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Sample records for controls planarian regeneration

  1. JNK controls the onset of mitosis in planarian stem cells and triggers apoptotic cell death required for regeneration and remodeling.

    Directory of Open Access Journals (Sweden)

    María Almuedo-Castillo

    2014-06-01

    Full Text Available Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo. The presence of a population of adult pluripotent stem cells combined with the ability to decode signaling after wounding enable planarians to regenerate a complete, correctly proportioned animal within a few days after any kind of amputation, and to adapt their size to nutritional changes without compromising functionality. Here, we demonstrate that the stress-activated c-jun-NH2-kinase (JNK links wound-induced apoptosis to the stem cell response during planarian regeneration. We show that JNK modulates the expression of wound-related genes, triggers apoptosis and attenuates the onset of mitosis in stem cells specifically after tissue loss. Furthermore, in pre-existing body regions, JNK activity is required to establish a positive balance between cell death and stem cell proliferation to enable tissue renewal, remodeling and the maintenance of proportionality. During homeostatic degrowth, JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling. Our findings indicate that JNK-dependent apoptotic cell death is crucial to coordinate tissue renewal and remodeling required to regenerate and to maintain a correctly proportioned animal. Hence, JNK might act as a hub, translating wound signals into apoptotic cell death, controlled stem cell proliferation and differentiation, all of which are required to coordinate regeneration and tissue renewal.

  2. A wound-induced Wnt expression program controls planarian regeneration polarity.

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    Petersen, Christian P; Reddien, Peter W

    2009-10-06

    Regeneration requires specification of the identity of new tissues to be made. Whether this process relies only on intrinsic regulative properties of regenerating tissues or whether wound signaling provides input into tissue repatterning is not known. The head-versus-tail regeneration polarity decision in planarians, which requires Wnt signaling, provides a paradigm to study the process of tissue identity specification during regeneration. The Smed-wntP-1 gene is required for regeneration polarity and is expressed at the posterior pole of intact animals. Surprisingly, wntP-1 was expressed at both anterior- and posterior-facing wounds rapidly after wounding. wntP-1 expression was induced by all types of wounds examined, regardless of whether wounding prompted tail regeneration. Regeneration polarity was found to require new expression of wntP-1. Inhibition of the wntP-2 gene enhanced the polarity phenotype due to wntP-1 inhibition, with new expression of wntP-2 in regeneration occurring subsequent to expression of wntP-1 and localized only to posterior-facing wounds. New expression of wntP-2 required wound-induced wntP-1. Finally, wntP-1 and wntP-2 expression changes occurred even in the absence of neoblast stem cells, which are required for regeneration, suggesting that the role of these genes in polarity is independent of and instructive for tail formation. These data indicate that wound-induced input is involved in resetting the normal polarized features of the body axis during regeneration.

  3. Temporal regulation of planarian eye regeneration

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    Deochand, Michelle E.; Birkholz, Taylor R.; Wendy S Beane

    2016-01-01

    Abstract While tissue regeneration is typically studied using standard injury models, in nature injuries vary greatly in the amount and location of tissues lost. Planarians have the unique ability to regenerate from many different injuries (including from tiny fragments with no brain), allowing us to study the effects of different injuries on regeneration timelines. We followed the timing of regeneration for one organ, the eye, after multiple injury types that involved tissue loss (single‐ an...

  4. Germ cell specification and regeneration in planarians.

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    Newmark, P A; Wang, Y; Chong, T

    2008-01-01

    In metazoans, two apparently distinct mechanisms specify germ cell fate: Determinate specification (observed in animals including Drosophila, Caenorhabditis elegans, zebra fish, and Xenopus) uses cytoplasmic factors localized to specific regions of the egg, whereas epigenetic specification (observed in many basal metazoans, urodeles, and mammals) involves inductive interactions between cells. Much of our understanding of germ cell specification has emerged from studies of model organisms displaying determinate specification. In contrast, our understanding of epigenetic/inductive specification is less advanced and would benefit from studies of additional organisms. Freshwater planarians--widely known for their remarkable powers of regeneration--are well suited for studying the mechanisms by which germ cells can be induced. Classic experiments showed that planarians can regenerate germ cells from body fragments entirely lacking reproductive structures, suggesting that planarian germ cells could be specified by inductive signals. Furthermore, the availability of the genome sequence of the planarian Schmidtea mediterranea, coupled with the animal's susceptibility to systemic RNA interference (RNAi), facilitates functional genomic analyses of germ cell development and regeneration. Here, we describe recent progress in studies of planarian germ cells and frame some of the critical unresolved questions for future work.

  5. Planarian regeneration under micro- and hyper-gravity simulated contexts

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    Auletta, Gennaro; Van Loon, ing.. Jack J. W. A.; Adell, Teresa; Salo, Emili

    Planarians are non-parasitic flatworms of the Turbellaria class, some of which show the striking ability to regenerate any part of their body, even the head, in few days. Planarians are common to many parts of the world, living in both saltwater and freshwater, as well as in terrestrial areas. Due to their plasticity Planarians have been a classical model for the study of the mechanisms of regeneration. Currently, their cheap and easy maintenance, as well as the establishment of robust genetic tools, have converted them into an essential system in the field of stem cells and regenerative medicine. The aim of our project is to study the effect that micro- and hyper- gravity could exert during the process of planarians regeneration. The reason for planarians extreme regenerative capability is the maintenance until adulthood of a population of totipotent stem cells as well as the continuous activation of the cell-cell communication molecular pathways. Our prediction is that the alteration of the forces could affect planarians regeneration at different levels: 1) To regenerate, planarians must activate both proliferative and apoptotic responses, in order to create new tissue and to remodel the pre-existing one, respectively. Both cellular processes have been reported to be altered in several models under differential gravitational forces; 2) In planarians, the main intercellular signalling pathways (Wnt, TGFb, BMP, Hh, EGF) must control the process of differentiation and determination of each cell. For instances, it has been demonstrated that the differential activity of the wnt/beta-catenin pathway specifies the posterior (tail) versus the anterior (head) identity. Those pathways rely on the distance that secreted molecules (morphogens) are able to reach. Either this mechanism consist in a passive diffusion or an active transport through phyllopodia, it could sense the magnitude of the gravitational force; 3) The epidermis of planarians is covered by cilia, which beat

  6. A regulatory program for excretory system regeneration in planarians

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    Scimone, M Lucila; Srivastava, Mansi; Bell, George W.; Reddien, Peter W.

    2011-01-01

    Planarians can regenerate any missing body part, requiring mechanisms for the production of organ systems in the adult, including their prominent tubule-based filtration excretory system called protonephridia. Here, we identify a set of genes, Six1/2-2, POU2/3, hunchback, Eya and Sall, that encode transcription regulatory proteins that are required for planarian protonephridia regeneration. During regeneration, planarian stem cells are induced to form a cell population in regeneration blastem...

  7. A Bmp/Admp regulatory circuit controls maintenance and regeneration of dorsal-ventral polarity in planarians.

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    Gaviño, Michael A; Reddien, Peter W

    2011-02-22

    Animal embryos have diverse anatomy and vary greatly in size. It is therefore remarkable that a common signaling pathway, BMP signaling, controls development of the dorsoventral (DV) axis throughout the Bilateria. In vertebrates, spatially opposed expression of the BMP family proteins Bmp4 and Admp (antidorsalizing morphogenetic protein) can promote restoration of DV pattern following tissue removal. bmp4 orthologs have been identified in all three groups of the Bilateria (deuterostomes, ecdysozoans, and lophotrochozoans). By contrast, the absence of admp orthologs in ecdysozoans such as Drosophila and C. elegans has suggested that a regulatory circuit of oppositely expressed bmp4 and admp genes represents a deuterostome-specific innovation. Here we describe the existence of spatially opposed bmp and admp expression in a protostome. An admp ortholog (Smed-admp) is expressed ventrally and laterally in adult Schmidtea mediterranea planarians, opposing the dorsal-pole expression of Smed-bmp4. Smed-admp is required for regeneration following parasagittal amputation. Furthermore, Smed-admp promotes Smed-bmp4 expression and Smed-bmp4 inhibits Smed-admp expression, generating a regulatory circuit that buffers against perturbations of Bmp signaling. These results suggest that a Bmp/Admp regulatory circuit is a central feature of the Bilateria, used broadly for the establishment, maintenance, and regeneration of the DV axis.

  8. Smed-betacatenin-1 is required for anteroposterior blastema polarity in planarian regeneration.

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    Petersen, Christian P; Reddien, Peter W

    2008-01-18

    Planarian flatworms can regenerate heads at anterior-facing wounds and tails at posterior-facing wounds throughout the body. How this regeneration polarity is specified has been a classic problem for more than a century. We identified a planarian gene, Smed-betacatenin-1, that controls regeneration polarity. Posterior-facing blastemas regenerate a head instead of a tail in Smed-betacatenin-1(RNAi) animals. Smed-betacatenin-1 is required after wounding and at any posterior-facing wound for polarity. Additionally, intact Smed-betacatenin-1(RNAi) animals display anteriorization during tissue turnover. Five Wnt genes and a secreted Frizzled-related Wnt antagonist-like gene are expressed in domains along the anteroposterior axis that reset to new positions during regeneration, which suggests that Wnts control polarity through Smed-betacatenin-1. Our data suggest that beta-catenin specifies the posterior character of the anteroposterior axis throughout the Bilateria and specifies regeneration polarity in planarians.

  9. EGFR signaling regulates cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis.

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    Fraguas, Susanna; Barberán, Sara; Cebrià, Francesc

    2011-06-01

    Similarly to development, the process of regeneration requires that cells accurately sense and respond to their external environment. Thus, intrinsic cues must be integrated with signals from the surrounding environment to ensure appropriate temporal and spatial regulation of tissue regeneration. Identifying the signaling pathways that control these events will not only provide insights into a fascinating biological phenomenon but may also yield new molecular targets for use in regenerative medicine. Among classical models to study regeneration, freshwater planarians represent an attractive system in which to investigate the signals that regulate cell proliferation and differentiation, as well as the proper patterning of the structures being regenerated. Recent studies in planarians have begun to define the role of conserved signaling pathways during regeneration. Here, we extend these analyses to the epidermal growth factor (EGF) receptor pathway. We report the characterization of three epidermal growth factor (EGF) receptors in the planarian Schmidtea mediterranea. Silencing of these genes by RNA interference (RNAi) yielded multiple defects in intact and regenerating planarians. Smed-egfr-1(RNAi) resulted in decreased differentiation of eye pigment cells, abnormal pharynx regeneration and maintenance, and the development of dorsal outgrowths. In contrast, Smed-egfr-3(RNAi) animals produced smaller blastemas associated with abnormal differentiation of certain cell types. Our results suggest important roles for the EGFR signaling in controlling cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis.

  10. Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration

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    Morokuma, Junji; Oviedo, Nestor J.; Walentek, Peter; Kema, Ido P.; Gu, Man Bock; Ahn, Joo-Myung; Hwang, Jung Shan; Gojobori, Takashi; Levin, Michael

    2010-01-01

    Having the ability to coordinate the behavior of stem cells to induce regeneration of specific large-scale structures would have far-reaching consequences in the treatment of degenerative diseases, acute injury, and aging. Thus, identifying and learning to manipulate the sequential steps that determ

  11. Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration

    NARCIS (Netherlands)

    Morokuma, Junji; Oviedo, Nestor J.; Walentek, Peter; Kema, Ido P.; Gu, Man Bock; Ahn, Joo-Myung; Hwang, Jung Shan; Gojobori, Takashi; Levin, Michael

    2010-01-01

    Having the ability to coordinate the behavior of stem cells to induce regeneration of specific large-scale structures would have far-reaching consequences in the treatment of degenerative diseases, acute injury, and aging. Thus, identifying and learning to manipulate the sequential steps that determ

  12. Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling.

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    Oviedo, Néstor J; Pearson, Bret J; Levin, Michael; Sánchez Alvarado, Alejandro

    2008-01-01

    We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, we also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTEN RNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians.

  13. A regulatory program for excretory system regeneration in planarians.

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    Scimone, M Lucila; Srivastava, Mansi; Bell, George W; Reddien, Peter W

    2011-10-01

    Planarians can regenerate any missing body part, requiring mechanisms for the production of organ systems in the adult, including their prominent tubule-based filtration excretory system called protonephridia. Here, we identify a set of genes, Six1/2-2, POU2/3, hunchback, Eya and Sall, that encode transcription regulatory proteins that are required for planarian protonephridia regeneration. During regeneration, planarian stem cells are induced to form a cell population in regeneration blastemas expressing Six1/2-2, POU2/3, Eya, Sall and Osr that is required for excretory system formation. POU2/3 and Six1/2-2 are essential for these precursor cells to form. Eya, Six1/2-2, Sall, Osr and POU2/3-related genes are required for vertebrate kidney development. We determined that planarian and vertebrate excretory cells express homologous proteins involved in reabsorption and waste modification. Furthermore, we identified novel nephridia genes. Our results identify a transcriptional program and cellular mechanisms for the regeneration of an excretory organ and suggest that metazoan excretory systems are regulated by genetic programs that share a common evolutionary origin.

  14. Regeneration in planarians and other worms: New findings, new tools, and new perspectives.

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    Saló, Emili; Baguñà, Jaume

    2002-05-01

    Molecular biology, recombinant DNA techniques, and new methods of cell lineage have reignited the interest of planarians and other worms (mainly annelids and nemerteans) as invertebrate model systems of regeneration. Here, the mean results produced in the last five years are reviewed, an update of the genes and molecules involved in planarian regeneration is provided, and a new morphallactic-epimorphic model of pattern formation is suggested. Moreover, and most importantly, we highlight the new strides brought upon by genomic/proteomic analyses, RNA interference (RNAi) to inactivate gene function, and Bromodeoxyuridine (BrdU) cell labelling. The raising hope to obtain transformed neoblasts and transgenic planarians is also stressed. Altogether, such approaches will eventually lead to solve the long-standing open questions on regeneration which still baffles us. Finally, we warn against overlooking the evident links between regeneration processes and those controlling the daily wear and tear of tissues and cells. Both processes act, at least in planarians, upon a unique stem-cell endowed with an unrivaled developmental potential in the animal kingdom-the neoblast. This cell could be considered the forebear and a model system for stem-cell analysis.

  15. pbx is required for pole and eye regeneration in planarians.

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    Chen, Chun-Chieh G; Wang, Irving E; Reddien, Peter W

    2013-02-01

    Planarian regeneration involves regionalized gene expression that specifies the body plan. After amputation, planarians are capable of regenerating new anterior and posterior poles, as well as tissues polarized along the anterior-posterior, dorsal-ventral and medial-lateral axes. Wnt and several Hox genes are expressed at the posterior pole, whereas Wnt inhibitory genes, Fgf inhibitory genes, and prep, which encodes a TALE-family homeodomain protein, are expressed at the anterior pole. We found that Smed-pbx (pbx for short), which encodes a second planarian TALE-family homeodomain transcription factor, is required for restored expression of these genes at anterior and posterior poles during regeneration. Moreover, pbx(RNAi) animals gradually lose pole gene expression during homeostasis. By contrast, pbx was not required for initial anterior-posterior polarized responses to wounds, indicating that pbx is required after wound responses for development and maintenance of poles during regeneration and homeostatic tissue turnover. Independently of the requirement for pbx in pole regeneration, pbx is required for eye precursor formation and, consequently, eye regeneration and eye replacement in homeostasis. Together, these data indicate that pbx promotes pole formation of body axes and formation of regenerative progenitors for eyes.

  16. Mechanism of anterior-posterior polarity control in planarians

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    Lange, C.S.; Steele, V.E.

    1978-01-01

    The substance which inhibits brain formation in the regenerating planarian Dugesia etrusca was found to be a large molecule, at least in part protein, which electrophoreses as an electronegative moiety in pH 6.8 buffer. A model is presented, based on this finding and previous studies, which proposes an electrochemical mechanism for the control of polarity and possibly for the maintenance of tissue organization in planarians. It is proposed that a bioelectric field exists and moves the electronegative brain-inhibiting substance in a posterior direction, establishing polarity. This model explains the polarity reversal experiments using external fields and many of the previously unexplained classical planarian experiments. Data are presented demonstrating the existence, magnitude, and polarity of this bioelectric field, which is not greatly altered upon decapitation, all in accord with predictions of the model.

  17. Inhibitory Smads and bone morphogenetic protein (BMP) modulate anterior photoreceptor cell number during planarian eye regeneration.

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    González-Sastre, Alejandro; Molina, Ma Dolores; Saló, Emili

    2012-01-01

    Planarians represent an excellent model to study the processes of body axis and organ re-specification during regeneration. Previous studies have revealed a conserved role for the bone morphogenetic protein (BMP) pathway and its intracellular mediators Smad1/5/8 and Smad4 in planarian dorsoventral (DV) axis re-establishment. In an attempt to gain further insight into the role of this signalling pathway in planarians, we have isolated and functionally characte-rized the inhibitory Smads (I-Smads) in Schmidtea mediterranea. Two I-Smad homologues have been identified: Smed-smad6/7-1 and Smed-smad6/7-2. Expression of smad6/7-1 was detected in the parenchyma, while smad6/7-2 was found to be ex-pressed in the central nervous system and the eyes. Neither single smad6/7-1 and smad6/7-2 nor double smad6/7-1,-2 silencing gave rise to any apparent disruption of the DV axis. However, both regenerating and intact smad6/7-2 (RNAi) planarians showed defects in eye morphogenesis and displayed small, rounded eyes that lacked the anterior subpopulation of photoreceptor cells. The number of pigment cells was also reduced in these animals at later stages of regeneration. In contrast, after low doses of Smed-bmp(RNAi), planarians regenerated larger eyes in which the anterior subpopulation of photoreceptor cells was expanded. Our results suggest that Smed-smad6/7-2 and Smed-bmp control the re-specification and maintenance of anterior photoreceptor cell number in S. mediterranea.

  18. Effects of Withania somnifera and Ginkgo biloba on Neural Regeneration using Planarian Model

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    Singhal, M.; Brinker, R.

    2016-12-01

    Elderly populations and associated age-related diseases, including damaged peripheral and central neural systems, are increasing. Both systems are vital, and methods to sustain function are sought. The purpose of this experiment was to determine whether Withania somnifera (WS) and Ginkgo biloba (GB) extracts are conducive to planarian regeneration. After acclimation, brown planaria were cut across lateral nerve cord. Experimental groups were treated with 100μg WS or GB extract. Planarian length was measured and piece tested for negative phototaxis. In phototactic test, planaria were allowed 30 seconds to cross petri dish and stay under dark side. A positive response signified photoreceptor presence, indicating regeneration. Both GB and WS groups expressed more favorable cumulative regeneration rates than control group (97.31%, 71.44%, and 40.60% respectively). The null hypothesis (identical regeneration rates) was rejected (p-value ≈ 0.0375). Because phototactic data wasn't taken on days 4 and 5, there was no significant difference in average day of first phototactic response. Most WS and GB planaria first responded on day 6, suggesting that, had data been taken on days 4 and 5, both plant-treated groups would have exhibited even sooner responses than control. Future studies include quantifying regeneration via planarian locomotive velocity (pLMV) and other stereotypical responses.

  19. Planarian GSK3s are involved in neural regeneration.

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    Adell, Teresa; Marsal, Maria; Saló, Emili

    2008-02-01

    Glycogen synthase kinase-3 (GSK3) is a key element in several signaling cascades that is known to be involved in both patterning and neuronal organization. It is, therefore, a good candidate to play a role in neural regeneration in planarians. We report the characterization of three GSK3 genes in Schmidtea mediterranea. Phylogenetic analysis shows that Smed-GSK3.1 is highly conserved compared to GSK3 sequences from other species, whereas Smed-GSK3.2 and Smed-GSK3.3 are more divergent. Treatment of regenerating planarians with 1-azakenpaullone, a synthetic GSK3 inhibitor, suggests that planarian GSK3s are essential for normal differentiation and morphogenesis of the nervous system. Cephalic ganglia appear smaller and disconnected in 1-azakenpaullone-treated animals, whereas visual axons are ectopically projected, and the pharynx does not regenerate properly. This phenotype is consistent with a role for Smed-GSK3s in neuronal polarization and axonal growth.

  20. Epimorphic regeneration of the distal part of the planarian pharynx.

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    Ito, H; Saito, Y; Watanabe, K; Orii, H

    2001-01-01

    The totipotent stem cells called neoblasts seem to be concerned with the remarkable regeneration ability of planarians. However, the pharynx is able to regenerate after the amputation of its distal part, in spite of a lack of neoblasts in the pharynx. The process of regeneration has been referred to as morphallaxis, based on conventional histochemical observations. We examined it again immuno-histochemically using anti-Dugesia japonica proliferating cell nuclear antigen (DjPCNA) antibody for neoblasts and anti-D. japonica myosin heavy chain-A (DjMHC-A) antibody for pharynx muscle fibers. This immuno-histochemical study, together with observations of the regeneration process of planarians irradiated with X-rays in particular regions, revealed that after the amputation, neoblasts from outside the pharynx entered that organ, moved through the mesenchyme of the pharynx to the wounded area, and differentiated into the cells that had been lost there. We show here that the regeneration after amputation of the distal part of the pharynx is an 'epimorphic' process.

  1. Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration.

    Directory of Open Access Journals (Sweden)

    Maria Emilia Isolani

    Full Text Available Matrix metalloproteinases (MMPs are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2 are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi. Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues

  2. Essential role for the planarian intestinal GATA transcription factor in stem cells and regeneration.

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    Flores, Natasha M; Oviedo, Néstor J; Sage, Julien

    2016-10-01

    The cellular turnover of adult tissues and injury-induced repair proceed through an exquisite integration of proliferation, differentiation, and survival signals that involve stem/progenitor cell populations, their progeny, and differentiated tissues. GATA factors are DNA binding proteins that control stem cells and the development of tissues by activating or repressing transcription. Here we examined the role of GATA transcription factors in Schmidtea mediterranea, a freshwater planarian that provides an excellent model to investigate gene function in adult stem cells, regeneration, and differentiation. Smed-gata4/5/6, the homolog of the three mammalian GATA-4,-5,-6 factors is expressed at high levels in differentiated gut cells but also at lower levels in neoblast populations, the planarian stem cells. Smed-gata4/5/6 knock-down results in broad differentiation defects, especially in response to injury. These defects are not restricted to the intestinal lineage. In particular, at late time points during the response to injury, loss of Smed-gata4/5/6 leads to decreased neoblast proliferation and to gene expression changes in several neoblast subpopulations. Thus, Smed-gata4/5/6 plays a key evolutionary conserved role in intestinal differentiation in planarians. These data further support a model in which defects in the intestinal lineage can indirectly affect other differentiation pathways in planarians.

  3. Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

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    Bonar, Nicolle A; Petersen, Christian P

    2017-03-01

    Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema.

  4. Go ahead, grow a head! A planarian's guide to anterior regeneration

    OpenAIRE

    Owlarn, Suthira; Bartscherer, Kerstin

    2016-01-01

    The unique ability of some planarian species to regenerate a head de novo, including a functional brain, provides an experimentally accessible system in which to study the mechanisms underlying regeneration. Here, we summarize the current knowledge on the key steps of planarian head regeneration (head‐versus‐tail decision, anterior pole formation and head patterning) and their molecular and cellular basis. Moreover, instructive properties of the anterior pole as a putative organizer and in co...

  5. Inferring regulatory networks from experimental morphological phenotypes: a computational method reverse-engineers planarian regeneration.

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    Lobo, Daniel; Levin, Michael

    2015-06-01

    Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method provides an automated

  6. Neoblast Specialization in Regeneration of the Planarian Schmidtea mediterranea

    Directory of Open Access Journals (Sweden)

    M. Lucila Scimone

    2014-08-01

    Full Text Available Planarians can regenerate any missing body part in a process requiring dividing cells called neoblasts. Historically, neoblasts have largely been considered a homogeneous stem cell population. Most studies, however, analyzed neoblasts at the population rather than the single-cell level, leaving the degree of heterogeneity in this population unresolved. We combined RNA sequencing of neoblasts from wounded planarians with expression screening and identified 33 transcription factors transcribed in specific differentiated cells and in small fractions of neoblasts during regeneration. Many neoblast subsets expressing distinct tissue-associated transcription factors were present, suggesting candidate specification into many lineages. Consistent with this possibility, klf, pax3/7, and FoxA were required for the differentiation of cintillo-expressing sensory neurons, dopamine-β-hydroxylase-expressing neurons, and the pharynx, respectively. Together, these results suggest that specification of cell fate for most-to-all regenerative lineages occurs within neoblasts, with regenerative cells of blastemas being generated from a highly heterogeneous collection of lineage-specified neoblasts.

  7. Synergistic interactions between temporal coupling of complex light and magnetic pulses upon melanoma cell proliferation and planarian regeneration.

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    Murugan, Nirosha J; Karbowski, Lukasz M; Persinger, Michael A

    2017-01-01

    Synergisms between a physiologically patterned magnetic field that is known to enhance planarian growth and suppress proliferation of malignant cells in culture and three light emitting diode (LED) generated visible wavelengths (blue, green, red) upon planarian regeneration and melanoma cell numbers were discerned. Five days of hourly exposures to either a physiologically patterned (2.5-5.0 μT) magnetic field, one of three wavelengths (3 kLux) or both treatments simultaneously indicated that red light (680 nm), blue light (470 nm) or the magnetic field significantly facilitated regeneration of planarian compared to sham field exposed planarian. Presentation of both light and magnetic field conditions enhanced the effect. Whereas the blue and red light diminished the growth of malignant (melanoma) cells, the effect was not as large as that produced by the magnetic field. Only the paired presentation of the blue light and magnetic field enhanced the suppression. On the other hand, the changes following green light (540 nm) exposure did not differ from the control condition and green light presented with the magnetic field eliminated its effects for both the planarian and melanoma cells. These results indicate specific colors affect positive adaptation that is similar to weak, physiologically patterned frequency modulated (8-24 Hz) magnetic fields and that the two forms of energy can synergistically summate or cancel.

  8. The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration

    Directory of Open Access Journals (Sweden)

    Luca Gentile

    2011-01-01

    Full Text Available Planarian flatworms are an exception among bilaterians in that they possess a large pool of adult stem cells that enables them to promptly regenerate any part of their body, including the brain. Although known for two centuries for their remarkable regenerative capabilities, planarians have only recently emerged as an attractive model for studying regeneration and stem cell biology. This revival is due in part to the availability of a sequenced genome and the development of new technologies, such as RNA interference and next-generation sequencing, which facilitate studies of planarian regeneration at the molecular level. Here, we highlight why planarians are an exciting tool in the study of regeneration and its underlying stem cell biology in vivo, and discuss the potential promises and current limitations of this model organism for stem cell research and regenerative medicine.

  9. Innate immune system and tissue regeneration in planarians: an area ripe for exploration.

    Science.gov (United States)

    Peiris, T Harshani; Hoyer, Katrina K; Oviedo, Néstor J

    2014-08-01

    The immune system has been implicated as an important modulator of tissue regeneration. However, the mechanisms driving injury-induced immune response and tissue repair remain poorly understood. For over 200 years, planarians have been a classical model for studies on tissue regeneration, but the planarian immune system and its potential role in repair is largely unknown. We found through comparative genomic analysis and data mining that planarians contain many potential homologs of the innate immune system that are activated during injury and repair of adult tissues. These findings support the notion that the relationship between adult tissue repair and the immune system is an ancient feature of basal Bilateria. Further analysis of the planarian immune system during regeneration could potentially add to our understanding of how the innate immune system and inflammatory responses interplay with regenerative signals to induce scar-less tissue repair in the context of the adult organism.

  10. Integrins are required for tissue organization and restriction of neurogenesis in regenerating planarians.

    Science.gov (United States)

    Seebeck, Florian; März, Martin; Meyer, Anna-Wiebke; Reuter, Hanna; Vogg, Matthias C; Stehling, Martin; Mildner, Karina; Zeuschner, Dagmar; Rabert, Franziska; Bartscherer, Kerstin

    2017-03-01

    Tissue regeneration depends on proliferative cells and on cues that regulate cell division, differentiation, patterning and the restriction of these processes once regeneration is complete. In planarians, flatworms with high regenerative potential, muscle cells express some of these instructive cues. Here, we show that members of the integrin family of adhesion molecules are required for the integrity of regenerating tissues, including the musculature. Remarkably, in regenerating β1-integrin RNAi planarians, we detected increased numbers of mitotic cells and progenitor cell types, as well as a reduced ability of stem cells and lineage-restricted progenitor cells to accumulate at wound sites. These animals also formed ectopic spheroid structures of neural identity in regenerating heads. Interestingly, those polarized assemblies comprised a variety of neural cells and underwent continuous growth. Our study indicates that integrin-mediated cell adhesion is required for the regenerative formation of organized tissues and for restricting neurogenesis during planarian regeneration.

  11. A dual platform approach to transcript discovery for the planarian Schmidtea mediterranea to establish RNAseq for stem cell and regeneration biology.

    Science.gov (United States)

    Blythe, Martin J; Kao, Damian; Malla, Sunir; Rowsell, Joanna; Wilson, Ray; Evans, Deborah; Jowett, Jamie; Hall, Amy; Lemay, Virginie; Lam, Sabrina; Aboobaker, A Aziz

    2010-12-14

    The use of planarians as a model system is expanding and the mechanisms that control planarian regeneration are being elucidated. The planarian Schmidtea mediterranea in particular has become a species of choice. Currently the planarian research community has access to this whole genome sequencing project and over 70,000 expressed sequence tags. However, the establishment of massively parallel sequencing technologies has provided the opportunity to define genetic content, and in particular transcriptomes, in unprecedented detail. Here we apply this approach to the planarian model system. We have sequenced, mapped and assembled 581,365 long and 507,719,814 short reads from RNA of intact and mixed stages of the first 7 days of planarian regeneration. We used an iterative mapping approach to identify and define de novo splice sites with short reads and increase confidence in our transcript predictions. We more than double the number of transcripts currently defined by publicly available ESTs, resulting in a collection of 25,053 transcripts described by combining platforms. We also demonstrate the utility of this collection for an RNAseq approach to identify potential transcripts that are enriched in neoblast stem cells and their progeny by comparing transcriptome wide expression levels between irradiated and intact planarians. Our experiments have defined an extensive planarian transcriptome that can be used as a template for RNAseq and can also help to annotate the S. mediterranea genome. We anticipate that suites of other 'omic approaches will also be facilitated by building on this comprehensive data set including RNAseq across many planarian regenerative stages, scenarios, tissues and phenotypes generated by RNAi.

  12. Regeneration of dopaminergic neurons after 6-hydroxydopamine-induced lesion in planarian brain.

    Science.gov (United States)

    Nishimura, Kaneyasu; Inoue, Takeshi; Yoshimoto, Kanji; Taniguchi, Takashi; Kitamura, Yoshihisa; Agata, Kiyokazu

    2011-12-01

    Planarians have robust regenerative ability dependent on X-ray-sensitive pluripotent stem cells, called neoblasts. Here, we report that planarians can regenerate dopaminergic neurons after selective degeneration of these neurons caused by treatment with a dopaminergic neurotoxin (6-hydroxydopamine; 6-OHDA). This suggests that planarians have a system to sense the degeneration of dopaminergic neurons and to recruit stem cells to produce dopaminergic neurons to recover brain morphology and function. We confirmed that X-ray-irradiated planarians do not regenerate brain dopaminergic neurons after 6-OHDA-induced lesioning, suggesting that newly generated dopaminergic neurons are indeed derived from pluripotent stem cells. However, we found that the majority of regenerated dopaminergic neurons were 5-bromo-2'-deoxyuridine-negative cells. Therefore, we carefully analyzed when proliferating stem cells became committed to become dopaminergic neurons during regeneration by a combination of 5-bromo-2'-deoxyuridine pulse-chase experiments, immunostaining/in situ hybridization, and 5-fluorouracil treatment. The results strongly suggested that G(2) -phase stem cells become committed to dopaminergic neurons in the mesenchymal space around the brain, after migration from the trunk region following S-phase. These new findings obtained from planarian regeneration provide hints about how to conduct cell-transplantation therapy for future regenerative medicine. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  13. nanos function is essential for development and regeneration of planarian germ cells.

    Science.gov (United States)

    Wang, Yuying; Zayas, Ricardo M; Guo, Tingxia; Newmark, Phillip A

    2007-04-03

    Germ cells are required for the successful propagation of sexually reproducing species. Understanding the mechanisms by which these cells are specified and how their totipotency is established and maintained has important biomedical and evolutionary implications. Freshwater planarians serve as fascinating models for studying these questions. They can regenerate germ cells from fragments of adult tissues that lack reproductive structures, suggesting that inductive signaling is involved in planarian germ cell specification. To study the development and regeneration of planarian germ cells, we have functionally characterized an ortholog of nanos, a gene required for germ cell development in diverse organisms, from Schmidtea mediterranea. In the hermaphroditic strain of this species, Smed-nanos mRNA is detected in developing, regenerating, and mature ovaries and testes. However, it is not detected in the vast majority of newly hatched planarians or in small tissue fragments that will ultimately regenerate germ cells, consistent with an epigenetic origin of germ cells. We show that Smed-nanos RNA interference (RNAi) results in failure to develop, regenerate, or maintain gonads in sexual planarians. Unexpectedly, Smed-nanos mRNA is also detected in presumptive testes primordia of asexual individuals that reproduce strictly by fission. These presumptive germ cells are lost after Smed-nanos RNAi, suggesting that asexual planarians specify germ cells, but their differentiation is blocked downstream of Smed-nanos function. Our results reveal a conserved function of nanos in germ cell development in planarians and suggest that these animals will serve as useful models for dissecting the molecular basis of epigenetic germ cell specification.

  14. Regeneration and maintenance of the planarian midline is regulated by a slit orthologue.

    Science.gov (United States)

    Cebrià, Francesc; Guo, Tingxia; Jopek, Jessica; Newmark, Phillip A

    2007-07-15

    Several families of evolutionarily conserved axon guidance cues orchestrate the precise wiring of the nervous system during embryonic development. The remarkable plasticity of freshwater planarians provides the opportunity to study these molecules in the context of neural regeneration and maintenance. Here we characterize a homologue of the Slit family of guidance cues from the planarian Schmidtea mediterranea. Smed-slit is expressed along the planarian midline, in both dorsal and ventral domains. RNA interference (RNAi) targeting Smed-slit results in the collapse of many newly regenerated tissues at the midline; these include the cephalic ganglia, ventral nerve cords, photoreceptors, and the posterior digestive system. Surprisingly, Smed-slit RNAi knockdown animals also develop morphologically distinguishable, ectopic neural structures near the midline in uninjured regions of intact and regenerating planarians. These results suggest that Smed-slit acts not only as a repulsive cue required for proper midline formation during regeneration but that it may also act to regulate the behavior of neural precursors at the midline in intact planarians.

  15. Eye Absence Does Not Regulate Planarian Stem Cells during Eye Regeneration.

    Science.gov (United States)

    LoCascio, Samuel A; Lapan, Sylvain W; Reddien, Peter W

    2017-02-27

    Dividing cells called neoblasts contain pluripotent stem cells and drive planarian flatworm regeneration from diverse injuries. A long-standing question is whether neoblasts directly sense and respond to the identity of missing tissues during regeneration. We used the eye to investigate this question. Surprisingly, eye removal was neither sufficient nor necessary for neoblasts to increase eye progenitor production. Neoblasts normally increase eye progenitor production following decapitation, facilitating regeneration. Eye removal alone, however, did not induce this response. Eye regeneration following eye-specific resection resulted from homeostatic rates of eye progenitor production and less cell death in the regenerating eye. Conversely, large head injuries that left eyes intact increased eye progenitor production. Large injuries also non-specifically increased progenitor production for multiple uninjured tissues. We propose a model for eye regeneration in which eye tissue production by planarian stem cells is not directly regulated by the absence of the eye itself. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The maintenance and regeneration of the planarian excretory system are regulated by EGFR signaling.

    Science.gov (United States)

    Rink, Jochen C; Vu, Hanh Thi-Kim; Sánchez Alvarado, Alejandro

    2011-09-01

    The maintenance of organs and their regeneration in case of injury are crucial to the survival of all animals. High rates of tissue turnover and nearly unlimited regenerative capabilities make planarian flatworms an ideal system with which to investigate these important processes, yet little is known about the cell biology and anatomy of their organs. Here we focus on the planarian excretory system, which consists of internal protonephridial tubules. We find that these assemble into complex branching patterns with a stereotyped succession of cell types along their length. Organ regeneration is likely to originate from a precursor structure arising in the blastema, which undergoes extensive branching morphogenesis. In an RNAi screen of signaling molecules, we identified an EGF receptor (Smed-EGFR-5) as a crucial regulator of branching morphogenesis and maintenance. Overall, our characterization of the planarian protonephridial system establishes a new paradigm for regenerative organogenesis and provides a platform for exploring its functional and evolutionary homologies with vertebrate excretory systems.

  17. A functional genomics screen identifies an Importin-α homolog as a regulator of stem cell function and tissue patterning during planarian regeneration

    OpenAIRE

    2015-01-01

    Background Planarians are renowned for their regenerative capacity and are an attractive model for the study of adult stem cells and tissue regeneration. In an effort to better understand the molecular mechanisms underlying planarian regeneration, we performed a functional genomics screen aimed at identifying genes involved in this process in Schmidtea mediterranea. Methods We used microarrays to detect changes in gene expression in regenerating and non-regenerating tissues in planarians rege...

  18. teashirt is required for head-versus-tail regeneration polarity in planarians.

    Science.gov (United States)

    Owen, Jared H; Wagner, Daniel E; Chen, Chun-Chieh; Petersen, Christian P; Reddien, Peter W

    2015-03-15

    Regeneration requires that the identities of new cells are properly specified to replace missing tissues. The Wnt signaling pathway serves a central role in specifying posterior cell fates during planarian regeneration. We identified a gene encoding a homolog of the Teashirt family of zinc-finger proteins in the planarian Schmidtea mediterranea to be a target of Wnt signaling in intact animals and at posterior-facing wounds. Inhibition of Smed-teashirt (teashirt) by RNA interference (RNAi) resulted in the regeneration of heads in place of tails, a phenotype previously observed with RNAi of the Wnt pathway genes β-catenin-1, wnt1, Dvl-1/2 or wntless. teashirt was required for β-catenin-1-dependent activation of posterior genes during regeneration. These findings identify teashirt as a transcriptional target of Wnt signaling required for Wnt-mediated specification of posterior blastemas.

  19. Go ahead, grow a head! A planarian's guide to anterior regeneration

    Science.gov (United States)

    2016-01-01

    Abstract The unique ability of some planarian species to regenerate a head de novo, including a functional brain, provides an experimentally accessible system in which to study the mechanisms underlying regeneration. Here, we summarize the current knowledge on the key steps of planarian head regeneration (head‐versus‐tail decision, anterior pole formation and head patterning) and their molecular and cellular basis. Moreover, instructive properties of the anterior pole as a putative organizer and in coordinating anterior midline formation are discussed. Finally, we highlight that regeneration initiation occurs in a two‐step manner and hypothesize that wound‐induced and existing positional cues interact to detect tissue loss and together determine the appropriate regenerative outcomes. PMID:27606065

  20. Go ahead, grow a head! A planarian's guide to anterior regeneration.

    Science.gov (United States)

    Owlarn, Suthira; Bartscherer, Kerstin

    2016-06-01

    The unique ability of some planarian species to regenerate a head de novo, including a functional brain, provides an experimentally accessible system in which to study the mechanisms underlying regeneration. Here, we summarize the current knowledge on the key steps of planarian head regeneration (head-versus-tail decision, anterior pole formation and head patterning) and their molecular and cellular basis. Moreover, instructive properties of the anterior pole as a putative organizer and in coordinating anterior midline formation are discussed. Finally, we highlight that regeneration initiation occurs in a two-step manner and hypothesize that wound-induced and existing positional cues interact to detect tissue loss and together determine the appropriate regenerative outcomes.

  1. Knockdown of the coenzyme Q synthesis gene Smed-dlp1 affects planarian regeneration and tissue homeostasis.

    Science.gov (United States)

    Shiobara, Yumiko; Harada, Chiaki; Shiota, Takeshi; Sakamoto, Kimitoshi; Kita, Kiyoshi; Tanaka, Saeko; Tabata, Kenta; Sekie, Kiyoteru; Yamamoto, Yorihiro; Sugiyama, Tomoyasu

    2015-12-01

    The freshwater planarian is a model organism used to study tissue regeneration that occupies an important position among multicellular organisms. Planarian genomic databases have led to the identification of genes that are required for regeneration, with implications for their roles in its underlying mechanism. Coenzyme Q (CoQ) is a fundamental lipophilic molecule that is synthesized and expressed in every cell of every organism. Furthermore, CoQ levels affect development, life span, disease and aging in nematodes and mice. Because CoQ can be ingested in food, it has been used in preventive nutrition. In this study, we investigated the role of CoQ in planarian regeneration. Planarians synthesize both CoQ9 and rhodoquinone 9 (RQ9). Knockdown of Smed-dlp1, a trans-prenyltransferase gene that encodes an enzyme that synthesizes the CoQ side chain, led to a decrease in CoQ9 and RQ9 levels. However, ATP levels did not consistently decrease in these animals. Knockdown animals exhibited tissue regression and curling. The number of mitotic cells decreased in Smed-dlp1 (RNAi) animals. These results suggested a failure in physiological cell turnover and stem cell function. Accordingly, regenerating planarians died from lysis or exhibited delayed regeneration. Interestingly, the observed phenotypes were partially rescued by ingesting food supplemented with α-tocopherol. Taken together, our results suggest that oxidative stress induced by reduced CoQ9 levels affects planarian regeneration and tissue homeostasis.

