •Di- and tripeptide pass actively through the epidermis.

  20. Sun Ginseng Protects Endothelial Progenitor Cells From Senescence Associated Apoptosis

    Im, Wooseok; Chung, Jin-Young; Bhan, Jaejun; Lim, Jiyeon; Lee, Soon-Tae; Chu, Kon; Kim, Manho

    2012-01-01

    Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside Rg3 prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG), which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by β-galactosidase (β-gal) staining. Staining with 4′-6-Diamidino-2-phenylindole verified that most adherent cells (93±2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of β-gal-positive EPCs was decreased from 93.8±2.0% to 62.5±3.6% by SG treatment. A fluorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms. PMID:23717107

  1. Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease

    Zhen Wei

    2016-01-01

    Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.

  2. Cytokine expression and signaling in drug-induced cellular senescence

    Nováková, Zora; Hubáčková, Soňa; Košař, Martin; Janderová-Rossmeislová, Lenka; Dobrovolná, Jana; Vašicová, Pavla; Vančurová, Markéta; Hořejší, Zuzana; Hozák, Pavel; Bartek, Jiří; Hodný, Zdeněk

    2010-01-01

    Roč. 29, č. 2 (2010), s. 273-284 ISSN 0950-9232 R&D Projects: GA AV ČR IAA500390501; GA ČR GA204/08/1418; GA MŠk LC545 Grant - others:EC(XE) TRIREME Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : cellular senescence * cytokines * JAK/STAT signaling pathway Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.414, year: 2010

  3. Der Nahostkonflikt und die Medien

    Carola Richter

    2014-06-01

    Full Text Available Diese Einführung in eine Themenausgabe zu den vielfältigen Rollen der Medien im Nahostkonflikt skizziert die Probleme, die sich für Medien und Journalisten als Akteure im Konflikt, Adressaten der Konfliktparteien und Anlass für Konflikt durch ihre Berichterstattung ergeben. Das Konfliktgebiet Israel und Palästina ist sowohl für Forschung über Auslandsbericht-erstattung, über transnationale Agenda Building- und Public Diplomacy-Prozesse als auch über mediensystemische Entwicklungen in Besatzer- und Besatzungsgebieten interessant. Der Artikel gibt einen Überblick über das Feld und führt dabei in die in der Themenausgabe präsentierten empirischen Studien zum Nahostkonflikt und den Medien ein.

  4. DIE VRYWILLIGERSMAGTE VAN GRIEKWALAND-WES

    teen gekant was, is dit op 15 Oktober 1880 by die Kaapkolonie ingelyf.9. Gedurende sy kortstondige bestaan van minder as 'n dekade lank het die kroonkolonie Griekwa- land-Wes met talle finansiele, ekonomiese, so- siale en ander probleme te doen gehad. Een van die ernstige probleme was die bedreiging wat.

  5. Die Gereformeerde Ekumeniese Sinode en Sending 1984

    opvatting. Indien 'n mens al die kerke wat aan die Gereformeerde. Ekumeniese Sinode (GES) behoort een vir een sendingmatig sal be- studeer, sal daar waarskynlik 'n sterk differensiasie tussen sommige kerke aan die lig kom. Die GES kan dus nie verantwoordelik gehou word vir individuele kerke se sendingopvatting nie.

  6. voorgeskiedenis tot die stigting van 'n unieverdedigingsmag

    gesien nie en toe die wetsontwerp op 23 Februa- rie 1912 deur Smuts in sy hoedanigheid as Mi- nister van Verdediging ingedien is, het Beyers heelwat kritiek daarop gehad. Beyers het be- weer dat dit op vergaderings geblyk het dat die volk wou he Engeland moet steeds die verdedi- ging waarneem aangesien die Unie ...

  7. Moderne diskoerse in die teologie vandag

    J.H. van Wyk

    2013-05-01

    Full Text Available In hierdie artikel word aandag gevra vir enkele moderne diskoerse in die teologie vandag. Volgens die outeur staan die vrae oor God, Jesus, die mens en die aarde in die sentrum van belangstelling en oorheers dit in ’n groot mate die teologiese debat. Die opkoms van die moderne aggressiewe ateïsme, die wetenskaplike navorsing oor die historiese Jesus, die groeiende vrae oor die mens en die menslike samelewing, asook die dreigende ekologiese krisis op aarde, sorg vir nuwe debatte van ongekende omvang. Die outeur bespreek hierdie debatte oorsigtelik, met kritiek waar nodig, en sluit af met enkele rigtingwysers van wat hy as ‘goeie teologie’ verstaan. In this article attention is paid to some modern discourses in theology today. According to the author the questions about God, Jesus, man and the earth are in the centre of interest and to a large extent dominate the theological debate. The rise of modern aggressive atheism, the scientific research on the historic Jesus, the growing questions about man and human society as well as the threatening ecological crisis on earth, provide new discourses of unparalleled magnitude. The author provides a broad summary of these discourses, with criticism where necessary, and concludes with some indicators of his view what can be called ‘good theology’.

  8. DIE BEPERKING VAN MULTIOVULASIES IN KARAKOELOOIE NA ...

    Die geboorte van meer as 2 lammers per ooi is egter ongewens in die Karakoelbedryf aangesien dit aanleiding gee tot kleiner pelse veral wanneer voedingstoestande nie opti- maal is nie. In stoetteling is selfs tweelinge nie gewens nie, aangesien die ware fenotipiese waarde van die lammers nie in tweelinge te voorskyn ...

  9. Calvyn en die kerklike orde: Enkele opmerkings

    Om dié saak verder te belig word ook van die latere uitsprake van Calvyn in hierdie verband in berekening gebring. Met hierdie beperkte studie word dus in die eerste plek die feit in herinnering geroep dat dit vanjaar 450 jaar gelede is dat Calvyn se. Institusie die eerste maal in Basel verskyn het. Terselfdertyd word hier-.

  10. Rab11b mediates melanin transfer between donor melanocytes and acceptor keratinocytes via coupled exo/endocytosis.

    Tarafder, Abul K; Bolasco, Giulia; Correia, Maria S; Pereira, Francisco J C; Iannone, Lucio; Hume, Alistair N; Kirkpatrick, Niall; Picardo, Mauro; Torrisi, Maria R; Rodrigues, Inês P; Ramalho, José S; Futter, Clare E; Barral, Duarte C; Seabra, Miguel C

    2014-04-01

    The transfer of melanin from melanocytes to keratinocytes is a crucial process underlying maintenance of skin pigmentation and photoprotection against UV damage. Here, we present evidence supporting coupled exocytosis of the melanin core, or melanocore, by melanocytes and subsequent endocytosis by keratinocytes as a predominant mechanism of melanin transfer. Electron microscopy analysis of human skin samples revealed three lines of evidence supporting this: (1) the presence of melanocores in the extracellular space; (2) within keratinocytes, melanin was surrounded by a single membrane; and (3) this membrane lacked the melanosomal membrane protein tyrosinase-related protein 1 (TYRP1). Moreover, co-culture of melanocytes and keratinocytes suggests that melanin exocytosis is specifically induced by keratinocytes. Furthermore, depletion of Rab11b, but not Rab27a, caused a marked decrease in both keratinocyte-stimulated melanin exocytosis and transfer to keratinocytes. Thus, we propose that the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes.