  2. Modeling planarian regeneration: a primer for reverse-engineering the worm.

    Science.gov (United States)

    Lobo, Daniel; Beane, Wendy S; Levin, Michael

    2012-01-01

    A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences-using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an engineering-like style

  3. Modeling planarian regeneration: a primer for reverse-engineering the worm.

    Directory of Open Access Journals (Sweden)

    Daniel Lobo

    Full Text Available A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences-using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an

  4. Amputation induces stem cell mobilization to sites of injury during planarian regeneration

    Science.gov (United States)

    Guedelhoefer, Otto C.; Alvarado, Alejandro Sánchez

    2012-01-01

    How adult stem cell populations are recruited for tissue renewal and repair is a fundamental question of biology. Mobilization of stem cells out of their niches followed by correct migration and differentiation at a site of tissue turnover or injury are important requirements for proper tissue maintenance and regeneration. However, we understand little about the mechanisms that control this process, possibly because the best studied vertebrate adult stem cell systems are not readily amenable to in vivo observation. Furthermore, few clear examples of the recruitment of fully potent stem cells, compared with limited progenitors, are known. Here, we show that planarian stem cells directionally migrate to amputation sites during regeneration. We also show that during tissue homeostasis they are stationary. Our study not only uncovers the existence of specific recruitment mechanisms elicited by amputation, but also sets the stage for the systematic characterization of evolutionarily conserved stem cell regulatory processes likely to inform stem cell function and dysfunction in higher organisms, including humans. PMID:22899852

  5. Coordination of size-control, reproduction and generational memory in freshwater planarians

    Science.gov (United States)

    Yang, Xingbo; Kaj, Kelson J.; Schwab, David J.; Collins, Eva-Maria S.

    2017-06-01

    Uncovering the mechanisms that control size, growth, and division rates of organisms reproducing through binary division means understanding basic principles of their life cycle. Recent work has focused on how division rates are regulated in bacteria and yeast, but this question has not yet been addressed in more complex, multicellular organisms. We have, over the course of several years, assembled a unique large-scale data set on the growth and asexual reproduction of two freshwater planarian species, Dugesia japonica and Girardia tigrina, which reproduce by transverse fission and succeeding regeneration of head and tail pieces into new planarians. We show that generation-dependent memory effects in planarian reproduction need to be taken into account to accurately capture the experimental data. To achieve this, we developed a new additive model that mixes multiple size control strategies based on planarian size, growth, and time between divisions. Our model quantifies the proportions of each strategy in the mixed dynamics, revealing the ability of the two planarian species to utilize different strategies in a coordinated manner for size control. Additionally, we found that head and tail offspring of both species employ different mechanisms to monitor and trigger their reproduction cycles. Thus, we find a diversity of strategies not only between species but between heads and tails within species. Our additive model provides two advantages over existing 2D models that fit a multivariable splitting rate function to the data for size control: firstly, it can be fit to relatively small data sets and can thus be applied to systems where available data is limited. Secondly, it enables new biological insights because it explicitly shows the contributions of different size control strategies for each offspring type.

  6. 涡虫神经再生的分子机制%Molecular actions guiding neural regeneration in planarian

    Institute of Scientific and Technical Information of China (English)

    张燕芬; 叶波平; 王大勇

    2008-01-01

    Planarian is among the simplest animals that possess a centralized nervous system (CNS),and its neural regeneration involves the replacement of cells lost to normal 'wear and tear' (cell turnover),and/or injury.In this review,we state and discuss the recent studies on molecular control of neural regeneration in planarians.The spatial and temporal expression patterns of genes in intact and regenerating planarian CNS have already been described relatively clearly.The bone morphogenetic protein (BMP) and Writ signaling pathways are identified to regulate neural regeneration.During neural regeneration,conserved axon guidance mechanisms are necessary for proper wiring of the nervous system.In addition,apoptosis may play an important role in controlling cell numbers,eliminating unnecessary tissues or cells and remodeling the old tissues for regenerating CNS.The bilateral symmetry is established by determination of anterior-posterior (A-P) and dorsal-ventral (D-V) patterns.Moreover,neurons positive to dopamine,serotonin (5-HT),and gamma-aminobutyric acid (GABA) have been detected in planarians.Therefore,planarians present us with new,experimentally accessible contexts to study the molecular actions guiding neural regeneration.%涡虫是具有简单中枢神经系统的模式动物之一,其神经再生过程包括受损细胞的替换以及细胞的再生过程.本文阐述并讨论了近年来利用涡虫进行神经再生研究取得的研究进展.目前,参与涡虫神经再生相关基因的时空间表达图谱己被相对清晰地勾勒出来.骨形成蛋白和Wnt信号通路已被鉴定参与神经再生的调控.在神经再生过程中,保守的轴突导向机制为神经系统网络的正确形成所必需.此外,细胞凋亡在控制细胞数量、消除多余组织和细胞以及重新塑造再生的神经系统中发挥着重要作用.而且,在涡虫中多巴胺能神经元、五羟色胺能神经元和γ-氨基丁酸能神经元可以被有效地予以标

  7. Smed-Evi/Wntless is required for beta-catenin-dependent and -independent processes during planarian regeneration.

    Science.gov (United States)

    Adell, Teresa; Salò, Emili; Boutros, Michael; Bartscherer, Kerstin

    2009-03-01

    Planarians can regenerate a whole animal from only a small piece of their body, and have become an important model for stem cell biology. To identify regenerative processes dependent on Wnt growth factors in the planarian Schmidtea mediterranea (Smed), we analyzed RNAi phenotypes of Evi, a transmembrane protein specifically required for the secretion of Wnt ligands. We show that, during regeneration, Smed-evi loss-of-function prevents posterior identity, leading to two-headed planarians that resemble Smed-beta-catenin1 RNAi animals. In addition, we observe regeneration defects of the nervous system that are not found after Smed-beta-catenin1 RNAi. By systematic knockdown of all putative Smed Wnts in regenerating planarians, we identify Smed-WntP-1 and Smed-Wnt11-2 as the putative posterior organizers, and demonstrate that Smed-Wnt5 is a regulator of neuronal organization and growth. Thus, our study provides evidence that planarian Wnts are major regulators of regeneration, and that they signal through beta-catenin-dependent and -independent pathways.

  8. PBX/extradenticle is required to re-establish axial structures and polarity during planarian regeneration.

    Science.gov (United States)

    Blassberg, Robert A; Felix, Daniel A; Tejada-Romero, Belen; Aboobaker, A Aziz

    2013-02-01

    Recent advances in a number of systems suggest many genes involved in orchestrating regeneration are redeployed from similar processes in development, with others being novel to the regeneration process in particular lineages. Of particular importance will be understanding the architecture of regenerative genetic regulatory networks and whether they are conserved across broad phylogenetic distances. Here, we describe the role of the conserved TALE class protein PBX/Extradenticle in planarians, a representative member of the Lophotrocozoa. PBX/Extradenticle proteins play central roles in both embryonic and post-embryonic developmental patterning in both vertebrates and insects, and we demonstrate a broad requirement during planarian regeneration. We observe that Smed-pbx has pleiotropic functions during regeneration, with a primary role in patterning the anterior-posterior (AP) axis and AP polarity. Smed-pbx is required for expression of polarity determinants notum and wnt1 and for correct patterning of the structures polarized along the AP axis, such as the brain, pharynx and gut. Overall, our data suggest that Smed-pbx functions as a central integrator of positional information to drive patterning of regeneration along the body axis.

  9. egr-4, a target of EGFR signaling, is required for the formation of the brain primordia and head regeneration in planarians.

    Science.gov (United States)

    Fraguas, Susanna; Barberán, Sara; Iglesias, Marta; Rodríguez-Esteban, Gustavo; Cebrià, Francesc

    2014-05-01

    During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/β-catenin and Hh signaling pathways in re-establishing anterior-posterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain- and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phases - an early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration.

  10. Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors.

    Science.gov (United States)

    Vogg, Matthias C; Owlarn, Suthira; Pérez Rico, Yuvia A; Xie, Jianlei; Suzuki, Yoko; Gentile, Luca; Wu, Wei; Bartscherer, Kerstin

    2014-06-15

    Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head - the anterior regeneration pole - and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue.

  11. Reactive Oxygen Species in Planarian Regeneration: An Upstream Necessity for Correct Patterning and Brain Formation

    Directory of Open Access Journals (Sweden)

    Nicky Pirotte

    2015-01-01

    Full Text Available Recent research highlighted the impact of ROS as upstream regulators of tissue regeneration. We investigated their role and targeted processes during the regeneration of different body structures using the planarian Schmidtea mediterranea, an organism capable of regenerating its entire body, including its brain. The amputation of head and tail compartments induces a ROS burst at the wound site independently of the orientation. Inhibition of ROS production by diphenyleneiodonium (DPI or apocynin (APO causes regeneration defaults at both the anterior and posterior wound sites, resulting in reduced regeneration sites (blastemas and improper tissue homeostasis. ROS signaling is necessary for early differentiation and inhibition of the ROS burst results in defects on the regeneration of the nervous system and on the patterning process. Stem cell proliferation was not affected, as indicated by histone H3-P immunostaining, fluorescence-activated cell sorting (FACS, in situ hybridization of smedwi-1, and transcript levels of proliferation-related genes. We showed for the first time that ROS modulate both anterior and posterior regeneration in a context where regeneration is not limited to certain body structures. Our results indicate that ROS are key players in neuroregeneration through interference with the differentiation and patterning processes.

  12. TOR signaling regulates planarian stem cells and controls localized and organismal growth.

    Science.gov (United States)

    Peiris, T Harshani; Weckerle, Frank; Ozamoto, Elyse; Ramirez, Daniel; Davidian, Devon; García-Ojeda, Marcos E; Oviedo, Néstor J

    2012-04-01

    Target of Rapamycin (TOR) controls an evolutionarily conserved signaling pathway that modulates cellular growth and division by sensing levels of nutrients, energy and stress. As such, TOR signaling is a crucial component of tissues and organs that translates systemic signals into cellular behavior. The ubiquitous nature of TOR signaling, together with the difficulty of analyzing tissue during cellular turnover and repair, have limited our understanding of how this kinase operates throughout the body. Here, we use the planarian model system to address TOR regulation at the organismal level. The planarian TOR homolog (Smed-TOR) is ubiquitously expressed, including stem cells (neoblasts) and differentiated tissues. Inhibition of TOR with RNA interference severely restricts cell proliferation, allowing the study of neoblasts with restricted proliferative capacity during regeneration and systemic cell turnover. Strikingly, TOR signaling is required for neoblast response to amputation and localized growth (blastema). However, in the absence of TOR signaling, regeneration takes place only within differentiated tissues. In addition, TOR is essential for maintaining the balance between cell division and cell death, and its dysfunction leads to tissue degeneration and lack of organismal growth in the presence of nutrients. Finally, TOR function is likely to be mediated through TOR Complex 1 as its disruption recapitulates signs of the TOR phenotype. Our data reveal novel roles for TOR signaling in controlling adult stem cells at a systemic level and suggest a new paradigm for studying TOR function during physiological turnover and regeneration.

  13. Early planarian brain regeneration is independent of blastema polarity mediated by the Wnt/β-catenin pathway.

    Science.gov (United States)

    Iglesias, Marta; Almuedo-Castillo, Maria; Aboobaker, A Aziz; Saló, Emili

    2011-10-01

    Analysis of anteroposterior (AP) axis specification in regenerating planarian flatworms has shown that Wnt/β-catenin signaling is required for posterior specification and that the FGF-like receptor molecule nou-darake (ndk) may be involved in restricting brain regeneration to anterior regions. The relationship between re-establishment of AP identity and correct morphogenesis of the brain is, however, still poorly understood. Here we report the characterization of two axin paralogs in the planarian Schmidtea mediterranea. Although Axins are well known negative regulators of Wnt/β-catenin signaling, no role in AP specification has previously been reported for axin genes in planarians. We show that silencing of Smed-axin genes by RNA interference (RNAi) results in two-tailed planarians, a phenotype previously reported after silencing of Smed-APC-1, another β-catenin inhibitor. More strikingly, we show for the first time that while early brain formation at anterior wounds remains unaffected, subsequent development of the brain is blocked in the two-tailed planarians generated after silencing of Smed-axin genes and Smed-APC-1. These findings suggest that the mechanisms underlying early brain formation can be uncoupled from the specification of AP identity by the Wnt/β-catenin pathway. Finally, the posterior expansion of the brain observed following Smed-ndk RNAi is enhanced by silencing Smed-APC-1, revealing an indirect relationship between the FGFR/Ndk and Wnt/β-catenin signaling systems in establishing the posterior limits of brain differentiation.

  14. The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians.

    Science.gov (United States)

    Molina, M Dolores; Saló, Emili; Cebrià, Francesc

    2007-11-01

    The bone morphogenetic protein (BMP) pathway has been shown to play an important role in the establishment of the dorsoventral axis during development in both vertebrate and invertebrate species. In an attempt to unravel the role of BMPs in pattern formation during planarian regeneration, we studied this signaling pathway in Schmidtea mediterranea. Here, we functionally characterize planarian homologues of two key elements of the pathway: Smed-BMP and Smed-Smad1. Whole-mount in situ hybridization showed that Smed-BMP is expressed at the planarian dorsal midline, suggesting a role in dorsoventral patterning, while Smed-Smad1 is widely expressed throughout the mesenchyme and in the central nervous system. RNA interference (RNAi) knockdowns of Smed-BMP or Smed-Smad1 led to the disappearance of dorsal markers along with the ectopic expression of ventral markers on the dorsal side of the treated animals. In almost all cases, a duplicated central nervous system differentiated dorsally after Smed-BMP or Smed-Smad1 RNAi. These defects were observed not only during regeneration but also in intact non-regenerating animals. Our results suggest that the BMP signaling pathway is conserved in planarians and that it plays a key role in the regeneration and maintenance of the dorsoventral axis.

  15. β-Catenin-Dependent Control of Positional Information along the AP Body Axis in Planarians Involves a Teashirt Family Member

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    Hanna Reuter

    2015-01-01

    Full Text Available Wnt/β-catenin signaling regulates tissue homeostasis and regeneration in metazoans. In planarians—flatworms with high regenerative potential—Wnt ligands are thought to control tissue polarity by shaping a β-catenin activity gradient along the anterior-posterior axis, yet the downstream mechanisms are poorly understood. We performed an RNA sequencing (RNA-seq-based screen and identified hundreds of β-catenin-dependent transcripts, of which several were expressed in muscle tissue and stem cells in a graded fashion. In particular, a teashirt (tsh ortholog was induced in a β-catenin-dependent manner during regeneration in planarians and zebrafish, and RNAi resulted in two-headed planarians. Strikingly, intact planarians depleted of tsh induced anterior markers and slowly transformed their tail into a head, reminiscent of β-catenin RNAi phenotypes. Given that β-catenin RNAi enhanced the formation of muscle cells expressing anterior determinants in tail regions, our study suggests that this pathway controls tissue polarity through regulating the identity of differentiating cells during homeostasis and regeneration.

  16. SMG-1 and mTORC1 act antagonistically to regulate response to injury and growth in planarians

    OpenAIRE

    Gonzalez-Estevez, Christina; Felix, Daniel A; Smith, Matthew D.; Paps, Jordi; Morley, Simon J.; James, Victoria; Sharp, Tyson V.; Aboobaker, A. Aziz

    2012-01-01

    Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth ...

  17. Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture.

    Science.gov (United States)

    Cebrià, Francesc; Newmark, Phillip A

    2005-08-01

    Conserved axon guidance mechanisms are essential for proper wiring of the nervous system during embryogenesis; however, the functions of these cues in adults and during regeneration remain poorly understood. Because freshwater planarians can regenerate a functional central nervous system (CNS) from almost any portion of their body, they are useful models in which to study the roles of guidance cues during neural regeneration. Here, we characterize two netrin homologs and one netrin receptor family member from Schmidtea mediterranea. RNAi analyses indicate that Smed-netR (netrin receptor) and Smed-netrin2 are required for proper CNS regeneration and that Smed-netR may mediate the response to Smed-netrin2. Remarkably, Smed-netR and Smed-netrin2 are also required in intact planarians to maintain the proper patterning of the CNS. These results suggest a crucial role for guidance cues, not only in CNS regeneration but also in maintenance of neural architecture.

  18. Regeneration of the epidermis and basement membrane of the planarian Dugesia japonica after total-body x irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hori, I.

    1979-03-01

    Fresh-water planarians were studied to examine effects of x rays on regeneration of the epidermis and basement membrane. During early stages of regeneration, free rhabdite-forming cells were associated with the wound epidermis and recruited it. In later stages, however, a gradual degeneration occurred in the epidermis and cells undergoing epithelization decreased in number. Eventually epidermal cells on the wound surface appeared necrotic as evidenced by pyknotic nuclei and vacuolized dense cytoplasm. The entire basement membrane could not be reconstituted in any stage after wounding though its precursor-like material was secreted in the interspace between epidermis and parenchyma. Morphological changes in extracellular products and in the cells surrounding the products suggest that epidermal cells which have covered the wound surface synthesize precursors of the basement membrane. Possible factors of a characteristic perturbation in epithelization and basement membrane formation after total-body irradiation are discussed.

  19. A forkhead transcription factor is wound-induced at the planarian midline and required for anterior pole regeneration.

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    M Lucila Scimone

    2014-01-01

    Full Text Available Planarian regeneration requires positional information to specify the identity of tissues to be replaced as well as pluripotent neoblasts capable of differentiating into new cell types. We found that wounding elicits rapid expression of a gene encoding a Forkhead-family transcription factor, FoxD. Wound-induced FoxD expression is specific to the ventral midline, is regulated by Hedgehog signaling, and is neoblast-independent. FoxD is subsequently expressed within a medial subpopulation of neoblasts at wounds involving head regeneration. Ultimately, FoxD is co-expressed with multiple anterior markers at the anterior pole. Inhibition of FoxD with RNA interference (RNAi results in the failure to specify neoblasts expressing anterior markers (notum and prep and in anterior pole formation defects. FoxD(RNAi animals fail to regenerate a new midline and to properly pattern the anterior blastema, consistent with a role for the anterior pole in organizing pattern of the regenerating head. Our results suggest that wound signaling activates a forkhead transcription factor at the midline and, if the head is absent, FoxD promotes specification of neoblasts at the prior midline for anterior pole regeneration.

  20. Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians.

    Science.gov (United States)

    Currie, Ko W; Pearson, Bret J

    2013-09-01

    In contrast to most adult organisms, freshwater planarians can regenerate any injured body part, including their entire nervous system. This allows for the analysis of genes required for both the maintenance and regeneration of specific neural subtypes. In addition, the loss of specific neural subtypes may uncover previously unknown behavioral roles for that neural population in the context of the adult animal. Here we show that two homeodomain transcription factor homologs, Smed-lhx1/5-1 and Smed-pitx, are required for the maintenance and regeneration of serotonergic neurons in planarians. When either lhx1/5-1 or pitx was knocked down by RNA interference, the expression of multiple canonical markers for serotonergic neurons was lost. Surprisingly, the loss of serotonergic function uncovered a role for these neurons in the coordination of motile cilia on the ventral epidermis of planarians that are required for their nonmuscular gliding locomotion. Finally, we show that in addition to its requirement in serotonergic neurons, Smed-pitx is required for proper midline patterning during regeneration, when it is required for the expression of the midline-organizing molecules Smed-slit in the anterior and Smed-wnt1 in the posterior.

  1. Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians.

    Science.gov (United States)

    Solana, Jordi; Irimia, Manuel; Ayoub, Salah; Orejuela, Marta Rodriguez; Zywitza, Vera; Jens, Marvin; Tapial, Javier; Ray, Debashish; Morris, Quaid; Hughes, Timothy R; Blencowe, Benjamin J; Rajewsky, Nikolaus

    2016-08-09

    In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans.

  2. Transplants in annelids, nemerteans and planarians: a tool for embryology, immunology, endocrinology and regeneration research

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    EE Zattara

    2015-09-01

    Full Text Available While transplantation procedures are often associated with biomedical applications, they are also an invaluable tool for basic research. This review focuses on how transplantation techniques have been used to understand the biology of three large lophotrochozoan phyla: Annelida, Nemertea and Platyhelmintha. I describe how transplantation paradigms have uncovered fundamental principles regarding the embryology, immunology, endocrinology and regeneration biology of representative species within these three groups. In particular, embryologists have used blastomere transplantations to show that both mosaic and regulative development occurs in animals within the phyla. Immunologists have used transplantation techniques to demonstrate that these invertebrates mount a variety of innate immune responses, some of which include surprising features that classically characterize adaptive immunity. Endocrinologists have used transplantation experiments to uncover hormonal requirements for sexual development and maturation. Meanwhile, regeneration biologists continue to address fundamental questions regarding tissue polarity, post-embryonic patterning, stem cell physiology, and the role of the nervous system in regeneration. Along with recent technical and conceptual advances, transplantation remains a powerful tool for invertebrate research.

  3. Effects of Copper on the Mobility and Regeneration of Planarian (Dugesia japonica)%铜对东亚三角涡虫运动和再生的影响

    Institute of Scientific and Technical Information of China (English)

    张秀芳; 毕思超; 仝昊; 庞秋香; 宋新华; 赵博生

    2013-01-01

    [目的]研究铜对涡虫运动和再生的影响.[方法]用不同浓度的铜溶液处理涡虫,分别进行了4和6d的培养试验,并设置空白对照组.[结果]成体涡虫24,48,72和96h运动的半抑制浓度(mIC50)分别为3.86,3.73,3.47和2.61 mg Cu2+/L.幼虫24,48,72和96 h运动的半抑制浓度(mIC50)分别为2.22,1.64,0.87和0.93 mg Cu2+/L.整体呈现出浓度效应关系.涡虫6d的眼点和耳突再生的半抑制浓度分别是0.76,0.78 mg Cu2+/L.呈现出浓度效应关系.[结论]支持涡虫作为水生生态系统的指示生物.%[Objective] A mobility measurement and a regeneration assay were conducted to explore the behavioral effects of Cu2+ on planarian Dugesia japonica.[Method] Dugesia japonica was respectively treated with different concentrations of copper solution for 4 and 6 d,and the blank control group was set.The mobility measurement and a regeneration assay of copper ions were determined by mlC50 and rlC50.[Result] The mobility IC50 for adult D.japonica at 24,48,72 and 96 h were 86,3.73,3.47 and 2.61 mg Cu2+/L,respectively.The mobility IC50s for newborns was 2.22,1.64,0.87 and 0.93 mg Cu2+/L,respectively.Although there was no significant difference between 24 and 48 h,and between 72 and 96 h of copper exposure,Cu2+ decreased newborns locomotor behavior in a concentration-dependent manner at sub-toxic concentrations.The regeneration IC50 of eyespots and auricles for adult D.japonica at 6 d were calculated as 0.76,0.78 mg Cu2+/L,respectively.The number of eyespots and auricles regeneration in planarian D.japonica showed a concentration-dependent manner.Results showed that newborns mobility and adult regeneration assay for D.japonica in a concentration-dependent manner.[Conclusion]The results of the present study suggest that planarians can be regarded as a useful bioindicator species for toxicological studies in the future.

  4. dlx and sp6-9 Control optic cup regeneration in a prototypic eye.

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    Sylvain W Lapan

    2011-08-01

    Full Text Available Optic cups are a structural feature of diverse eyes, from simple pit eyes to camera eyes of vertebrates and cephalopods. We used the planarian prototypic eye as a model to study the genetic control of optic cup formation and regeneration. We identified two genes encoding transcription factors, sp6-9 and dlx, that were expressed in the eye specifically in the optic cup and not the photoreceptor neurons. RNAi of these genes prevented formation of visible optic cups during regeneration. Planarian regeneration requires an adult proliferative cell population with stem cell-like properties called the neoblasts. We found that optic cup formation occurred only after migration of progressively differentiating progenitor cells from the neoblast population. The eye regeneration defect caused by dlx and sp6-9 RNAi can be explained by a failure to generate these early optic cup progenitors. Dlx and Sp6-9 genes function as a module during the development of diverse animal appendages, including vertebrate and insect limbs. Our work reveals a novel function for this gene pair in the development of a fundamental eye component, and it utilizes these genes to demonstrate a mechanism for total organ regeneration in which extensive cell movement separates new cell specification from organ morphogenesis.

  5. Morphological and molecular development of the eyes during embryogenesis of the freshwater planarian Schmidtea polychroa.

    Science.gov (United States)

    Martín-Durán, José María; Monjo, Francisco; Romero, Rafael

    2012-03-01

    Photoreception is one of the most primitive sensory functions in metazoans. Despite the diversity of forms and components of metazoan eyes, many studies have demonstrated the existence of a common cellular and molecular basis for their development. Genes like pax6, sine oculis, eyes absent, dachshund, otx, Rx and atonal are known to be associated with the specification and development of the eyes. In planarians, sine oculis, eyes absent and otxA play an essential role during the formation of the eye after decapitation, whereas pax6, considered by many authors as a master control gene for eye formation, does not seem to be involved in adult eye regeneration. Whether this is a peculiarity of adult planarians or, on the contrary, is also found in embryogenesis remains unknown. Herein, we characterize embryonic eye development in the planarian species Schmidtea polychroa using histological sections and molecular markers. Additionally, we analyse the expression pattern of the pax6-sine oculis-eyes absent-dachshund network, and the genes Rx, otxA, otxB and atonal. We demonstrate that eye formation in planarian embryos shows great similarities to adult eye regeneration, both at the cellular and molecular level. We thus conclude that planarian eyes exhibit divergent molecular patterning mechanisms compared to the prototypic ancestral metazoan eye.

  6. Planarians Sense Simulated Microgravity and Hypergravity

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    Teresa Adell

    2014-01-01

    Full Text Available Planarians are flatworms, which belong to the phylum Platyhelminthes. They have been a classical subject of study due to their amazing regenerative ability, which relies on the existence of adult totipotent stem cells. Nowadays they are an emerging model system in the field of developmental, regenerative, and stem cell biology. In this study we analyze the effect of a simulated microgravity and a hypergravity environment during the process of planarian regeneration and embryogenesis. We demonstrate that simulated microgravity by means of the random positioning machine (RPM set at a speed of 60 °/s but not at 10 °/s produces the dead of planarians. Under hypergravity of 3 g and 4 g in a large diameter centrifuge (LDC planarians can regenerate missing tissues, although a decrease in the proliferation rate is observed. Under 8 g hypergravity small planarian fragments are not able to regenerate. Moreover, we found an effect of gravity alterations in the rate of planarian scission, which is its asexual mode of reproduction. No apparent effects of altered gravity were found during the embryonic development.

  7. Comparative analysis of septic injury-inducible genes in phylogenetically distant model organisms of regeneration and stem cell research, the planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris

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    Vilcinskas Andreas

    2008-04-01

    Full Text Available Abstract Background The planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris have emerged as valuable model organisms in regeneration and stem cell research because of their prominent ability to regenerate a complete organism from any small body fragment. Under natural conditions wounding may result from predator attacks. These injuries open their innermost to a wide array of microbes present in the environment. Therefore, we established the hypothesis that regeneration processes may be linked to or at least accompanied by innate immune responses. In order to screen for septic wounding inducible genes we dissected individuals using a scalpel in the presence of a crude bacterial lipopolysaccharide preparation that is commonly used to elicit innate immune responses in animals and applied the suppression subtractive hybridization technique that selectively amplifies cDNAs of differentially expressed genes. Results This analysis revealed the induced expression of 27 genes in immune challenged Schmidtea and 35 genes in immune challenged Hydra. Identified genes from both animals encode proteins that share sequence similarities with potential homologues from other organisms known to be involved in signaling (e.g. calreticulin in Schmidtea and major vault protein in Hydra, stress responses (e.g. Hsp20 in Schmidtea and a PRP19/PSO4 DNA repair protein in Hydra, or to represent potential antimicrobial effectors (e.g. perforin-like protein in Schmidtea and PR-1-like protein and neutrophil cytosolic factor 1 in Hydra. As expected, septic wounding also induces expression of genes in Schmidtea and Hydra potentially involved in tissue remodeling associated with regeneration processes (e.g. matrix metalloproteinase in Schmidtea and a potential von Willebrand factor in Hydra. Conclusion We identified numerous immune-inducible genes in Hydra and Schmidtea that show a similar distribution corresponding to their physiological roles, although lineages of

  8. Nociception and escape behavior in planarians

    Science.gov (United States)

    Schoetz Collins, Eva-Maria

    2015-03-01

    Planarians are famous and widely studied for their regenerative capabilities. When a moving planarian is cut through the middle, the resulting head and tail pieces instantaneously retract and exhibit a characteristic escape response that differs from normal locomotion. In asexual animals, a similar reaction is observed when the planarian undergoes fission, suggesting that reproduction through self-tearing is a rather traumatic event for the animal. Using a multiscale approach, we unravel the dynamics, mechanics, and functional aspects of the planarian escape response. This musculature-driven gait was found to be a dominating response that supersedes the urge to feed or reproduce and quantitatively differs from other modes of planarian locomotion (gliding, peristalsis). We show that this escape gait constitutes the animal's pain response mediated by TRP like receptors and the neurotransmitter histamine, and that it can be induced through adverse thermal, mechanical, electrical or chemical stimuli. Ultimately, we will examine the neuronal subpopulations involved in mediating escape reflexes in planarians and how they are functionally restored during regeneration, thereby gaining mechanistic insight into the neuronal circuits required for specific behaviors. Supported by BWF CASI and Sloan Foundation.

  9. Dynamics of asexual reproduction in planarians

    Science.gov (United States)

    Schoetz, Eva-Maria; Lincoln, Bryan; Quinodoz, Sofia

    2011-03-01

    Planaria research is experiencing a resurgence due to the development of molecular tools, the Planarian genome project and database resources. Despite the resulting progress in planarian biology research, an extensive study of their physical properties remains to be undertaken. We developed a method to collect a large amount of data on the dynamics of clonal reproduction in the freshwater planarian S.mediterranea. The capability of planarians to regenerate an entire organism from a minuscule body part is based on a homogeneously distributed stem cell population that comprises 25-30% of all cells. Due to this stem cell contingent, planarians can reproduce spontaneously by dividing into a larger head and a smaller tail piece, which then will rebuild the missing body parts, including a central nervous system, within about a week. Time-lapse imaging allows us to characterize the fission process in detail, revealing the stages of the process as well as capturing the nature of the rupture itself. A traction force measurement setup is being developed to allow us to quantify the forces planarians exert on the substrate during reproduction, a macroscopic analog to the Traction Force Microscopy setups used to determine local cellular forces. We are particularly interested in the molecular processes during division and the interplay between tissue mechanics and cell signaling.

  10. Effects of irradiation on stem cell response to differentiation inhibitors in the Planarian Dugesia etrusca

    Energy Technology Data Exchange (ETDEWEB)

    Steele, V.E.; Lange, C.S.

    1976-07-01

    The planarian owes its extensive powers of regeneration to the possession of a totipotential stem cell system. The survival of the animal after irradiation depends mainly upon this system. In this respect the planarian is analogous to mammalian organ systems such as bone marrow or gut epithelium. The differentiated cells control the course of stem cell mediated tissue renewal by the secretion of differentiator and/or inhibitor substances. One such inhibitor substance, present in extracts prepared from homogenized whole planarians, specifically inhibits brain formation. This substance is organ specific, but not species specific. The differentiative integrity of the stem cells after irradiation is measured by comparing the regenerated brain volumes resulting from the presence or absence of the brain inhibitory extract during the regeneration period. Our data suggest that increasing doses of x irradiation decreases the ability of the stem cells to respond to differentiative substances. The data presented also explore the possibility of altering the postirradiation recovery pattern by shifting the differentiative demands placed on the stem cells. The final proportions of animals (one-half regenerated with, and one-half without, the extract) surviving after 60 days were not significantly different.

  11. Toxicity of tributyltin (TBT) to the freshwater planarian Schmidtea mediterranea.

    Science.gov (United States)

    Ofoegbu, Pearl U; Simão, Fátima C P; Cruz, Andreia; Mendo, Sónia; Soares, Amadeu M V M; Pestana, João L T

    2016-04-01

    The freshwater planarian Schmidtea mediterranea, one of the best characterized animal models for regeneration research and developmental biology, is being recognised as a useful species for ecotoxicological studies. Sensitive endpoints related to planarians' behaviour and regeneration can be easily evaluated after exposure to environmental stressors. In this work the sensitivity of S. mediterranea to a gradient of environmentally relevant concentrations of TBT was studied using multiple endpoints like survival, locomotion, head regeneration and DNA damage. In addition, a feeding assay based on planarian's predatory behaviour was performed. Results indicated that TBT is toxic to planarians with LC50's of 1.87 μg L(-1) Sn and 1.31 μg L(-1) Sn at 48 h and 96 h of exposure respectively. Sub-lethal exposures to TBT significantly reduced locomotion and feeding, delayed head regeneration and caused DNA damage in planarians. The behavioural endpoints (feeding and locomotion) and head regeneration were the most sensitive parameters followed by DNA damage. Similar to other aquatic model organisms, S. mediterranea showed high sensitivity towards TBT exposure. Based on our results, and though further research is required concerning their sensitivity to other pollutants, the use of freshwater planarians as a model species in ecotoxicology is discussed.

  12. SMG-1 and mTORC1 act antagonistically to regulate response to injury and growth in planarians.

    Directory of Open Access Journals (Sweden)

    Cristina González-Estévez

    Full Text Available Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling.

  13. SMG-1 and mTORC1 act antagonistically to regulate response to injury and growth in planarians.

    Science.gov (United States)

    González-Estévez, Cristina; Felix, Daniel A; Smith, Matthew D; Paps, Jordi; Morley, Simon J; James, Victoria; Sharp, Tyson V; Aboobaker, A Aziz

    2012-01-01

    Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling.

  14. Gap junction proteins: master regulators of the planarian stem cell response to tissue maintenance and injury.

    Science.gov (United States)

    Peiris, T Harshani; Oviedo, Néstor J

    2013-01-01

    Gap junction (GJ) proteins are crucial mediators of cell-cell communication during embryogenesis, tissue regeneration and disease. GJ proteins form plasma membrane channels that facilitate passage of small molecules across cells and modulate signaling pathways and cellular behavior in different tissues. These properties have been conserved throughout evolution, and in most invertebrates GJ proteins are known as innexins. Despite their critical relevance for physiology and disease, the mechanisms by which GJ proteins modulate cell behavior are poorly understood. This review summarizes findings from recent work that uses planarian flatworms as a paradigm to analyze GJ proteins in the complexity of the whole organism. The planarian model allows access to a large pool of adult somatic stem cells (known as neoblasts) that support physiological cell turnover and tissue regeneration. Innexin proteins are present in planarians and play a fundamental role in controlling neoblast behavior. We discuss the possibility that GJ proteins participate as cellular sensors that inform neoblasts about local and systemic physiological demands. We believe that functional analyses of GJ proteins will bring a complementary perspective to studies that focus on the temporal expression of genes. Finally, integrating functional studies along with molecular genetics and epigenetic approaches would expand our understanding of cellular regulation in vivo and greatly enhance the possibilities for rationally modulating stem cell behavior in their natural environment. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. HOX gene complement and expression in the planarian Schmidtea mediterranea

    Directory of Open Access Journals (Sweden)

    Ko W. Currie

    2016-03-01

    Full Text Available Abstract Background Freshwater planarians are well known for their regenerative abilities. Less well known is how planarians maintain spatial patterning in long-lived adult animals or how they re-pattern tissues during regeneration. HOX genes are good candidates to regulate planarian spatial patterning, yet the full complement or genomic clustering of planarian HOX genes has not yet been described, primarily because only a few have been detectable by in situ hybridization, and none have given morphological phenotypes when knocked down by RNAi. Results Because the planarian Schmidtea mediterranea (S. mediterranea is unsegmented, appendage less, and morphologically simple, it has been proposed that it may have a simplified HOX gene complement. Here, we argue against this hypothesis and show that S. mediterranea has a total of 13 HOX genes, which represent homologs to all major axial categories, and can be detected by whole-mount in situ hybridization using a highly sensitive method. In addition, we show that planarian HOX genes do not cluster in the genome, yet 5/13 have retained aspects of axially restricted expression. Finally, we confirm HOX gene axial expression by RNA deep-sequencing 6 anterior–posterior “zones” of the animal, which we provide as a dataset to the community to discover other axially restricted transcripts. Conclusions Freshwater planarians have an unappreciated HOX gene complexity, with all major axial categories represented. However, we conclude based on adult expression patterns that planarians have a derived body plan and their asexual lifestyle may have allowed for large changes in HOX expression from the last common ancestor between arthropods, flatworms, and vertebrates. Using our in situ method and axial zone RNAseq data, it should be possible to further understand the pathways that pattern the anterior–posterior axis of adult planarians.

  16. Size Matters!. Birth Size and a Size-Independent Stochastic Term Determine Asexual Reproduction Dynamics in Freshwater Planarians

    Science.gov (United States)

    Thomas, Michael A.; Quinodoz, Sofia; Schötz, Eva-Maria

    2012-09-01

    Asexual reproduction by division in higher organisms is rare, because a prerequisite is the ability to regenerate an entire organism from a piece of the original body. Freshwater planarians are one of the few animals that can reproduce this way, but little is known about the regulation of their reproduction cycles or strategies. We have previously shown that a planarian's reproduction strategy is randomized to include fragmentations, producing multiple offspring, as well as binary fissions, and can be partially explained by a maximum relative entropy principle. In this study we attempt to decompose the factors controlling their reproduction cycle. Based on recent studies on the cell cycle of budding yeast, which suggest that molecular noise in gene expression and cell size at birth together control cell cycle variability, we investigated whether the variability in planarian reproduction waiting times could be similarly regulated. We find that such a model can indeed explain the observed distribution of waiting times between birth and next reproductive event, suggesting that birth size and a stochastic noise term govern the reproduction dynamics of asexual planarians.

  17. Scrunching: a novel escape gait in planarians

    Science.gov (United States)

    Cochet-Escartin, Olivier; Mickolajczyk, Keith J.; Collins, Eva-Maria S.

    2015-10-01

    The ability to escape a predator or other life-threatening situations is central to animal survival. Different species have evolved unique strategies under anatomical and environmental constraints. In this study, we describe a novel musculature-driven escape gait in planarians, ‘scrunching’, which is quantitatively different from other planarian gaits, such as gliding and peristalsis. We show that scrunching is a conserved gait among different flatworm species, underlying its importance as an escape mechanism. We further demonstrate that it can be induced by a variety of physical stimuli, including amputation, high temperature, electric shock and low pH. We discuss the functional basis for scrunching as the preferential gait when gliding is impaired due to a disruption of mucus production. Finally, we show that the key mechanical features of scrunching are adequately captured by a simple biomechanical model that is solely based on experimental data from traction force microscopy and tissue rheology without fit parameters. Together, our results form a complete description of this novel form of planarian locomotion. Because scrunching has distinct dynamics, this gait can serve as a robust behavioral readout for studies of motor neuron and muscular functions in planarians and in particular the restoration of these functions during regeneration.

  18. Estimation of the toxicity of silver nanoparticles by using planarian flatworms.

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    Kustov, Leonid; Tiras, Kharlampii; Al-Abed, Souhail; Golovina, Natalia; Ananyan, Mikhail

    2014-03-01

    The regeneration of planarian flatworms - specifically, changes to the area of the regeneration bud (blastema) after surgical dissection - was proposed for use as a robust tool for estimating the toxicity of silver nanoparticles. The use of Planaria species, due to their unique regenerative capacity, could result in a reduction in the use of more-traditional laboratory animals for toxicity testing. With our novel approach, silver nanoparticles were found to be moderately toxic to the planarian, Girardia tigrina.

  19. The use of planarians as in vivo animal model to study laser biomodulation effects

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    Munin, Egberto; Garcia, Neila Maria Rocha; Braz, Allison Gustavo; de Souza, Sandra Cristina; Alves, Leandro Procópio; Salgado, Miguel Angel Castillo; Pilla, Viviane

    2007-02-01

    A variety of effects is attributed to the photo stimulation of tissues, such as improved healing of ulcers, analgesic and anti-inflammatory effects, stimulation of the proliferation of cells of different origins and stimulation of bone repair. Some investigations that make qualitative evaluations, like wound healing and evaluation of pain and edema, can be conducted in human subjects. However, deeper investigations on the mechanisms of action of the light stimulus and other quantitative works that requires biopsies or destructive analysis has to be carried out in animal models or in cell cultures. In this work, we propose the use of planarians as a model to study laser-tissue interaction. Contrasting with cell cultures and unicellular organisms, planarians are among the simplest organism having tissue layers, central nerve system, digestive and excretory system that might have been platforms for the evolution of the complex and highly organized tissues and organs found in higher organisms. For the present study, 685 nm laser radiation was employed. Planarians were cut transversally, in a plane posterior to the auricles. The body fragments were left to regenerate and the proliferation dynamics of stem cells was studied by using histological analysis. Maximum cell count was obtained for the laser treated group at the 4 th experimental day. At that experimental time, we also had the largest difference between the irradiated and the non-irradiated control group. We concluded that the studied flatworm could be an interesting animal model for in vivo studies of laser-tissue interactions.

  20. An X-ray shielded irradiation assay reveals EMT transcription factors control pluripotent adult stem cell migration in vivo in planarians.

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    Abnave, Prasad; Aboukhatwa, Ellen; Kosaka, Nobuyoshi; Thompson, James; Hill, Mark A; Aboobaker, A Aziz

    2017-09-11

    Migration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infections. Inappropriate migration also underpins the formation of metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in planarians. We demonstrate that we can use this system to study the molecular control of stem cell migration and show that snail-1, snail-2 and zeb-1 EMT transcription factor homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. We also observed that stem cells undergo homeostatic migration to anterior regions without local stem cells, in the absence of injury, maintaining tissue homeostasis. This requires the polarity determinant notum Our work establishes planarians as a suitable model for further in depth study of the processes controlling stem cell migration in vivo. © 2017. Published by The Company of Biologists Ltd.

  1. Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn planarians.

    Science.gov (United States)

    Nayak, Sunil; Roberts, Adam; Bires, Kristofer; Tallarida, Christopher S; Kim, Erin; Wu, Michael; Rawls, Scott M

    2016-09-01

    Planarians spend less time in light versus dark environments. We hypothesized that planarians withdrawn from cocaine or ethanol would spend even less time in the light than drug-naive planarians and that a benzodiazepine would inhibit this response. Planarians pretreated in cocaine or ethanol were placed at the midline of a Petri dish containing spring water that was split evenly into dark and light compartments. Planarians withdrawn from cocaine (1, 10, 100 μmol/l) or ethanol (0.01%) spent less time in the light compartment than water controls; however, this withdrawal response to cocaine (100 μmol/l) or ethanol (0.01%) was abolished by clorazepate (0-100 μmol/l). These data suggest that planarians, similar to rodents, show benzodiazepine-sensitive, anxiogenic-like responses during cocaine or alcohol withdrawal.