  11. Leerteoretiese basis van die andragogie

    C. J. A. Simpson

    1991-06-01

    Full Text Available Learning theory basis of andragogy. A cursory glance at andragogy creates the impression that humanistic learning theory plays an all encompassing role in the learner centered approach andragogy espouses. A closer look, however, reveals that Knowles (1973, after having made an intensive study of learning theory, created an extensive framework within which human resource development can take place. The fact that Knowles attracted critique from different areas, led to a need to ascertain the role different learning theories, if any, played in the emergence of andragogy. Having looked at the assumptions displayed by the andragogical approach, as well as a comparison of different learning theories and their connection with andragogy, it became clear that andragogy contains elements of various learning theories in an adapted way. These adaptations resulted in an approach to adult education in which learners are given the opportunity to be part of the learning process in such a way that they themselves contribute to the development which takes place. Opsomming Met 'n eerste oogopslag wil dit voorkom asof humanistiese leerteorie 'n oorheersende rol in die leerdergesentreerde benadering van andragogie speel. By nadere ondersoek blyk dit egter dat Knowles (1973, na 'n deeglike studie van verskillende leerteoretiese beginsels, 'n omvangryke raamwerk geskep het waarbinne, aan die hand van verskeie aangepaste leerteoretiese beginsels, menslike hulpbronontwikkeling kan plaasvind. As gevolg van die feit dat Knowles vanuit verskillende oorde kritiek op die lyf geloop het, is besluit om die rol wat verskillende leerteorieë in andragogie speel, te bestudeer. Dit blyk dat andragogie nie net elemente van verskillende leerteorieë bevat nie, maar dat toepaslike aspekte van die teoriee wat ondersoek is, benut en aangepas is om 'n geintegreerde benadering te bewerkstellig waarin veral volwassene-leerders by leergeleenthede en hulle selfontwikkeling betrek word.

  12. Method of treating tool steel die materials

    Cook, C.S.; Damon, S.

    1981-01-01

    In a method of hardening pilger dies to provide a hard case containing residual compressive stresses and tough body, the tool steel die is heated to the austenitizing temperature range, followed by selectively removing heat from the die at a predetermined faster rate in the direction of the desired case than the rate of heat removal from the balance of the die, and thereafter tempering the die. The invention provides a fully hardened and tempered case on the working surface of the die and a tough body in the balance of the die, usually of lower hardness. (author)

  13. Die «ASEAN-Wirtschaftsgemeinschaft»

    Juego, Bonn

    2014-01-01

    Seit dem Ende der 1990er-Jahre verfolgt die ASEAN die Vision einer politischen, wirtschaftlichen und sozialen Gemeinschaft. Doch wie realistisch ist die Umsetzung eines solch ambitionierten Vorhabens vor dem Hintergrund der enormen Heterogenität der Region? ASEAN vereint Staaten auf...... Entwicklungsstufen, wie sie unterschiedlicher kaum sein können. Der Autor, Bonn Juego, nimmt die ASEAN Vision 2020 sowie die Debatten, die diesbezüglich in den einzelnen Ländern geführt werden, unter die Lupe. Er geht dem Potenzial des ASEANAnsatzes zu sozialer Teilhabe und wirtschaftlicher Verteilungsgerechtigkeit...

  14. Die pastorale begeleiding van predikante van die Nederduitse ...

    21 Jan 2013 ... Stone, M.F., 1999, Coaching, counselling & mentoring: How to choose & use the right technique to boost employee performance, AMACOM, New York. Strydom, W.A., 2011, 'Pastoraat aan getraumatiseerde kinders in die intensiewesorgeenheid: 'n Gestalt benadering', DD tesis, Universiteit van Suid-. Afrika ...

  15. 'n Begronde bedieningsmodel vir die diakonia van die gemeente

    15 Feb 2012 ... At first, various angles of approach to the research on ministry in ... Lingenfelter 2005; Armour & Browning 2000) en daarmee saam die ...... Grobler, A.B. & Van der Walt, A.L., 2008, 'An assessment of the management skills.