  2. The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians.

    Science.gov (United States)

    Zhu, Shu Jun; Pearson, Bret J

    2013-01-15

    Freshwater planarians are flatworms of the Lophotrochozoan superphylum and are well known for their regenerative abilities, which rely on a large population of pluripotent adult stem cells. However, the mechanisms by which planarians maintain a precise population of adult stem cells while balancing proliferation and cell death, remain to be elucidated. Here we have identified, characterized, and functionally tested the core Retinoblastoma (Rb) pathway components in planarian adult stem cell biology. The Rb pathway is an ancient and conserved mechanism of proliferation control from plants to animals and is composed of three core components: an Rb protein, and a transcription factor heterodimer of E2F and DP proteins. Although the planarian genome contains all components of the Rb pathway, we found that they have undergone gene loss from the ancestral state, similar to other species in their phylum. The single Rb homolog (Smed-Rb) was highly expressed in planarian stem cells and was required for stem cell maintenance, similar to the Rb-homologs p107 and p130 in vertebrates. We show that planarians and their phylum have undergone the most severe reduction in E2F genes observed thus far, and the single remaining E2F was predicted to be a repressive-type E2F (Smed-E2F4-1). Knockdown of either Smed-E2F4-1 or its dimerization partner Dp (Smed-Dp) by RNAi resulted in temporary hyper-proliferation. Finally, we showed that known Rb-interacting genes in other systems, histone deacetylase 1 and cyclinD (Smed-HDAC1; Smed-cycD), were similar to Rb in expression and phenotypes when knocked down by RNAi, suggesting that these established interactions with Rb may also be conserved in planarians. Together, these results showed that planarians use the conserved components of the Rb tumor suppressor pathway to control proliferation and cell survival.

  3. Control of Energy Regeneration for Electric Vehicle

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi; MAO Xiao-jian; LI Li-ming; ZHUO Bn

    2008-01-01

    To extend electric vehicle (EV) running distance, the vehicle energy regeneration (ER) method and vehicle control strategy were designed based on the original vehicle braking system. The ER principle of direct current (DC) brushless motor was studied, the motor mathematical model and PI control method with torque close-loop were built. This control method was applied to pure EV and the real road tests were evaluated.The ER control does not make any significant uncomfortable influence brake feeling and can save about 10% battery energy based on 3 times economic commission for Europe (ECE) driving cycles.

  4. Planarians in pharmacology: parthenolide is a specific behavioral antagonist of cocaine in the planarian Girardia tigrina.

    Science.gov (United States)

    Pagán, Oné R; Baker, Debra; Deats, Sean; Montgomery, Erica; Tenaglia, Matthew; Randolph, Clinita; Kotturu, Dharini; Tallarida, Christopher; Bach, Daniel; Wilk, Galia; Rawls, Scott; Raffa, Robert B

    2012-01-01

    Planarians are traditional animal models in developmental and regeneration biology. Recently, these organisms are arising as vertebrate-relevant animal models in neuropharmacology. Using an adaptation of published behavioral protocols, we have described the alleviation of cocaine-induced planarian seizure-like movements (pSLM) by a naturally-occurring sesquiterpene lactone, parthenolide. Interestingly, parthenolide does not prevent the expression of pSLM induced by amphetamines; in vertebrates, amphetamines interact with the same protein target as cocaine. Parthenolide is also unable to prevent pSLM elicited by the cholinergic com-pounds nicotine and cytisine or by the glutamatergic agents L- or D- glutamic acid or NMDA. Thus, we conclude that parthenolide is a specific anti-cocaine agent in this experimental organism.

  5. The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea.

    Science.gov (United States)

    Scimone, M Lucila; Meisel, Joshua; Reddien, Peter W

    2010-04-01

    Freshwater planarians are able to regenerate any missing part of their body and have extensive tissue turnover because of the action of dividing cells called neoblasts. Neoblasts provide an excellent system for in vivo study of adult stem cell biology. We identified the Smed-CHD4 gene, which is predicted to encode a chromatin-remodeling protein similar to CHD4/Mi-2 proteins, as required for planarian regeneration and tissue homeostasis. Following inhibition of Smed-CHD4 with RNA interference (RNAi), neoblast numbers were initially normal, despite an inability of the animals to regenerate. However, the proliferative response of neoblasts to amputation or growth stimulation in Smed-CHD4(RNAi) animals was diminished. Smed-CHD4(RNAi) animals displayed a dramatic reduction in the numbers of certain neoblast progeny cells. Smed-CHD4 was required for the formation of these neoblast progeny cells. Together, these results indicate that Smed-CHD4 is required for neoblasts to produce progeny cells committed to differentiation in order to control tissue turnover and regeneration and suggest a crucial role for CHD4 proteins in stem cell differentiation.

  6. The use of lectins as markers for differentiated secretory cells in planarians.

    Science.gov (United States)

    Zayas, Ricardo M; Cebrià, Francesc; Guo, Tingxia; Feng, Junjie; Newmark, Phillip A

    2010-11-01

    Freshwater planarians have reemerged as excellent models to investigate mechanisms underlying regeneration. The introduction of molecular tools has facilitated the study of planarians, but cell- and tissue-specific markers are still needed to examine differentiation of most cell types. Here we report the utility of fluorescent lectin-conjugates to label tissues in the planarian Schmidtea mediterranea. We show that 16 lectin-conjugates stain planarian cells or tissues; 13 primarily label the secretory cells, their cytoplasmic projections, and terminal pores. Thus, we examined regeneration of the secretory system using lectin markers and functionally characterized two genes expressed in the secretory cells: marginal adhesive gland-1 (mag-1) and Smed-reticulocalbin1 (Smed-rcn1). RNAi knockdown of these genes caused a dramatic reduction of secretory cell lectin staining, suggesting a role for mag-1 and Smed-rcn1 in secretory cell differentiation. Our results provide new insights into planarian secretory system regeneration and add new markers for labeling several planarian tissues.

  7. Comparative transcriptome analysis between planarian Dugesia japonica and other platyhelminth species

    Science.gov (United States)

    2012-01-01

    Background Planarians are considered to be among the extant animals close to one of the earliest groups of organisms that acquired a central nervous system (CNS) during evolution. Planarians have a bilobed brain with nine lateral branches from which a variety of external signals are projected into different portions of the main lobes. Various interneurons process different signals to regulate behavior and learning/memory. Furthermore, planarians have robust regenerative ability and are attracting attention as a new model organism for the study of regeneration. Here we conducted large-scale EST analysis of the head region of the planarian Dugesia japonica to construct a database of the head-region transcriptome, and then performed comparative analyses among related species. Results A total of 54,752 high-quality EST reads were obtained from a head library of the planarian Dugesia japonica, and 13,167 unigene sequences were produced by de novo assembly. A new method devised here revealed that proteins related to metabolism and defense mechanisms have high flexibility of amino-acid substitutions within the planarian family. Eight-two CNS-development genes were found in the planarian (cf. C. elegans 3; chicken 129). Comparative analysis revealed that 91% of the planarian CNS-development genes could be mapped onto the schistosome genome, but one-third of these shared genes were not expressed in the schistosome. Conclusions We constructed a database that is a useful resource for comparative planarian transcriptome studies. Analysis comparing homologous genes between two planarian species showed that the potential of genes is important for accumulation of amino-acid substitutions. The presence of many CNS-development genes in our database supports the notion that the planarian has a fundamental brain with regard to evolution and development at not only the morphological/functional, but also the genomic, level. In addition, our results indicate that the planarian CNS

  8. Comparative transcriptome analysis between planarian Dugesia japonica and other platyhelminth species

    Directory of Open Access Journals (Sweden)

    Nishimura Osamu

    2012-06-01

    Full Text Available Abstract Background Planarians are considered to be among the extant animals close to one of the earliest groups of organisms that acquired a central nervous system (CNS during evolution. Planarians have a bilobed brain with nine lateral branches from which a variety of external signals are projected into different portions of the main lobes. Various interneurons process different signals to regulate behavior and learning/memory. Furthermore, planarians have robust regenerative ability and are attracting attention as a new model organism for the study of regeneration. Here we conducted large-scale EST analysis of the head region of the planarian Dugesia japonica to construct a database of the head-region transcriptome, and then performed comparative analyses among related species. Results A total of 54,752 high-quality EST reads were obtained from a head library of the planarian Dugesia japonica, and 13,167 unigene sequences were produced by de novo assembly. A new method devised here revealed that proteins related to metabolism and defense mechanisms have high flexibility of amino-acid substitutions within the planarian family. Eight-two CNS-development genes were found in the planarian (cf. C. elegans 3; chicken 129. Comparative analysis revealed that 91% of the planarian CNS-development genes could be mapped onto the schistosome genome, but one-third of these shared genes were not expressed in the schistosome. Conclusions We constructed a database that is a useful resource for comparative planarian transcriptome studies. Analysis comparing homologous genes between two planarian species showed that the potential of genes is important for accumulation of amino-acid substitutions. The presence of many CNS-development genes in our database supports the notion that the planarian has a fundamental brain with regard to evolution and development at not only the morphological/functional, but also the genomic, level. In addition, our results indicate

  9. Freshwater Planarians as an Alternative Animal Model for Neurotoxicology.

    Science.gov (United States)

    Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S

    2015-09-01

    Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. SILAC Proteomics of Planarians Identifies Ncoa5 as a Conserved Component of Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Alexander Böser

    2013-11-01

    Full Text Available Planarian regeneration depends on the presence of pluripotent stem cells in the adult. We developed an in vivo stable isotope labeling by amino acids in cell culture (SILAC protocol in planarians to identify proteins that are enriched in planarian stem cells. Through a comparison of SILAC proteomes of normal and stem cell-depleted planarians and of a stem cell-enriched population of sorted cells, we identified hundreds of stem cell proteins. One of these is an ortholog of nuclear receptor coactivator-5 (Ncoa5/CIA, which is known to regulate estrogen-receptor-mediated transcription in human cells. We show that Ncoa5 is essential for the maintenance of the pluripotent stem cell population in planarians and that a putative mouse ortholog is expressed in pluripotent cells of the embryo. Our study thus identifies a conserved component of pluripotent stem cells, demonstrating that planarians, in particular, when combined with in vivo SILAC, are a powerful model in stem cell research.

  11. Dishevelled is essential for neural connectivity and planar cell polarity in planarians.

    Science.gov (United States)

    Almuedo-Castillo, Maria; Saló, Emili; Adell, Teresa

    2011-02-15

    The Wingless/Integrated (Wnt) signaling pathway controls multiple events during development and homeostasis. It comprises multiple branches, mainly classified according to their dependence on β-catenin activation. The Wnt/β-catenin branch is essential for the establishment of the embryonic anteroposterior (AP) body axis throughout the phylogenetic tree. It is also required for AP axis establishment during planarian regeneration. Wnt/β-catenin-independent signaling encompasses several different pathways, of which the most extensively studied is the planar cell polarity (PCP) pathway, which is responsible for planar polarization of cell structures within an epithelial sheet. Dishevelled (Dvl) is the hub of Wnt signaling because it regulates and channels the Wnt signal into every branch. Here, we analyze the role of Schmidtea mediterranea Dvl homologs (Smed-dvl-1 and Smed-dvl-2) using gene silencing. We demonstrate that in addition to a role in AP axis specification, planarian Dvls are involved in at least two different β-catenin-independent processes. First, they are essential for neural connectivity through Smed-wnt5 signaling. Second, Smed-dvl-2, together with the S. mediterranea homologs of Van-Gogh (Vang) and Diversin (Div), is required for apical positioning of the basal bodies of epithelial cells. These data represent evidence not only of the function of the PCP network in lophotrocozoans but of the involvement of the PCP core elements Vang and Div in apical positioning of the cilia.

  12. Sucrose produces withdrawal and dopamine-sensitive reinforcing effects in planarians.

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    Zhang, Charlie; Tallarida, Christopher S; Raffa, Robert B; Rawls, Scott M

    2013-03-15

    Sucrose produces physical dependence and reinforcing effects in rats. We hypothesized that similar effects could be demonstrated in planarians, the earliest animal with a centralized nervous system. We used two assays, one that quantifies withdrawal responses during drug absence as a reduction in motility and another that quantifies reinforcing effects using a conditioned place preference (CPP) design. In withdrawal experiments, planarians exposed to sucrose (1%) for 60 min and then tested in water for 5 min displayed reduced motility compared to water controls. Acute or continuous sucrose (1%) exposure did not affect motility. CPP experiments used a biased design to capitalize upon planarians' natural preference for the dark (pretest, sucrose conditioning in the light, posttest). Planarians conditioned with sucrose (1%) displayed a greater preference shift than sucrose-naïve planarians. Glucose (0.1, 1%), but not the non-digestible disaccharide lactulose (0.1, 1%), also produced a greater preference shift than water-exposed planarians. Development of sucrose-induced CPP was inhibited when sucrose (1%) conditioning was conducted in combination with dopamine receptor antagonists SCH 23390 (1 μM) or sulpiride (1 μM). These results suggest that the rewarding and reinforcing effects of sugar are highly conserved across species and that planarians offer an invertebrate model to provide insight into the pharmacological effects of sucrose and related sweeteners.

  13. PLETHORA Genes Control Regeneration by a Two-Step Mechanism.

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    Kareem, Abdul; Durgaprasad, Kavya; Sugimoto, Kaoru; Du, Yujuan; Pulianmackal, Ajai J; Trivedi, Zankhana B; Abhayadev, Pazhoor V; Pinon, Violaine; Meyerowitz, Elliot M; Scheres, Ben; Prasad, Kalika

    2015-04-20

    Regeneration, a remarkable example of developmental plasticity displayed by both plants and animals, involves successive developmental events driven in response to environmental cues. Despite decades of study on the ability of the plant tissues to regenerate a complete fertile shoot system after inductive cues, the mechanisms by which cells acquire pluripotency and subsequently regenerate complete organs remain unknown. Here, we show that three PLETHORA (PLT) genes, PLT3, PLT5, and PLT7, regulate de novo shoot regeneration in Arabidopsis by controlling two distinct developmental events. Cumulative loss of function of these three genes causes the intermediate cell mass, callus, to be incompetent to form shoot progenitors, whereas induction of PLT5 or PLT7 can render shoot regeneration hormone-independent. We further show that PLT3, PLT5, and PLT7 establish pluripotency by activating root stem cell regulators PLT1 and PLT2, as reconstitution of either PLT1 or PLT2 in the plt3; plt5-2; plt7 mutant re-established the competence to regenerate shoot progenitor cells but did not lead to the completion of shoot regeneration. PLT3, PLT5, and PLT7 additionally regulate and require the shoot-promoting factor CUP-SHAPED COTYLEDON2 (CUC2) to complete the shoot-formation program. Our findings uncouple the acquisition of competence to regenerate shoot progenitor cells from completion of shoot formation, indicating a two-step mechanism of de novo shoot regeneration that operates in all tested plant tissues irrespective of their origin. Our studies reveal intermediate developmental phases of regeneration and provide a deeper understanding into the mechanistic basis of regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The CCR4-NOT complex mediates deadenylation and degradation of stem cell mRNAs and promotes planarian stem cell differentiation.

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    Jordi Solana

    Full Text Available Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology.

  15. The CCR4-NOT complex mediates deadenylation and degradation of stem cell mRNAs and promotes planarian stem cell differentiation.

    Science.gov (United States)

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology.

  16. Inhibition of planar cell polarity extends neural growth during regeneration, homeostasis, and development.

    Science.gov (United States)

    Beane, Wendy S; Tseng, Ai-Sun; Morokuma, Junji; Lemire, Joan M; Levin, Michael

    2012-08-10

    The ability to stop producing or replacing cells at the appropriate time is essential, as uncontrolled growth can lead to loss of function and even cancer. Tightly regulated mechanisms coordinate the growth of stem cell progeny with the patterning needs of the host organism. Despite the importance of proper termination during regeneration, cell turnover, and embryonic development, very little is known about how tissues determine when patterning is complete during these processes. Using planarian flatworms, we show that the planar cell polarity (PCP) pathway is required to stop the growth of neural tissue. Although traditionally studied as regulators of tissue polarity, we found that loss of the PCP genes Vangl2, DAAM1, and ROCK by RNA interference (individually or together) resulted in supernumerary eyes and excess optical neurons in intact planarians, while regenerating planarians had continued hyperplasia throughout the nervous system long after controls ceased new growth. This failure to terminate growth suggests that neural tissues use PCP as a readout of patterning, highlighting a potential role for intact PCP as a signal to stem and progenitor cells to halt neuronal growth when patterning is finished. Moreover, we found this mechanism to be conserved in vertebrates. Loss of Vangl2 during normal development, as well as during Xenopus tadpole tail regeneration, also leads to the production of excess neural tissue. This evolutionarily conserved function of PCP represents a tractable new approach for controlling the growth of nerves.

  17. Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response.

    Science.gov (United States)

    Gurley, Kyle A; Elliott, Sarah A; Simakov, Oleg; Schmidt, Heiko A; Holstein, Thomas W; Sánchez Alvarado, Alejandro

    2010-11-01

    Regeneration is widespread throughout the animal kingdom, but our molecular understanding of this process in adult animals remains poorly understood. Wnt/β-catenin signaling plays crucial roles throughout animal life from early development to adulthood. In intact and regenerating planarians, the regulation of Wnt/β-catenin signaling functions to maintain and specify anterior/posterior (A/P) identity. Here, we explore the expression kinetics and RNAi phenotypes for secreted members of the Wnt signaling pathway in the planarian Schmidtea mediterranea. Smed-wnt and sFRP expression during regeneration is surprisingly dynamic and reveals fundamental aspects of planarian biology that have been previously unappreciated. We show that after amputation, a wounding response precedes rapid re-organization of the A/P axis. Furthermore, cells throughout the body plan can mount this response and reassess their new A/P location in the complete absence of stem cells. While initial stages of the amputation response are stem cell independent, tissue remodeling and the integration of a new A/P address with anatomy are stem cell dependent. We also show that WNT5 functions in a reciprocal manner with SLIT to pattern the planarian mediolateral axis, while WNT11-2 patterns the posterior midline. Moreover, we perform an extensive phylogenetic analysis on the Smed-wnt genes using a method that combines and integrates both sequence and structural alignments, enabling us to place all nine genes into Wnt subfamilies for the first time.

  18. A list of image files of planarians analyzed by in situ hybridication and immunohistochemical staining - Plabrain DB | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available aining Data detail Data name A list of image files of planarians analyzed by in situ hybridication and immun...ohistochemical staining Description of data contents This list includes file names of image... immunohistochemical staining in intact planarians or planarian head regions in the regeneration process. A set of the image... In situ hybridication and immunohistochemical staining . Data file File name: planaria_image_list.zip File ...URL: ftp://ftp.biosciencedbc.jp/archive/plabrain-db/LATEST/planaria_image_list.zip File size: 1KB Simple sea

  19. Tuning the orchestra: transcriptional pathways controlling axon regeneration

    Directory of Open Access Journals (Sweden)

    Andrea eTedeschi

    2012-01-01

    Full Text Available Trauma in the adult mammalian central nervous system leads to irreversible structural and functional impairment due to failed regeneration attempts. In contrast, neurons in the peripheral nervous system exhibit a greater regenerative ability. It has been proposed that an orchestrated sequence of transcriptional events controlling the expression of specific sets of genes may be the underlying basis of an early cell-autonomous regenerative response. Understanding whether transcriptional fine tuning, in parallel with strategies aimed at counteracting extrinsic impediments promotes axon re-growth following central nervous system injuries represents an exciting challenge for future studies. Transcriptional pathways controlling axon regeneration are presented and discussed in this review.

  20. Memory and obesity affect the population dynamics of asexual freshwater planarians

    Science.gov (United States)

    Dunkel, Jörn; Talbot, Jared; Schötz, Eva-Maria

    2011-04-01

    Asexual reproduction in multicellular organisms is a complex biophysical process that is not yet well understood quantitatively. Here, we report a detailed population study for the asexual freshwater planarian Schmidtea mediterranea, which can reproduce via transverse fission due to a large stem cell contingent. Our long-term observations of isolated non-interacting planarian populations reveal that the characteristic fission waiting time distributions for head and tail fragments differ significantly from each other. The stochastic fission dynamics of tail fragments exhibits non-negligible memory effects, implying that an accurate mathematical description of future data should be based on non-Markovian tree models. By comparing the effective growth of non-interacting planarian populations with those of self-interacting populations, we are able to quantify the influence of interactions between flatworms and physical conditions on the population growth. A surprising result is the non-monotonic relationship between effective population growth rate and nutrient supply: planarians exhibit a tendency to become 'obese' if the feeding frequency exceeds a critical level, resulting in a decreased reproduction activity. This suggests that these flatworms, which possess many genes homologous to those of humans, could become a new model system for studying dietary effects on reproduction and regeneration in multicellular organisms.

  1. [Asexual reproduction of planarians: metric studies].

    Science.gov (United States)

    Sheĭman, I M; Sedel'nikov, Z V; Shkutin, M F; Kreshchenko, N D

    2006-01-01

    A relationship was studied between fission and restoration of body and its individual parts under different experimental conditions in planarians of the Dugesia tigrina asexual race. The body and its fragments were studied morphomterically. After fission, the growth of planarians demonstrated topographic differences. The separated tail fragments and postpharyngeal area, in which the zone of fission is formed, were growing at the highest rate. More active growth was also noted over the long body axis. Fission and growth were more active in isolated planarians, as compared to those kept in groups.

  2. Regenerable Polyelectrolyte Membrane for Ultimate Fouling Control in Forward Osmosis.

    Science.gov (United States)

    Kang, Yan; Zheng, Sunxiang; Finnerty, Casey; Lee, Michael J; Mi, Baoxia

    2017-03-21

    This study demonstrated the feasibility of using regenerable polyelectrolyte membranes to ultimately control the irreversible membrane fouling in a forward osmosis (FO) process. The regenerable membrane was fabricated by assembling multiple polyethylenimine (PEI) and poly(acrylic acid) (PAA) bilayers on a polydopamine-functionalized polysulfone support. The resulting membrane exhibited higher water flux and lower solute flux in FO mode (with the active layer facing feed solution) than in PRO mode (with the active layer facing draw solution) using trisodium citrate as draw solute, most likely due to the unique swelling behavior of the polyelectrolyte membrane. Membrane regeneration was conducted by first dissembling the existing PEI-PAA bilayers using strong acid and then reassembling fresh PEI-PAA bilayers on the membrane support. It was found that, after the acid treatment, the first covalently bonded PEI layer and some realigned PAA remained on the membrane support, acting as a beneficial barrier that prevented the acid-foulant mixture from penetrating into the porous support during acid treatment. The water and solute flux of the regenerated membrane was very similar to that of the original membrane regardless of alginate fouling, suggesting an ultimate solution to eliminating the irreversible membrane fouling in an FO process. With a procedure similar to the typical membrane cleaning protocol, in situ membrane regeneration is not expected to noticeably increase the membrane operational burden but can satisfactorily avoid the expensive replacement of the entire membrane module after irreversible fouling, thereby hopefully reducing the overall cost of the membrane-based water-treatment system.

  3. miRNA control of tissue repair and regeneration.

    Science.gov (United States)

    Sen, Chandan K; Ghatak, Subhadip

    2015-10-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics.

  4. [Control of growth and expression of protooncogenes in regenerating liver].

    Science.gov (United States)

    Zou, Y; Gong, D Z; Cui, X Y; Mei, M H

    1996-01-01

    There are many humoral factors involved in the control of growth in regenerating liver. The complete hepatocyte mitogens such as hepatocyte growth factor (HGF), hepatic stimulator substance (HSS) can strongly stimulate hepatocyte DNA synthesis and mitosis. The hepatocyte growth inhibitors such as transforming growth factor beta 1 (TGF beta 1), however, do not stimulate DNA synthesis, but inhibit EGF mitogenesis. In addition, the comitogens such as norepinephrine and insulin are necessary to regulate the growth of regenerating liver. It has become clear that the hepatocyte proliferation and protooncogenes are linked closely. Some protooncogenes can express specifically as markers in the different phases of the cell cycle and in hepatocytes that enter the cell cycle (G0 to G1 transit) and continue to progress.

  5. Ultrastructural study of the chromatoid body in planarian regenerative cells

    Energy Technology Data Exchange (ETDEWEB)

    Hori, I. (Kanazawa Medical Univ., Ishikawa (Japan))

    1982-04-01

    The present paper deals with the ultrastructural changes of chromatoid bodies in planarian regenerative cells under normal and experimental conditions. A close relationship was usually observed between chromatoid bodies and pore regions of the nuclear envelope in these cells. The chromatoid bodies continued to decrease in size during cytodifferentiation of regenerative cells, though they did not disappear entirely throughout the regeneration processes. Cytochemistry and (/sup 3/H)uridine autoradiography have shown that the chromatoid body contains RNA. The typical morphological effect of actinomycin D became apparent in three organelles, i.e., nucleolus, polysome and chromatoid body. Ultrastructural changes in nucleoli were observed to occur after actinomycin treatment (20 ..mu..g/ml). The exposure to a higher dose of actinomycin (50 ..mu..g/ml) caused a decay of chromatoid bodies while nuclear envelopes retained numerous pores. Both the nucleoli and the chromatoid bodies disappeared in the sequential stages. Within the cytoplasm of such cells disintegration of a polysomal pattern was correlated with the disappearance of chromatoid bodies. The significance of the planarian chromatoid body is discussed in relation to differentiation of the regenerative cells.

  6. Exotic freshwater planarians currently known from Japan

    NARCIS (Netherlands)

    Sluys, R.; Kawakatsu, M.; Yamamoto, K.

    2010-01-01

    Biogeographical and taxonomic information on the four non-indigenous freshwater planarians of Japan is reviewed, viz. Dugesia austroasiatica Kawakatsu, 1985, Girardia tigrina (Girard, 1850), G. dorotocephala (Woodworth, 1897), and Rhodax evelinae? Marcus, 1947. The occurrence of Girardia dorotocepha

  7. The planarian P2X homolog in the regulation of asexual reproduction.

    Science.gov (United States)

    Sakurai, Toshihide; Lee, Hayoung; Kashima, Makoto; Saito, Yumi; Hayashi, Tetsutaro; Kudome-Takamatsu, Tomomi; Nishimura, Osamu; Agata, Kiyokazu; Shibata, Norito

    2012-01-01

    The growth in size of freshwater planarians in response to nutrient intake is limited by the eventual separation of tail and body fragments in a process called fission. The resulting tail fragment regenerates the entire body as an artificially amputated tail fragment would do, and the body fragment regenerates a tail, resulting in two whole planarians. This regenerative ability is supported by pluripotent somatic stem cells, called neoblasts, which are distributed throughout almost the entire body of the planarian. Neoblasts are the only planarian cells with the ability to continuously proliferate and give rise to all types of cells during regeneration, asexual reproduction, homeostasis, and growth. In order to investigate the molecular characteristics of neoblasts, we conducted an extensive search for neoblast-specific genes using the High Coverage Expression Profiling (HiCEP) method, and tested the function of the resulting candidates by RNAi. Disruption of the expression of one candidate gene, DjP2X-A (Dugesia japonica membrane protein P2X homologue), resulted in a unique phenotype. DjP2X-A RNAi leads to an increase of fission events upon feeding. We confirmed by immunohistochemistry that DjP2X-A is a membrane protein, and elucidated its role in regulating neoblast proliferation, thereby explaining its unique phenotype. We found that DjP2X-A decreases the burst of neoblast proliferation that normally occurs after feeding. We also found that DjP2X-A is required for normal proliferation in starved animals. We propose that DjP2X-A modulates stem cell proliferation in response to the nutritional condition.

  8. Fgf signalling controls diverse aspects of fin regeneration.

    Science.gov (United States)

    Shibata, Eri; Yokota, Yuki; Horita, Natsumi; Kudo, Akira; Abe, Gembu; Kawakami, Koichi; Kawakami, Atsushi

    2016-08-15

    Studies have shown that fibroblast growth factor (Fgf) signalling is necessary for appendage regeneration, but its exact function and the ligands involved during regeneration have not yet been elucidated. Here, we performed comprehensive expression analyses and identified fgf20a and fgf3/10a as major Fgf ligands in the wound epidermis and blastema, respectively. To reveal the target cells and processes of Fgf signalling, we performed a transplantation experiment of mesenchymal cells that express the dominant-negative Fgf receptor 1 (dnfgfr1) under control of the heat-shock promoter. This mosaic knockdown analysis suggested that Fgf signalling is directly required for fin ray mesenchyme to form the blastema at the early pre-blastema stage and to activate the regenerative cell proliferation at a later post-blastema stage. These results raised the possibility that the early epidermal Fgf20a and the later blastemal Fgf3/10a could be responsible for these respective processes. We demonstrated by gain-of-function analyses that Fgf20a induces the expression of distal blastema marker junbl, and that Fgf3 promotes blastema cell proliferation. Our study highlights that Fgfs in the wound epidermis and blastema have distinct functions to regulate fin regeneration cooperatively.

  9. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength

    OpenAIRE

    Paskin, Taylor R.; John Jellies; Jessica Bacher; Wendy S Beane

    2014-01-01

    Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli), planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian b...

  10. Proteomic profiling of the planarian Schmidtea mediterranea and its mucous reveals similarities with human secretions and those predicted for parasitic flatworms.

    Science.gov (United States)

    Bocchinfuso, Donald G; Taylor, Paul; Ross, Eric; Ignatchenko, Alex; Ignatchenko, Vladimir; Kislinger, Thomas; Pearson, Bret J; Moran, Michael F

    2012-09-01

    The freshwater planarian Schmidtea mediterranea has been used in research for over 100 years, and is an emerging stem cell model because of its capability of regenerating large portions of missing body parts. Exteriorly, planarians are covered in mucous secretions of unknown composition, implicated in locomotion, predation, innate immunity, and substrate adhesion. Although the planarian genome has been sequenced, it remains mostly unannotated, challenging both genomic and proteomic analyses. The goal of the current study was to annotate the proteome of the whole planarian and its mucous fraction. The S. mediterranea proteome was analyzed via mass spectrometry by using multidimensional protein identification technology with whole-worm tryptic digests. By using a proteogenomics approach, MS data were searched against an in silico translated planarian transcript database, and by using the Swiss-Prot BLAST algorithm to identify proteins similar to planarian queries. A total of 1604 proteins were identified. The mucous subproteome was defined through analysis of a mucous trail fraction and an extract obtained by treating whole worms with the mucolytic agent N-acetylcysteine. Gene Ontology analysis confirmed that the mucous fractions were enriched with secreted proteins. The S. mediterranea proteome is highly similar to that predicted for the trematode Schistosoma mansoni associated with intestinal schistosomiasis, with the mucous subproteome particularly highly conserved. Remarkably, orthologs of 119 planarian mucous proteins are present in human mucosal secretions and tear fluid. We suggest planarians have potential to be a model system for the characterization of mucous protein function and relevant to parasitic flatworm infections and diseases underlined by mucous aberrancies, such as cystic fibrosis, asthma, and other lung diseases.

  11. Wavelengths and regenerators sharing in GMPLS-controlled WSONs

    DEFF Research Database (Denmark)

    Manolova, Anna Vasileva; Giorgetti, A.; Cerutti, I.

    2010-01-01

    In Wavelength Switched Optical Networks (WSONs), sharing of protection wavelengths is an attractive strategy to increase survivability against failures. However, to guarantee an acceptable quality of transmission (QoT), both working and protection paths may need to undergo optical...... as for providing wavelength conversion. The main objective of this paper is the study of different strategies for the selection of regenerators and wavelengths in WSON with a GMPLS-based distributed control plane. Simulation results show a trade-off between the strategies achieving a high wavelength sharing...

  12. The More the Merrier?. Entropy and Statistics of Asexual Reproduction in Freshwater Planarians

    Science.gov (United States)

    Quinodoz, Sofia; Thomas, Michael A.; Dunkel, Jörn; Schötz, Eva-Maria

    2011-04-01

    The trade-off between traits in life-history strategies has been widely studied for sexual and parthenogenetic organisms, but relatively little is known about the reproduction strategies of asexual animals. Here, we investigate clonal reproduction in the freshwater planarian Schmidtea mediterranea, an important model organism for regeneration and stem cell research. We find that these flatworms adopt a randomized reproduction strategy that comprises both asymmetric binary fission and fragmentation (generation of multiple offspring during a reproduction cycle). Fragmentation in planarians has primarily been regarded as an abnormal behavior in the past; using a large-scale experimental approach, we now show that about one third of the reproduction events in S. mediterranea are fragmentations, implying that fragmentation is part of their normal reproductive behavior. Our analysis further suggests that certain characteristic aspects of the reproduction statistics can be explained in terms of a maximum relative entropy principle.

  13. Image files of planarians analyzed by in situ hybridication and immunohistochemical staining - Plabrain DB | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available ans or planarian head regions in the regeneration process. Images are displayed in A list of image files of ...file File name: planaria_image.zip File URL: ftp://ftp.biosciencedbc.jp/archive/p...labrain-db/LATEST/planaria_image.zip File size: 2.74MB Simple search URL - Data acquisition method Whole-mou

  14. The TALE class homeobox gene Smed-prep defines the anterior compartment for head regeneration.

    Directory of Open Access Journals (Sweden)

    Daniel A Felix

    2010-04-01

    Full Text Available Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is

  15. The TALE class homeobox gene Smed-prep defines the anterior compartment for head regeneration.

    Science.gov (United States)

    Felix, Daniel A; Aboobaker, A Aziz

    2010-04-22

    Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi) leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi) animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation) to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is required for

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Existence of two sexual races in the planarian species switching between asexual and sexual reproduction.

    Science.gov (United States)

    Kobayashi, Kazuya; Maezawa, Takanobu; Nakagawa, Haruka; Hoshi, Motonori

    2012-04-01

    In certain planarian species that are able to switch between asexual and sexual reproduction, determining whether a sexual has the ability to switch to the asexual state is problematic, which renders the definition of sexuals controversial. We experimentally show the existence of two sexual races, acquired and innate, in the planarian Dugesia ryukyuensis. Acquired sexuals used in this study were experimentally switched from asexuals. Inbreeding of acquired sexuals produced both innate sexuals and asexuals, but inbreeding of innate sexuals produced innate sexuals only and no asexuals. Acquired sexuals, but not innate sexuals, were forced to become asexuals by ablation and regeneration (asexual induction). This suggests that acquired sexuals somehow retain asexual potential, while innate sexuals do not. We also found that acquired sexuals have the potential to develop hyperplastic and supernumerary ovaries, while innate sexuals do not. In this regard, acquired sexuals were more prolific than innate sexuals. The differences between acquired and innate sexuals will provide a structure for examining the mechanism underlying asexual and sexual reproduction in planarians.

  18. PLETHORA genes control regeneration by a two-step mechanism

    NARCIS (Netherlands)

    Kareem, Abdul; Durgaprasad, Kavya; Sugimoto, Kaoru; Du, Yujuan; Pulianmackal, Ajai J.; Trivedi, Zankhana B.; Abhayadev, Pazhoor V.; Pinon, Violaine; Meyerowitz, Elliot M.; Scheres, Ben; Prasad, Kalika

    2015-01-01

    Summary Regeneration, a remarkable example of developmental plasticity displayed by both plants and animals, involves successive developmental events driven in response to environmental cues. Despite decades of study on the ability of the plant tissues to regenerate a complete fertile shoot syste

  19. An integrated view of asteroid regeneration: tissues, cells and molecules.

    Science.gov (United States)

    Ben Khadra, Yousra; Sugni, Michela; Ferrario, Cinzia; Bonasoro, Francesco; Varela Coelho, Ana; Martinez, Pedro; Candia Carnevali, Maria Daniela

    2017-03-22

    The potential for repairing and replacing cells, tissues, organs and body parts is considered a primitive attribute of life shared by all the organisms, even though it may be expressed to a different extent and which is essential for the survival of both individual and whole species. The ability to regenerate is particularly evident and widespread within invertebrates. In spite of the wide availability of experimental models, regeneration has been comprehensively explored in only a few animal systems (i.e., hydrozoans, planarians, urodeles) leaving many other animal groups unexplored. The regenerative potential finds its maximum expression in echinoderms. Among echinoderm classes, asteroids offer an impressive range of experimental models in which to study arm regeneration at different levels. Many studies have been recently carried out in order to understand the regenerative mechanisms in asteroids and the overall morphological processes have been well documented in different starfish species, such as Asterias rubens, Leptasterias hexactis and Echinaster sepositus. In contrast, very little is known about the molecular mechanisms that control regeneration development and patterning in these models. The origin and the fate of cells involved in the regenerative process remain a matter of debate and clear insights will require the use of complementary molecular and proteomic approaches to study this problem. Here, we review the current knowledge regarding the cellular, proteomic and molecular aspects of asteroid regeneration.

  20. Smed-dynA-1 is a planarian nervous system specific dynamin 1 homolog required for normal locomotion

    Directory of Open Access Journals (Sweden)

    Jared A. Talbot

    2014-06-01

    Full Text Available Dynamins are GTPases that are required for separation of vesicles from the plasma membrane and thus are key regulators of endocytosis in eukaryotic cells. This role for dynamin proteins is especially crucial for the proper function of neurons, where they ensure that synaptic vesicles and their neurotransmitter cargo are recycled in the presynaptic cell. Here we have characterized the dynamin protein family in the freshwater planarian Schmidtea mediterranea and showed that it possesses six dynamins with tissue specific expression profiles. Of these six planarian homologs, two are necessary for normal tissue homeostasis, and the loss of another, Smed-dynA-1, leads to an abnormal behavioral phenotype, which we have quantified using automated center of mass tracking. Smed-dynA-1 is primarily expressed in the planarian nervous system and is a functional homolog of the mammalian Dynamin I. The distinct expression profiles of the six dynamin genes makes planarians an interesting new system to reveal novel dynamin functions, which may be determined by their differential tissue localization. The observed complexity of neurotransmitter regulation combined with the tools of quantitative behavioral assays as a functional readout for neuronal activity, renders planarians an ideal system for studying how the nervous system controls behavior.

  1. Smed-dynA-1 is a planarian nervous system specific dynamin 1 homolog required for normal locomotion.

    Science.gov (United States)

    Talbot, Jared A; Currie, Ko W; Pearson, Bret J; Collins, Eva-Maria S

    2014-06-20

    Dynamins are GTPases that are required for separation of vesicles from the plasma membrane and thus are key regulators of endocytosis in eukaryotic cells. This role for dynamin proteins is especially crucial for the proper function of neurons, where they ensure that synaptic vesicles and their neurotransmitter cargo are recycled in the presynaptic cell. Here we have characterized the dynamin protein family in the freshwater planarian Schmidtea mediterranea and showed that it possesses six dynamins with tissue specific expression profiles. Of these six planarian homologs, two are necessary for normal tissue homeostasis, and the loss of another, Smed-dynA-1, leads to an abnormal behavioral phenotype, which we have quantified using automated center of mass tracking. Smed-dynA-1 is primarily expressed in the planarian nervous system and is a functional homolog of the mammalian Dynamin I. The distinct expression profiles of the six dynamin genes makes planarians an interesting new system to reveal novel dynamin functions, which may be determined by their differential tissue localization. The observed complexity of neurotransmitter regulation combined with the tools of quantitative behavioral assays as a functional readout for neuronal activity, renders planarians an ideal system for studying how the nervous system controls behavior.

  2. Planarians sense simulated microgravity and hypergravity

    NARCIS (Netherlands)

    T. Adell; E. Sálo; J.J.W.A. van Loon; G. Auletta

    2014-01-01

    Planarians are flatworms, which belong to the phylum Platyhelminthes. They have been a classical subject of study due to their amazing regenerative ability, which relies on the existence of adult totipotent stem cells. Nowadays they are an emerging model system in the field of developmental, regener

  3. [Regulation of asexual reproduction in the planarian Dugesia tigrina].

    Science.gov (United States)

    Sheĭman, I M; Sakharova, N Iu; Tiras, Kh P; Shkutin, M F; Isaeva, V V

    2003-01-01

    We studied asexual reproduction of planarians under the natural and artificial photoperiodic conditions. It was shown that light inhibits the fission of planarians, while darkness stimulates it. The diurnal dynamics of the fission of planarians demonstrated a circadian rhythm. This rhythm is stable, which is expressed when the conditions are experimentally changed: constant darkness, unnatural rhythm of light-darkness succession). However, this stability is affected at the time zone change. The planarians are adapted to new conditions and begin to fission at once in correspondence with the new diurnal regime.

  4. Signaling-based Joint Selection of Wavelengths and Regenerator Points in GMPLS-controlled WSONs

    DEFF Research Database (Denmark)

    Fagertun, Anna Manolova; Cerutti, I.; Andriolli, N.

    2011-01-01

    In wavelength switched optical networks (WSON), quality of transmission (QoT) can be guaranteed by regenerating the optical signal in intermediate nodes. Regeneration can also offer wavelength conversion. When only few regenerators are placed in the WSON, the main issue is to optimally select the....... Simulation results show a significant improvement of the connection blocking and fairness, as well as a reduced amount of used regenerators in the network compared with existing strategies, which are based on disjoint and non-distributed resource selection.......In wavelength switched optical networks (WSON), quality of transmission (QoT) can be guaranteed by regenerating the optical signal in intermediate nodes. Regeneration can also offer wavelength conversion. When only few regenerators are placed in the WSON, the main issue is to optimally select...... the nodes where regeneration and wavelength conversion should take place. This paper proposes a distributed strategy for joint selection of wavelengths and regeneration locations (points) in a dynamic WSON with GMPLS control plane. To support the strategy, extensions to the RSVP-TE protocol are proposed...

  5. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part.

  6. Silencing of Smed-betacatenin1 generates radial-like hypercephalized planarians.

    Science.gov (United States)

    Iglesias, Marta; Gomez-Skarmeta, Jose Luis; Saló, Emili; Adell, Teresa

    2008-04-01

    Little is known about the molecular mechanisms responsible for axis establishment during non-embryonic processes such as regeneration and homeostasis. To address this issue, we set out to analyze the role of the canonical Wnt pathway in planarians, flatworms renowned for their extraordinary morphological plasticity. Canonical Wnt signalling is an evolutionarily conserved mechanism to confer polarity during embryonic development, specifying the anteroposterior (AP) axis in most bilaterians and the dorsoventral (DV) axis in early vertebrate embryos. beta-Catenin is a key element in this pathway, although it is a bifunctional protein that is also involved in cell-cell adhesion. Here, we report the characterization of two beta-catenin homologs from Schmidtea mediterranea (Smed-betacatenin1/2). Loss of function of Smed-betacatenin1, but not Smed-betacatenin2, in both regenerating and intact planarians, generates radial-like hypercephalized planarians in which the AP axis disappears but the DV axis remains unaffected, representing a unique example of a striking body symmetry transformation. The radial-like hypercephalized phenotype demonstrates the requirement for Smed-betacatenin1 in AP axis re-establishment and maintenance, and supports a conserved role for canonical Wnt signalling in AP axis specification, whereas the role of beta-catenin in DV axis establishment would be a vertebrate innovation. When considered alongside the protein domains present in each S. mediterranea beta-catenin and the results of functional assays in Xenopus embryos demonstrating nuclear accumulation and axis induction with Smed-betacatenin1, but not Smed-betacatenin2, these data suggest that S. mediterranea beta-catenins could be functionally specialized and that only Smed-betacatenin1 is involved in Wnt signalling.

  7. Maturity Control on the Patterns of Hydrocarbon Regeneration from Coal

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Rock-Eval pyrolysis and Py-GC experiments on naturally and artificially matured coal samples were carried out. The results suggest that both depolymerization and defuctionalization exist during the maturation and evolution of coal. The patterns of hydrocarbon regeneration are diverse at different stages of the maturation and evolution. When the vitrinite reflectance (R0) is 0.7%- 0.9%, bitumen is the richest in coal while activation energy is the minimum, and the temperature of peak yield is lower than that of primary hydrocarbon generation. However, if reflectance is greater than 0.9%, defunctionalization predominates and the temperature of peak regeneration is shown in lagging compared with the primary hydrocarbon generation. When reflectance is out of the "oil window", the peak temperature of hydrocarbon regeneration and that of the primary hydrocarbon generation seems to be continuous.

  8. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength.

    Directory of Open Access Journals (Sweden)

    Taylor R Paskin

    Full Text Available Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli, planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green, as well as ultraviolet (UV and infrared (IR which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV causing the most intense photophobic responses while longer wavelengths produce no effect (red or an apparent attraction (IR. In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment.

  9. Transcriptional regulators in the Hippo signaling pathway control organ growth in Xenopus tadpole tail regeneration.

    Science.gov (United States)

    Hayashi, Shinichi; Ochi, Haruki; Ogino, Hajime; Kawasumi, Aiko; Kamei, Yasuhiro; Tamura, Koji; Yokoyama, Hitoshi

    2014-12-01

    The size and shape of tissues are tightly controlled by synchronized processes among cells and tissues to produce an integrated organ. The Hippo signaling pathway controls both cell proliferation and apoptosis by dual signal-transduction states regulated through a repressive kinase cascade. Yap1 and Tead, transcriptional regulators that act downstream of the Hippo signaling kinase cascade, have essential roles in regulating cell proliferation. In amphibian limb or tail regeneration, the local tissue outgrowth terminates when the correct size is reached, suggesting that organ size is strictly controlled during epimorphic organ-level regeneration. We recently demonstrated that Yap1 is required for the regeneration of Xenopus tadpole limb buds (Hayashi et al., 2014, Dev. Biol. 388, 57-67), but the molecular link between the Hippo pathway and organ size control in vertebrate epimorphic regeneration is not fully understood. To examine the requirement of Hippo pathway transcriptional regulators in epimorphic regeneration, including organ size control, we inhibited these regulators during Xenopus tadpole tail regeneration by overexpressing a dominant-negative form of Yap (dnYap) or Tead4 (dnTead4) under a heat-shock promoter in transgenic animal lines. Each inhibition resulted in regeneration defects accompanied by reduced cell mitosis and increased apoptosis. Single-cell gene manipulation experiments indicated that Tead4 cell-autonomously regulates the survival of neural progenitor cells in the regenerating tail. In amphibians, amputation at the proximal level of the tail (deep amputation) results in faster regeneration than that at the distal level (shallow amputation), to restore the original-sized tail with similar timing. However, dnTead4 overexpression abolished the position-dependent differential growth rate of tail regeneration. These results suggest that the transcriptional regulators in the Hippo pathway, Tead4 and Yap1, are required for general vertebrate

  10. Scaffolds to control inflammation and facilitate dental pulp regeneration.

    Science.gov (United States)

    Colombo, John S; Moore, Amanda N; Hartgerink, Jeffrey D; D'Souza, Rena N

    2014-04-01

    In dentistry, the maintenance of a vital dental pulp is of paramount importance because teeth devitalized by root canal treatment may become more brittle and prone to structural failure over time. Advanced carious lesions can irreversibly damage the dental pulp by propagating a sustained inflammatory response throughout the tissue. Although the inflammatory response initially drives tissue repair, sustained inflammation has an enormously destructive effect on the vital pulp, eventually leading to total necrosis of the tissue and necessitating its removal. The implications of tooth devitalization have driven significant interest in the development of bioactive materials that facilitate the regeneration of damaged pulp tissues by harnessing the capacity of the dental pulp for self-repair. In considering the process by which pulpitis drives tissue destruction, it is clear that an important step in supporting the regeneration of pulpal tissues is the attenuation of inflammation. Macrophages, key mediators of the immune response, may play a critical role in the resolution of pulpitis because of their ability to switch to a proresolution phenotype. This process can be driven by the resolvins, a family of molecules derived from fatty acids that show great promise as therapeutic agents. In this review, we outline the importance of preserving the capacity of the dental pulp to self-repair through the rapid attenuation of inflammation. Potential treatment modalities, such as shifting macrophages to a proresolving phenotype with resolvins are described, and a range of materials known to support the regeneration of dental pulp are presented. Copyright © 2014. Published by Elsevier Inc.

  11. Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

    Directory of Open Access Journals (Sweden)

    James J Collins

    Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

  12. Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons.

    Science.gov (United States)

    Berg, Daniel A; Kirkham, Matthew; Wang, Heng; Frisén, Jonas; Simon, András

    2011-04-08

    Appropriate termination of regenerative processes is critical for producing the correct number of cells in tissues. Here we provide evidence for an end-product inhibition of dopamine neuron regeneration that is mediated by dopamine. Ablation of midbrain dopamine neurons leads to complete regeneration in salamanders. Regeneration involves extensive neurogenesis and requires activation of quiescent ependymoglia cells, which express dopamine receptors. Pharmacological compensation for dopamine loss by L-dopa inhibits ependymoglia proliferation and regeneration in a dopamine receptor-signaling-dependent manner, specifically after ablation of dopamine neurons. Systemic administration of the dopamine receptor antagonist haloperidol alone causes ependymoglia proliferation and the appearance of excessive number of neurons. Our data show that stem cell quiescence is under dopamine control and provide a model for termination once normal homeostasis is restored. The findings establish a role for dopamine in the reversible suppression of neurogenesis in the midbrain and have implications for regenerative strategies in Parkinson's disease.

  13. MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary Alveolar Regeneration

    Directory of Open Access Journals (Sweden)

    Zhe Liu

    2016-08-01

    Full Text Available The pulmonary alveolar epithelium undergoes extensive regeneration in response to lung injuries, including lung resection. In recent years, our understanding of cell lineage relationships in the pulmonary alveolar epithelium has improved significantly. However, the molecular and cellular mechanisms that regulate pneumonectomy (PNX-induced alveolar regeneration remain largely unknown. In this study, we demonstrate that mechanical-tension-induced YAP activation in alveolar stem cells plays a major role in promoting post-PNX alveolar regeneration. Our results indicate that JNK and p38 MAPK signaling is critical for mediating actin-cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells. Moreover, we show that Cdc42-controlled actin remodeling is required for the activation of JNK, p38, and YAP in post-PNX lungs. Our findings together establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for promoting alveolar regeneration in response to mechanical tension in the lung.

  14. Smed-SmB, a member of the LSm protein superfamily, is essential for chromatoid body organization and planarian stem cell proliferation.

    Science.gov (United States)

    Fernandéz-Taboada, Enrique; Moritz, Sören; Zeuschner, Dagmar; Stehling, Martin; Schöler, Hans R; Saló, Emili; Gentile, Luca

    2010-04-01

    Planarians are an ideal model system to study in vivo the dynamics of adult pluripotent stem cells. However, our knowledge of the factors necessary for regulating the 'stemness' of the neoblasts, the adult stem cells of planarians, is sparse. Here, we report on the characterization of the first planarian member of the LSm protein superfamily, Smed-SmB, which is expressed in stem cells and neurons in Schmidtea mediterranea. LSm proteins are highly conserved key players of the splicing machinery. Our study shows that Smed-SmB protein, which is localized in the nucleus and the chromatoid body of stem cells, is required to safeguard the proliferative ability of the neoblasts. The chromatoid body, a cytoplasmatic ribonucleoprotein complex, is an essential regulator of the RNA metabolism required for the maintenance of metazoan germ cells. However, planarian neoblasts and neurons also rely on its functions. Remarkably, Smed-SmB dsRNA-mediated knockdown results in a rapid loss of organization of the chromatoid body, an impairment of the ability to post-transcriptionally process the transcripts of Smed-CycB, and a severe proliferative failure of the neoblasts. This chain of events leads to a quick depletion of the neoblast pool, resulting in a lethal phenotype for both regenerating and intact animals. In summary, our results suggest that Smed-SmB is an essential component of the chromatoid body, crucial to ensure a proper RNA metabolism and essential for stem cell proliferation.

  15. A novel invertebrate trophic factor related to invertebrate neurotrophins is involved in planarian body regional survival and asexual reproduction.

    Science.gov (United States)

    Bueno, David; Fernàndez-Rodríguez, Juana; Cardona, Albert; Hernàndez-Hernàndez, Victor; Romero, Rafael

    2002-12-15

    Trophic factors are a heterogeneous group of molecules that promote cell growth and survival. In freshwater planarians, the small secreted protein TCEN49 is linked to the regional maintenance of the planarian central body region. To investigate its function in vivo, we performed loss-of-function and gain-of-function experiments by RNA interference and by the implantation of microbeads soaked in TCEN49, respectively. We show that TCEN49 behaves as a trophic factor involved in central body region neuron survival. In planarian tail regenerates, tcen49 expression inhibition by double-stranded RNA interference causes extensive apoptosis in various cell types, including nerve cells. This phenotype is rescued by the implantation of microbeads soaked in TCEN49 after RNA interference. On the other hand, in organisms committed to asexual reproduction, both tcen49 mRNA and its protein are detected not only in the central body region but also in the posterior region, expanding from cells close to the ventral nerve chords. In some cases, the implantation of microbeads soaked in TCEN49 in the posterior body region drives organisms to reproduce asexually, and the inhibition of tcen49 expression obstructs this process, suggesting a link between the central nervous system, TCEN49, regional induction, and asexual reproduction. Finally, the distribution of TCEN49 cysteine and tyrosine residues also points to a common evolutionary origin for TCEN49 and molluscan neurotrophins.

  16. Tissue absence initiates regeneration through follistatin-mediated inhibition of activin signaling.

    Science.gov (United States)

    Gaviño, Michael A; Wenemoser, Danielle; Wang, Irving E; Reddien, Peter W

    2013-09-10

    Regeneration is widespread, but mechanisms that activate regeneration remain mysterious. Planarians are capable of whole-body regeneration and mount distinct molecular responses to wounds that result in tissue absence and those that do not. A major question is how these distinct responses are activated. We describe a follistatin homolog (Smed-follistatin) required for planarian regeneration. Smed-follistatin inhibition blocks responses to tissue absence but does not prevent normal tissue turnover. Two activin homologs (Smed-activin-1 and Smed-activin-2) are required for the Smed-follistatin phenotype. Finally, Smed-follistatin is wound-induced and expressed at higher levels following injuries that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed-Activin proteins to trigger regeneration specifically following injuries involving tissue absence and identify a mechanism critical for regeneration initiation, a process important across the animal kingdom. DOI:http://dx.doi.org/10.7554/eLife.00247.001.

  17. A taste for exotic food: Neotropical land planarians feeding on an invasive flatworm

    Directory of Open Access Journals (Sweden)

    Piter K. Boll

    2015-10-01

    Full Text Available Invasive species establish successfully in new habitats especially due to their ability to include new species in their diet and due to the freedom from natural enemies. However, native species may also adapt to the use of new elements in their ecosystem. The planarian Endeavouria septemlineata, first recorded in Hawaii, was later found in Brazil. Recently, we found it in human-disturbed areas in southern Brazil and here we investigate its interactions with other invertebrates both in the field and in the laboratory. We observed the species in the field during collecting activities and hence maintained some specimens alive in small terraria in the laboratory, where we offered different invertebrate species as potential prey and also put them in contact with native land planarians in order to examine their interaction. Both in the field and in the laboratory, E. septemlineata showed a gregarious behavior and was found feeding on woodlice, millipedes, earwigs and gastropods. In the laboratory, specimens often did not attack live prey, but immediately approached dead specimens, indicating a scavenging behavior. In an experiment using the slug Deroceras laeve and the woodlouse Atlantoscia floridana, there was a higher consumption of dead specimens of woodlice and slugs compared to live specimens, as well as a higher consumption of dead woodlice over dead slugs. Four native land planarians of the genus Obama and one of the genus Paraba attacked and consumed E. septemlineata, which, after the beginning of the attack, tried to escape by tumbling or using autotomy. As a scavenger, E. septemlineata would have no impact on the populations of species used as food, but could possibly exclude native scavengers by competition. On the other hand, its consumption by native land planarians may control its spread and thus reduce its impact on the ecosystem.

  18. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    Directory of Open Access Journals (Sweden)

    Jessica P Hollenbach

    Full Text Available Lynch syndrome (LS leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  19. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    Science.gov (United States)

    Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  20. Design of a Regenerable Air Revitalization Control System for the ABRS Plant Growth Facility

    Science.gov (United States)

    Monje, Oscar; Monje, Oscar; Shellack, James; Mortenson, Todd; Wells, Howard

    Design of a Regenerable Air Revitalization Control System for the ABRS Plant Growth Facility. O. Monje Space Life Sciences Laboratory, Dynamac Corp., DYN-3, Kennedy Space Center, FL 32899, USA J.L. Shellack, T.E. Mortenson, and H.W. Wells. Bionetics Corporation, BIO-1, Kennedy Space Center, FL 32899, USA The Advanced Biological Research System (ABRS) is a rear-breathing, single middeck locker equivalent plant growth system. ABRS is composed of two independently controlled growth chambers (each with 330 cm2 of growth area). The air revitalization system in each chamber is composed of two subsystems: CO2 Control and a Ethylene/VOC Control. The CO2 Control subsystem must control chamber [CO2] within a range of 300-2000 ppm, with a nominal setpoint of 1500 ppm. The Ethylene/VOC Control subsystem is required to maintain chamber ethylene concentration at ¡50 ppb. Previous spaceflight plant payloads have used non-regenerable cartridges for CO2 control and photocatalytic scrubbers for controlling concentrations of volatile organic compounds (VOCs). Non-regenerable systems have used LiOH cartridges for [CO2] control with a combination of Purafil (KMnO4)/Activated charcoal for scrubbing VOCs. Regenerable air revitalization systems offer the potential for reducing the mass and volume of consumables used during spaceflight plant experiments. A system utilizing technologies employing regenerable adsorbents: zeolites 13X and 5A for CO2 control and Carbosieve SIII (C molecular sieve) for VOC control has been designed for ABRS. The filter cartridges were sized using expected chamber leak rates, measurements of adsorptive capacities, and measured CO2 consumption and VOC generation rates.

  1. Ten year regeneration of southern Appalachian hardwood clearcuts after controlling residual trees

    Science.gov (United States)

    P.M. Zaldivar-Garcia; D.T. Tew

    1991-01-01

    Two upland hardwood stands were clearcut in 1978 and three treatments to control the unmerchantable and/or cull trees were applied. The treatments applied to the residual trees were chainsaw felling, herbicide injection, and a control, where residual trees were left standing. Regeneration was sampled 10 years after the cutting.

  2. [Toxic effects of essential oil of Cannabis sativa L. and main constituents on planarian (Dugesia tigrina) (author's transl)].

    Science.gov (United States)

    Fournier, G; Lenicque, P M; Paris, M R

    1978-11-01

    Regenerating pieces of planarian worms are able to absorbe insoluble substances deposited on the base of the vessels in which they are cultivated. This biological test was used to study the toxic effects of the essential oil of Cannabis sativa L. The hydrocarbons such as pinene (alpha and beta), caryophyllene and so on were not toxic. On the contrary caryophyllene oxide was highly toxic. It was not possible to detect any protection by 5-hydroxytryptamine as it was the case against delta 1-tétrahydro-cannabinol and cannabidiol.

  3. Argonaute-2 regulates the proliferation of adult stem cells in planarian

    Institute of Scientific and Technical Information of China (English)

    Yong-Qin Li; An Zeng; Xiao-Shuai Han; Chen Wang; Ge Li; Zhen-Chao Zhang; Jian-Yong Wang; Yong-Wen Qin; Qing Jing

    2011-01-01

    Dear Editor,Planarian Schmidtea mediterranea has extraordinary regeneration capabilities due to the abundance of adult stem cells (ASCs) known as neoblasts,which make planarian a powerful in vivo system to study ASC biology [ 1 ].The Argonaute (AGO) family proteins are defined by the presence of Piwi-Argonaute-Zwille (PAZ)) and PIWI domains [2],and mediate silencing via cleavage of mRNAs [3] or inhibition of translation [4].The AGO family proteins fall into two subfamilies,one named after Arabidopsis Argonaute and the other after Drosophila PIWI [5].In most organisms investigated so far,PIWI proteins bind Piwi-interacting RNAs (piRNAs) and are functionally involved in the regulation of germ cells [6,7].By contrast,AGO proteins have distinct roles in the smallRNA-mediated gene silencing pathway.In Drosophila,AGO1 has been illustrated to be engaged in the miRNA pathway,while AGO2 plays an important role in the siRNA-mediated gene regulation [4].

  4. Egf Signaling Directs Neoblast Repopulation by Regulating Asymmetric Cell Division in Planarians.

    Science.gov (United States)

    Lei, Kai; Thi-Kim Vu, Hanh; Mohan, Ryan D; McKinney, Sean A; Seidel, Chris W; Alexander, Richard; Gotting, Kirsten; Workman, Jerry L; Sánchez Alvarado, Alejandro

    2016-08-22

    A large population of proliferative stem cells (neoblasts) is required for physiological tissue homeostasis and post-injury regeneration in planarians. Recent studies indicate that survival of a few neoblasts after sublethal irradiation results in the clonal expansion of the surviving stem cells and the eventual restoration of tissue homeostasis and regenerative capacity. However, the precise mechanisms regulating the population dynamics of neoblasts remain largely unknown. Here, we uncovered a central role for epidermal growth factor (EGF) signaling during in vivo neoblast expansion mediated by Smed-egfr-3 (egfr-3) and its putative ligand Smed-neuregulin-7 (nrg-7). Furthermore, the EGF receptor-3 protein localizes asymmetrically on the cytoplasmic membrane of neoblasts, and the ratio of asymmetric to symmetric cell divisions decreases significantly in egfr-3(RNAi) worms. Our results not only provide the first molecular evidence of asymmetric stem cell divisions in planarians, but also demonstrate that EGF signaling likely functions as an essential regulator of neoblast clonal expansion.

  5. A mex3 homolog is required for differentiation during planarian stem cell lineage development.

    Science.gov (United States)

    Zhu, Shu Jun; Hallows, Stephanie E; Currie, Ko W; Xu, ChangJiang; Pearson, Bret J

    2015-06-26

    Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

  6. Planarian (Platyhelminthes, Tricladida Diversity and Molecular Markers: A New View of an Old Group

    Directory of Open Access Journals (Sweden)

    Marta Álvarez-Presas

    2014-04-01

    Full Text Available Planarians are a group of free-living platyhelminths (triclads best-known largely due to long-standing regeneration and pattern formation research. However, the group’s diversity and evolutionary history has been mostly overlooked. A few taxonomists have focused on certain groups, resulting in the description of many species and the establishment of higher-level groups within the Tricladida. However, the scarcity of morphological features precludes inference of phylogenetic relationships among these taxa. The incorporation of molecular markers to study their diversity and phylogenetic relationships has facilitated disentangling many conundrums related to planarians and even allowed their use as phylogeographic model organisms. Here, we present some case examples ranging from delimiting species in an integrative style, and barcoding them, to analysing their evolutionary history on a lower scale to infer processes affecting biodiversity origin, or on a higher scale to understand the genus level or even higher relationships. In many cases, these studies have allowed proposing better classifications and resulted in taxonomical changes. We also explain shortcomings resulting in a lack of resolution or power to apply the most up-to-date data analyses. Next-generation sequencing methodologies may help improve this situation and accelerate their use as model organisms.

  7. Slo1 regulates ethanol-induced scrunching in freshwater planarians

    Science.gov (United States)

    Cochet-Escartin, Olivier; Carter, Jason A.; Chakraverti-Wuerthwein, Milena; Sinha, Joydeb; Collins, Eva-Maria S.

    2016-10-01

    When freshwater planarians are exposed to a low-percentage (0.5%-1%) alcohol solution, they display a characteristic ‘drunken’ phenotype. Here we show that this drunken phenotype is a mixture of cilia-mediated gliding and scrunching, a muscular-based planarian gait which we recently demonstrated to be triggered by adverse environmental stimuli. At exogenous ethanol concentrations ≥2% (v/v), planarians become gradually immobilized and ultimately die. Using RNA interference (RNAi) for targeted gene knockdown, we elucidate the molecular basis for ethanol sensing and show that the big potassium ion channel SLO1 is necessary for ethanol sensitivity in planarians. Because slo1(RNAi) animals maintain their ability to scrunch in response to other adverse triggers, these results suggest that slo1 specifically regulates ethanol sensitivity and not the scrunching gait per se. Furthermore, this study demonstrates the ease of performing pharmacological studies in planarians. Combined with the worms’ amenability to quantitative behavioral assays and targeted gene knockdown, planarians are a valuable model organism for studying the effect of neuroactive compounds on brain function and behavior.

  8. Temperature control during regeneration of activated carbon fiber cloth with resistance-feedback.

    Science.gov (United States)

    Johnsen, David L; Rood, Mark J

    2012-10-16

    Electrothermal swing adsorption (ESA) of organic compounds from gas streams with activated carbon fiber cloth (ACFC) reduces emissions to the atmosphere and recovers feedstock for reuse. Local temperature measurement (e.g., with a thermocouple) is typically used to monitor/control adsorbent regeneration cycles. Remote electrical resistance measurement is evaluated here as an alternative to local temperature measurement. ACFC resistance that was modeled based on its physical properties was within 10.5% of the measured resistance values during electrothermal heating. Resistance control was developed based on this measured relationship and used to control temperature to within 2.3% of regeneration set-point temperatures. Isobutane-laden adsorbent was then heated with resistance control. After 2 min of heating, the temperature of the adsorbent with isobutane was 13% less than the adsorbent without isobutane. This difference decreased to 2.1% after 9 min of heating, showing desorption of isobutane. An ACFC cartridge was also heated to 175 °C for 900 cycles with its resistance and adsorption capacity values remaining within 3% and 2%, respectively. This new method to control regeneration power application based on rapid sensing of the adsorbent's resistance removes the need for direct-contact temperature sensors providing a simple, cost-efficient, and long-term regeneration technique for ESA systems.

  9. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

    2005-01-01

    Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...... created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...

  10. Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

    Energy Technology Data Exchange (ETDEWEB)

    Rauscher, J.D.

    1988-01-01

    Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects of Se and Cu on planarians.

  11. Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration.

    Science.gov (United States)

    Kizil, Caghan; Otto, Georg W; Geisler, Robert; Nüsslein-Volhard, Christiane; Antos, Christopher L

    2009-01-15

    Two hallmarks of vertebrate epimorphic regeneration are a significant increase in the proliferation of normally quiescent cells and a re-activation of genes that are active during embryonic development. It is unclear what the molecular determinants are that regulate these events and how they are coordinated. Zebrafish have the ability to regenerate several compound structures by regulating cell proliferation and gene transcription. We report that fam53b/simplet (smp) regulates both cell proliferation and the transcription of specific genes. In situ hybridization and quantitative RT-PCR experiments showed that amputation of zebrafish hearts and fins resulted in strong up-regulation of the smp gene. In regenerating adult fin, smp expression remained strong in the distal mesenchyme which later expanded to the basal layers of the distal epidermis and distal tip epithelium. Morpholino knockdown of smp reduced regenerative outgrowth by decreasing cell proliferation as measured by BrdU incorporation and histone H3 phosphorylation. In addition, smp knockdown increased the expression of msxb, msxc, and shh, as well as the later formation of ectopic bone. Taken together, these data indicate a requirement for smp in fin regeneration through control of cell proliferation, the regulation of specific genes and proper bone patterning.

  12. Sexually dimorphic fin regeneration in zebrafish controlled by androgen/GSK3 signaling.

    Science.gov (United States)

    Nachtrab, Gregory; Czerwinski, Michael; Poss, Kenneth D

    2011-11-22

    Certain fish and amphibians regenerate entire fins and limbs after amputation, whereas such potential is absent in birds and limited in mammals to digit tips [1, 2]. Additionally, regenerative success can change during life stages. Anuran tadpoles gradually lose the capacity to regenerate limbs [3, 4], and digit regeneration occurs more effectively in fetal mice and human children than adults [5-8]. Little is known about mechanisms that control regenerative capacity. Here, we identify an unexpected difference between male and female zebrafish in the regenerative potential of a major appendage. Males display regenerative defects in amputated pectoral fins, caused by impaired blastemal proliferation. This regenerative failure emerges after sexual maturity, is mimicked in androgen-treated females, and is suppressed in males by androgen receptor antagonism. Androgen signaling maintains expression of dkk1b and igfbp2a, which encode secreted inhibitors of Wnt and Igf signaling, respectively. Furthermore, the regulatory target of Wnts and Igfs, GSK3β, is inefficiently inactivated in male fin regenerates compared with females. Pharmacological inhibition of GSK3 in males increases blastemal proliferation and restores regenerative pattern. Our findings identify a natural sex bias in appendage regenerative capacity and indicate an underlying regulatory circuit in which androgen locally restricts key morphogenetic programs after amputation.

  13. Macromolecular Interactions Control Structural and Thermal Properties of Regenerated Tri-Component Blended Films

    Directory of Open Access Journals (Sweden)

    Ashley Lewis

    2016-11-01

    Full Text Available With a growing need for sustainable resources research has become highly interested in investigating the structure and physical properties of biomaterials composed of natural macromolecules. In this study, we assessed the structural, morphological, and thermal properties of blended, regenerated films comprised of cellulose, lignin, and hemicellulose (xylan using the ionic liquid 1-allyl-3-methylimidazolium chloride (AMIMCl. Attenuated total reflectance Fourier transform infrared (ATR-FTIR analysis, scanning electron microscopy (SEM, atomic force microscopy (AFM, X-ray scattering, and thermogravimetric analysis (TGA were used to qualitatively and quantitatively measure bonding interactions, morphology, and thermal stability of the regenerated films. The results demonstrated that the regenerated films’ structural, morphological, and thermal character changed as a function of lignin-xylan concentration. The decomposition temperature rose according to an increase in lignin content and the surface topography of the regenerated films changed from fibrous to spherical patterns. This suggests that lignin-xylan concentration alters the self-assembly of lignin and the cellulose microfibril development. X-ray scattering confirms the extent of the morphological and molecular changes. Our data reveals that the inter- and intra-molecular interactions with the cellulose crystalline domains, along with the amount of disorder in the system, control the microfibril dimensional characteristics, lignin self-assembly, and possibly the overall material′s structural and thermal properties.

  14. Glycemic control promotes pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice.

    Directory of Open Access Journals (Sweden)

    Eric J Grossman

    Full Text Available BACKGROUND: Pancreatic beta-cells proliferate following administration of the beta-cell toxin streptozotocin. Defining the conditions that promote beta-cell proliferation could benefit patients with diabetes. We have investigated the effect of insulin treatment on pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice, and, in addition, report on a new approach to quantify beta-cell regeneration in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Streptozotocin-induced diabetic were treated with either syngeneic islets transplanted under the kidney capsule or subcutaneous insulin implants. After either 60 or 120 days of insulin treatment, the islet transplant or insulin implant were removed and blood glucose levels monitored for 30 days. The results showed that both islet transplants and insulin implants restored normoglycemia in the 60 and 120 day treated animals. However, only the 120-day islet and insulin implant groups maintained euglycemia (<200 mg/dl following discontinuation of insulin treatment. The beta-cell was significantly increased in all the 120 day insulin-treated groups (insulin implant, 0.69+/-0.23 mg; and islet transplant, 0.91+/-0.23 mg compared non-diabetic control mice (1.54+/-0.25 mg. We also show that we can use bioluminescent imaging to monitor beta-cell regeneration in living MIP-luc transgenic mice. CONCLUSIONS/SIGNIFICANCE: The results show that insulin treatment can promote beta-cell regeneration. Moreover, the extent of restoration of beta-cell function and mass depend on the length of treatment period and overall level of glycemic control with better control being associated with improved recovery. Finally, real-time bioluminescent imaging can be used to monitor beta-cell recovery in living MIP-luc transgenic mice.

  15. Morphology control of zinc regeneration for zinc-air fuel cell and battery

    Science.gov (United States)

    Wang, Keliang; Pei, Pucheng; Ma, Ze; Xu, Huachi; Li, Pengcheng; Wang, Xizhong

    2014-12-01

    Morphology control is crucial both for zinc-air batteries and for zinc-air fuel cells during zinc regeneration. Zinc dendrite should be avoided in zinc-air batteries and zinc pellets are yearned to be formed for zinc-air fuel cells. This paper is mainly to analyze the mechanism of shape change and to control the zinc morphology during charge. A numerical three-dimensional model for zinc regeneration is established with COMSOL software on the basis of ionic transport theory and electrode reaction electrochemistry, and some experiments of zinc regeneration are carried out. The deposition process is qualitatively analyzed by the kinetics Monte Carlo method to study the morphological change from the electrocrystallization point of view. Morphological evolution of deposited zinc under different conditions of direct currents and pulse currents is also investigated by simulation. The simulation shows that parametric variables of the flowing electrolyte, the surface roughness and the structure of the electrode, the charging current and mode affect morphological evolution. The uniform morphology of deposited zinc is attained at low current, pulsating current or hydrodynamic electrolyte, and granular morphology is obtained by means of an electrode of discrete columnar structure in combination with high current and flowing electrolyte.

  16. Randomized controlled trial on collagen/oxidized regenerated cellulose/silver treatment

    DEFF Research Database (Denmark)

    Gottrup, Finn; Cullen, Breda Mary; Karlsmark, Tonny;

    2014-01-01

    Collagen/oxidized regenerated cellulose (ORC)/silver therapy has been designed to facilitate wound healing by normalizing the microenvironment and correcting biochemical imbalances in chronic wounds. The aim of this study was to compare collagen/ORC/silver therapy to control (standard treatment......). Patients with diabetic foot ulcers were randomized to either collagen/ORC/silver (24) or control treatment (15). Wound area measurements and wound fluid samples were taken weekly. Protease levels were measured in wound fluid samples to investigate differences between responders (≥50% reduction in wound...

  17. Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome.

    Science.gov (United States)

    Galloni, Mireille

    2012-01-01

    Stem cells are the closest relatives of the totipotent primordial cell, which is able to spawn millions of daughter cells and hundreds of cell types in multicellular organisms. Stem cells are involved in tissue homeostasis and regeneration, and may play a major role in cancer development. Among animals, planarians host a model stem cell type, called the neoblast, which essentially confers immortality. Gaining insights into the global transcriptional landscape of these exceptional cells takes an unprecedented turn with the advent of Next Generation Sequencing methods. Two Digital Gene Expression transcriptomes of Schmidtea mediterranea planarians, with or without neoblasts lost through irradiation, were produced and analyzed. Twenty one bp NlaIII tags were mapped to transcripts in the Schmidtea and Dugesia taxids. Differential representation of tags in normal versus irradiated animals reflects differential gene expression. Canonical and non-canonical tags were included in the analysis, and comparative studies with human orthologs were conducted. Transcripts fell into 3 categories: invariant (including housekeeping genes), absent in irradiated animals (potential neoblast-specific genes, IRDOWN) and induced in irradiated animals (potential cellular stress response, IRUP). Different mRNA variants and gene family members were recovered. In the IR-DOWN class, almost all of the neoblast-specific genes previously described were found. In irradiated animals, a larger number of genes were induced rather than lost. A significant fraction of IRUP genes behaved as if transcript versions of different lengths were produced. Several novel potential neoblast-specific genes have been identified that varied in relative abundance, including highly conserved as well as novel proteins without predicted orthologs. Evidence for a large body of antisense transcripts, for example regulated antisense for the Smed-piwil1 gene, and evidence for RNA shortening in irradiated animals is presented

  18. Regenerated silk fibroin films with controllable nanostructure size and secondary structure for drug delivery.

    Science.gov (United States)

    Zhou, Juan; Zhang, Bin; Shi, Lijun; Zhong, Jian; Zhu, Jun; Yan, Juan; Wang, Ping; Cao, Chuanbao; He, Dannong

    2014-12-24

    The ability of drug release from SF materials was governed largely by their secondary structure. It is known that the breakage degree of the peptide chain during the silk fibroin (SF) dissolution can affect the structure, property, and applications of SF materials. To deeply understand this effect, we designed a reaction system based on CaCl2/H2O/C2H5OH ternary solvent with different ethanol content to obtain the regenerated SF films with different morphologies and secondary structures. The results showed that the globule-like nanostructure was observed in all regenerated SF films, and their size decreased significantly with reducing the ethanol content in the solvent. Correspondingly, the β-sheet structure content of the SF films increased. In addition, the contact angle and the elongation ratio increased, and water absorption decreased significantly with decreasing the ethanol content in the solvent. The accumulated release percents of doxorubicin from these SF films were significantly different with increasing the time. With smaller nanostructure size and more β-sheet content, the SF films had a slower drug release at the beginning. This study indicated the importance of the ethanol content in the solvent in controlling the structure and properties of the regenerated SF films, which would improve the application of SF in drug delivery.

  19. Effectiveness of fencing and hunting to control Lama guanicoe browsing damage: Implications for Nothofagus pumilio regeneration in harvested forests.

    Science.gov (United States)

    Martínez Pastur, Guillermo; Soler, Rosina; Ivancich, Horacio; Lencinas, María V; Bahamonde, Héctor; Peri, Pablo L

    2016-03-01

    Browsing damage by native ungulates is often to be considered one of the reasons of regeneration failure in Nothofagus pumilio silvicultural systems. Fencing and hunting in forests at regeneration phase have been proposed to mitigate browsing effects. This study aims to determine effectiveness of these control methods in harvested forests, evaluating browsing damage over regeneration, as well as climate-related constraints (freezing or desiccation). Forest structure and regeneration plots were established in two exclosures against native ungulates (Lama guanicoe) by wire fences in the Chilean portion of Tierra del Fuego island, where tree regeneration density, growth, abiotic damage and quality (multi-stems and base/stem deformation) were assessed. Exclosures did not influence regeneration density (at the initial stage with 1.3 m high). However, sapling height at 10-years old was significantly lower outside (40-50 cm high) than inside exclosures (80-100 cm), and also increased their annual height growth, probably as a hunting effect. Likewise, quality was better inside exclosures. Alongside browsing, abiotic conditions negatively influenced sapling quality in the regeneration phase (20%-28% of all seedlings), but greatly to taller plants (as those from inside exclosure). This highlights the importance of considering climatic factors when analysing browsing effects. For best results, control of guanaco in recently harvested areas by fencing should be applied in combination with a reduction of guanaco density through continuous hunting. The benefits of mitigation actions (fencing and hunting) on regeneration growth may shorten the regeneration phase period in shelterwood cutting forests (30-50% less time), but incremental costs must be analysed in the framework of management planning by means of long-term studies.

  20. Study on the Energy-Regeneration-based Velocity Control of the Hydraulic-Hybrid Vehicle

    Directory of Open Access Journals (Sweden)

    SONG Yunpu

    2012-11-01

    Full Text Available This paper simplifies the energy regenerationbased vehicle velocity system of the hydraulichybrid businto a process in which the extension rod of the hydraulic cylinder drives the secondary-element variable delivery pump/motor to change its displacement. This process enables braking of the vehicle and also allows recovery of energy. The stability, energy efficiency and other characteristics of the system are studied based on analysis of mathematical models of the vehicle velocity control. The relevant controller is designed to study effects of the controller on system characteristics. The vehicle velocity control module of the energy regeneration system is stable and able to recovery the inertia energy generated in vehicle braking. After the controller intended to improve response speed is added, system response becomes quicker but energy recovery rate declines.

  1. Characterization of an organ-specific differentiator substance in the planarian Dugesia etrusca

    Energy Technology Data Exchange (ETDEWEB)

    Steele, V.E.; Lange, C.S.

    1977-01-01

    A substance which inhibits brain formation in decapitated regenerating planarians (Dugesia etrusca) was characterized and partially purified. The substance's inhibitory activity was followed during each purification procedure by adding freshly decapitated animals of a standard size to each fraction, and later measuring the resultant regenerated brain volume. The inhibitory activity remained in the supernatant after a 10000 g centrifugation of a cell-free homogenate. Most of the activity sedimented when the 10000 g supernatant was centrifuged at 32000 g. The degree of inhibitory activity increased with increased numbers of animals in the initial homogenate. The substance has an apparent molecular weight between 2 x 10/sup 5/ and 4 x 10/sup 5/ daltons. Digestion by pronase destroyed the activity, but treatment with RNase, DNase I, or lipase had no significant effect. The inhibiting substance has an isoelectric point (pI) of between 4.75 and 5.38 and migrates to the anode when electrophorezed in pH 6.8 buffer.

  2. 5-HT1A-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians

    OpenAIRE

    Rawls, Scott M.; Shah, Hardik; Ayoub, George; Raffa, Robert B.

    2010-01-01

    No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 µM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal)...

  3. Epimorphic regeneration in mice is p53-independent.

    Science.gov (United States)

    Arthur, L Matthew; Demarest, Renee M; Clark, Lise; Gourevitch, Dmitri; Bedelbaeva, Kamila; Anderson, Rhonda; Snyder, Andrew; Capobianco, Anthony J; Lieberman, Paul; Feigenbaum, Lionel; Heber-Katz, E

    2010-09-15

    The process of regeneration is most readily studied in species of sponge, hydra, planarian and salamander (i.e., newt and axolotl). The closure of MRL mouse ear pinna through-and-through holes provides a mammalian model of unusual wound healing/regeneration in which a blastema-like structure closes the ear hole and cartilage and hair follicles are replaced. Recent studies, based on a broad level of DNA damage and a cell cycle pattern of G₂/M "arrest," showed that p21(Cip1/Waf1) was missing from the MRL mouse ear and that a p21-null mouse could close its ear holes. Given the p53/p21 axis of control of DNA damage, cell cycle arrest, apoptosis and senescence, we tested the role of p53 in the ear hole regenerative response. Using backcross mice, we found that loss of p53 in MRL mice did not show reduced healing. Furthermore, cross sections of MRL. p53(-/-) mouse ears at 6 weeks post-injury showed an increased level of adipocytes and chondrocytes in the region of healing whereas MRL or p21(-/-) mice showed chondrogenesis alone in this same region, though at later time points. In addition, we also investigated other cell cycle-related mutant mice to determine how p21 was being regulated. We demonstrate that p16 and Gadd45 null mice show little healing capacity. Interestingly, a partial healing phenotype in mice with a dual Tgfβ/Rag2 knockout mutation was seen. These data demonstrate an independence of p53 signaling for mouse appendage regeneration and suggest that the role of p21 in this process is possibly through the abrogation of the Tgfβ/Smad pathway.

  4. Spatiotemporally controlled and multifactor involved assay of neuronal compartment regeneration after chemical injury in an integrated microfluidics.

    Science.gov (United States)

    Li, Li; Ren, Li; Liu, Wenming; Wang, Jian-Chun; Wang, Yaolei; Tu, Qin; Xu, Juan; Liu, Rui; Zhang, Yanrong; Yuan, Mao-Sen; Li, Tianbao; Wang, Jinyi

    2012-08-07

    Studies on the degeneration and regeneration of neurons as individual compartments of axons or somata can provide critical information for the clinical therapy of nervous system diseases. A controllable in vitro platform for multiple purposes is key to such studies. In the present study, we describe an integrated microfluidic device designed for achieving localized stimulation to neuronal axons or somata. We observed neuronal compartment degeneration after localized chemical stimulation and regeneration under the accessorial function of an interesting compound treatment or coculture with desired cells in controllable chambers. In a spatiotemporally controlled manner, this device was used to investigate hippocampal neuronal soma and axon degeneration after acrylamide stimulation, as well as subsequent regeneration after treatment with the monosialoganglioside GM1 or with cocultured glial cells (astrocytes or Schwann cells). To gain insight into the molecular mechanisms that mediate neuronal injury and regeneration, as well as to investigate whether acrylamide stimulation to neurons induces changes in Ca(2+) concentrations, the related neuronal genes and real-time Ca(2+) signal in neurons were also analyzed. The results showed that neuronal axons were more resistant to acrylamide injury than neuronal somata. Under localized stimulation, axons had self-destruct programs different from somata, and somatic injury caused the secondary response of axon collapse. This study provides a foundation for future in-depth analyses of spatiotemporally controlled and multifactor neuronal compartment regeneration after various injuries. The microfluidic device is also useful in evaluating potential therapeutic strategies to treat chemical injuries involving the central nervous system.