  16. Die ontwikkeling van menslike potensiaal in die Republiek van Suid ...

    Erna Kinsey

    Dit het dus ook te doen met lewenstandaard, aangesien lewenstandaard `n bepalende faktor is met betrekking tot die optimale ontwikkeling van menslike potensiaal. Ander minder materiële aspekte van menslike potensiaal het te doen met menslike vryheid, waaronder vryheid van spraak, beweging en keuse ter sake is.

  17. UIT DIE VOORGESKIEDENIS VAN DIE SUID-AFRIKAANSE VLOOT ...

    20 van 1898 van die Kaapkolonie, getiteld The Navy Contribution. Act, i898 is a.m. ... as a contribution towards the annual expenditure by the ...... The above are inclusive of all allowances for lodging and provisions. Petty Officer Ins ...... that system we can retain full constitutional control not only in theory but also complete ...

  18. Die Korallenfauna des Perm von Timor und die permische Vereisung

    Gerth, H.

    1926-01-01

    Bei den zahlreichen Rekonstruktionen der klimatologischen Verhältnisse, die man für das Ende des Palaeozoikums gemacht hat, ist man fast immer von der Kohlenbildung, der Florenverbreitung und den Vereisungserscheinungen ausgegangen. Der marinen Tierwelt hat man bei der Behandlung dieser Fragen meist

  19. Mechanisms of Diabetes-Induced Endothelial Cell Senescence: Role of Arginase 1

    Esraa Shosha

    2018-04-01

    Full Text Available We have recently found that diabetes-induced premature senescence of retinal endothelial cells is accompanied by NOX2-NADPH oxidase-induced increases in the ureohydrolase enzyme arginase 1 (A1. Here, we used genetic strategies to determine the specific involvement of A1 in diabetes-induced endothelial cell senescence. We used A1 knockout mice and wild type mice that were rendered diabetic with streptozotocin and retinal endothelial cells (ECs exposed to high glucose or transduced with adenovirus to overexpress A1 for these experiments. ABH [2(S-Amino-6-boronohexanoic acid] was used to inhibit arginase activity. We used Western blotting, immunolabeling, quantitative PCR, and senescence associated β-galactosidase (SA β-Gal activity to evaluate senescence. Analyses of retinal tissue extracts from diabetic mice showed significant increases in mRNA expression of the senescence-related proteins p16INK4a, p21, and p53 when compared with non-diabetic mice. SA β-Gal activity and p16INK4a immunoreactivity were also increased in retinal vessels from diabetic mice. A1 gene deletion or pharmacological inhibition protected against the induction of premature senescence. A1 overexpression or high glucose treatment increased SA β-Gal activity in cultured ECs. These results demonstrate that A1 is critically involved in diabetes-induced senescence of retinal ECs. Inhibition of arginase activity may therefore be an effective therapeutic strategy to alleviate diabetic retinopathy by preventing premature senescence.

  20. Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit.

    Puvvula, Pavan Kumar; Desetty, Rohini Devi; Pineau, Pascal; Marchio, Agnés; Moon, Anne; Dejean, Anne; Bischof, Oliver

    2014-11-19

    Cellular senescence is a stable cell cycle arrest that limits the proliferation of pre-cancerous cells. Here we demonstrate that scaffold-attachment-factor A (SAFA) and the long noncoding RNA PANDA differentially interact with polycomb repressive complexes (PRC1 and PRC2) and the transcription factor NF-YA to either promote or suppress senescence. In proliferating cells, SAFA and PANDA recruit PRC complexes to repress the transcription of senescence-promoting genes. Conversely, the loss of SAFA-PANDA-PRC interactions allows expression of the senescence programme. Accordingly, we find that depleting either SAFA or PANDA in proliferating cells induces senescence. However, in senescent cells where PANDA sequesters transcription factor NF-YA and limits the expression of NF-YA-E2F-coregulated proliferation-promoting genes, PANDA depletion leads to an exit from senescence. Together, our results demonstrate that PANDA confines cells to their existing proliferative state and that modulating its level of expression can cause entry or exit from senescence.