  5. Periodontal tissue regeneration using fibroblast growth factor-2: randomized controlled phase II clinical trial.

    Directory of Open Access Journals (Sweden)

    Masahiro Kitamura

    Full Text Available BACKGROUND: The options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation. METHODOLOGY/PRINCIPAL FINDINGS: We used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured > or = 3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC containing 0.1% FGF-2; and Group H, given HPC containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 microL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021 in rate of increase in alveolar bone height was identified between Group P (23.92% and Group H (58.62% at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132. No serious adverse events attributable to the investigational drug were identified. CONCLUSIONS: Although no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021 between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration

  6. Chemo-klino-kinesis in planarian food location.

    Science.gov (United States)

    Mason, P R

    1975-05-01

    The effects of a homologous series of buffered fatty acid solutions on planarian behaviour were measured as the change in klino-kinetic activity. On the basis of the results obtained a model demonstrating the function of this behaviour pattern in the food-locating response was proposed. The model suggested that qualitative rather than quantitative gradients were effective in stimulating klino-kinetic orientation.

  7. Planarians in toxicology. Responses of asexual Dugesia dorotocephala to selected metals

    Energy Technology Data Exchange (ETDEWEB)

    Kapu, M.M.; Schaeffer, D.J. (Univ. of Illinois, Urbana (United States))

    1991-08-01

    The planarian Dugesia dorotocephala is a freshwater invertebrate found in unpolluted flowing surface waters. Planarians have a sensitive nervous system with synapses and true brain and evidence these in a variety of social and response behaviors. The inclusion of planarians in a screening battery would provide improved sensitivity in detecting toxicity because planarians commonly respond to lower levels of contamination than do other species. Numerous toxicity test have been conducted to determine the acute and chronic effects of toxicants to provide data necessary for the development of water quality criteria. The appropriateness of Illinois water quality standards for metals was investigated using a 1-hr behavioral test based on the responses of the planarian D. dorotocephala. One possible difficulty with water quality standards for metals is that the standard for each metal is usually established without regard to the effects of other metals present in the receiving water.

  8. A premeiotic function for boule in the planarian Schmidtea mediterranea.

    Science.gov (United States)

    Iyer, Harini; Issigonis, Melanie; Sharma, Prashant P; Extavour, Cassandra G; Newmark, Phillip A

    2016-06-21

    Mutations in Deleted in Azoospermia (DAZ), a Y chromosome gene, are an important cause of human male infertility. DAZ is found exclusively in primates, limiting functional studies of this gene to its homologs: boule, required for meiotic progression of germ cells in invertebrate model systems, and Daz-like (Dazl), required for early germ cell maintenance in vertebrates. Dazl is believed to have acquired its premeiotic role in a vertebrate ancestor following the duplication and functional divergence of the single-copy gene boule. However, multiple homologs of boule have been identified in some invertebrates, raising the possibility that some of these genes may play other roles, including a premeiotic function. Here we identify two boule paralogs in the freshwater planarian Schmidtea mediterranea Smed-boule1 is necessary for meiotic progression of male germ cells, similar to the known function of boule in invertebrates. By contrast, Smed-boule2 is required for the maintenance of early male germ cells, similar to vertebrate Dazl To examine if Boule2 may be functionally similar to vertebrate Dazl, we identify and functionally characterize planarian homologs of human DAZL/DAZ-interacting partners and DAZ family mRNA targets. Finally, our phylogenetic analyses indicate that premeiotic functions of planarian boule2 and vertebrate Dazl evolved independently. Our study uncovers a premeiotic role for an invertebrate boule homolog and offers a tractable invertebrate model system for studying the premeiotic functions of the DAZ protein family.

  9. Spontaneous Behaviors and Wall-Curvature Lead to Apparent Wall Preference in Planarian.

    Directory of Open Access Journals (Sweden)

    Yoshitaro Akiyama

    Full Text Available The planarian Dugesia japonica tends to stay near the walls of its breeding containers and experimental dishes in the laboratory, a phenomenon called "wall preference". This behavior is thought to be important for environmental adaptation, such as hiding by planarians in nature. However, the mechanisms regulating wall-preference behavior are not well understood, since this behavior occurs in the absence of any particular stimulation. Here we show the mechanisms of wall-preference behavior. Surprisingly, planarian wall-preference behavior was also shown even by the head alone and by headless planarians. These results indicate that planarian "wall-preference" behavior only appears to be a "preference" behavior, and is actually an outcome of spontaneous behaviors, rather than of brain function. We found that in the absence of environmental cues planarians moved basically straight ahead until they reached a wall, and that after reaching a wall, they changed their direction of movement to one tangential to the wall, suggesting that this spontaneous behavior may play a critical role in the wall preference. When we tested another spontaneous behavior, the wigwag movement of the planarian head, using computer simulation with various wigwag angles and wigwag intervals, large wigwag angle and short wigwag interval reduced wall-preference behavior. This indicated that wigwag movement may determine the probability of staying near the wall or leaving the wall. Furthermore, in accord with this simulation, when we tested planarian wall-preference behavior using several assay fields with different curvature of the wall, we found that concavity and sharp curvature of walls negatively impacted wall preference by affecting the permissible angle of the wigwag movement. Together, these results indicate that planarian wall preference may be involuntarily caused by the combination of two spontaneous planarian behaviors: moving straight ahead until reaching a wall and

  10. GH receptor plays a major role in liver regeneration through the control of EGFR and ERK1/2 activation.

    Science.gov (United States)

    Zerrad-Saadi, Amal; Lambert-Blot, Martine; Mitchell, Claudia; Bretes, Hugo; Collin de l'Hortet, Alexandra; Baud, Véronique; Chereau, Fanny; Sotiropoulos, Athanassia; Kopchick, John J; Liao, Lan; Xu, Jianming; Gilgenkrantz, Hélène; Guidotti, Jacques-Emmanuel

    2011-07-01

    GH is a pleiotropic hormone that plays a major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested that GH signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was to identify the mechanisms by which GH controls liver regeneration. We performed two thirds partial hepatectomies in GH receptor (GHR)-deficient mice and wild-type littermates and showed a blunted progression in the G(1)/S transition phase of the mutant hepatocytes. This impaired liver regeneration was not corrected by reestablishing IGF-1 expression. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between mutant and wild-type mice, cell cycle progression was significantly blunted in mutant mice. The main defect in GHR-deficient mice was the deficiency of the epidermal growth factor receptor activation during the process of liver regeneration. Finally, among the pathways activated downstream of GHR during G(1) phase progression, namely Erk1/2, Akt, and signal transducer and activator of transcription 3, we only found a reduced Erk1/2 phosphorylation in mutant mice. In conclusion, our results demonstrate that GH signaling plays a major role in liver regeneration and strongly suggest that it acts through the activation of both epidermal growth factor receptor and Erk1/2 pathways.

  11. Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

    NARCIS (Netherlands)

    Clevers, Hans; Loh, Kyle M; Nusse, Roel

    2014-01-01

    Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

  12. Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

    NARCIS (Netherlands)

    Clevers, Hans; Loh, Kyle M; Nusse, Roel

    2014-01-01

    Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

  13. Control of guided hard-tissue regeneration using phosphorylated gelatin and OCT imaging of calcification

    Science.gov (United States)

    Ishii, Katsunori; Ma, Zhenhe; Ninomiya, Yoshihisa; Takegoshi, Minori; Kushibiki, Toshihiro; Yamamoto, Masaya; Hinds, Monica; Tabata, Yasuhiko; Wang, Ruikang K.; Awazu, Kunio

    2007-02-01

    Tendon and ligament are the transition tissues from a hard tissue to a soft tissue. The regenerative medicine of tendons needs reasonable biomaterials to regenerate precisely from the view point of composition and adhesion properties. In regenerative medicine of hard tissues, it has been reported that calcifications are influenced by phosphorylated proteins (phosphate groups) and the biomaterial possessing phosphate groups promote or inhibit the formation of HAP. We have studied to develop and evaluate the phosphorylated soft biomaterials, which is possible to control a calcification by the introduction ratio of phosphate groups, as biomaterials for tendon regeneration. In addition, we have studied measurement technologies. In the present study, we studied a FT-IR analysis of gelatins with different introduction ratio of phosphate groups, an evaluation of calcifications by the difference of introduction ratio of phosphate groups, and a fundamental survey on OCT imaging for calcifications of a gelatin and a phosphorylated gelatin. We use phosphorylated gelatins with different introduction ratios of phosphate group linked by ester bonds. The introduction ratios are measured by the FT-IR calibrated by a molybdenum blue method. Phosphorylated gelatin sheets were calcified using 1.5SBF soaking process and alternative soaking process. These gelatin sheets with different calcification conditions were measured using SD-OCT systems with 843nm centered wavelength SLD. As a result, we demonstrated that it was possible to measure the calcification on/in the gelatin sheets and sponges and phosphorylated using OCT. The main mechanism is the strong back scattering and the high scattering of deposited calcium particles.

  14. Regeneration and control of human fibroblast cell density by intermittently delivered pulsed electric fields.

    Science.gov (United States)

    Golberg, Alexander; Bei, Marianna; Sheridan, Robert L; Yarmush, Martin L

    2013-06-01

    Proliferative scarring is a human disease with neither available effective treatment nor relevant animal model. One of the hypotheses for scar formation involves deregulation of fibroblast signaling and delayed apoptosis. Here, we introduce a new chemical-free method for fibroblast density control in culture by intermittently delivered pulsed electric fields (IDPEF), which cause irreversible damage to cell membranes. Using 5-100 pulses with electric field strength of 150 V/mm, pulse duration 70 µs, and frequency of 1 Hz, we investigated the effects of PEF application on growth, death, and regeneration of normal human dermal fibroblasts in culture. We found that the fraction of fibroblasts that survive depends on the number of pulses applied and follows a Weibull distribution. We have successfully developed an IDPEF protocol that controls fibroblasts density in culture. Specifically, through application of IDPEF every 72 h for 12 days, we maintain a normal human dermal fibroblast density in the 3.1 ± 0.2 × 10(5) -1.4 ± 0.2 × 10(5)  cell/mL range. Our results suggest that IDPEFs may prove useful as a non-chemical method for fibroblast density control in human wound healing.

  15. Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria

    Science.gov (United States)

    Adler, Carolyn E; Seidel, Chris W; McKinney, Sean A; Sánchez Alvarado, Alejandro

    2014-01-01

    Planarian flatworms regenerate every organ after amputation. Adult pluripotent stem cells drive this ability, but how injury activates and directs stem cells into the appropriate lineages is unclear. Here we describe a single-organ regeneration assay in which ejection of the planarian pharynx is selectively induced by brief exposure of animals to sodium azide. To identify genes required for pharynx regeneration, we performed an RNAi screen of 356 genes upregulated after amputation, using successful feeding as a proxy for regeneration. We found that knockdown of 20 genes caused a wide range of regeneration phenotypes and that RNAi of the forkhead transcription factor FoxA, which is expressed in a subpopulation of stem cells, specifically inhibited regrowth of the pharynx. Selective amputation of the pharynx therefore permits the identification of genes required for organ-specific regeneration and suggests an ancient function for FoxA-dependent transcriptional programs in driving regeneration. DOI: http://dx.doi.org/10.7554/eLife.02238.001 PMID:24737865

  16. Using polymeric materials to control stem cell behavior for tissue regeneration.

    Science.gov (United States)

    Zhang, Nianli; Kohn, David H

    2012-03-01

    Patients with organ failure often suffer from increased morbidity and decreased quality of life. Current strategies of treating organ failure have limitations, including shortage of donor organs, low efficiency of grafts, and immunological problems. Tissue engineering emerged about two decades ago as a strategy to restore organ function with a living, functional engineered substitute. However, the ability to engineer a functional organ is limited by a limited understanding of the interactions between materials and cells that are required to yield functional tissue equivalents. Polymeric materials are one of the most promising classes of materials for use in tissue engineering, due to their biodegradability, flexibility in processing and property design, and the potential to use polymer properties to control cell function. Stem cells offer potential in tissue engineering because of their unique capacity to self-renew and differentiate into neurogenic, osteogenic, chondrogenic, and myogenic lineages under appropriate stimuli from extracellular components. This review examines recent advances in stem cell-polymer interactions for tissue regeneration, specifically highlighting control of polymer properties to direct adhesion, proliferation, and differentiation of stem cells, and how biomaterials can be designed to provide some of the stimuli to cells that the natural extracellular matrix does.

  17. The evaluation of the activity of medicinal remedies of plant and animal origin on the regeneration of the earthworms′ tail segments

    Directory of Open Access Journals (Sweden)

    Viktor Alexandrovich Bybin

    2015-01-01

    Full Text Available Now, in the global community there is enough hard recommendation to replace the vertebrate test animals into simpler organisms at the development, testing, and evaluation of the quality pharmaceuticals. The feature of planarian to regenerate in new individual planarian from a piece, which is only 1/7 of the original animal, allowed to create the alternative methods of testing of drugs, dietary supplements, water quality, influence of electromagnetic fields, and other radiations. The tests on planarian can replace the ones that are held today on mammals. However, the lacks of the bioassays based on the planarian regeneration are the need for complex and expensive video equipment for recording the regrowth of worms′ body, the difficulties of culturing of flatworms and fairly long period of response. These difficulties can be avoided by using another group of the worms of type Annelida. The new individual can be fully recovered only from the front half of the body in many species of earthworms. Thus, the influence of the pharmaceuticals from earthworms, mummy, and Orthilia secunda on the ability of earthworms to regenerate lost tail segments has been investigated. The relations of the activity of preparations tested with doses and the time of the storage have been revealed. The principal possibility of applicability of the test reaction studied as a way to evaluate the effects and quality of remedies based on medicinal plants and earthworms has been shown.

  18. Apoptosis, stem cells, and tissue regeneration.

    Science.gov (United States)

    Bergmann, Andreas; Steller, Hermann

    2010-10-26

    Most metazoans have at least some ability to regenerate damaged cells and tissues, although the regenerative capacity varies depending on the species, organ, or developmental stage. Cell replacement and regeneration occur in two contexts: renewal of spent cells during tissue homeostasis (homeostatic growth), and in response to external injury, wounding, or amputation (epimorphic regeneration). Model organisms that display remarkable regenerative capacity include amphibians, planarians, Hydra, and the vertebrate liver. In addition, several mammalian organs--including the skin, gut, kidney, muscle, and even the human nervous system--have some ability to replace spent or damaged cells. Although the regenerative response is complex, it typically involves the induction of new cell proliferation through formation of a blastema, followed by cell specification, differentiation, and patterning. Stem cells and undifferentiated progenitor cells play an important role in both tissue homeostasis and tissue regeneration. Stem cells are typically quiescent or passing slowly through the cell cycle in adult tissues, but they can be activated in response to cell loss and wounding. A series of studies, mostly performed in Drosophila as well as in Hydra, Xenopus, and mouse, has revealed an unexpected role of apoptotic caspases in the production of mitogenic signals that stimulate the proliferation of stem and progenitor cells to aid in tissue regeneration. This Review summarizes some of the key findings and discusses links to stem cell biology and cancer.

  19. Metabolic Heat Regenerated Temperature Swing Adsorption for CO2, Thermal and Humidity Control Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is proposed for a Portable Life Support System to remove and reject heat and carbon dioxide...

  20. Compact, Regenerable, Low Power Adsorber for Spacesuit CO2, Humidity, and Trace Contaminant Control Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Current approaches planned for space suit atmosphere revitalization (AR) are neither compatible with each other nor regenerable in space, and have a high life cycle...

  1. Neurobehavioral toxicity of cadmium sulfate to the planarian Dugesia dorotocephala

    Energy Technology Data Exchange (ETDEWEB)

    Grebe, E.; Schaeffer, D.J. (Univ. of Illinois, Urbana (United States))

    1991-05-01

    The authors are developing bioassays which use planarians (free-living platyhelminthes) for the rapid determination of various types of toxicity, including acute mortality, tumorigenicity, and short-term neurobehavioral responses. Their motivation for using these animals is due to their importance as components of the aquatic ecology of unpolluted streams their sensitivity to low concentrations of environmental toxicants and the presence of a sensitive neurological system with a true brain which allows for complex social behavior. A previous paper described the results of a neurobehavioral bioassay using phenol in a crossover study. This paper reports a similar crossover study using cadmium sulfate.

  2. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control.

    Science.gov (United States)

    Clevers, Hans; Loh, Kyle M; Nusse, Roel

    2014-10-03

    Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified, which constrains them to act as short-range cellular signals. The locality of Wnt signaling dictates that stem cells exiting the Wnt signaling domain differentiate, spatially delimiting the niche in certain tissues. In some instances, stem cells may act as or generate their own niche, enabling the self-organization of patterned tissues. In this Review, we discuss the various ways by which Wnt operates in stem cell control and, in doing so, identify an integral program for tissue renewal and regeneration.

  3. Ergot Alkaloids (Regenerate New Leads as Antiparasitics.

    Directory of Open Access Journals (Sweden)

    John D Chan

    Full Text Available Praziquantel (PZQ is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors.

  4. Evaluation of clinical, antiinflammatory and antiinfective properties of amniotic membrane used for guided tissue regeneration: A randomized controlled trial

    OpenAIRE

    Aravind Kumar; Rampalli Viswa Chandra; Aileni Amarender Reddy; Bavigadda Harish Reddy; Chakravarthy Reddy; Anumala Naveen

    2015-01-01

    Background: The objective of this study was to evaluate the antiinflammatory, antiinfective and clinical properties of amniotic membrane (AM) when used for guided tissue regeneration (GTR) in contained interdental defects. Materials and Methods: A total of 30 subjects participated in this study. Two sites in each subject were randomly assigned into each of the following experimental groups; test group: AM with bone graft and control group: Bone graft only. Clinical parameters included rec...

  5. Towards a phylogenetic classification of dendrocoelid freshwater planarians (Platyhelminthes): a morphological and eclectic approach

    NARCIS (Netherlands)

    Sluys, R.; Kawakatsu, M.

    2006-01-01

    We explore and review the taxonomic distribution of morphological features that may be used as supporting apomorphies for the monophyletic status of various taxa in future, more comprehensive phylogenetic analyses of the dendrocoelid freshwater planarians and their close relatives. Characters

  6. Comparative acute toxicity of DDT metabolites among American and European species of planarians.

    Science.gov (United States)

    Bonner, J C; Wells, M R

    1987-01-01

    1. DDT metabolism in a North American species of planarian leads to the formation of metabolites more toxic than the parent compound. 2. The increased toxicity of DDT metabolites is similar to acute toxicity data reported previously in a European species. 3. It is suggested that planarians lack a direct mechanism for DDT detoxification, since two North American and one European species are known to metabolize DDT initially to DDE and DDD.

  7. First report of the land planarian Diversibipalium multilineatum (Makino & Shirasawa, 1983) (Platyhelminthes, Tricladida, Continenticola) in Europe.

    Science.gov (United States)

    Mazza, Giuseppe; Menchetti, Mattia; Sluys, Ronald; Solà, Eduard; Riutort, Marta; Tricarico, Elena; Justine, Jean-Lou; Cavigioli, Luca; Mori, Emiliano

    2016-01-26

    Introduction of alien species may significantly affect soil ecosystems, through predation or disruption of components of native ecosystems (Winsor et al. 2004; Álvarez-Presas et al. 2014; Justine et al. 2014). Land planarians have been reported as alien species in soils throughout the world and, among those, some species are considered to be successful invaders, e.g. Platydemus manokwari de Beauchamp, 1963, Arthurdendyus triangulatus (Dendy, 1894), Bipalium adventitium Hyman, 1943, Bipalium kewense Moseley, 1878 and Dolichoplana striata Moseley, 1877 (Winsor et al. 2004; Álvarez-Presas et al. 2014; Justine et al. 2014, 2015). Soil moisture status seems to be an important element for their successful invasion (Fraser & Boag 1998). In Europe at least 18 species of alien land planarians have been recorded since now and some of them are considered as invasive ones, e.g. P. manokwari (cf. Justine et al. 2014). Although the alien land planarian B. kewense has been reported to occur in many greenhouses in Italy (Bello et al. 1995), no data are available on its establishment and/or impact on natural environments. On 28th September 2014, 20 specimens (~1 individual/m2) of the land planarian Diversibipalium multilineatum (Makino & Shirasawa, 1983) (Fig. 1), native to Japan, were collected under pots, branches and plastic materials in a private garden located in the center of Bologna (Emilia Romagna, Central Italy), near the urban park Giardini Margherita (44°29' N, 11°21' E; WGS84). Thirty plant species (both indigenous and alien), mainly cultivated as bonsai (e.g. Lagerstroemia indica L., Juniperus procumbens (Siebold ex Endl.) Miquel), were present in this shady, wet garden (25 m2). Between March 2014 and June 2015, 70 more specimens of D. multilineatum were collected at the same site, mainly at dusk and dawn after rain. Reproduction by fission and regeneration processes were observed in several of those specimens, which were kept for some time in captivity. A specimen

  8. Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration.

    Science.gov (United States)

    Blum, Nicola; Begemann, Gerrit

    2012-01-01

    Adult teleosts rebuild amputated fins through a proliferation-dependent process called epimorphic regeneration, in which a blastema of cycling progenitor cells replaces the lost fin tissue. The genetic networks that control formation of blastema cells from formerly quiescent stump tissue and subsequent blastema function are still poorly understood. Here, we investigated the cellular and molecular consequences of genetically interfering with retinoic acid (RA) signaling for the formation of the zebrafish blastema. We show that RA signaling is upregulated within the first few hours after fin amputation in the stump mesenchyme, where it controls Fgf, Wnt/β-catenin and Igf signaling. Genetic inhibition of the RA pathway at this stage blocks blastema formation by inhibiting cell cycle entry of stump cells and impairs the formation of the basal epidermal layer, a signaling center in the wound epidermis. In the established blastema, RA signaling remains active to ensure the survival of the highly proliferative blastemal population by controlling expression of the anti-apoptotic factor bcl2. In addition, RA signaling maintains blastema proliferation through the activation of growth-stimulatory signals mediated by Fgf and Wnt/β-catenin signaling, as well as by reducing signaling through the growth-inhibitory non-canonical Wnt pathway. The endogenous roles of RA in adult vertebrate appendage regeneration are uncovered here for the first time. They provide a mechanistic framework to understand previous observations in salamanders that link endogenous sources of RA to the regeneration process itself and support the hypothesis that the RA signaling pathway is an essential component of vertebrate tissue regeneration.

  9. Highly bioactive polysiloxane modified bioactive glass-poly(ethylene glycol) hybrids monoliths with controlled surface structure for bone tissue regeneration

    Science.gov (United States)

    Chen, Jing; Que, Wenxiu; Xing, Yonglei; Lei, Bo

    2015-03-01

    Crack-free monoliths with controllable surface microstructure have high bioactivities and therefore potential applications in bone tissue regeneration. In this paper, crack-free polydimethylsiloxane-modified bioactive glass-poly (ethylene glycol) (PDMS-BG-PEG) hybrids monoliths were fabricated via using a modified sol-gel process. Results show that the addition of PEG plays an important part in the formation of crack-free and gelation of the monoliths, and surface microstructures of the as-prepared hybrid monoliths were significantly influenced by the concentration and molecular weight of PEG. The samples obtained from PEG 300 had porous surface result in higher bioactivity (apatite formation) in simulated body fluid (SBF), while the samples obtained from PEG 600 had the smooth surface and inhibited the formation of apatite layer in SBF. These as-prepared hybrid monoliths can be used as a good candidate of implant and scaffold for highly efficient bone tissue regeneration.

  10. Combining control electronics with SOA to equalize packet-to-packet power variations for optical 3R regeneration in optical networks at 10 Gbit/s

    DEFF Research Database (Denmark)

    Wessing, Henrik; Lavigne, B.; Sørensen, Brian Michael;

    2004-01-01

    We report on the combined effects of control electronics and a SOA as to suppress packet to packet power fluctuations. Associated to a SOA-MZI based 3R regenerator, we demonstrate a power dynamic range of 9 dB.......We report on the combined effects of control electronics and a SOA as to suppress packet to packet power fluctuations. Associated to a SOA-MZI based 3R regenerator, we demonstrate a power dynamic range of 9 dB....

  11. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate.

    Science.gov (United States)

    Cai, D; Qiu, J; Cao, Z; McAtee, M; Bregman, B S; Filbin, M T

    2001-07-01

    Unlike neonatal axons, mammalian adult axons do not regenerate after injury. Likewise, myelin, a major factor in preventing regeneration in the adult, inhibits regeneration from older but not younger neurons. Identification of the molecular events responsible for this developmental loss of regenerative capacity is believed key to devising strategies to encourage regeneration in adults after injury. Here, we report that the endogenous levels of the cyclic nucleotide, cAMP, are dramatically higher in young neurons in which axonal growth is promoted both by myelin in general and by a specific myelin component, myelin-associated glycoprotein (MAG), than in the same types of neurons that, when older, are inhibited by myelin-MAG. Inhibiting a downstream effector of cAMP [protein kinase A (PKA)] prevents myelin-MAG promotion from young neurons, and elevating cAMP blocks myelin-MAG inhibition of neurite outgrowth in older neurons. Importantly, developmental plasticity of spinal tract axons in neonatal rat pups in vivo is dramatically reduced by inhibition of PKA. Thus, the switch from promotion to inhibition by myelin-MAG, which marks the developmental loss of regenerative capacity, is mediated by a developmentally regulated decrease in endogenous neuronal cAMP levels.

  12. Topiramate antagonism of L-glutamate-induced paroxysms in planarians

    Science.gov (United States)

    Raffa, Robert B.; Finno, Kristin E.; Tallarida, Christopher S.; Rawls, Scott M.

    2010-01-01

    We recently reported that NMDA (N-Methyl-D-aspartate) and AMPA (α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induce concentration-dependent paroxysms in planarians (Dugesia dorotocephala). Since the postulated mechanisms of action of the sulfamate-substituted monosaccharide antiepileptic drug topiramate include inhibition of glutamate-activated ion channels, we tested the hypothesis that topiramate would inhibit glutamate-induced paroxysms in our model. We demonstrate that: (1) L-glutamate (1–10 mM), but not D-glutamate, induced dose-related paroxysms, and that (2) topiramate dose-relatedly (0.3–3 mM) inhibited L-glutamate-induced paroxysms. These results provide further evidence of a topiramate-sensitive glutamate receptor-mediated activity in this model. PMID:20863783

  13. THE LAW CONTROLLING THE QUANTITY OF REGENERATION IN THE STEM OF BRYOPHYLLUM CALYCINUM.

    Science.gov (United States)

    Loeb, J

    1918-09-20

    1. A method is given which allows us to measure the influence of the mass of a leaf upon the quantity of shoots regenerated in an isolated piece of stem. This method consists in isolating a piece of stem with only two leaves left at the basal node and then splitting the stem lengthwise so that each half has one basal leaf. By leaving one leaf intact while the size of the sister leaf is reduced, the influence of the mass of the leaf upon the quantity of shoots regenerated by the stem can be measured. 2. This method has yielded the result that the mass of shoots regenerated at the apex of such a piece of stem increases under equal conditions and in equal time with the mass of the leaf, and is approximately proportional to the mass of the leaf. 3. Such an influence of the mass of the leaf upon the mass of shoots produced by the stem is only intelligible on the assumption that the growth of the regenerating shoot occurs at the expense of material furnished by the basal leaf. 4. This assumption is supported by two facts: first, that in the dark this influence of the leaf disappears more or less completely; and, second, that a leaf attached to the base of a regenerating stem after some time weighs markedly less than does a sister leaf completely detached from the stem, but otherwise under equal conditions. 5. This latter fact that a leaf when attached to the base of an excised piece of stem wilts more rapidly than when completely isolated is the reason that the proportionality between mass of a basal leaf and mass of shoot regenerated at the apex of an isolated piece of stem cannot always be demonstrated with the same degree of accuracy as the proportionality between the mass of completely isolated leaves and the mass of shoots they produce. 6. The material furnished by the leaf to the stem is not restricted to water but includes also the solutes, since not only the fresh weight but also the dry weight of the shoot regenerated by a piece of stem increases with the mass

  14. Guided tissue regeneration in Class II furcation involved maxillary molars: a controlled study of 8 split-mouth cases.

    Science.gov (United States)

    Avera, J B; Camargo, P M; Klokkevold, P R; Kenney, E B; Lekovic, V

    1998-09-01

    The purpose of this study was to clinically evaluate the effectiveness of polytetrafluoroethylene membranes in the healing of interproximal Class II furcation defects in maxillary molars using a surgical treatment technique based on the principles of guided tissue regeneration. Eight subjects with similar bilateral Class II furcation lesions on the mesial aspect of maxillary first molars participated in this study. Patients received initial therapy consisting of oral hygiene instructions, scaling and root planing, and occlusal adjustment if necessary. Clinical parameters evaluated included plaque index, sulcular bleeding index, probing depth, attachment level, gingival recession, and open horizontal and vertical furcation fill. An acrylic occlusal stent was used to assure reproducibility of measurements. Experimental sites received a polytetrafluoroethylene membrane following surgical exposure of the furcation. Control sites were treated in the exact same manner but without a membrane. Membranes were removed at 6 weeks after the first surgery. Reentry surgeries were performed at 9 months. Postsurgical results showed a significant improvement in probing depth, attachment level, and open horizontal furcation fill for both groups when compared to baseline values, with experimental sites performing significantly better than controls. Control sites showed a slight loss in open vertical furcation fill while experimental sites remained unchanged. This study suggests that guided tissue regeneration using polytetrafluoroethylene membranes is of some but limited value in the treatment of maxillary molar interpoximal Class II furcation lesions.

  15. KARYOTYPE ANALYSIS OF THE FRESHWATER DUGESI4 PLANARIANS FROM YUNNAN PROVINCE, CHINA%中国云南三产地淡水三角涡虫核型分析

    Institute of Scientific and Technical Information of China (English)

    陈广文; 田士瑞; 刘涛; 刘德增

    2011-01-01

    利用空气干燥法,对采自云南省丽江市束河古镇、保山市龙王塘和香格里拉市小中甸3产地淡水三角涡虫(Dugesia sp.)的染色体和核型进行分析,结果表明:丽江市束河古镇淡水三角涡虫体细胞的染色体数目以16条为主,为二倍体(2n=2x=16=16m);保山市龙王塘淡水三角涡虫体细胞的染色体数目以24条为主(2n=3x=24=24m),少数为16条(2n=2x=16=16m),为三倍体和为二倍体的混合倍体;值得注意的是:香格里拉市小中甸淡水三角涡虫体细胞的染色体数目以极少见的26条为主(2n=3x+2=24+2=21m+3st+2m),少数为25条(2n=3x+1=24+1=21m+3st+1m)和24条(2n=3x=24=21m+3st),为三倍性混合倍体.研究根据核型结果对上述三产地淡水三角涡虫的分类和染色体非整倍性进行了分析.%In order to provide evidence for taxonomy, evolutionary biology, biogeography and phylogenetics of the genus Dugesia, the chromosomes and karyotypes of the freshwater planarians, Dugesia sp., collected from Shuhe town in Lijiang City, Longwangtang pond in Baoshan City, and Xiaozhaongdian town in Xianggelila City, Yunnan Province,were studied. The adult planarians, 15-20 mm in length and 1.5-2.0 mm in width, were used. After starving for a week, each planarian was transversally cut into five pieces, the planarian pieces were cultured in distilled water for three or four days to regenerate. For the karyological analysis, the metaphase chromosomes were prepared from regenerating blastemas by an air-drying method. Chromosome numbers of over 100 well-spreaded cells were counted and the chromosomes were photographed using Leica DMLB light microscope. The karyotype parameters of five well-spreaded metaphase plates from five individuals were measured. Relative length (r.l.) was calculated as chromosome length × 100/total length of haploid genome. Centromeric index (c.i.) was calculated as length of the short arm× 100/total length of the chromosome. Arm ratio (a.r.) was calculated

  16. Land planarian assemblages in protected areas of the interior atlantic forest: implications for conservation.

    Directory of Open Access Journals (Sweden)

    Lisandro Negrete

    Full Text Available Land planarians are an interesting group of free-living flatworms that can be useful as bioindicators because of their high sensitivity to environmental changes and low dispersal capacity. In this study, we describe and compare assemblages of land planarians from areas with different conservation degrees of the Interior Atlantic Forest (Misiones, Argentina, and assess factors that could be related to their abundance and richness. Eight sites were tracked in search of land planarians in Reserva de Vida Silvestre Urugua-í (RVSU and Campo Anexo Manuel Belgrano (CAMB. Diurnal and nocturnal surveys were performed in each site along nine sampling campaigns. We collected 237 individuals belonging to 18 species of the subfamily Geoplaninae. All sites were dominated by Geoplana sp. 1 and Pasipha hauseri. The richness estimators showed that there would be more species in RVSU than in CAMB. The abundance and richness of land planarians was high during the night and after rainfalls, suggesting an increased activity of flatworms under such conditions. The abundance and richness of land planarians were also related to the conservation condition of the sites. Disturbed sites showed less abundance and richness, and were segregated from non-disturbed ones by nmMDS analysis. Beta diversity between sites was higher than expected, indicating that the species turnover between sites contributed more to the total richness (gamma diversity than the alpha diversity.

  17. Land Planarian Assemblages in Protected Areas of the Interior Atlantic Forest: Implications for Conservation

    Science.gov (United States)

    Negrete, Lisandro; Colpo, Karine D.; Brusa, Francisco

    2014-01-01

    Land planarians are an interesting group of free-living flatworms that can be useful as bioindicators because of their high sensitivity to environmental changes and low dispersal capacity. In this study, we describe and compare assemblages of land planarians from areas with different conservation degrees of the Interior Atlantic Forest (Misiones, Argentina), and assess factors that could be related to their abundance and richness. Eight sites were tracked in search of land planarians in Reserva de Vida Silvestre Urugua-í (RVSU) and Campo Anexo Manuel Belgrano (CAMB). Diurnal and nocturnal surveys were performed in each site along nine sampling campaigns. We collected 237 individuals belonging to 18 species of the subfamily Geoplaninae. All sites were dominated by Geoplana sp. 1 and Pasipha hauseri. The richness estimators showed that there would be more species in RVSU than in CAMB. The abundance and richness of land planarians was high during the night and after rainfalls, suggesting an increased activity of flatworms under such conditions. The abundance and richness of land planarians were also related to the conservation condition of the sites. Disturbed sites showed less abundance and richness, and were segregated from non-disturbed ones by nmMDS analysis. Beta diversity between sites was higher than expected, indicating that the species turnover between sites contributed more to the total richness (gamma diversity) than the alpha diversity. PMID:24598934

  18. What role do annelid neoblasts play? A comparison of the regeneration patterns in a neoblast-bearing and a neoblast-lacking enchytraeid oligochaete.

    Directory of Open Access Journals (Sweden)

    Maroko Myohara

    Full Text Available The term 'neoblast' was originally coined for a particular type of cell that had been observed during annelid regeneration, but is now used to describe the pluripotent/totipotent stem cells that are indispensable for planarian regeneration. Despite having the same name, however, planarian and annelid neoblasts are morphologically and functionally distinct, and many annelid species that lack neoblasts can nonetheless substantially regenerate. To further elucidate the functions of the annelid neoblasts, a comparison was made between the regeneration patterns of two enchytraeid oligochaetes, Enchytraeus japonensis and Enchytraeus buchholzi, which possess and lack neoblasts, respectively. In E. japonensis, which can reproduce asexually by fragmentation and subsequent regeneration, neoblasts are present in all segments except for the eight anterior-most segments including the seven head-specific segments, and all body fragments containing neoblasts can regenerate a complete head and a complete tail, irrespective of the region of the body from which they were originally derived. In E. japonensis, therefore, no antero-posterior gradient of regeneration ability exists in the trunk region. However, when amputation was carried out within the head region, where neoblasts are absent, the number of regenerated segments was found to be dependent on the level of amputation along the body axis. In E. buchholzi, which reproduces only sexually and lacks neoblasts in all segments, complete heads were never regenerated and incomplete (hypomeric heads could be regenerated only from the anterior region of the body. Such an antero-posterior gradient of regeneration ability was observed for both the anterior and posterior regeneration in the whole body of E. buchholzi. These results indicate that the presence of neoblasts correlates with the absence of an antero-posterior gradient of regeneration ability along the body axis, and suggest that the annelid neoblasts are

  19. β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina

    Directory of Open Access Journals (Sweden)

    Meyers Jason R

    2012-08-01

    Full Text Available Abstract Background The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood. Results We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL. Conclusions β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that

  20. Regenerative medicine for diseases of the head and neck: principles of in vivo regeneration.

    Science.gov (United States)

    Löwenheim, H

    2003-09-01

    The application of endogenous regeneration in regenerative medicine is based on the concept of inducing regeneration of damaged or lost tissues from residual tissues in situ. Therefore, endogenous regeneration is also termed in vivo regeneration as opposed to mechanisms of ex vivo regeneration which are applied, for example, in the field of tissue engineering. The basic science foundation for mechanisms of endogenous regeneration is provided by the field of regenerative biology. The ambitious vision for the application of endogenous regeneration in regenerative medicine is stimulated by investigations in the model organisms of regenerative biology, most notably hydra, planarians and urodeles. These model organisms demonstrate remarkable regenerative capabilities, which appear to be conserved over large phylogenetical stretches with convincing evidence for a homologue origin of an endogenous regenerative capability. Although the elucidation of the molecular and cellular mechanisms of these endogenous regenerative phenomena is still in its beginning, there are indications that these processes have potential to become useful for human benefit. Such indications also exist for particular applications in diseases of the head and neck region. As such epimorphic regeneration without blastema formation may be relevant to regeneration of sensorineural epithelia of the inner ear or the olphactory epithelium. Complex tissue lesions of the head and neck as they occur after trauma or tumor resections may be approached on the basis of relevant mechanisms in epimorphic regeneration with blastema formation.

  1. Controlling mercury and selenium emissions from coal-fired combustors using a novel regenerable natural product

    Energy Technology Data Exchange (ETDEWEB)

    Schlager, R.J.; Marmaro, R.W.; Roberts, D.L. [ADA Technologies, Inc., Englewood, CO (United States)

    1995-11-01

    This program successfully demonstrated the key components that are needed for a practical, regenerable sorption process for removing and recovering mercury from flue gas streams: (1) a proprietary natural product removed mercuric chloride from synthetic flue gas, (2) several new noble metal sorbents were shown to capture elemental gas-phase mercury from synthetic coal combustion flue gas, and (3) both the natural product and the noble metal sorbents could be regenerated in the laboratory (chemical method for the natural product, thermal method for noble metal sorbents). Several sorbents were tested for their ability to collect selenium oxide during the program. These tests, however, were not definitive due to inconclusive analytical results. If follow-on testing is funded, the ability of the proposed sorbents to collect selenium and other metals will be evaluated during the field testing phase of the program. A preliminary economic analysis indicates that the cost of the process appears to be substantially less than the cost of the state-of-the-art method, namely injection of activated carbon, and it also appears to cost less than using noble metal sorbents alone.

  2. Controlled release strategies for modulating immune responses to promote tissue regeneration.

    Science.gov (United States)

    Dumont, Courtney M; Park, Jonghyuck; Shea, Lonnie D

    2015-12-10

    Advances in the field of tissue engineering have enhanced the potential of regenerative medicine, yet the efficacy of these strategies remains incomplete, and is limited by the innate and adaptive immune responses. The immune response associated with injury or disease combined with that mounted to biomaterials, transplanted cells, proteins, and gene therapies vectors can contribute to the inability to fully restore tissue function. Blocking immune responses such as with anti-inflammatory or immunosuppressive agents are either ineffective, as the immune response contributes significantly to regeneration, or have significant side effects. This review describes targeted strategies to modulate the immune response in order to limit tissue damage following injury, promote an anti-inflammatory environment that leads to regeneration, and induce antigen (Ag)-specific tolerance that can target degenerative diseases that destroy tissues and promote engraftment of transplanted cells. Focusing on targeted immuno-modulation, we describe local delivery techniques to sites of inflammation as well as systemic approaches that preferentially target subsets of immune populations.

  3. A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages.

    Science.gov (United States)

    Pearson, Bret J; Sánchez Alvarado, Alejandro

    2010-01-01

    The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus far. Planaria have a single p53 family member, Smed-p53, which is predominantly expressed in newly made stem cell progeny. When Smed-p53 is targeted by RNAi, the stem cell population increases at the expense of progeny, resulting in hyper-proliferation. However, ultimately the stem cell population fails to self-renew. Our results suggest that prior to the vertebrates, an ancestral p53-like molecule already had functions in stem cell proliferation control and self-renewal.

  4. A simple method for fabrication of electrospun fibers with controlled degree of alignment having potential for nerve regeneration applications

    Energy Technology Data Exchange (ETDEWEB)

    Vimal, Sunil Kumar; Ahamad, Nadim; Katti, Dhirendra S., E-mail: dsk@iitk.ac.in

    2016-06-01

    In peripheral nerve injuries where direct suturing of nerve endings is not feasible, nerve regeneration has been facilitated through the use of artificially aligned fibrous scaffolds that provide directional growth of neurons to bridge the gap. The degree of fiber alignment is crucial and can impact the directionality of cells in a fibrous scaffold. While there have been multiple approaches that have been used for controlling fiber alignment, however, they have been associated with a compromised control on other properties, such as diameter, morphology, curvature, and topology of fibers. Therefore, the present study demonstrates a modified electrospinning set-up, that enabled fabrication of electrospun fibers with controlled degree of alignment from non-aligned (NA), moderately aligned (MA, 75%) to highly aligned (HA, 95%) sub-micron fibers while keeping other physical properties unchanged. The results demonstrate that the aligned fibers (MA and HA) facilitated directional growth of human astrocytoma cells (U373), wherein the aspect ratio of cells was found to increase with an increase in degree of fibers alignment. In contrast to NA and MA fibers, the HA fibers showed improved contact guidance to U373 cells that was demonstrated by a significantly higher cell aspect ratio and nuclear aspect ratio. In conclusion, the present study demonstrated a modified electrospinning setup to fabricate differentially aligned fibrous scaffolds with the HA fibers showing potential for use in neural tissue engineering. - Highlights: • Modified electrospinning set-up for fabrication of fibers with controlled alignment • Three parameter-based control on the degree of alignment of fibers • The aligned fibers enhanced cell elongation and cell-cell contact. • The aligned fibers show potential for use in nerve regeneration.

  5. Chemical genetics and regeneration.

    Science.gov (United States)

    Sengupta, Sumitra; Zhang, Liyun; Mumm, Jeff S

    2015-01-01

    Regeneration involves interactions between multiple signaling pathways acting in a spatially and temporally complex manner. As signaling pathways are highly conserved, understanding how regeneration is controlled in animal models exhibiting robust regenerative capacities should aid efforts to stimulate repair in humans. One way to discover molecular regulators of regeneration is to alter gene/protein function and quantify effect(s) on the regenerative process: dedifferentiation/reprograming, stem/progenitor proliferation, migration/remodeling, progenitor cell differentiation and resolution. A powerful approach for applying this strategy to regenerative biology is chemical genetics, the use of small-molecule modulators of specific targets or signaling pathways. Here, we review advances that have been made using chemical genetics for hypothesis-focused and discovery-driven studies aimed at furthering understanding of how regeneration is controlled.

  6. A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration.

    Directory of Open Access Journals (Sweden)

    Benjamin L King

    Full Text Available Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs.These studies identified a core group of 5 microRNAs (miRNAs that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5.Our extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation for future

  7. A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration

    Science.gov (United States)

    King, Benjamin L.; Yin, Viravuth P.

    2016-01-01

    Background Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs. Results These studies identified a core group of 5 microRNAs (miRNAs) that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5. Conclusions Our extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation

  8. Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

    Science.gov (United States)

    Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

    2011-03-01

    In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

  9. AtTCTP2, an Arabidopsis thaliana homolog of Translationally Controlled Tumor Protein, enhances in vitro plant regeneration

    Directory of Open Access Journals (Sweden)

    Roberto eToscano-Morales

    2015-07-01

    Full Text Available The Translationally Controlled Tumor Protein (TCTP is a central regulator of cell proliferation and differentiation in animals, and probably also in plants. Arabidopsis harbors two TCTP genes, AtTCTP1 (At3g16640, which is an important mitotic regulator, and AtTCTP2 (At3g05540, which is considered a pseudogene. Nevertheless, we have obtained evidence suggesting that this gene is functional. Indeed, a T-DNA insertion mutant, SALK_045146, displays a lethal phenotype during early rosette stage. Also, both the AtTCTP2 promoter and structural gene are functional, and heterozygous plants show delayed development. AtTCTP1 cannot compensate for the loss of AtTCTP2, since the accumulation levels of the AtTCTP1 transcript are even higher in heterozygous plants than in wild-type plants. Leaf explants transformed with Agrobacterium rhizogenes harboring AtTCTP2, but not AtTCTP1, led to whole plant regeneration with a high frequency. Insertion of a sequence present in AtTCTP1 but absent in AtTCP2 demonstrates that this suppresses the capacity for plant regeneration; also, this phenomenon requires the presence of TCTP (AtTCTP1 or 2 in the nuclei of root cells. This confirms that AtTCTP2 is not a pseudogene and suggests the involvement of certain TCTP isoforms in vegetative reproduction in some plant species.

  10. AtTCTP2, an Arabidopsis thaliana homolog of Translationally Controlled Tumor Protein, enhances in vitro plant regeneration

    Science.gov (United States)

    Toscano-Morales, Roberto; Xoconostle-Cázares, Beatriz; Cabrera-Ponce, José L.; Hinojosa-Moya, Jesús; Ruiz-Salas, Jorge L.; Galván-Gordillo, Santiago V.; Guevara-González, Ramón G.; Ruiz-Medrano, Roberto

    2015-01-01

    The Translationally Controlled Tumor Protein (TCTP) is a central regulator of cell proliferation and differentiation in animals, and probably also in plants. Arabidopsis harbors two TCTP genes, AtTCTP1 (At3g16640), which is an important mitotic regulator, and AtTCTP2 (At3g05540), which is considered a pseudogene. Nevertheless, we have obtained evidence suggesting that this gene is functional. Indeed, a T-DNA insertion mutant, SALK_045146, displays a lethal phenotype during early rosette stage. Also, both the AtTCTP2 promoter and structural gene are functional, and heterozygous plants show delayed development. AtTCTP1 cannot compensate for the loss of AtTCTP2, since the accumulation levels of the AtTCTP1 transcript are even higher in heterozygous plants than in wild-type plants. Leaf explants transformed with Agrobacterium rhizogenes harboring AtTCTP2, but not AtTCTP1, led to whole plant regeneration with a high frequency. Insertion of a sequence present in AtTCTP1 but absent in AtTCTP2 demonstrates that it suppresses the capacity for plant regeneration; also, this phenomenon is enhanced by the presence of TCTP (AtTCTP1 or 2) in the nuclei of root cells. This confirms that AtTCTP2 is not a pseudogene and suggests the involvement of certain TCTP isoforms in vegetative reproduction in some plant species. PMID:26191065

  11. Cell proliferation is necessary for the regeneration of oral structures in the anthozoan cnidarian Nematostella vectensis

    Directory of Open Access Journals (Sweden)

    Passamaneck Yale J

    2012-12-01

    Full Text Available Abstract Background The contribution of cell proliferation to regeneration varies greatly between different metazoan models. Planarians rely on pluripotent neoblasts and amphibian limb regeneration depends upon formation of a proliferative blastema, while regeneration in Hydra can occur in the absence of cell proliferation. Recently, the cnidarian Nematostella vectensis has shown potential as a model for studies of regeneration because of the ability to conduct comparative studies of patterning during embryonic development, asexual reproduction, and regeneration. The present study investigates the pattern of cell proliferation during the regeneration of oral structures and the role of cell proliferation in this process. Results In intact polyps, cell proliferation is observed in both ectodermal and endodermal tissues throughout the entire oral-aboral axis, including in the tentacles and physa. Following bisection, there is initially little change in proliferation at the wound site of the aboral fragment, however, beginning 18 to 24 hours after amputation there is a dramatic increase in cell proliferation at the wound site in the aboral fragment. This elevated level of proliferation is maintained throughout the course or regeneration of oral structures, including the tentacles, the mouth, and the pharynx. Treatments with the cell proliferation inhibitors hydroxyurea and nocodazole demonstrate that cell proliferation is indispensable for the regeneration of oral structures. Although inhibition of regeneration by nocodazole was generally irreversible, secondary amputation reinitiates cell proliferation and regeneration. Conclusions The study has found that high levels of cell proliferation characterize the regeneration of oral structures in Nematostella, and that this cell proliferation is necessary for the proper progression of regeneration. Thus, while cell proliferation contributes to regeneration of oral structures in both Nematostella and

  12. Air regenerating and conditioning

    Science.gov (United States)

    Grishayenkov, B. G.

    1975-01-01

    Various physicochemical methods of regenerating and conditioning air for spacecraft are described with emphasis on conditions which affect efficiency of the system. Life support systems used in closed, hermetically sealed environments are discussed with references to actual application in the Soviet Soyuz and Voskhod manned spacecraft. Temperature and humidity control, removal of carbon dioxide, oxygen regeneration, and removal of bacteria and viruses are among the factors considered.

  13. Biocomposite nanofibrous strategies for the controlled release of biomolecules for skin tissue regeneration.

    Science.gov (United States)

    Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Bhaarathy, Velmurugan; Ramakrishna, Seeram; Kumar, Srinivasan Dinesh

    2014-01-01

    Nanotechnology and tissue engineering have enabled engineering of nanostructured strategies to meet the current challenges in skin tissue regeneration. Electrospinning technology creates porous nanofibrous scaffolds to mimic extracellular matrix of the native tissues. The present study was performed to gain some insights into the applications of poly(l-lactic acid)-co-poly-(ε-caprolactone) (PLACL)/silk fibroin (SF)/vitamin E (VE)/curcumin (Cur) nanofibrous scaffolds and to assess their potential for being used as substrates for the culture of human dermal fibroblasts for skin tissue engineering. PLACL/SF/VE/Cur nanofibrous scaffolds were fabricated by electrospinning and characterized by fiber morphology, membrane porosity, wettability, mechanical strength, and chemical properties by Fourier transform infrared (FTIR) analysis. Human dermal fibroblasts were cultured on these scaffolds, and the cell scaffold interactions were analyzed by cell proliferation, cell morphology, secretion of collagen, expression of F-actin, and 5-chloromethylfluorescein diacetate (CMFDA) dye. The electrospun nanofiber diameter was obtained between 198±4 nm and 332±13 nm for PLACL, PLACL/SF, PLACL/SF/VE, and PLACL/SF/VE/Cur nanofibrous scaffolds. FTIR analysis showed the presence of the amide groups I, II, and III, and a porosity of up to 92% obtained on these nanofibrous scaffolds. The results showed that the fibroblast proliferation, cell morphology, F-actin, CMFDA dye expression, and secretion of collagen were significantly increased in PLACL/SF/VE/Cur when compared to PLACL nanofibrous scaffolds. The accessibility of human dermal fibroblasts cultured on PLACL/SF/VE/Cur nanofibrous scaffolds proved to be a potential scaffold for skin tissue regeneration.

  14. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  15. Evaluation of clinical, antiinflammatory and antiinfective properties of amniotic membrane used for guided tissue regeneration: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Aravind Kumar

    2015-01-01

    Full Text Available Background: The objective of this study was to evaluate the antiinflammatory, antiinfective and clinical properties of amniotic membrane (AM when used for guided tissue regeneration (GTR in contained interdental defects. Materials and Methods: A total of 30 subjects participated in this study. Two sites in each subject were randomly assigned into each of the following experimental groups; test group: AM with bone graft and control group: Bone graft only. Clinical parameters included recording site-specific measures of plaque, gingivitis, probing pocket depth (PPD, and clinical attachment loss (CAL. The levels of interleukin-1β (IL-1β and human beta-defensin-2 (hBD-2 levels in gingival crevicular fluid (GCF from the test and control sites were measured by using commercially available enzyme linked immunosorbent assay kits. The evaluation of bone fill was performed by using digital subtraction technique and morphometric area analysis. One-way analysis of variance followed by the post-hoc test was used for intragroup and intergroup comparison. A P < 0.05 was considered as statistically significant. Results: Combination therapy using an AM increased bone fill and reduced PPD and CAL when compared to controls. AM also resulted in a significant reduction of GCF IL-1β levels and insignificant increase in the hBD-2 levels. Conclusion: From this trial conducted over a period of 24 weeks, AM demonstrated a marked antiinflammatory effect and its use resulted in an improvement in periodontal parameters. AM has the potential to function as a barrier for GTR and the unique properties associated with this material can augment its potential as a matrix for periodontal regeneration.

  16. Tingkat Insidensi Malaria di Wilayah Pemanasan Kelambu Berinsektisida Tahan Lama dan Wilayah Kontrol (MALARIA INCIDENCE RATE OF HEAT ASSISTED REGENERATION LONG LASTING INSECTICIDAL NETS AREA AND CONTROL

    Directory of Open Access Journals (Sweden)

    Etih Sudarnika

    2012-03-01

    Full Text Available Long lasting insecticidal nets (LLIN is one effective way to prevent malaria. Permethrin treatedLLIN is one type of LLIN which is recommended by WHO. Several studies have shown that these types ofLLIN requiring heat assisted regeneration after washing to enhance the biological activity of insecticidethat contained in the LLIN fibers. This study aimed to compare the incidence rates of malaria in childrenunder five years old who live in the intervention area (where the heat assisted regeneration on LLIN afterwashing was applied and control area (where the heat assisted regeneration on LLIN after washing wasnot applied. Data of malaria cases was collected from laboratory log book at all health centers in BangkaDistrict, in the period of June June 2007 until July 2008. Data were analyzed with Poisson regressionmodels. The results showed that the incidence rate of malaria in children under five years old was notsignificantly different between the treatment and control areas.

  17. Making Heads or Tails: Planarian Stem Cells in the Classroom†

    Science.gov (United States)

    Srougi, Melissa C.; Thomas-Swanik, Jackie; Chan, John D.; Marchant, Jonathan S.; Carson, Susan

    2014-01-01

    Stem cells hold great promise in the treatment of diseases ranging from cancer to dementia. However, as rapidly as the field of stem cell biology has emerged, heated political debate has followed, scrutinizing the ethical implications of stem cell use. It is therefore imperative to promote scientific literacy by educating students about stem cell biology. Yet, there is a definite lack of material to engage students in this subject at the basic science level. Therefore, we have developed and implemented a hands-on introductory laboratory module that introduces students to stem cell biology and can be easily incorporated into existing curricula. Students learn about stem cell biology using an in vivo planarian model system in which they down-regulate two genes important in stem cell differentiation using RNA interference and then observe the regenerative phenotype. The module was piloted at the high school, community college, and university levels. Here, we report that introductory biology students enrolled at a community college were able to demonstrate gains in learning after completion of a one-hour lecture and four 45-minute laboratory sessions over the course of three weeks. These gains in learning outcomes were objectively evaluated both before and after its execution using a student quiz and experimental results. Furthermore, students’ self-assessments revealed increases in perceived knowledge as well as a general interest in stem cells. Therefore, these data suggest that this module is a simple, useful way to engage and to teach students about stem cell biology. PMID:24839511

  18. Making Heads or Tails: Planarian Stem Cells in the Classroom

    Directory of Open Access Journals (Sweden)

    Melissa C. Srougi

    2014-02-01

    Full Text Available Stem cells hold great promise in the treatment of diseases ranging from cancer to dementia. However, as rapidly as the field of stem cell biology has emerged, heated political debate has followed, scrutinizing the ethical implications for their use. It is therefore imperative to promote scientific literacy by educating students about stem cell biology. Yet, there is a definitive lack of material to engage students in this subject at the basic science level. Therefore, we have developed and implemented a hands-on introductory laboratory module that introduces students to stem cell biology, and can be easily incorporated into existing curricula.  Students learn about stem cell biology using an in vivo planarian model system in which they down-regulate two genes important in stem cell differentiation using RNA interference and then observe the regenerative phenotype. The module was piloted at the high school, community college and university levels. Here, we report that introductory biology students enrolled at a community college were able to demonstrate gains in learning after completion of a one hour lecture and four, forty five minute laboratory sessions over the course of three weeks. These gains in learning outcomes were objectively evaluated both before and after its execution using a student quiz and experimental results. Furthermore, students’ self-assessments revealed increases in perceived knowledge as well as a general interest in stem cells. Therefore, these data suggest that this module is a simple, useful way to engage and to teach students about stem cell biology.

  19. Germline Defects Caused by Smed-boule RNA-Interference Reveal That Egg Capsule Deposition Occurs Independently of Fertilization, Ovulation, Mating, or the Presence of Gametes in Planarian Flatworms.

    Directory of Open Access Journals (Sweden)

    Jessica Kathryne Steiner

    2016-05-01

    Full Text Available Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue to lay egg capsules. Production of sterile capsules is even observed in virgin Smed-boule(RNAi and control planarians maintained in complete isolation, demonstrating that egg production in S. mediterranea occurs independently of ovulation, fertilization, or mating. Evidence suggests that this is a conserved feature amongst Platyhelminthes, and therefore relevant to the pathology and dissemination of parasitic flatworms. These findings demonstrate that Smed-boule functions at different stages during male and female germline stem cell development, and also demonstrate that egg capsule production by planarian flatworms occurs independently of signals produced by mating or ova.

  20. Germline Defects Caused by Smed-boule RNA-Interference Reveal That Egg Capsule Deposition Occurs Independently of Fertilization, Ovulation, Mating, or the Presence of Gametes in Planarian Flatworms.

    Science.gov (United States)

    Steiner, Jessica Kathryne; Tasaki, Junichi; Rouhana, Labib

    2016-05-01

    Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule) production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi) causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue to lay egg capsules. Production of sterile capsules is even observed in virgin Smed-boule(RNAi) and control planarians maintained in complete isolation, demonstrating that egg production in S. mediterranea occurs independently of ovulation, fertilization, or mating. Evidence suggests that this is a conserved feature amongst Platyhelminthes, and therefore relevant to the pathology and dissemination of parasitic flatworms. These findings demonstrate that Smed-boule functions at different stages during male and female germline stem cell development, and also demonstrate that egg capsule production by planarian flatworms occurs independently of signals produced by mating or ova.

  1. Local Regeneration of Dentin-Pulp Complex Using Controlled Release of FGF-2 and Naturally Derived Sponge-Like Scaffolds

    Directory of Open Access Journals (Sweden)

    Chiaki Kitamura

    2012-01-01

    Full Text Available Restorative and endodontic procedures have been recently developed in an attempt to preserve the vitality of dental pulp after exposure to external stimuli, such as caries infection or traumatic injury. When damage to dental pulp is reversible, pulp wound healing can proceed, whereas irreversible damage induces pathological changes in dental pulp, eventually requiring its removal. Nonvital teeth lose their defensive abilities and become severely damaged, resulting in extraction. Development of regeneration therapy for the dentin-pulp complex is important to overcome limitations with presently available therapies. Three strategies to regenerate the dentin-pulp complex have been proposed; regeneration of the entire tooth, local regeneration of the dentin-pulp complex from amputated dental pulp, and regeneration of dental pulp from apical dental pulp or periapical tissues. In this paper, we focus on the local regeneration of the dentin-pulp complex by application of exogenous growth factors and scaffolds to amputated dental pulp.

  2. Towards a phylogenetic classification of dendrocoelid freshwater planarians (Platyhelminthes): a morphological and eclectic approach

    NARCIS (Netherlands)

    Sluys, R.; Kawakatsu, M.

    2006-01-01

    We explore and review the taxonomic distribution of morphological features that may be used as supporting apomorphies for the monophyletic status of various taxa in future, more comprehensive phylogenetic analyses of the dendrocoelid freshwater planarians and their close relatives. Characters examin

  3. Unusually Large Number of Mutations in Asexually Reproducing Clonal Planarian Dugesia japonica.

    Directory of Open Access Journals (Sweden)

    Osamu Nishimura

    Full Text Available We established a laboratory clonal strain of freshwater planarian (Dugesia japonica that was derived from a single individual and that continued to undergo autotomous asexual reproduction for more than 20 years, and we performed large-scale genome sequencing and transcriptome analysis on it. Despite the fact that a completely clonal strain of the planarian was used, an unusually large number of mutations were detected. To enable quantitative genetic analysis of such a unique organism, we developed a new model called the Reference Gene Model, and used it to conduct large-scale transcriptome analysis. The results revealed large numbers of mutations not only outside but also inside gene-coding regions. Non-synonymous SNPs were detected in 74% of the genes for which valid ORFs were predicted. Interestingly, the high-mutation genes, such as metabolism- and defense-related genes, were correlated with genes that were previously identified as diverse genes among different planarian species. Although a large number of amino acid substitutions were apparently accumulated during asexual reproduction over this long period of time, the planarian maintained normal body-shape, behaviors, and physiological functions. The results of the present study reveal a unique aspect of asexual reproduction.

  4. Unusually Large Number of Mutations in Asexually Reproducing Clonal Planarian Dugesia japonica.

    Science.gov (United States)

    Nishimura, Osamu; Hosoda, Kazutaka; Kawaguchi, Eri; Yazawa, Shigenobu; Hayashi, Tetsutaro; Inoue, Takeshi; Umesono, Yoshihiko; Agata, Kiyokazu

    2015-01-01

    We established a laboratory clonal strain of freshwater planarian (Dugesia japonica) that was derived from a single individual and that continued to undergo autotomous asexual reproduction for more than 20 years, and we performed large-scale genome sequencing and transcriptome analysis on it. Despite the fact that a completely clonal strain of the planarian was used, an unusually large number of mutations were detected. To enable quantitative genetic analysis of such a unique organism, we developed a new model called the Reference Gene Model, and used it to conduct large-scale transcriptome analysis. The results revealed large numbers of mutations not only outside but also inside gene-coding regions. Non-synonymous SNPs were detected in 74% of the genes for which valid ORFs were predicted. Interestingly, the high-mutation genes, such as metabolism- and defense-related genes, were correlated with genes that were previously identified as diverse genes among different planarian species. Although a large number of amino acid substitutions were apparently accumulated during asexual reproduction over this long period of time, the planarian maintained normal body-shape, behaviors, and physiological functions. The results of the present study reveal a unique aspect of asexual reproduction.

  5. Screening molecules for control of citrus huanglongbing using an optimized regeneration system for 'Candidatus Liberibacter asiaticus'-infected periwinkle (Catharanthus roseus) cuttings.

    Science.gov (United States)

    Zhang, Muqing; Duan, Yongping; Zhou, Lijuan; Turechek, William W; Stover, Ed; Powell, Charles A

    2010-03-01

    Citrus huanglongbing is one of the most destructive diseases of citrus worldwide. The disease is associated with three different species of 'Candidatus Liberibacter', of which 'Ca. L. asiaticus' is the most widely distributed. An optimized system using 'Ca. L. asiaticus'-infected periwinkle cuttings was developed to screen chemical compounds effective for controlling the bacterial population while simultaneously assessing their phytotoxicity. The optimal regeneration conditions were determined to be the use of vermiculite as a growth medium for the cuttings, and a fertilization routine using half-strength Murashige and Tucker medium supplemented with both naphthalene acetic acid (4 microg/ml) and indole-3-butyric acid (4 microg/ml). This system allowed a plant regeneration rate of 60.6% for 'Ca. L. asiaticus'-infected cuttings in contrast to the <1% regeneration rate with water alone. Two chemical agents, penicillin G sodium and 2,2-dibromo-3-nitrilopropionamide (DBNPA), were found to be effective at eliminating or suppressing the 'Ca. L. asiaticus' bacterium in this periwinkle regeneration system. When treated with penicillin G sodium at 50 microg/ml, all plants regenerated from 'Ca. L. asiaticus'-infected cuttings were 'Ca. L. asiaticus' negative as determined by both nested polymerase chain reaction (PCR) and quantitative real-time PCR. In addition, DBNPA was also able to significantly reduce the percentage of 'Ca. L. asiaticus'-positive plants and the titer of the 'Ca. L. asiaticus' bacterium at 200 microl/liter.

  6. Complete genome sequence of a novel extrachromosomal virus-like element identified in planarian Girardia tigrina

    Directory of Open Access Journals (Sweden)

    Vagner Loura L

    2002-06-01

    Full Text Available Abstract Background Freshwater planarians are widely used as models for investigation of pattern formation and studies on genetic variation in populations. Despite extensive information on the biology and genetics of planaria, the occurrence and distribution of viruses in these animals remains an unexplored area of research. Results Using a combination of Suppression Subtractive Hybridization (SSH and Mirror Orientation Selection (MOS, we compared the genomes of two strains of freshwater planarian, Girardia tigrina. The novel extrachromosomal DNA-containing virus-like element denoted PEVE (Planarian Extrachromosomal Virus-like Element was identified in one planarian strain. The PEVE genome (about 7.5 kb consists of two unique regions (Ul and Us flanked by inverted repeats. Sequence analyses reveal that PEVE comprises two helicase-like sequences in the genome, of which the first is a homolog of a circoviral replication initiator protein (Rep, and the second is similar to the papillomavirus E1 helicase domain. PEVE genome exists in at least two variant forms with different arrangements of single-stranded and double-stranded DNA stretches that correspond to the Us and Ul regions. Using PCR analysis and whole-mount in situ hybridization, we characterized PEVE distribution and expression in the planarian body. Conclusions PEVE is the first viral element identified in free-living flatworms. This element differs from all known viruses and viral elements, and comprises two potential helicases that are homologous to proteins from distant viral phyla. PEVE is unevenly distributed in the worm body, and is detected in specific parenchyma cells.

  7. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  8. Occurrence and abundance of a mariner-like element in freshwater and terrestrial planarians (Platyhelminthes, Tricladida from southern Brazil

    Directory of Open Access Journals (Sweden)

    Fernanda Sperb

    2009-01-01

    Full Text Available Transposable elements are DNA sequences present in all the large phylogenetic groups, both capable of changing position within the genome and constituting a significant part of eukaryotic genomes. The mariner family of transposons is one of the few which occurs in a wide variety of taxonomic groups, including freshwater planarians. Nevertheless, so far only five planarian species have been reported to carry mariner-like elements (MLEs, although several different species have been investigated. Regarding the number of copies of MLEs, Girardia tigrina is the only planarian species in which this has been evaluated, with an estimation of 8,000 copies of the element per haploid genome. Preliminary results obtained in our laboratory demonstrated that MLE is found in a large number of different species of planarians, including terrestrial. With this in mind, the aim was to evaluate the occurrence and estimate the number of MLE copies in different planarian species collected in south Brazil. Twenty-eight individuals from 15 planarian species were analyzed. By using PCR and the hybridization of nucleic acids, it was found that MLE was present in all the analyzed species, the number of copies being high, probably over 10³ per haploid genome.

  9. Optimal control of end-port glass tank furnace regenerator temperature based on artificial neural network

    Institute of Scientific and Technical Information of China (English)

    CHEN Xi; ZHAO Guo-zhu

    2005-01-01

    In the paper, an artificial neural network (ANN) method is put forward to optimize melting temperature control, which reveals the nonlinear relationships of tank melting temperature disturbances with secondary wind flow and fuel pressure, implements dynamic feed-forward complementation and dynamic correctional ratio between air and fuel in the main control system. The application to Anhui Fuyang Glass Factory improved the control character of the melting temperature greatly.

  10. [Life support of the Mars exploration crew. Control of a zeolite system for carbon dioxide removal from space cabin air within a closed air regeneration cycle].

    Science.gov (United States)

    Chekov, Iu F

    2009-01-01

    The author describes a zeolite system for carbon dioxide removal integrated into a closed air regeneration cycle aboard spacecraft. The continuous operation of a double-adsorbent regeneration system with pCO2-dependable productivity is maintained through programmable setting of adsorption (desorption) semicycle time. The optimal system regulation curve is presented within the space of statistical performance family obtained in quasi-steady operating modes with controlled parameters of the recurrent adsorption-desorption cycle. The automatically changing system productivity ensures continuous intake of concentrated CO2. Control of the adsorption-desorption process is based on calculation of the differential adsorption (desorption) heat from gradient of adsorbent and test inert substance temperatures. The adaptive algorithm of digital control is implemented through the standard spacecraft interface with the board computer system and programmable microprocessor-based controllers.

  11. Metabolic Heat Regenerated Temperature Swing Adsorption for CO2, Thermal and Humidity Control Project

    Data.gov (United States)

    National Aeronautics and Space Administration — MTSA technology specifically addresses the thermal, CO2 and humidity control challenges faced by Portable Life Support Systems (PLSS) to be used in NASA's...

  12. Gravity and light control of the developmental polarity of regenerating protoplasts isolated from prothallial cells of the fern Ceratopteris richardii

    Science.gov (United States)

    Edwards, E. S.; Roux, S. J.

    1998-01-01

    A procedure has been developed for isolating protoplasts from prothalli of Ceratopteris richardii which can be cultured and are capable of regeneration. Protoplasts were isolated from 2-week-old gametophytes in a medium containing wall-digesting enzymes in 0.5 M sucrose, followed by purification of the released protoplasts by floating them up into a 0.5 M sorbitol layer. Regeneration occurred over a period of 10-24 days, and, under optimal osmotic conditions, followed the developmental pattern seen during spore germination, in that the first division gave rise to a primary rhizoid. Thus, prothallial protoplasts are comparable to germinating spores as suitable models for studies of developmental polarity in single cells. As in germinating spores, the polarity of development in regenerating protoplasts is influenced by the vectors of gravity and unilateral light. However, the relative influence of light in fixing this polarity is greater in regenerating protoplasts, while in germinating spores, the influence of gravity is greater.

  13. Regenerated cellulose capsules for controlled drug delivery: Part IV. In-vitro evaluation of novel self-pore forming regenerated cellulose capsules.

    Science.gov (United States)

    Bhatt, Bhavik; Kumar, Vijay

    2017-01-15

    In the present work, the release mechanisms of active pharmaceutical ingredients (APIs) enclosed in self-pore forming regenerated cellulose (RC) two-piece hard shell capsules are described. The RC capsules were fabricated using a modified dip-coating approach, which yielded an assembled dosage form that was equivalent in size and shape to a conventional gelatin two-piece hard shell capsule. Drug release characteristics from RC capsules were evaluated using potassium chloride, diphenhydramine hydrochloride, tramadol hydrochloride, niacinamide, acetaminophen and ketoprofen as model APIs. The RC capsules act as a barrier coated reservoir device that releases the enclosed API at a zero order release rate. When comparing all the API's release behavior from RC capsules, a power-law relationship was observed between their zero-order release rates and their respective aqueous solubilities. Osmotic as well as diffusive mechanisms are involved in the release of the enclosed API. The osmotic mechanism's contribution to zero order release rate increases as the aqueous solubility of the tested APIs inside the capsule increases. The osmotic mediated flux and the apparent diffusivity of the APIs through the capsule wall is a competitive process and the osmotic mediated flux of the enclosed API begins to override its diffusivity through the capsule wall as the API solubility increases. This behavior is attributed to the wide range of pore sizes observed in RC membranes, from our prior analysis. The fluid permeability analysis shows that the RC capsules presented in this work may be better suited for osmotic drug delivery applications than conventional encapsulated systems described in the literature. Copyright © 2016. Published by Elsevier B.V.

  14. Platelet Rich Fibrin (PRF) in Regeneration of Intrabony Defects- A Randomized Controlled Trial.

    Science.gov (United States)

    Kumar Patel, Gauresh; Kumar Gujjari, Sheela; Kumar S C, Veerendra

    2017-08-18

    Platelet-rich fibrin (PRF) is a autologous non transfusional hemo-component with a high concentration of platelets. It incorporates leukocytes, platelets and growth factors within the dense fibrin matrix and can be used as healing biomaterial. This study assessed the adjunctive use of PRF in regenerative management of intrabony defects in comparison with open flap debridement. 26 bilateral defects (13 per group) in 13 patients were randomized as either PRF (Test group) or Open flap debridement alone (control group) sites. Probing depth (PD), clinical attachment level (CAL) and bone probing depth were recorded. Reduction in defect depth and percentage of bone fill was assessed radiographically. Primary outcomes assessed were the changes in pocket depth, attachment level and percentage of bone fill assessed at 6months, 9 months and 12 months. Secondary outcome was assessment of wound healing using a wound healing index. The PRF group showed significant improvement in clinical parameters over control group at 6, 9, and 12 months. PRF group showed a bone fill of 45.18±7.57 percent which was statistically significant compared to 21.6±9.3 percent seen in control group at end of study period. Wound healing index (WHI) also showed significant advantages for the PRF group. PRF also showed significant soft tissue healing and reduction in probing depth. The adjunctive use of PRF to conventional open flap debridement may be potentially used in the treatment of intrabony defects.

  15. My Regeneration:

    DEFF Research Database (Denmark)

    Carter, Dale

    2016-01-01

    and cultural referents shows that it offers an index to the album. Using its frontier setting and a variety of sacred and secular myths, symbols and icons, ‘Heroes and Villains,’ like Smile as a whole, offers historically-informed visions of national decline, crisis and regeneration that are at once critical...

  16. Local controlled release of VEGF and PDGF from a combined brushite-chitosan system enhances bone regeneration.

    Science.gov (United States)

    De la Riva, Beatriz; Sánchez, Esther; Hernández, Antonio; Reyes, Ricardo; Tamimi, Faleh; López-Cabarcos, Enrique; Delgado, Araceli; Evora, Carmen

    2010-04-02

    The two growth factors VEGF and PDGF are involved in the process of bone regeneration. For this reason, we developed a brushite-chitosan system which controls the release kinetics of incorporated VEGF and PDGF to enhance bone healing. PDGF (250 ng) was incorporated in the liquid phase. Alginate microsphere-encapsulated VEGF (350 ng) was pre-included in small cylindrical chitosan sponges. VEGF and PDGF release kinetics and tissue distribution were determined using iodinated ((125)I) growth factor. In vivo, PDGF was more rapidly delivered from these systems implanted in rabbit femurs than VEGF. 80% of PDGF was released by the end of two weeks while only 70% of VEGF was delivered after a period of three weeks. Both GFs released from the brushite-chitosan constructs remained located around the implantation site (5 cm) with negligible systemic exposure. A PDGF bone peak concentration of approximately 5 ng/g was achieved on the 4th day. Thereafter, PDGF concentrations stayed higher than 2 ng/g during the first week. These scaffolds also provided a local VEGF bone concentration above 3 ng/g during a total of 4weeks, with a peak concentration of 5.5 ng/g on the 7th day. The present work demonstrates that our brushite-chitosan system is capable of controlling the release rate and localization of both GFs within a bone defect. The effect on bone formation was considerably enhanced with PDGF loaded brushite-chitosan scaffolds as well as with the PDGF/VEGF combination.

  17. Poly(ester amide)s from Poly(ethylene terephthalate) Waste for Enhancing Bone Regeneration and Controlled Release.

    Science.gov (United States)

    Natarajan, Janeni; Madras, Giridhar; Chatterjee, Kaushik

    2017-08-30

    The present study elucidates the facile synthesis and exceptional properties of a family of novel poly(ester amide)s (PEAs) based on bis(2-hydroxy ethylene) terephthalamide that was obtained from the poly(ethylene terephthalate) waste. Fourier transform infrared and (1)H NMR were used to verify the presence of ester and amide in the polymer backbone. Differential scanning calorimetry data showed that the glass transition temperature decreased with as the chain length of dicarboxylic acids increased. Dynamic mechanical analysis and contact angle studies proved that the modulus values and hydrophobicity increased with as the chain lengths of dicarboxylic acids increased. In vitro hydrolytic degradation and dye release studies demonstrated that the degradation and release decreased with as the chain lengths of dicarboxylic acids increased. Modeling these data illustrated that degradation and release follow first-order degradation and zero-order release, respectively. The in vitro cytocompatibility studies confirmed the minimal toxicity characteristic of these polymers. Osteogenic studies proved that these polymers can be highly influential in diverting the cells toward osteogenic lineage. Alizarin red staining evinced the presence of twice the amount of calcium phosphate deposits by the cells on these polymers when compared to the control. The observed result was also corroborated by the increased expression of alkaline phosphatase. These findings were further validated by the markedly higher mRNA expressions for known osteogenic markers using real time polymerase chain reaction. Therefore, these polymers efficiently promoted osteogenesis. This study demonstrates that the physical properties, degradation, and release kinetics can be altered to meet the specific requirements in organ regeneration as well as facilitate simultaneous polymer resorption through control of the chain length of the monomers. The findings of this study have significant implications for

  18. Some principles of regeneration in mammalian systems.

    Science.gov (United States)

    Carlson, Bruce M

    2005-11-01

    This article presents some general principles underlying regenerative phenomena in vertebrates, starting with the epimorphic regeneration of the amphibian limb and continuing with tissue and organ regeneration in mammals. Epimorphic regeneration following limb amputation involves wound healing, followed shortly by a phase of dedifferentiation that leads to the formation of a regeneration blastema. Up to the point of blastema formation, dedifferentiation is guided by unique regenerative pathways, but the overall developmental controls underlying limb formation from the blastema generally recapitulate those of embryonic limb development. Damaged mammalian tissues do not form a blastema. At the cellular level, differentiation follows a pattern close to that seen in the embryo, but at the level of the tissue and organ, regeneration is strongly influenced by conditions inherent in the local environment. In some mammalian systems, such as the liver, parenchymal cells contribute progeny to the regenerate. In others, e.g., skeletal muscle and bone, tissue-specific progenitor cells constitute the main source of regenerating cells. The substrate on which regeneration occurs plays a very important role in determining the course of regeneration. Epimorphic regeneration usually produces an exact replica of the structure that was lost, but in mammalian tissue regeneration the form of the regenerate is largely determined by the mechanical environment acting on the regenerating tissue, and it is normally an imperfect replica of the original. In organ hypertophy, such as that occurring after hepatic resection, the remaining liver mass enlarges, but there is no attempt to restore the original form.

  19. Nonlinear isobologram and superadditive withdrawal from cocaine: cannabinoid combinations in planarians.

    Science.gov (United States)

    Raffa, Robert B; Stagliano, Gregory W; Tallarida, Ronald J

    2007-02-05

    Elucidation of interactions between drugs used in polydrug abuse is especially important. However, the necessary experimental conditions for precise quantitative analysis are difficult to establish. Because withdrawal effects of cocaine and the cannabinoid receptor agonist WIN 55212-2 are easily quantified in planarians, demonstration of synergistic effects (P<0.01) of certain ratios of this combination was possible. This synergy, here analyzed with the latest (nonlinear) isobolographic methodology, is now quantitatively established for the first time.

  20. Nonlinear isobologram and superadditive withdrawal from cocaine:cannabinoid combinations in planarians

    OpenAIRE

    Raffa, Robert B.; Stagliano, Gregory W.; Tallarida, Ronald J.

    2006-01-01

    Elucidation of interactions between drugs used in polydrug abuse is especially important. However, the necessary experimental conditions for precise quantitative analysis are difficult to establish. Because withdrawal effects of cocaine and the cannabinoid receptor agonist WIN 55212-2 are easily quantified in planarians, demonstration of synergistic effects (P < 0.01) of certain ratios of this combination was possible. This synergy, here analyzed with the latest (nonlinear) isobolographic met...

  1. The impact of hybrid and electric powertrains on vehicle dynamics, control systems and energy regeneration

    Science.gov (United States)

    Crolla, David A.; Cao, Dongpu

    2012-01-01

    The background to the development of so-called green or low-carbon vehicles continues to be relentlessly reviewed throughout the literature. Research and development (R&D) on novel powertrains - often based on electric or hybrid technology - has been dominating automotive engineering around the world for the first two decades of the twenty-first century. Inevitably, most of the R&D has focused on powertrain technology and energy management challenges. However, as new powertrains have started to become commercially available, their effects on other aspects of vehicle performance have become increasingly important. This article focuses on the review of the integration of new electrified powertrains with the vehicle dynamics and control systems. The integration effects can be discussed in terms of three generic aspects of vehicle motions, namely roll-plane, pitch-plane and yaw-plane, which however are strongly coupled. The topic on regenerative suspension is further discussed. It quickly becomes clear that this integration poses some interesting future engineering challenges to maintain currently accepted levels of ride, handling and stability performance.

  2. The Basis of Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    Antonio Musarò

    2014-01-01

    Full Text Available Muscle regeneration recapitulates many aspects of embryonic myogenesis and is an important homeostatic process of the adult skeletal muscle, which, after development, retains the capacity to regenerate in response to appropriate stimuli, activating the muscle compartment of stem cells, namely, satellite cells, as well as other precursor cells. Moreover, significant evidence suggests that while stem cells represent an important determinant for tissue regeneration, a “qualified” environment is necessary to guarantee and achieve functional results. It is therefore plausible that the loss of control over these cell fate decisions could lead to a pathological transdifferentiation, leading to pathologic defects in the regenerative process. This review provides an overview about the general aspects of muscle development and discusses the cellular and molecular aspects that characterize the five interrelated and time-dependent phases of muscle regeneration, namely, degeneration, inflammation, regeneration, remodeling, and maturation/functional repair.

  3. Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

    Science.gov (United States)

    Moustakas, Dimitrios; Mezzio, Michael; Rodriguez, Branden R.; Constable, Mic Andre; Mulligan, Margaret E.; Voura, Evelyn B.

    2015-01-01

    The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of guarana over caffeine alone. Yet, despite the growing use of guarana as an additive in energy drinks, and a burgeoning market for it as a nutritional supplement, the science examining guarana and how it affects other dietary ingredients is lacking. To appreciate the stimulant effects of guarana and other natural products, a straightforward model to investigate their physiological properties is needed. The planarian provides such a system. The locomotor activity and convulsive response of planarians with substance exposure has been shown to provide an excellent system to measure the effects of drug stimulation, addiction and withdrawal. To gauge the stimulant effects of guarana we studied how it altered the locomotor activity of the planarian species Dugesia tigrina. We report evidence that guarana seeds provide additional stimulation over caffeine alone, and document the changes to this stimulation in the context of both caffeine and glucose. PMID:25880065

  4. Guarana provides additional stimulation over caffeine alone in the planarian model.

    Directory of Open Access Journals (Sweden)

    Dimitrios Moustakas

    Full Text Available The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of guarana over caffeine alone. Yet, despite the growing use of guarana as an additive in energy drinks, and a burgeoning market for it as a nutritional supplement, the science examining guarana and how it affects other dietary ingredients is lacking. To appreciate the stimulant effects of guarana and other natural products, a straightforward model to investigate their physiological properties is needed. The planarian provides such a system. The locomotor activity and convulsive response of planarians with substance exposure has been shown to provide an excellent system to measure the effects of drug stimulation, addiction and withdrawal. To gauge the stimulant effects of guarana we studied how it altered the locomotor activity of the planarian species Dugesia tigrina. We report evidence that guarana seeds provide additional stimulation over caffeine alone, and document the changes to this stimulation in the context of both caffeine and glucose.

  5. Tryptophan hydroxylase Is Required for Eye Melanogenesis in the Planarian Schmidtea mediterranea.

    Directory of Open Access Journals (Sweden)

    Bramwell G Lambrus

    Full Text Available Melanins are ubiquitous and biologically important pigments, yet the molecular mechanisms that regulate their synthesis and biochemical composition are not fully understood. Here we present a study that supports a role for serotonin in melanin synthesis in the planarian Schmidtea mediterranea. We characterize the tryptophan hydroxylase (tph gene, which encodes the rate-limiting enzyme in serotonin synthesis, and demonstrate by RNA interference that tph is essential for melanin production in the pigment cups of the planarian photoreceptors. We exploit this phenotype to investigate the biological function of pigment cups using a quantitative light-avoidance behavioral assay. Planarians lacking eye pigment remain phototactic, indicating that eye pigmentation is not essential for light avoidance in S. mediterranea, though it improves the efficiency of the photophobic response. Finally, we show that the eye pigmentation defect observed in tph knockdown animals can be rescued by injection of either the product of TPH, 5-hydroxytryptophan (5-HTP, or serotonin. Together, these results highlight a role for serotonin in melanogenesis, perhaps as a regulatory signal or as a pigment substrate. To our knowledge, this is the first example of this relationship to be reported outside of mammalian systems.

  6. Molecular phylogeny of land and freshwater planarians (Tricladida, Platyhelminthes): from freshwater to land and back.

    Science.gov (United States)

    Alvarez-Presas, Marta; Baguñà, Jaume; Riutort, Marta

    2008-05-01

    The suborder Tricladida (phylum Platyhelminthes) comprises the well-known free-living flatworms, taxonomically grouped into three infraorders according to their ecology: Maricola (marine planarians), Paludicola (freshwater planarians), and Terricola (land planarians). Molecular analyses have demonstrated that the Paludicola are paraphyletic, the Terricola being the sister group of one of the three paludicolan families, the Dugesiidae. However, neither 18S rDNA nor COI based trees have been able to resolve the relationships among species of Terricola and Dugesiidae, particularly the monophyly of Terricola. Here, we present new molecular data including sequences of nuclear genes (18S rDNA, 28S rDNA) and a mitochondrial gene (COI) of a wider sample of dugesiid and terricolan species. The new sequences have been analyzed, together with those previously obtained, in independent and concatenated analyses using maximum likelihood and bayesian methods. The results show that, although some parts of the trees remain poorly resolved, they support a monophyletic origin for Terricola followed by a likely return of some species to freshwater habitats. Relationships within the monophyletic group of Dugesiidae are clearly resolved, and relationships among some terricolan subfamilies are also clearly established and point to the need for a thorough revision of Terricola taxonomy.

  7. Climatic controls on ecosystem resilience: Postfire regeneration in the Cape Floristic Region of South Africa

    Science.gov (United States)

    Wilson, Adam M.; Latimer, Andrew M.; Silander, John A.

    2015-01-01

    Conservation of biodiversity and natural resources in a changing climate requires understanding what controls ecosystem resilience to disturbance. This understanding is especially important in the fire-prone Mediterranean systems of the world. The fire frequency in these systems is sensitive to climate, and recent climate change has resulted in more frequent fires over the last few decades. However, the sensitivity of postfire recovery and biomass/fuel load accumulation to climate is less well understood than fire frequency despite its importance in driving the fire regime. In this study, we develop a hierarchical statistical framework to model postfire ecosystem recovery using satellite-derived observations of vegetation as a function of stand age, topography, and climate. In the Cape Floristic Region (CFR) of South Africa, a fire-prone biodiversity hotspot, we found strong postfire recovery gradients associated with climate resulting in faster recovery in regions with higher soil fertility, minimum July (winter) temperature, and mean January (summer) precipitation. Projections using an ensemble of 11 downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5) general circulation models (GCMs) suggest that warmer winter temperatures in 2080–2100 will encourage faster postfire recovery across the region, which could further increase fire frequency due to faster fuel accumulation. However, some models project decreasing precipitation in the western CFR, which would slow recovery rates there, likely reducing fire frequency through lack of fuel and potentially driving local biome shifts from fynbos shrubland to nonburning semidesert vegetation. This simple yet powerful approach to making inferences from large, remotely sensed datasets has potential for wide application to modeling ecosystem resilience in disturbance-prone ecosystems globally. PMID:26150521

  8. Periodontal regeneration.

    Science.gov (United States)

    Ivanovski, S

    2009-09-01

    The ultimate goal of periodontal therapy is the regeneration of the tissues destroyed as a result of periodontal disease. Currently, two clinical techniques, based on the principles of "guided tissue regeneration" (GTR) or utilization of the biologically active agent "enamel matrix derivative" (EMD), can be used for the regeneration of intrabony and Class II mandibular furcation periodontal defects. In cases where additional support and space-making requirements are necessary, both of these procedures can be combined with a bone replacement graft. There is no evidence that the combined use of GTR and EMD results in superior clinical results compared to the use of each material in isolation. Great variability in clinical outcomes has been reported in relation to the use of both EMD and GTR, and these procedures can be generally considered to be unpredictable. Careful case selection and treatment planning, including consideration of patient, tooth, site and surgical factors, is required in order to optimize the outcomes of treatment. There are limited data available for the clinical effectiveness of other biologically active molecules, such as growth factors and platelet concentrates, and although promising results have been reported, further clinical trials are required in order to confirm their effectiveness. Current active areas of research are centred on tissue engineering and gene therapy strategies which may result in more predictable regenerative outcomes in the future.

  9. fgf20 is essential for initiating zebrafish fin regeneration.

    Science.gov (United States)

    Whitehead, Geoffrey G; Makino, Shinji; Lien, Ching-Ling; Keating, Mark T

    2005-12-23

    Epimorphic regeneration requires the presence or creation of pluripotent cells capable of reproducing lost organs. Zebrafish fin regeneration is mediated by the creation of blastema cells. Here, we characterize the devoid of blastema (dob) mutant that fails fin regeneration during initial steps, forms abnormal regeneration epithelium, and does not form blastema. This mutation has no impact on embryonic survival. Dob results from an fgf20a null mutation, Y148S. Fgf20a is expressed during initiation of fin regeneration at the epithelial-mesenchymal boundary and later overlaps with the blastema marker msxb. Thus, fgf20a has a regeneration-specific requirement, initiating fin regeneration, and controlling blastema formation.

  10. Regenerator seal

    Science.gov (United States)

    Davis, Leonard C.; Pacala, Theodore; Sippel, George R.

    1981-01-01

    A method for manufacturing a hot side regenerator cross arm seal assembly having a thermally stablilized wear coating with a substantially flat wear surface thereon to seal between low pressure and high pressure passages to and from the hot inboard side of a rotary regenerator matrix includes the steps of forming a flat cross arm substrate member of high nickel alloy steel; fixedly securing the side edges of the substrate member to a holding fixture with a concave surface thereacross to maintain the substrate member to a slightly bent configuration on the fixture surface between the opposite ends of the substrate member to produce prestress therein; applying coating layers on the substrate member including a wear coating of plasma sprayed nickel oxide/calcium flouride material to define a wear surface of slightly concave form across the restrained substrate member between the free ends thereon; and thereafter subjecting the substrate member and the coating thereon to a heat treatment of 1600.degree. F. for sixteen hours to produce heat stabilizing growth in the coating layers on the substrate member and to produce a thermally induced growth stress in the wear surface that substantially equalizes the prestress in the substrate whereby when the cross arm is removed from the fixture surface following the heat treatment step a wear face is formed on the cross arm assembly that will be substantially flat between the ends.

  11. Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

    Directory of Open Access Journals (Sweden)

    Deborah J Evans

    Full Text Available The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi or Smed-ptc(RNAi lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new

  12. Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

    Science.gov (United States)

    Evans, Deborah J; Owlarn, Suthira; Tejada Romero, Belen; Chen, Chen; Aboobaker, A Aziz

    2011-01-01

    The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then

  13. A numerical method of regenerator

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Shaowei [Aisin Seiki Co. Ltd., Aichi (Japan); Matsubara, Yoichi [Nihon Univ., Chiba (Japan). Inst. of Quantum Science

    2004-02-01

    A numerical method for regenerators is introduced in this paper. It is not only suitable for the regenerators in cryocoolers and Stirling engines, but also suitable for the stacks in acoustic engines and the pulse tubes in pulse tube refrigerators. The numerical model is one dimensional periodic unsteady flow model. The numerical method is based on the control volume concept with the implicitly solve method. The iteration acceleration method, which considers the one-dimensional periodic unsteady problem as the steady two-dimensional problem, is used for decreasing the calculation time. By this method, the regenerator in an inertance tube pulse tube refrigerator was simulated. The result is useful for understanding how the inefficiency of the regenerator changes with the inertance effect. (author)

  14. A numerical method of regenerator

    Science.gov (United States)

    Zhu, Shaowei; Matsubara, Yoichi

    2004-02-01

    A numerical method for regenerators is introduced in this paper. It is not only suitable for the regenerators in cryocoolers and Stirling engines, but also suitable for the stacks in acoustic engines and the pulse tubes in pulse tube refrigerators. The numerical model is one dimensional periodic unsteady flow model. The numerical method is based on the control volume concept with the implicitly solve method. The iteration acceleration method, which considers the one-dimensional periodic unsteady problem as the steady two-dimensional problem, is used for decreasing the calculation time. By this method, the regenerator in an inertance tube pulse tube refrigerator was simulated. The result is useful for understanding how the inefficiency of the regenerator changes with the inertance effect.

  15. Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

    Science.gov (United States)

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy.

  16. Terrestrial planarians (Platyhelminthes, Tricladida, Terricola) from the Iberian Peninsula: New records and description of three new species

    NARCIS (Netherlands)

    Vila-Farré, M.; Mateos, E.; Sluys, R.; Romero, R.

    2008-01-01

    Little is known about the taxonomy and distribution of terrestrial planarians on the Iberian Peninsula. Few studies have tried to investigate the local diversity of these animals, due to both their lack of economic interest and their low abundance. In this study we have made extensive searches and c

  17. Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid-chitosan nanoparticles enhances periodontal regeneration in dogs

    Directory of Open Access Journals (Sweden)

    Lee BS

    2016-01-01

    Full Text Available Bor-Shiunn Lee,1 Chien-Chen Lee,2 Yi-Ping Wang,2 Hsiao-Jan Chen,3 Chern-Hsiung Lai,4 Wan-Ling Hsieh,1 Yi-Wen Chen2 1Graduate Institute of Oral Biology, 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University and National Taiwan University Hospital, 3Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 4College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid (PLGA nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in

  18. Proteomic analysis of zebrafish caudal fin regeneration.

    Science.gov (United States)

    Saxena, Sandeep; Singh, Sachin K; Lakshmi, Mula G Meena; Meghah, Vuppalapaty; Bhatti, Bhawna; Swamy, Cherukuvada V Brahmendra; Sundaram, Curam S; Idris, Mohammed M

    2012-06-01

    The epimorphic regeneration of zebrafish caudal fin is rapid and complete. We have analyzed the biomechanism of zebrafish caudal fin regeneration at various time points based on differential proteomics approaches. The spectrum of proteome changes caused by regeneration were analyzed among controls (0 h) and 1, 12, 24, 48, and 72 h postamputation involving quantitative differential proteomics analysis based on two-dimensional gel electrophoresis matrix-assisted laser desorption/ionization and differential in-gel electrophoresis Orbitrap analysis. A total of 96 proteins were found differentially regulated between the control nonregenerating and regenerating tissues of different time points for having at least 1.5-fold changes. 90 proteins were identified as differentially regulated for regeneration based on differential in-gel electrophoresis analysis between the control and regenerating tissues. 35 proteins were characterized for its expression in all of the five regenerating time points against the control samples. The proteins identified and associated with regeneration were found to be directly allied with various molecular, biological, and cellular functions. Based on network pathway analysis, the identified proteome data set for regeneration was majorly associated in maintaining cellular structure and architecture. Also the proteins were found associated for the cytoskeleton remodeling pathway and cellular immune defense mechanism. The major proteins that were found differentially regulated during zebrafish caudal fin regeneration includes keratin and its 10 isoforms, cofilin 2, annexin a1, skeletal α1 actin, and structural proteins. Annexin A1 was found to be exclusively undergoing phosphorylation during regeneration. The obtained differential proteome and the direct association of the various proteins might lead to a new understanding of the regeneration mechanism.

  19. Molecular barcoding and phylogeography of sexual and asexual freshwater planarians of the genus Dugesia in the Western Mediterranean (Platyhelminthes, Tricladida, Dugesiidae)

    NARCIS (Netherlands)

    Lázaro, E.M.; Sluys, R.; Pala, M.; Stocchino, G.A.; Baguñà, J.; Riutort, M.

    2009-01-01

    Planarians of the genus Dugesia have a worldwide distribution with high species diversity in the Mediterranean area. In this area, populations with a triploid karyotype that reproduce by fissiparity are exceptionally frequent, outnumbering the sexual populations. This situation poses interesting

  20. Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea.

    Science.gov (United States)

    Barberán, Sara; Martín-Durán, José M; Cebrià, Francesc

    2016-06-21

    The EGFR pathway is an essential signaling system in animals, whose core components are the epidermal growth factors (EGF ligands) and their trans-membrane tyrosine kinase receptors (EGFRs). Despite extensive knowledge in classical model organisms, little is known of the composition and function of the EGFR pathway in most animal lineages. Here, we have performed an extensive search for the presence of EGFRs and EGF ligands in representative species of most major animal clades, with special focus on the planarian Schmidtea mediterranea. With the exception of placozoans and cnidarians, we found that the EGFR pathway is potentially present in all other analyzed animal groups, and has experienced frequent independent expansions. We further characterized the expression domains of the EGFR/EGF identified in S. mediterranea, revealing a wide variety of patterns and localization in almost all planarian tissues. Finally, functional experiments suggest an interaction between one of the previously described receptors, Smed-egfr-5, and the newly found ligand Smed-egf-6. Our findings provide the most comprehensive overview to date of the EGFR pathway, and indicate that the last common metazoan ancestor had an initial complement of one EGFR and one putative EGF ligand, which was often expanded or lost during animal evolution.

  1. Kinetic profiling an abundantly expressed planarian serotonergic GPCR identifies bromocriptine as a perdurant antagonist

    Directory of Open Access Journals (Sweden)

    John D. Chan

    2016-12-01

    Full Text Available The diversity and uniqueness of flatworm G protein coupled receptors (GPCRs provides impetus for identifying ligands useful as tools for studying flatworm biology, or as therapeutics for treating diseases caused by parasitic flatworm infections. To catalyse this discovery process, technologies optimized for mammalian GPCR high throughput screening need be transposed for screening flatworm GPCRs. Here, we demonstrate the utility of a genetically encoded cAMP biosensor for resolving the properties of an abundantly expressed planarian serotonergic GPCR (S7.1R. Application of this methodology resolved the real time kinetics of GPCR modulation by ligands and demonstrated a marked difference in the kinetic action of antagonists at S7.1R. Notably, bromocriptine caused a protracted inhibition of S7.1R activity in vitro and a protracted paralysis of planarian movement, replicating the effect of S7.1R in vivo RNAi. The lengthy inhibition of function caused by bromocriptine at this abundantly expressed GPCR provides a useful tool to ablate serotonergic signaling in vivo, and is a noteworthy feature for exploitation as an anthelmintic vulnerability.

  2. Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

    Science.gov (United States)

    Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

    2015-10-01

    To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

  3. Re-membering the body: applications of computational neuroscience to the top-down control of regeneration of limbs and other complex organs.

    Science.gov (United States)

    Pezzulo, G; Levin, M

    2015-12-01

    A major goal of regenerative medicine and bioengineering is the regeneration of complex organs, such as limbs, and the capability to create artificial constructs (so-called biobots) with defined morphologies and robust self-repair capabilities. Developmental biology presents remarkable examples of systems that self-assemble and regenerate complex structures toward their correct shape despite significant perturbations. A fundamental challenge is to translate progress in molecular genetics into control of large-scale organismal anatomy, and the field is still searching for an appropriate theoretical paradigm for facilitating control of pattern homeostasis. However, computational neuroscience provides many examples in which cell networks - brains - store memories (e.g., of geometric configurations, rules, and patterns) and coordinate their activity towards proximal and distant goals. In this Perspective, we propose that programming large-scale morphogenesis requires exploiting the information processing by which cellular structures work toward specific shapes. In non-neural cells, as in the brain, bioelectric signaling implements information processing, decision-making, and memory in regulating pattern and its remodeling. Thus, approaches used in computational neuroscience to understand goal-seeking neural systems offer a toolbox of techniques to model and control regenerative pattern formation. Here, we review recent data on developmental bioelectricity as a regulator of patterning, and propose that target morphology could be encoded within tissues as a kind of memory, using the same molecular mechanisms and algorithms so successfully exploited by the brain. We highlight the next steps of an unconventional research program, which may allow top-down control of growth and form for numerous applications in regenerative medicine and synthetic bioengineering.

  4. Speed Control of Brushless Dc Motor Using Current Fed Quasi Z-source Inverter with Regeneration Capability

    Directory of Open Access Journals (Sweden)

    A. Santhi Mary Antony

    2015-06-01

    Full Text Available Current fed Quasi Z-Source Inverters (qZSI have the advantages of voltage buck-boost capability, improved reliability, reduced passive component ratings, continuous input current, a common dc rail between source and inverter and unique regeneration capability. This current-fed qZSIs are bidirectional with an additional diode, unlike the voltage-fed ZSI that needs a switch to achieve bidirectional power flow. Since current fed quasi Z Source Inverter has many advantages it can be employed for motor drive applications such as Brushless DC motor (BLDC drive. Therefore this study proposes the use of qZSI for BLDC motor. The simulation results for the same are presented in this study.

  5. The Molecular and Cellular Choreography of Appendage Regeneration.

    Science.gov (United States)

    Tanaka, Elly M

    2016-06-16

    Recent advances in limb regeneration are revealing the molecular events that integrate growth control, cell fate programming, and positional information to yield the exquisite replacement of the amputated limb. Parallel progress in several invertebrate and vertebrate models has provided a broader context for understanding the mechanisms and the evolution of regeneration. Together, these discoveries provide a foundation for describing the principles underlying regeneration of complex, multi-tissue structures. As such these findings should provide a wealth of ideas for engineers seeking to reconstitute regeneration from constituent parts or to elicit full regeneration from partial regeneration events.

  6. Active magnetic regenerator

    Science.gov (United States)

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  7. Helping the Retina Regenerate

    Science.gov (United States)

    ... Briefs > Helping the retina regenerate Helping the retina regenerate NEI Audacious Goals Initiative report outlines strategies to replace or reprogram neurons in the retina News Brief 03/30/17 ...

  8. Modulation of Host Osseointegration during Bone Regeneration by Controlling Exogenous Stem Cells Differentiation Using a Material Approach.

    Science.gov (United States)

    Yu, Xiaohua; Wang, Liping; Xia, Zengmin; Chen, Li; Jiang, Xi; Rowe, David; Wei, Mei

    2014-02-01

    Stem cell-based tissue engineering for large bone defect healing has attracted enormous attention in regenerative medicine. However, sufficient osseointegration of the grafts combined with exogenous stem cells still remains a major challenge. Here we developed a material approach to modulate the integration of the grafts to the host tissue when exogenous bone marrow stromal cells (BMSCs) were used as donor cells. Distinctive osseointegration of bone grafts was observed as we varied the content of hydroxyapatite (HA) in the tissue scaffolds implanted in a mouse femur model. More than 80% of new bone was formed in the first two weeks of implantation in high HA content scaffold but lack of host integration while only less than 5% of the new bone was formed during this time period in the no HA group but with much stronger host integration. Cell origin analysis leveraging GFP reporter indicates new bone in HA containing groups was mainly derived from donor BMSCs. In comparison, both host and donor cells were found on new bone surface in the no HA groups which led to seamless bridging between host tissue and the scaffold. Most importantly, host integration during bone formation is closely dictated to the content of HA present in the scaffolds. Taken together, we demonstrate a material approach to modulate the osseointegration of bone grafts in the context of exogenous stem cell-based bone healing strategy which might lead to fully functional bone tissue regeneration.

  9. Process for the regeneration of an additive used to control emissions during the combustion of high sulfur fuel

    Energy Technology Data Exchange (ETDEWEB)

    Polanco, D.R.; Bueno, C.O.; Salazar, R.; Chamorra, F.A.S

    1989-05-23

    A process is described for regenerating a sulfur capturing additive used in the preparation of a hydrocarbon in water emulsion for combustion as a fuel comprising: (a) forming a hydrocarbon in water emulsion by admixing a sulfur containing hydrocarbon and water with an emulsifier and a water soluble sulfur capturing additive wherein the sulfur capturing additive is selected from the group consisting of Na/sup +/, K/sup +/, Li/sup +/, Ca/sup ++/, Ba/sup ++/, Mg/sup ++/, Fe/sup +++/ and mixtures thereof; (b) burning the emulsion so as to form a combustion ash containing the water soluble additive as a sulfate compound; (c) leaching the combustion ash wherein the combustion ash is leached with water in a water to ash ratio in ml to grams of 1:1 to 30:1 so as to dissolve the water soluble additive sulfate compound to form a pregnant leach liquor containing the additive; (d) separating the pregnant leach liquor containing the additive; (e) adjusting the pregnant leach liquor with a basic precipitating agent wherein the base precipitating agent is selected from the group consisting of NH/sub 4/OH, NaOH, Ca(OH)/sub 2/, NaCO/sub 3/ and mixtures thereof wherein the pregnant leach liquor is adjusted with the base to a pH of greater than 7 so as to precipitate an additive compound; and (f) recovering the additive compound.

  10. Electrically heated particulate filter regeneration methods and systems for hybrid vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Gonze, Eugene V. (Pinckney, MI); Paratore, Jr., Michael J. (Howell, MI)

    2010-10-12

    A control system for controlling regeneration of a particulate filter for a hybrid vehicle is provided. The system generally includes a regeneration module that controls current to the particulate filter to initiate regeneration. An engine control module controls operation of an engine of the hybrid vehicle based on the control of the current to the particulate filter.

  11. Topiramate-antagonism of L-glutamate-induced paroxysms in planarians.

    Science.gov (United States)

    Raffa, Robert B; Finno, Kristin E; Tallarida, Christopher S; Rawls, Scott M

    2010-12-15

    We recently reported that NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induce concentration-dependent paroxysms in planarians (Dugesia dorotocephala). Since the postulated mechanisms of action of the sulfamate-substituted monosaccharide antiepileptic drug topiramate include inhibition of glutamate-activated ion channels, we tested the hypothesis that topiramate would inhibit glutamate-induced paroxysms in our model. We demonstrate that: (1) L-glutamate (1-10 mM), but not D-glutamate, induced dose-related paroxysms, and that (2) topiramate dose-relatedly (0.3-3 mM) inhibited L-glutamate-induced paroxysms. These results provide further evidence of a topiramate-sensitive glutamate receptor-mediated activity in this model.

  12. Two new land planarian species (Platyhelminthes: Tricladida from the Brazilian Atlantic Forest

    Directory of Open Access Journals (Sweden)

    Ana Laura Almeida

    2012-10-01

    Full Text Available The Brazilian Atlantic Forest harbors the world's richest areas of land planarians (Platyhelminthes: Tricladida. Nevertheless, the number of undiscovered species from this biological unit remains seemingly high. Herein we describe Geoplana piriana Almeida & Carbayo, sp. nov. from the state of Rio de Janeiro, and Geoplana tingauna Kishimoto & Carbayo, sp. nov. from the state of Santa Catarina. Each species shows a dorsum with a unique color pattern among Geoplaninae species. Their internal morphology also differs: G. piriana sp. nov. shows a unique combination of features, including an extrabulbar, non-bifurcated prostatic vesicle, a non-folded male atrium, a horizontal, cylindrical penis papilla, a female atrium anteriorly narrowed, and lined with an epithelium with multilayered aspect. Geoplana tingauna sp. nov. possesses a prostatic vesicle constituted of a pair of branches opening into the very distal portion of a tubular, unpaired portion, a feature not seen in other Geoplaninae species.

  13. Evidence for the persistence of the land planarian species Microplana terrestris (Müller, 1774) (Platyhelminthes, Tricladida) in microrefugia during the Last Glacial Maximum in the northern section of the Iberian Peninsula

    NARCIS (Netherlands)

    Álvarez-Presas, M.; Mateos, E.; Vila-Farré, M.; Sluys, R.; Riutort, M.

    2012-01-01

    The land planarian species Microplana terrestris (Müller, 1774), shows a wide distribution in the north of the Iberian Peninsula, where mature humid forests can be found. Since most terrestrial planarians require the presence and good condition of wet forests to survive, a parallel evolution of the

  14. Crack-free polydimethylsiloxane-bioactive glass-poly(ethylene glycol) hybrid monoliths with controlled biomineralization activity and mechanical property for bone tissue regeneration.

    Science.gov (United States)

    Chen, Jing; Du, Yuzhang; Que, Wenxiu; Xing, Yonglei; Chen, Xiaofeng; Lei, Bo

    2015-12-01

    Crack-free organic-inorganic hybrid monoliths with controlled biomineralization activity and mechanical property have an important role for highly efficient bone tissue regeneration. Here, biomimetic and crack-free polydimethylsiloxane (PDMS)-modified bioactive glass (BG)-poly(ethylene glycol) (PEG) (PDMS-BG-PEG) hybrids monoliths were prepared by a facile sol-gel technique. Results indicate that under the assist of co-solvents, BG sol and PDMS and PEG could be hybridized at a molecular level, and effects of the PEG molecular weight on the structure, biomineralization activity, and mechanical property of the as-prepared hybrid monoliths were also investigated in detail. It is found that an addition of low molecular weight PEG can significantly prevent the formation of cracks and speed up the gelation of the hybrid monoliths, and the surface microstructure of the hybrid monoliths can be changed from the porous to the smooth as the PEG molecular weight increases. Additionally, the hybrid monoliths with low molecular weight PEG show the high formation of the biological apatite layer, while the hybrids with high molecular weight PEG exhibit negligible biomineralization ability in simulated body fluid (SBF). Furthermore, the PDMS-BG-PEG 600 hybrid monolith has significantly high compressive strength (32 ± 3 MPa) and modulus (153 ± 11 MPa), as well as good cell biocompatibility by supporting osteoblast (MC3T3-E1) attachment and proliferation. These results indicate that the as-prepared PDMS-BG-PEG hybrid monoliths may have promising applications for bone tissue regeneration.

  15. A review of precipitation and temperature control on seedling emergence and establishment for ponderosa and lodgepole pine forest regeneration

    Science.gov (United States)

    Petrie, Matthew; Wildeman, A.M.; Bradford, John B.; Hubbard, R.M.; Lauenroth, W.K.

    2016-01-01

    The persistence of ponderosa pine and lodgepole pine forests in the 21st century depends to a large extent on how seedling emergence and establishment are influenced by driving climate and environmental variables, which largely govern forest regeneration. We surveyed the literature, and identified 96 publications that reported data on dependent variables of seedling emergence and/or establishment and one or more independent variables of air temperature, soil temperature, precipitation and moisture availability. Our review suggests that seedling emergence and establishment for both species is highest at intermediate temperatures (20 to 25 °C), and higher precipitation and higher moisture availability support a higher percentage of seedling emergence and establishment at daily, monthly and annual timescales. We found that ponderosa pine seedlings may be more sensitive to temperature fluctuations whereas lodgepole pine seedlings may be more sensitive to moisture fluctuations. In a changing climate, increasing temperatures and declining moisture availability may hinder forest persistence by limiting seedling processes. Yet, only 23 studies in our review investigated the effects of driving climate and environmental variables directly. Furthermore, 74 studies occurred in a laboratory or greenhouse, which do not often replicate the conditions experienced by tree seedlings in a field setting. It is therefore difficult to provide strong conclusions on how sensitive emergence and establishment in ponderosa and lodgepole pine are to these specific driving variables, or to investigate their potential aggregate effects. Thus, the effects of many driving variables on seedling processes remain largely inconclusive. Our review stresses the need for additional field and laboratory studies to better elucidate the effects of driving climate and environmental variables on seedling emergence and establishment for ponderosa and lodgepole pine.

  16. [Effect of weak and superweak magnetic fields on intensity and asexual reproduction of the planarian Dugesia tigrina].

    Science.gov (United States)

    Novikov, V V; Sheĭman, I M; Fesenko, E E

    2002-01-01

    It was shown that the exposure to combined weak and extraweak magnetic fields (permanent component 42 microT; variable component of an amplitude of 100 nT, frequency 1-60 Hz) increases the intensity of asexual propagation of planarians Dugesia tigrina. The effect of combined magnetic fields is most pronounced at frequencies of 1, 3.7, and 32 Hz. The presence of concomitant technogeneous fields (50 Hz, 30 nT) does not markedly influence the effects of weak magnetic fields with a small variable component. Upon realization of effects of weak magnetic fields, their both components are of great importance; the absence of one (permanent) component changes the sing of the effect to the opposite. The transfer of the effect to planarians through water pretreated with magnetic fields probably indicates that aqueous medium is involved in the realization of biological effects of weak magnetic fields.

  17. Toxicity profiles and solvent-toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure.

    Science.gov (United States)

    Stevens, An-Sofie; Pirotte, Nicky; Plusquin, Michelle; Willems, Maxime; Neyens, Thomas; Artois, Tom; Smeets, Karen

    2015-03-01

    To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound-induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent-toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short- (1 day) and long-term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l(-1) ) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long-term exposure set-up, a concentration of 500 µl l(-1) DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l(-1) DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l(-1) DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l(-1) in this organism. In the second part of our study, we propose a statistical approach to account for solvent-toxicant interactions and discuss full-scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea.

  18. A Stable Thoracic Hox Code and Epimorphosis Characterize Posterior Regeneration in Capitella teleta.

    Directory of Open Access Journals (Sweden)

    Danielle M de Jong

    Full Text Available Regeneration, the ability to replace lost tissues and body parts following traumatic injury, occurs widely throughout the animal tree of life. Regeneration occurs either by remodeling of pre-existing tissues, through addition of new cells by cell division, or a combination of both. We describe a staging system for posterior regeneration in the annelid, Capitella teleta, and use the C. teleta Hox gene code as markers of regional identity for regenerating tissue along the anterior-posterior axis. Following amputation of different posterior regions of the animal, a blastema forms and by two days, proliferating cells are detected by EdU incorporation, demonstrating that epimorphosis occurs during posterior regeneration of C. teleta. Neurites rapidly extend into the blastema, and gradually become organized into discrete nerves before new ganglia appear approximately seven days after amputation. In situ hybridization shows that seven of the ten Hox genes examined are expressed in the blastema, suggesting roles in patterning the newly forming tissue, although neither spatial nor temporal co-linearity was detected. We hypothesized that following amputation, Hox gene expression in pre-existing segments would be re-organized to scale, and the remaining fragment would express the complete suite of Hox genes. Surprisingly, most Hox genes display stable expression patterns in the ganglia of pre-existing tissue following amputation at multiple axial positions, indicating general stability of segmental identity. However, the three Hox genes, CapI-lox4, CapI-lox2 and CapI-Post2, each shift its anterior expression boundary by one segment, and each shift includes a subset of cells in the ganglia. This expression shift depends upon the axial position of the amputation. In C. teleta, thoracic segments exhibit stable positional identity with limited morphallaxis, in contrast with the extensive body remodeling that occurs during regeneration of some other annelids

  19. A Stable Thoracic Hox Code and Epimorphosis Characterize Posterior Regeneration in Capitella teleta.

    Science.gov (United States)

    de Jong, Danielle M; Seaver, Elaine C

    2016-01-01

    Regeneration, the ability to replace lost tissues and body parts following traumatic injury, occurs widely throughout the animal tree of life. Regeneration occurs either by remodeling of pre-existing tissues, through addition of new cells by cell division, or a combination of both. We describe a staging system for posterior regeneration in the annelid, Capitella teleta, and use the C. teleta Hox gene code as markers of regional identity for regenerating tissue along the anterior-posterior axis. Following amputation of different posterior regions of the animal, a blastema forms and by two days, proliferating cells are detected by EdU incorporation, demonstrating that epimorphosis occurs during posterior regeneration of C. teleta. Neurites rapidly extend into the blastema, and gradually become organized into discrete nerves before new ganglia appear approximately seven days after amputation. In situ hybridization shows that seven of the ten Hox genes examined are expressed in the blastema, suggesting roles in patterning the newly forming tissue, although neither spatial nor temporal co-linearity was detected. We hypothesized that following amputation, Hox gene expression in pre-existing segments would be re-organized to scale, and the remaining fragment would express the complete suite of Hox genes. Surprisingly, most Hox genes display stable expression patterns in the ganglia of pre-existing tissue following amputation at multiple axial positions, indicating general stability of segmental identity. However, the three Hox genes, CapI-lox4, CapI-lox2 and CapI-Post2, each shift its anterior expression boundary by one segment, and each shift includes a subset of cells in the ganglia. This expression shift depends upon the axial position of the amputation. In C. teleta, thoracic segments exhibit stable positional identity with limited morphallaxis, in contrast with the extensive body remodeling that occurs during regeneration of some other annelids, planarians and acoel

  20. Regeneration of periodontal tissues: guided tissue regeneration.

    Science.gov (United States)

    Villar, Cristina C; Cochran, David L

    2010-01-01

    The concept that only fibroblasts from the periodontal ligament or undifferentiated mesenchymal cells have the potential to re-create the original periodontal attachment has been long recognized. Based on this concept, guided tissue regeneration has been applied with variable success to regenerate periodontal defects. Quantitative analysis of clinical outcomes after guided tissue regeneration suggests that this therapy is a successful and predictable procedure to treat narrow intrabony defects and class II mandibular furcations, but offers limited benefits in the treatment of other types of periodontal defects.

  1. Molecular cloning and characterization of SL3: a stem cell-specific SL RNA from the planarian Schmidtea mediterranea.

    Science.gov (United States)

    Rossi, Alessandro; Ross, Eric J; Jack, Antonia; Sánchez Alvarado, Alejandro

    2014-01-01

    Spliced leader (SL) trans-splicing is a biological phenomenon, common among many metazoan taxa, consisting in the transfer of a short leader sequence from a small SL RNA to the 5' end of a subset of pre-mRNAs. While knowledge of the biochemical mechanisms driving this process has accumulated over the years, the functional consequences of such post-transcriptional event at the organismal level remain unclear. In addition, the fact that functional analyses have been undertaken mainly in trypanosomes and nematodes leaves a somehow fragmented picture of the possible biological significance and evolution of SL trans-splicing in eukaryotes. Here, we analyzed the spatial expression of SL RNAs in the planarian flatworm Schmidtea mediterranea, with the goal of identifying novel developmental paradigms for the study of trans-splicing in metazoans. Besides the previously identified SL1 and SL2, S. mediterranea expresses a third SL RNA described here as SL3. While, SL1 and SL2 are collectively expressed in a broad range of planarian cell types, SL3 is highly enriched in a subset of the planarian stem cells engaged in regenerative responses. Our findings provide new opportunities to study how trans-splicing may regulate the phenotype of a cell.

  2. Hamstring Tendon Regeneration After Harvesting: A Systematic Review.

    Science.gov (United States)

    Suijkerbuijk, Mathijs A M; Reijman, Max; Lodewijks, Susanne J M; Punt, Jorien; Meuffels, Duncan E

    2015-10-01

    Hamstring tendons are often used as autografts for anterior cruciate ligament (ACL) reconstruction. However, no systematic review has been performed describing consequences such as hamstring tendon regeneration rate and determinants of hamstring tendon regeneration. To summarize the current literature regarding hamstring tendon rate regeneration, the time course of regeneration, and determinants of hamstring regeneration. Systematic review. A search was performed in the Embase, Medline (OvidSP), Web of Science, Cochrane, PubMed, and Google Scholar databases up to June 2014 to identify relevant articles. A study was eligible if it met the following inclusion criteria: tendons were harvested, regeneration at harvest site was assessed, population size was at least 10 human subjects, full-text article was available, and the study design was either a randomized controlled trial, prospective cohort study, retrospective cohort study, or case control study. A risk of bias assessment of the eligible articles was determined. Data describing hamstring tendon regeneration rates were pooled per time period. A total of 18 publications met the inclusion criteria. The mean regeneration rate for the semitendinosus and gracilis tendons was, in all cases, 70% or higher. More than 1 year after harvesting, 79% (median [IQR], 80 [75.5-90]) of the semitendinosus tendons and 72% (median [IQR], 80 [61-88.5]) of the gracilis tendons were regenerated. No significant differences in regeneration rate could be found considering patient sex, age, height, weight, or duration of immobilization. Results did not clearly show whether absence of regeneration disadvantages the subsequent hamstring function. Five studies measured the regeneration rate at different moments in time. Hamstring tendons regenerated in the majority of patients after ACL reconstruction. The majority of the hamstring tendon regeneration was found to occur between 1 month and 1 year after harvest. No significant determinants for

  3. SpolvlgA is a DDX3/PL10-related DEAD-box RNA helicase expressed in blastomeres and embryonic cells in planarian embryonic development.

    Science.gov (United States)

    Solana, Jordi; Romero, Rafael

    2009-01-01

    Planarian flatworms have an impressive regenerative power. Although their embryonic development is still poorly studied and is highly derived it still displays some simple characteristics. We have identified SpolvlgA, a Schmidtea polychroa homolog of the DDX3/PL10 DEAD-box RNA helicase DjvlgA from the planarian species Dugesia japonica. This gene has been previously described as being expressed in planarian adult stem cells (neoblasts), as well as the germ line. Here we present the expression pattern of SpolvlgA in developing embryos of S. polychroa and show that it is expressed from the first cleavage rounds in blastomere cells and blastomere-derived embryonic cells. These cells are undifferentiated cells that engage in a massive wave of differentiation during stage 5 of development. SpolvlgA expression highlights this wave of differentiation, where nearly all previous structures are substituted by blastomere-derived embryonic cells. In late stages of development SpolvlgA is expressed in most proliferating and differentiating cells. Thus, SpolvlgA is a gene expressed in planarian embryos from the first stages of development and a good marker for the zygote-derived cell lineage in these embryos. Expression in adult worms is also monitored and is found in the planarian germ line, where it is showed to be expressed in spermatogonia, spermatocytes and differentiating spermatids.

  4. SpolvlgA is a DDX3/PL10-related DEAD-box RNA helicase expressed in blastomeres and embryonic cells in planarian embryonic development

    Directory of Open Access Journals (Sweden)

    Jordi Solana, Rafael Romero

    2009-01-01

    Full Text Available Planarian flatworms have an impressive regenerative power. Although their embryonic development is still poorly studied and is highly derived it still displays some simple characteristics. We have identified SpolvlgA, a Schmidtea polychroa homolog of the DDX3/PL10 DEAD-box RNA helicase DjvlgA from the planarian species Dugesia japonica. This gene has been previously described as being expressed in planarian adult stem cells (neoblasts, as well as the germ line. Here we present the expression pattern of SpolvlgA in developing embryos of S. polychroa and show that it is expressed from the first cleavage rounds in blastomere cells and blastomere-derived embryonic cells. These cells are undifferentiated cells that engage in a massive wave of differentiation during stage 5 of development. SpolvlgA expression highlights this wave of differentiation, where nearly all previous structures are substituted by blastomere-derived embryonic cells. In late stages of development SpolvlgA is expressed in most proliferating and differentiating cells. Thus, SpolvlgA is a gene expressed in planarian embryos from the first stages of development and a good marker for the zygote-derived cell lineage in these embryos. Expression in adult worms is also monitored and is found in the planarian germ line, where it is showed to be expressed in spermatogonia, spermatocytes and differentiating spermatids.

  5. Notch Signaling Inhibits Axon Regeneration

    OpenAIRE

    Bejjani, Rachid El; Hammarlund, Marc

    2012-01-01

    Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian CNS do not regenerate, and even neurons in the PNS often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neuron...

  6. Fibrous guided tissue regeneration membrane loaded with anti-inflammatory agent prepared by coaxial electrospinning for the purpose of controlled release

    Science.gov (United States)

    He, Min; Xue, Jiajia; Geng, Huan; Gu, Hao; Chen, Dafu; Shi, Rui; Zhang, Liqun

    2015-04-01

    Here, with the aim of inhibiting inflammation during guided tissue regeneration membrane (GTRM) implant surgery, coaxial electrospinning was used to fabricate drug-loaded core/sheath nanofiber GTRMs capable of controlled drug release. Various amounts of the anti-inflammatory agent metronidazole (MNA) were encapsulated into the core/sheath nanofibers (where PCL was the core, gelatin the sheath, and the gelatin shell was crosslinked with genipin) in order to establish the minimal drug content necessary to achieve the appropriate anti-inflammatory effect. By using TEM and SEM, the core/sheath structure was confirmed. In vitro drug disolution results showed that the core/sheath nanofibers exhibited sustained release profiles that were superior to those nanofibers produced by blending electrospinning. Additionally, the membrane significantly inhibited the colonization of anaerobic bacteria. Furthermore, with gelatin as a shell, the core/shell nanofiber membranes showed improved hydrophilicity, which resulted in better cell adhesion and proliferation without cytotoxicity. Therefore, in this study, a simple and effective coaxial electrospinning approach was demonstrated for the fabrication of anti-inflammatory GTRMs capable of providing controlled drug release.

  7. Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics.

    Science.gov (United States)

    Yan, Qi; Xiao, Li-Qun; Tan, Lei; Sun, Wei; Wu, Tao; Chen, Liang-Wen; Mei, Yan; Shi, Bin

    2015-11-01

    Reports on the local delivery of drug loaded injectable hydrogels for bone regeneration are currently limited. This study assessed the effect of controlled simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo. We successfully manufactured and evaluated thermo-sensitive poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and osteoblastic differentiation was analyzed after cultivation with the hydrogel extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in mineralization and osteogenic gene expression compared to the other two groups. Additionally, the characteristics of this composite in vivo were demonstrated using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA hydrogel showed increased new bone formation compared to samples treated with PLGA-PEG-PLGA and control samples. The results of this study suggest that SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing.

  8. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration.

    Directory of Open Access Journals (Sweden)

    Mimi C Sammarco

    Full Text Available Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3 in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.

  9. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration.

    Science.gov (United States)

    Sammarco, Mimi C; Simkin, Jennifer; Cammack, Alexander J; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.

  10. Stirling convertor regenerators

    CERN Document Server

    Ibrahim, Mounir B

    2011-01-01

    Stirling Convertor Regenerators addresses the latest developments and future possibilities in the science and practical application of Stirling engine regenerators and technology. Written by experts in the vanguard of alternative energy, this invaluable resource presents integral scientific details and design concepts associated with Stirling converter regenerators. Content is reinforced with novel insights and remarkable firsthand experience that the authors and their colleagues acquired while working at the National Aeronautics and Space Administration (NASA) and other leading organizations.

  11. Reparative inflammation takes charge of tissue regeneration.

    Science.gov (United States)

    Karin, Michael; Clevers, Hans

    2016-01-21

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an evolutionarily important process. Recent insights have shed light on the cellular and molecular processes through which conventional inflammatory cytokines and Wnt factors control mammalian tissue repair and regeneration. This is particularly important for regeneration in the gastrointestinal system, especially for intestine and liver tissues in which aberrant and deregulated repair results in severe pathologies.

  12. Bottom-up versus top-down control of tree regeneration in the Bialowieza Primeval Forest, Poland

    NARCIS (Netherlands)

    Kuijper, D.P.J.; Cromsigt, J.P.G.M.; Jedrzejewska, B.A.; Miscicki, S.C.; Jedrzejewski, W.A.; Kweczlich, I.C.

    2010-01-01

    We tested the interactions between biotic and abiotic factors in structuring temperate forest communities by comparing tree recruitment after 7 years inside 30 pairs of exclosure (excluding ungulates: red deer, roe deer, bison, moose, wild boar) and control plots (7 × 7 m each) in one of the most na

  13. Design, fabrication and evaluation of two-dimensional to three-dimensional nanostructured ceramic/polymer composites for orthopedic regeneration and controlled drug delivery

    Science.gov (United States)

    Liu, Huinan

    Desirable cytocompatibility properties of nano-sized ceramics were combined with the tunable degradability and deformability of a select polymer (poly-lactide-co-glycolide, or PLGA) to optimize biological and mechanical properties for orthopedic tissue regeneration. Nanophase ceramics mimic the size scale of constituent components of natural bone and enhance the adsorption of proteins that mediate bone cell adhesion. Results have shown significantly promoted osteoblast (bone-forming cell) adhesion and long-term functions (alkaline phosphatase activity and calcium deposition) on nanophase ceramics compared to conventional (micron-scale) ceramics. Therefore, nano-titania particles were first dispersed in a model polymer (PLGA) matrix using sonication to imitate the nano-sized surface features and distribution of nano-ceramics in/on bone. Surface characteristics of the composites (such as topography, surface area and surface roughness) were studied. Importantly, results showed that osteoblast adhesion was the greatest when surface roughness values of the composites were closer to that of natural bone; this was mediated by controlling the dispersion of titania in PLGA. Moreover, this study demonstrated that the dispersion of nanophase titania in PLGA decreased the harmful acidic pH changes of PLGA as it degrades. From the perspective of mechanical properties, compared to agglomerated nano-titania in PLGA, well-dispersed nanophase titania in PLGA improved the tensile and compressive moduli and strength of these composites. In order to mimic the hierarchical structure of bone, a novel aerosol-based 3D printing technique was used to further fabricate nanostructured 3D ceramic/polymer composites. Osteoblast interactions with these 3D scaffolds provided evidence of an even further promoted bone cell infiltration into such 3D structures. Lastly, nanocomposites were used as novel drug delivery systems to promote bone growth. Specifically, a bone morphogenetic protein (BMP-7

  14. 控释技术在牙周组织再生治疗中的应用%Application of controlled release technology in periodontal tissue regeneration

    Institute of Scientific and Technical Information of China (English)

    张静(综述); 李纾(审校)

    2013-01-01

    Periodontitis?is?a?chronic?inflammatory?disease?that?causes?progressive?destruction?of?the?tooth-supporting?apparatus,?which?potentially?leads?to?tooth?loss.?Current?methods?to?reconstruct?lost?periodontal?tissues?mainly?rely?on?tissue-engineering?technology.?The?release?and?delivery?of?growth?factors?at?an?optimized?ratio?in?a?specific?spatiotemporal?mode?is?thus?of?particular?importance.?This?study?reviews?research?progress?on?controlled?release?technologies?in?periodontal?regeneration?medicine.%牙周病是发生在牙体周围支持组织的一种慢性炎性破坏性疾病,其特点是渐进性地破坏牙周支持组织直至牙体脱落。目前,牙周组织再生术研究较为广泛的是组织工程技术,其中又以生长因子的适量和适时传递尤为重要。本文就牙周组织再生术中生长因子控释技术的装载战略和控释技术的应用等研究进展作一综述。

  15. AtTCTP2, an Arabidopsis thaliana homolog of Translationally Controlled Tumor Protein, enhances in vitro plant regeneration

    OpenAIRE

    Roberto eToscano-Morales; Beatriz eXoconostle-Cázares; José Luis eCabrera-Ponce; Jesús eHinojosa-Moya; Jorge Luis eRuiz-Salas; Valentin eGalván-Gordillo; Ramon Gerardo eGuevara-González; Roberto eRuiz-Medrano

    2015-01-01

    The Translationally Controlled Tumor Protein (TCTP) is a central regulator of cell proliferation and differentiation in animals, and probably also in plants. Arabidopsis harbors two TCTP genes, AtTCTP1 (At3g16640), which is an important mitotic regulator, and AtTCTP2 (At3g05540), which is considered a pseudogene. Nevertheless, we have obtained evidence suggesting that this gene is functional. Indeed, a T-DNA insertion mutant, SALK_045146, displays a lethal phenotype during early rosette stage...

  16. Ethanol and cocaine: environmental place conditioning, stereotypy, and synergism in planarians.

    Science.gov (United States)

    Tallarida, Christopher S; Bires, Kristopher; Avershal, Jacob; Tallarida, Ronald J; Seo, Stephanie; Rawls, Scott M

    2014-09-01

    More than 90% of individuals who use cocaine also report concurrent ethanol use, but only a few studies, all conducted with vertebrates, have investigated pharmacodynamic interactions between ethanol and cocaine. Planaria, a type of flatworm often considered to have the simplest 'brain,' is an invertebrate species especially amenable to the quantification of drug-induced behavioral responses and identification of conserved responses. Here, we investigated stereotypical and environmental place conditioning (EPC) effects of ethanol administered alone and in combination with cocaine. Planarians displayed concentration-related increases in C-shaped movements following exposure to ethanol (0.01-1%) (maximal effect: 9.9±1.1 C-shapes/5 min at 0.5%) or cocaine (0.1-5 mM) (maximal effect: 42.8±4.1 C-shapes/5 min at 5 mM). For combined administration, cocaine (0.1-5 mM) was tested with submaximal ethanol concentrations (0.01, 0.1%); the observed effect for the combination was enhanced compared to its predicted effect, indicating synergism for the interaction. The synergy with ethanol was specific for cocaine, as related experiments revealed that combinations of ethanol and nicotine did not result in synergy. For EPC experiments, ethanol (0.0001-1%) concentration-dependently increased EPC, with significant environmental shifts detected at 0.01 and 1%. Cocaine (0.001-1 μM) produced an inverted U-shaped concentration-effect curve, with a significant environmental shift observed at 0.01 μM. For combined exposure, variable cocaine concentrations (0.001-1 μM) were administered with a statistically ineffective concentration of ethanol (0.0001%). For each concentration of cocaine, the environmental shift was enhanced by ethanol, with significance detected at 1 μM. Cocaethylene, a metabolite of cocaine and ethanol, also produced C-shapes and EPC. Lidocaine (0.001-10 μM), an anesthetic and analog of cocaine, did not produce EPC or C-shaped movements. Evidence from planarians

  17. Cooperative inputs of Bmp and Fgf signaling induce tail regeneration in urodele amphibians.

    Science.gov (United States)

    Makanae, Aki; Mitogawa, Kazumasa; Satoh, Akira

    2016-02-01

    Urodele amphibians have remarkable organ regeneration ability. They can regenerate not only limbs but also a tail throughout their life. It has been demonstrated that the regeneration of some organs are governed by the presence of neural tissues. For instance, limb regeneration cannot be induced without nerves. Thus, identifying the nerve factors has been the primary focus in amphibian organ regeneration research. Recently, substitute molecules for nerves in limb regeneration, Bmp and Fgfs, were identified. Cooperative inputs of Bmp and Fgfs can induce limb regeneration in the absence of nerves. In the present study, we investigated whether similar or same regeneration mechanisms control another neural tissue governed organ regeneration, i.e., tail regeneration, in Ambystoma mexicanum. Neural tissues in a tail, which is the spinal cord, could transform wound healing responses into organ regeneration responses, similar to nerves in limb regeneration. Furthermore, the identified regeneration inducer Fgf2+Fgf8+Bmp7 showed similar inductive effects. However, further analysis revealed that the blastema cells induced by Fgf2+Fgf8+Bmp7 could participate in the regeneration of several tissues, but could not organize a patterned tail. Regeneration inductive ability of Fgf2+Fgf8+Bmp7 was confirmed in another urodele, Pleurodeles waltl. These results suggest that the organ regeneration ability in urodele amphibians is controlled by a common mechanism.

  18. Erythropoietin stimulates hepatocyte regeneration after liver resection

    OpenAIRE

    Schön, Michael R.; Hogrebe, Esther; Hengstler, Jan Georg; Donaubauer, Bernd; Faber, Sonya C.; Bauer, Alexander; Pietsch, Uta-Carolin; Jelkmann, Wolfgang; Thiery, Joachim; Hauss, Johann Peter; Tannapfel, Andrea

    2008-01-01

    The increased relevance of liver surgery and transplantation as a therapeutic modality over the last two decades mandates the development of novel strategies to improve liver regeneration. Here we studied whether erythropoietin (EPO) improves liver regeneration after hepatectomy in pigs. Eighteen female pigs underwent laparoscopic left lateral liver resection and were allocated randomly into three groups. No EPO was administered to the control group (group 1, n=6). Group 2 (...

  19. Non-Uniform Heat Transfer in Thermal Regenerators

    DEFF Research Database (Denmark)

    Jensen, Jesper Buch

    This thesis presents investigations on the heat transfer in complex heat ex- changers in general and in regenerative heat exchangers (regenerators) in par- ticular. The motivation for this work is a result of inconsistencies obeserved in the results from a series of experiments on active magnetic...... regenerators (AMRs) with parallel plates. The results suggest that random variations in the regenerator geometries causes maldistributed fluid flow inside the regener- ators, which affects the regenerator performance. In order to study the heat transfer processes in regenerators with non-uniform geometries......, a numerical model, which simulates a single-blow operation in a parallel-plate regenerator, was developed and used to model the heat transfer under various conditions. In addition to the modeling of the heat transfer, a series of experiments on passive regenerators with non-uniform, but precisely controlled...

  20. Modulation of tissue repair by regeneration enhancer elements.

    Science.gov (United States)

    Kang, Junsu; Hu, Jianxin; Karra, Ravi; Dickson, Amy L; Tornini, Valerie A; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A; Black, Brian L; Poss, Kenneth D

    2016-04-14

    How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.

  1. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

    Science.gov (United States)

    Marchand, Catherine; Chen, Gaoping; Tran-Khanh, Nicolas; Sun, Jun; Chen, Hongmei; Buschmann, Michael D; Hoemann, Caroline D

    2012-03-01

    This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled

  2. The cancer paradigms of mammalian regeneration: can mammals regenerate as amphibians?

    Science.gov (United States)

    Sarig, Rachel; Tzahor, Eldad

    2017-04-01

    Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells. Interestingly, regenerating amphibian cells are highly resistant to oncogenic transformation. Therapeutic approaches to improve mammalian regeneration mainly include stem-cell transplantations; but, these have proved unsuccessful in non-regenerating organs such as the heart. A recently developed approach is to induce de-differentiation of mature cardiomyocytes using factors that trigger their re-entry into the cell cycle. This novel approach raises numerous questions regarding the balance between transformation and regeneration induced by de-differentiation of mature mammalian somatic cells. Can this balance be controlled artificially? Do de-differentiated cells acquire the protection mechanisms seen in regenerating cells of lower organisms? Is this model unique to the cardiac tissue, which rarely develops tumors? This review describes regeneration processes in both mammals and lower organisms and, particularly, the ability of regenerating cells to avoid transformation. By comparing the characteristics of mammalian embryonic and somatic cells, we discuss therapeutic strategies of using various cell populations for regeneration. Finally, we describe a novel cardiac regeneration approach and its implications for regenerative medicine. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email

  3. Fibrous guided tissue regeneration membrane loaded with anti-inflammatory agent prepared by coaxial electrospinning for the purpose of controlled release

    Energy Technology Data Exchange (ETDEWEB)

    He, Min; Xue, Jiajia [Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Geng, Huan; Gu, Hao [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Chen, Dafu [Laboratory of Bone Tissue Engineering of Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035 (China); Shi, Rui, E-mail: sharell@126.com [Laboratory of Bone Tissue Engineering of Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035 (China); Zhang, Liqun, E-mail: zhanglq@mail.buct.edu.cn [Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China)

    2015-04-30

    Graphical abstract: The metronidazole released from PCL/gelatin core/sheath nanofiber membranes can effectively inhibit the colonization of anerobic bacteria. - Highlights: • Core/sheath PCL/gelatin nanofiber membrane loaded with metronidazole in a wide range of drug loading (5–35 wt.%) were successfully fabricated in good quality. • The encapsulation of gelatin can effectively alleviate the initial burst release of drugs. • The membrane can inhibit the growth of bacteria as the drug content reaches 10% (w/w), and the bacterial inhibition ability can effectively last at least 4 weeks. • The encapsulation of gelatin can overcome the disadvantage of PCL's hydrophobicity, which can effectively promote the adhesion and proliferation of cells. - Abstract: Here, with the aim of inhibiting inflammation during guided tissue regeneration membrane (GTRM) implant surgery, coaxial electrospinning was used to fabricate drug-loaded core/sheath nanofiber GTRMs capable of controlled drug release. Various amounts of the anti-inflammatory agent metronidazole (MNA) were encapsulated into the core/sheath nanofibers (where PCL was the core, gelatin the sheath, and the gelatin shell was crosslinked with genipin) in order to establish the minimal drug content necessary to achieve the appropriate anti-inflammatory effect. By using TEM and SEM, the core/sheath structure was confirmed. In vitro drug disolution results showed that the core/sheath nanofibers exhibited sustained release profiles that were superior to those nanofibers produced by blending electrospinning. Additionally, the membrane significantly inhibited the colonization of anaerobic bacteria. Furthermore, with gelatin as a shell, the core/shell nanofiber membranes showed improved hydrophilicity, which resulted in better cell adhesion and proliferation without cytotoxicity. Therefore, in this study, a simple and effective coaxial electrospinning approach was demonstrated for the fabrication of anti

  4. Intrinsic determinants of optic nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-lin; CHO Kin-Sang; GUO Chen-ying; CHEW Justin; CHEN Dong-feng; YANG Liu

    2013-01-01

    Objective To review the functions of these intracellular signals in their regulation of retinal ganglion cell (RGC) axon regeneration.Data sources Relevant articles published in English or Chinese from 1970 to present were selected from PubMed.Searches were made using the terms "intrinsic determinants,axon regeneration,RGC,optic nerve regeneration,and central nervous system axon regeneration."Study selection Articles studying the mechanisms controlling RGC and central nervous system (CNS) axon regeneration were reviewed.Articles focusing on the intrinsic determinants of axon regeneration were selected.Results Like other CNS neurons of mammals,RGCs undergo a developmental loss in their ability to grow axons as they mature,which is a critical contributing factor to the failure of nerve regeneration and repair after injury.This growth failure can be attributed,at least in part,by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation.Key intracellular signals and transcription factors,including B cell lymphoma/leukemia 2,cyclic adenine monophosphate,mammalian target of rapamycin,and Krüppel-like transcription factors,have been identified to play central roles in this process.Conclusions Intense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration.More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.

  5. The Analysis of Activated Carbon Regeneration Technologies

    Institute of Scientific and Technical Information of China (English)

    姚芳

    2014-01-01

    A series of methods for activated carbon regeneration were briefly introduced.Such as thermal regeneration,chemical regeneration,biochemical regeneration,and newly supercritical fluid regeneration, electrochemical regeneration,light-catalyzed regeneration,and microwave radiation method,and the developing trend of activated carbon regeneration was predicted.

  6. Efficacy of intervertebral disc regeneration with stem cells - a systematic review and meta-analysis of animal controlled trials.

    Science.gov (United States)

    Wang, Zhen; Perez-Terzic, Carman M; Smith, Jay; Mauck, William D; Shelerud, Randy A; Maus, Timothy P; Yang, Tai-Hua; Murad, Mohammad Hassan; Gou, Shanmiao; Terry, Marisa J; Dauffenbach, Jason P; Pingree, Mathew J; Eldrige, Jason S; Mohammed, Khaled; Benkhadra, Khalid; van Wijnen, Andre J; Qu, Wenchun

    2015-06-10

    Management of intervertebral disc (IVD) degenerative disease is challenging, as it is accompanied by irreversible loss of IVD cells. Stem cell transplantation to the disc has shown promise in decelerating or arresting the degenerative process. Multiple pre-clinical animal trials have been conducted, but with conflicting outcomes. To assess the effect of stem cell transplantation, a systematic review and meta-analysis was performed. A comprehensive literature search was conducted through Week 3, 2015. Inclusion criteria consisted of controlled animal trials. Two reviewers screened abstracts and full texts. Disagreements were resolved by a third reviewer. Random effects models were constructed to pool standardized mean difference (SMD). Twenty two studies were included; nine of which were randomized. Statistically significant differences were found with the stem cell group exhibiting increased disc height index (SMD=3.64, 95% confidence interval (CI): 2.49, 4.78; panimal species, study designs, and transplanted cell types. Stem cells transplanted to the IVD in quadruped animals decelerate or arrest the IVD degenerative process. Further studies in human clinical trials will be needed to understand if such benefit can be translated to bipedal humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Toxicity of a hazardous chemical mixture in the planarian, Dugesia dorotocephala

    Energy Technology Data Exchange (ETDEWEB)

    Ramsdell, H.S.; Matthews, C.M. [Colorado State Univ., Ft. Collins, CO (United States)

    1995-12-31

    The responses of the planarian, Dugesia dorotocephala to toxic chemical mixtures representative of water contaminants associated with hazardous waste sites have been studied in laboratory experiments. These free-living flatworms are readily maintained under laboratory conditions and are a useful invertebrate model for toxicology studies. Their widespread occurrence also makes them potentially useful for environmental studies. Mature asexual Dugesia dorotocephala were exposed for 14 days to mixtures of seven contaminants frequently detected in water at hazardous waste sites. The complete 1X mixture contained both metals (As, 3.1 ppm; Cr, 0.7 ppm; Pb, 3.7 ppm) and organics (chloroform, 1.5 ppm; benzene, 5.0 ppm; phenol, 3.4 ppm; trichloroethylene, 3.8 ppm). Groups of planaria were treated with the complete mixture at 0.1X, 1X and 10X concentrations. Additional groups were exposed to the metals-only or organics-only submixtures, also at 0.1X, 1X and 10X concentrations. Treatment solutions were renewed daily. Suppression of fissioning was observed in all of the 1X and 10X treatment groups. Significant mortality occurred only in the 10X complete and 1 0X metals-only treatments. It appears that the toxic effects of the complete mixture are primarily associated with the metal components.

  8. Ultrastructure of spermatogenesis and mature spermatozoon of the freshwater planarian Schmidtea mediterranea (Platyhelminthes, Paludicola).

    Science.gov (United States)

    Harrath, Abdul Halim; Alwasel, Saleh; Zghal, Fathia; Tekaya, Saïda

    2012-02-01

    The aim of this study was to characterize for the first time spermatogenesis and spermiogenesis in the freshwater planarian Schmidtea mediterranea using both light and electron microscopy. Starting from the border towards the testis lumen we found types I and II spermatogonia, clusters of primary and secondary spermatocytes, spermatids and free spermatozoa. Light microscope observations show that type I spermatogonia have a large and pale nucleus whereas type II spermatogonia are significantly smaller than the one of type I, and show a darker and central bulky nucleus. At the ultrastructure level, both type I and type II spermatogonia are characterized by a wide nucleus with scanty cytoplasm containing free ribosomes, mitochondria and a dense chromatoid body whereas endoplasmic reticulum and Golgi complex were not observed. The cytoplasm of primary and secondary spermatocytes displays numerous free ribosomes and many endoplasmic reticulum cisternae and Golgi complexes, suggesting that the development of these organelles during spermatogenesis might contribute to the synthesis of hormones and proteins such as testosterone, transcription factors and tubulin. Mature spermatozoa structure closely resembles those of other freshwater triclads with a nucleus, a single fused mitochondrion, a row of cortical microtubules and a pair of flagella conforming to the 9+'1' microtubule pattern described for other Platyhelminthes.

  9. Argyrophil Reaction of Histological Structure on Planarians (Dugesia japonica )%日本三角涡虫组织结构嗜银反应观察

    Institute of Scientific and Technical Information of China (English)

    范红军; 李晶; 高伶丽; 陈广文

    2012-01-01

    涡虫在动物系统演化史上占有十分重要的地位,雌雄同体,具有很强的再生能力,因此,对其组织结构嗜银反应进行研究具有重要的意义.本文用Grimellus还原银法显示了H本三角涡虫(Dugesia japonica)嗜银反应阳性的组织结构.结果表明:肠上皮细胞内有很多染成棕褐色的圆形泡状结构.肠上皮下的实质组织细胞中分布很多黑色颗粒;交配囊上皮细胞可见染成棕褐色的颗粒;在雄腔和交配囊柄两侧和后部可见染成棕褐色的三角形区域;纵神经索嗜银反应较弱,呈浅褐色.因此,可以确定肠上皮下实质组织中存在APUD系统.%Hermaphroditic plartatians are possessed of a very important position in the systematic evolutionary history of animal,and a powerful capacity of complete regeneration. Hence,the careful researches of argyrophil reaction on the histologi-cal structure are very important. The positive histological structure of argyrophil reaction on Dugesia japonica is revealed with Grimellus silver-deoxidized method,and observed with light microscope. The results show that there are a lot of round vacuole stained brown in the intestinal epithelial cells. There are many black granules in the parenchyma cells under the intestinal epithelium. There are a few granules stained brown in the epithelial cells of copulatory bursa. A triangular area stained brown,which is located at two sides and tail of male antrum and bursa stalk,can be observed. Argyrophil reaction of vertical nerve cable stained sandy beige is weaker. Hence,it is demonstrated that APUD system exists in the parenchyma under the intestinal epithelium of planarian.

  10. The neurochemistry of peripheral nerve regeneration

    Science.gov (United States)

    Benga, Andreea; Zor, Fatih; Korkmaz, Ahmet; Marinescu, Bogdan; Gorantla, Vijay

    2017-01-01

    Peripheral nerve injuries (PNIs) can be most disabling, resulting in the loss of sensitivity, motor function and autonomic control in the involved anatomical segment. Although injured peripheral nerves are capable of regeneration, sub-optimal recovery of function is seen even with the best reconstruction. Distal axonal degeneration is an unavoidable consequence of PNI. There are currently few strategies aimed to maintain the distal pathway and/or target fidelity during regeneration across the zone of injury. The current state of the art approaches have been focussed on the site of nerve injury and not on their distal muscular targets or representative proximal cell bodies or central cortical regions. This is a comprehensive literature review of the neurochemistry of peripheral nerve regeneration and a state of the art analysis of experimental compounds (inorganic and organic agents) with demonstrated neurotherapeutic efficacy in improving cell body and neuron survival, reducing scar formation and maximising overall nerve regeneration. PMID:28615804

  11. Advanced Fabrication Techniques for Precisely Controlled Micro and Nano Scale Environments for Complex Tissue Regeneration and Biomedical Applications

    Science.gov (United States)

    Holmes, Benjamin

    As modern medicine advances, it is still very challenging to cure joint defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The current clinical standard for catastrophic or late stage joint degradation is a total joint implant, where the damaged joint is completely excised and replaced with a metallic or artificial joint. However, these procedures still only lasts for 10-15 years, and there are hosts of recovery complications which can occur. Thus, these studies have sought to employ advanced biomaterials and scaffold fabricated techniques to effectively regrow joint tissue, instead of merely replacing it with artificial materials. We can hypothesize here that the inclusion of biomimetic and bioactive nanomaterials with highly functional electrospun and 3D printed scaffold can improve physical characteristics (mechanical strength, surface interactions and nanotexture) enhance cellular growth and direct stem cell differentiation for bone, cartilage and vascular growth as well as cancer metastasis modeling. Nanomaterial inclusion and controlled 3D printed features effectively increased nano surface roughness, Young's Modulus and provided effective flow paths for simulated arterial blood. All of the approaches explored proved highly effective for increasing cell growth, as a result of increasing micro-complexity and nanomaterial incorporation. Additionally, chondrogenic and osteogenic differentiation, cell migration, cell to cell interaction and vascular formation were enhanced. Finally, growth-factor(gf)-loaded polymer nanospheres greatly improved vascular cell behavior, and provided a highly bioactive scaffold for mesenchymal stem cell (MSC) and human umbilical vein endothelial cell (HUVEC) co-culture and bone formation. In conclusion, electrospinning and 3D printing when combined effectively with biomimetic and bioactive nanomaterials (i.e. carbon nanomaterials, collagen, nHA, polymer

  12. DjRock2 involved in regeneration activities in Dugesia japonica%DjRock2参与东亚三角涡虫再生调节

    Institute of Scientific and Technical Information of China (English)

    魏飞; 赵博生

    2014-01-01

    In vitro transcription of RNA synthesized DjRock2 gene probe, the detection efficiency of RNA probe, and regeneration of adult planarians in situ hybridization.Then insert DjRock2 gene to the vector L4440, construct L4440-DjRock2 interference vector, synthetic dsRNA and microinjection planarian, using RT-PCR and Western blot technique to detect interference regeneration process expressing down effect on DjRock2 mRNA and protein.The results showed that:DjRock2 genes specifically expressed in mature planarian central nervous system regeneration blastema wound posi-tion has a positive signal;interfere adult planarian regeneration of the first three days at the head, middle and tail of the embryo group has, but the first five days at the beginning of the wound apoptosis, adult stem cells do not complete the normal differentiation of the head , middle and tail regeneration is inhibited, not the normal completion of regeneration, and even death.RT-PCR technique significantly decreased DjRock2 mRNA expression was detected after RNA interfer-ence.Upon detection of interference Western blot protein expression DjRock2 down.Constructed L4440-DjRock2 high interference carrier interference efficiency, phenotypic changes significantly, the analysis of gene and protein, laid the foundation for further research Rock2 gene function.%利用体外转录的方法合成DjRock2基因的RNA探针,检测RNA探针效率后,对成体及再生过程中的涡虫进行原位杂交试验;将DjRock2基因插入到L4440载体中,构建L4440-DjRock2干扰载体,合成dsRNA并微注射涡虫,利用RT-PCR和Western blot技术检测干扰后再生过程中DjRock2 mRNA和蛋白表达的下调作用。结果表明:DjRock2基因在成熟涡虫中枢神经系统中特异性表达,再生过程中伤口处胚基位置有阳性信号;干扰成体涡虫在再生第3天,头部、中部、尾部都有胚基的形成,但是第5天开始伤口处细胞凋亡,成体干细胞没有完成

  13. Sexual selection drives the evolution of limb regeneration in Harmonia axyridis (Coleoptera: Coccinellidae).

    Science.gov (United States)

    Wang, S; Tan, X L; Michaud, J P; Shi, Z K; Zhang, F

    2015-04-01

    When Harmonia axyridis larvae were subjected to amputation of a foreleg in the fourth instar, 83% survived and, of these, 75% regenerated the leg during pupation. Regenerators pupated at heavier weights than controls (unoperated) or non-regenerators, and spent longer in pupation. Regenerated males were preferred by females in choice tests and produced more viable progeny than control males. Unregenerated males were less preferred by females, copulated for shorter periods than control males, and reduced female fecundity. Amputation diminished beneficial paternal effects, whether males regenerated or not, resulting in progeny with slower development and smaller adult body mass relative to control paternity. Progeny of unregenerated males had lower survival and body mass, whether male or female, confirming that regeneration was an honest signal of mate quality. When offspring had a foreleg amputated, a regenerated paternity yielded higher survival than control paternity, but similar rates of regeneration, whereas an unregenerated paternity yielded lower rates of survival and leg regeneration than control paternity. Regenerating beetles were twice as likely to be melanic as non-regenerating or control beetles, suggesting pleiotropic effects of melanism on processes involved in regeneration. This is the first report of complete limb regeneration by a holometabolous insect in the pupal stage, and the first example of sexual selection for regenerative capacity.

  14. Guided tissue regeneration. Absorbable barriers.

    Science.gov (United States)

    Wang, H L; MacNeil, R L

    1998-07-01

    Over the past 15 years, techniques aimed at regeneration of lost periodontal tissue have become widely used and accepted in clinical practice. Among these techniques are those which use the principles of guided tissue regeneration (GTR), wherein barriers (i.e., membranes) are used to control cell and tissue repopulation of the periodontal wound. A variety of non-absorbable and absorbable barriers have been developed and used for this purpose, with a trend in recent years toward increased use of absorbable GTR materials. This article describes the evolution of absorbable barrier materials and overview materials available for clinical use today. In addition, advantages and disadvantages of these materials are discussed, as well as possible new developments in barrier-based GTR therapy.

  15. Development and regeneration of the inner ear.

    Science.gov (United States)

    Kwan, Tao; White, Patricia M; Segil, Neil

    2009-07-01

    Loss of sensory hair cells is the leading cause of deafness in humans. The mammalian cochlea cannot regenerate its complement of sensory hair cells. Thus at present, the only treatment for deafness due to sensory hair cell loss is the use of prosthetics, such as hearing aids and cochlear implants. In contrast, in nonmammalian vertebrates, such as birds, hair cell regeneration occurs following the death of hair cells and leads to the restoration of hearing. Regeneration in birds is successful because supporting cells that surround the hair cells can divide and are able to subsequently differentiate into new hair cells. However, supporting cells in mammals do not normally divide or transdifferentiate when hair cells are lost, and so regeneration does not occur. To understand the failure of mammalian cochlear hair cell regeneration, we need to understand the molecular mechanisms that underlie cell division control and hair cell differentiation, both during embryogenesis and in the postnatal mouse. In this review, we present a discussion of the regulation of cell proliferation in embryogenesis and during postnatal maturation. We also discuss the role of the Cip/Kip cell cycle inhibitors and Notch signaling in the control of stability of the differentiated state of early postnatal supporting cells. Finally, recent data indicate that some early postnatal mammalian supporting cells retain a latent capacity to divide and transdifferentiate into sensory hair cells. Together, these observations make supporting cells important therapeutic targets for continued efforts to induce hair cell regeneration.

  16. Large-scale and highly efficient synthesis of micro- and nano-fibers with controlled fiber morphology by centrifugal jet spinning for tissue regeneration.

    Science.gov (United States)

    Ren, Liyun; Pandit, Vaibhav; Elkin, Joshua; Denman, Tyler; Cooper, James A; Kotha, Shiva P

    2013-03-21

    PLLA fibrous tissue scaffolds with controlled fiber nanoscale surface roughness are fabricated with a novel centrifugal jet spinning process. The centrifugal jet spinning technique is a highly efficient synthesis method for micron- to nano-sized fibers with a production rate up to 0.5 g min(-1). During the centrifugal jet spinning process, a polymer solution jet is stretched by the centrifugal force of a rotating chamber. By engineering the rheological properties of the polymer solution, solvent evaporation rate and centrifugal force that are applied on the solution jet, polyvinylpyrrolidone (PVP) and poly(l-lactic acid) (PLLA) composite fibers with various diameters are fabricated. Viscosity measurements of polymer solutions allowed us to determine critical polymer chain entanglement limits that allow the generation of continuous fiber as opposed to beads or beaded fibers. Above a critical concentration at which polymer chains are partially or fully entangled, lower polymer concentrations and higher centrifugal forces resulted in thinner fibers. Etching of PVP from the PLLA-PVP composite fibers doped with increasing PVP concentrations yielded PLLA fibers with increasing nano-scale surface roughness and porosity, which increased the fiber hydrophilicity dramatically. Scanning electron micrographs of the etched composite fibers suggest that PVP and PLLA were co-contiguously phase separated within the composite fibers during spinning and nano-scale roughness features were created after the partial etching of PVP. To study the tissue regeneration efficacy of the engineered PLLA fiber matrix, human dermal fibroblasts are used to simulate partial skin graft. Fibers with increased PLLA surface roughness and porosity demonstrated a trend towards higher cell attachment and proliferation.

  17. Regeneration and reprogramming compared

    Directory of Open Access Journals (Sweden)

    Robles Vanesa

    2010-01-01

    Full Text Available Abstract Background Dedifferentiation occurs naturally in mature cell types during epimorphic regeneration in fish and some amphibians. Dedifferentiation also occurs in the induction of pluripotent stem cells when a set of transcription factors (Oct4, Sox2, Klf4 and c-Myc is over expressed in mature cell types. Results We hypothesised that there are parallels between dedifferentiation or reprogramming of somatic cells to induced pluripotent stem cells and the natural process of dedifferentiation during epimorphic regeneration. We analysed expression levels of the most commonly used pluripotency associated factors in regenerating and non-regenerating tissue and compared them with levels in a pluripotent reference cell. We found that some of the pluripotency associated factors (oct4/pou5f1, sox2, c-myc, klf4, tert, sall4, zic3, dppa2/4 and fut1, a homologue of ssea1 were expressed before and during regeneration and that at least two of these factors (oct4, sox2 were also required for normal fin regeneration in the zebrafish. However these factors were not upregulated during regeneration as would be expected if blastema cells acquired pluripotency. Conclusions By comparing cells from the regeneration blastema with embryonic pluripotent reference cells we found that induced pluripotent stem and blastema cells do not share pluripotency. However, during blastema formation some of the key reprogramming factors are both expressed and are also required for regeneration to take place. We therefore propose a link between partially reprogrammed induced pluripotent stem cells and the half way state of blastema cells and suggest that a common mechanism might be regulating these two processes.

  18. Strategies for lung regeneration

    Directory of Open Access Journals (Sweden)

    Thomas H. Petersen

    2011-05-01

    Full Text Available Due to the limited ability of the adult lung to regenerate and the frequency of lung disease, the lung is a tissue that can especially benefit from regenerative medicine. Prospects for lung regeneration have made great strides in the past year. In this review, we summarize recent progress and key challenges for approaches in lung regenerative medicine. With a focus on the matrix components critical for the development of regenerative lung tissues, we discuss possible cell sources for lung regeneration, key matrix effects on cell repopulation, and physical stimuli that will aid in the growth of lung tissues in vitro.

  19. Tooth regeneration: Current status

    Directory of Open Access Journals (Sweden)

    Dadu Shifali

    2009-01-01

    Full Text Available Regeneration of a functional tooth has the potential to be a promising therapeutic strategy. Experiments have shown that with the use of principles of bioengineering along with adult stem cells, scaffold material, and signaling molecules, tooth regeneration is possible. Research work is in progress on creating a viable bioroot with all its support. A new culture needs to be created that can possibly provide all the nutrients to the stem cells. With the ongoing research, tissue engineering is likely to revolutionize dental health and well-being of people by regenerating teeth over the next decade.

  20. Tooth regeneration: current status.

    Science.gov (United States)

    Dadu, Shifali S

    2009-01-01

    Regeneration of a functional tooth has the potential to be a promising therapeutic strategy. Experiments have shown that with the use of principles of bioengineering along with adult stem cells, scaffold material, and signaling molecules, tooth regeneration is possible. Research work is in progress on creating a viable bioroot with all its support. A new culture needs to be created that can possibly provide all the nutrients to the stem cells. With the ongoing research, tissue engineering is likely to revolutionize dental health and well-being of people by regenerating teeth over the next decade.

  1. Regeneration Heat Exchange

    Energy Technology Data Exchange (ETDEWEB)

    J. Lin

    2003-07-30

    The original project goals were to establish the viability of the proposed gas turbine regenerator concept by performing the following tasks: (1) Perform detailed design of a working model of the regenerator concept. (2) Construct a ''bench-top'' model of the regenerator concept based upon the detail design. (3) Test the bench-top model and gather data to support the concept's viability. The project funding was used to acquire the tools and material to perform the aforementioned tasks.

  2. Terrestrial planarians (Platyhelminthes, Tricladida, Terricola) from the Iberian peninsula: first records of the family Rhynchodemidae, with the description of a new Microplana species

    NARCIS (Netherlands)

    Mateos, Eduardo; Giribet, Gonzalo; Carranza, Salvador

    1998-01-01

    The first records of terrestrial planarians belonging to the family Rhynchodemidae are reported for the Iberian Peninsula. A new endemic species from the Spanish Pyrenees, Microplana nana sp. nov., is described. The characteristic features of this species are: i) small size (8-10 mm) in adult

  3. Terrestrial planarians (Platyhelminthes, Tricladida, Terricola) from the Iberian peninsula: first records of the family Rhynchodemidae, with the description of a new Microplana species

    NARCIS (Netherlands)

    Mateos, Eduardo; Giribet, Gonzalo; Carranza, Salvador

    1998-01-01

    The first records of terrestrial planarians belonging to the family Rhynchodemidae are reported for the Iberian Peninsula. A new endemic species from the Spanish Pyrenees, Microplana nana sp. nov., is described. The characteristic features of this species are: i) small size (8-10 mm) in adult indivi

  4. Research of Energy Regeneration Technology in Electric Vehicle

    Institute of Scientific and Technical Information of China (English)

    陈家新; 江建中; 汪信尧

    2003-01-01

    The theory of energy regeneration in electric vehicle (EV) has been introduced in most papers, but the mathematic model of EV energy regeneration system was little studied. In this paper the mathematic model of EV energy regeneration system is studied,and then the system ability under four control strategies is analyzed. In the end the system reliability is researched, and the calcula-tion model of system reliability is proposed.

  5. Mass loss and nutrient concentrations of buried wood as a function of organic matter removal, soil compaction, and vegetation control in a regenerating oak-pine forest

    Science.gov (United States)

    Felix Ponder; John M. Kabrick; Mary Beth Adams; Deborah S. Page-Dumroese; Marty F. Jurgensen

    2017-01-01

    Mass loss and nutrient concentrations of northern red oak (Quercus rubra) and white oak (Q. alba) wood stakes were measured 30 months after their burial in the upper 10 cm of soil in a regenerating forest after harvesting and soil disturbance. Disturbance treatments were two levels of organic matter (OM) removal (only...

  6. Nanostructured Biomaterials for Regeneration**

    OpenAIRE

    Wei, Guobao; Ma, Peter X.

    2008-01-01

    Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/dysfunctional tissues or organs. Biomaterials (scaffolds) serve as temporary 3D substrates to guide neo tissue formation and organization. It is often beneficial for a scaffolding material to mimic the characteristics of extracellular matrix (ECM) at the nanometer scale and to induce certain natural developmental or/and wound healing processes for tissue regeneration applications. This article...

  7. Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

    Directory of Open Access Journals (Sweden)

    Ariel A. Simerman

    2016-01-01

    Full Text Available Muse cells are a novel population of nontumorigenic pluripotent stem cells, highly resistant to cellular stress. These cells are present in every connective tissue and intrinsically express pluripotent stem markers such as Nanog, Oct3/4, Sox2, and TRA1-60. Muse cells are able to differentiate into cells from all three embryonic germ layers both spontaneously and under media-specific induction. Unlike ESCs and iPSCs, Muse cells exhibit low telomerase activity and asymmetric division and do not undergo tumorigenesis or teratoma formation when transplanted into a host organism. Muse cells have a high capacity for homing into damaged tissue and spontaneous differentiation into cells of compatible tissue, leading to tissue repair and functional restoration. The ability of Muse cells to restore tissue function may demonstrate the role of Muse cells in a highly conserved cellular mechanism related to cell survival and regeneration, in response to cellular stress and acute injury. From an evolutionary standpoint, genes pertaining to the regenerative capacity of an organism have been lost in higher mammals from more primitive species. Therefore, Muse cells may offer insight into the molecular and evolutionary bases of autonomous tissue regeneration and elucidate the molecular and cellular mechanisms that prevent mammals from regenerating limbs and organs, as planarians, newts, zebrafish, and salamanders do.

  8. Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

    Science.gov (United States)

    2016-01-01

    Muse cells are a novel population of nontumorigenic pluripotent stem cells, highly resistant to cellular stress. These cells are present in every connective tissue and intrinsically express pluripotent stem markers such as Nanog, Oct3/4, Sox2, and TRA1-60. Muse cells are able to differentiate into cells from all three embryonic germ layers both spontaneously and under media-specific induction. Unlike ESCs and iPSCs, Muse cells exhibit low telomerase activity and asymmetric division and do not undergo tumorigenesis or teratoma formation when transplanted into a host organism. Muse cells have a high capacity for homing into damaged tissue and spontaneous differentiation into cells of compatible tissue, leading to tissue repair and functional restoration. The ability of Muse cells to restore tissue function may demonstrate the role of Muse cells in a highly conserved cellular mechanism related to cell survival and regeneration, in response to cellular stress and acute injury. From an evolutionary standpoint, genes pertaining to the regenerative capacity of an organism have been lost in higher mammals from more primitive species. Therefore, Muse cells may offer insight into the molecular and evolutionary bases of autonomous tissue regeneration and elucidate the molecular and cellular mechanisms that prevent mammals from regenerating limbs and organs, as planarians, newts, zebrafish, and salamanders do. PMID:28070194

  9. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat.

    Science.gov (United States)

    Diaz Quiroz, Juan Felipe; Tsai, Eve; Coyle, Matthew; Sehm, Tina; Echeverri, Karen

    2014-06-01

    Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs) that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum) and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b) is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal's functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander's regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries.

  10. The blue land planarian Caenoplana coerulea, an invader in Argentina La planaria terrestre azul Caenoplana coerulea, un invasor en Argentina

    Directory of Open Access Journals (Sweden)

    Lisandro Héctor Luis-Negrete

    2011-03-01

    Full Text Available The blue land planarian Caenoplana coerulea is reported from Argentina (Buenos Aires province. We found C. coerulea in the east central region of Argentina in anthropic environments. The specimens that we found have the characteristic of the species found in others regions; that is, a bluish dorsal surface with a yellow mid-dorsal stripe and eyes forming a single row around the anterior tip, clustered laterally. This is the first record of this species from the Neotropical Region, and together with Bipalium kewense are the only 2 species of exotic terrestrial planarians so far recorded in Argentina.La planaria terrestre azul Caenoplana coerulea se registra para el centro este de Argentina (provincia de Buenos Aires, en ambientes antropizados. Los ejemplares encontrados presentan las características de la especie registrada en otras regiones, con una superficie dorsal azulada y una hilera medio dorsal amarilla, y ojos formando una hilera alrededor del extremo anterior, agrupados lateralmente. Es la primera vez que se cita dicha especie en la Región Neotropical, y junto a Bipalium kewense son las únicas planarias terrestres exóticas registradas en Argentina.

  11. Neuromodulatory nerve regeneration: adipose tissue-derived stem cells and neurotrophic mediation in peripheral nerve regeneration.

    Science.gov (United States)

    Widgerow, Alan D; Salibian, Ara A; Lalezari, Shadi; Evans, Gregory R D

    2013-12-01

    Peripheral nerve injury requiring nerve gap reconstruction remains a major problem. In the quest to find an alternative to autogenous nerve graft procedures, attempts have been made to differentiate mesenchymal stem cells into neuronal lineages in vitro and utilize these cellular constructs for nerve regeneration. Unfortunately, this has produced mixed results, with no definitive procedure matching or surpassing traditional nerve grafting procedures. This review presents a different approach to nerve regeneration. The literature was reviewed to evaluate current methods of using adipose-derived stem cells (ADSCs) for peripheral nerve regeneration in in vivo models of animal peripheral nerve injury. The authors present cited evidence for directing nerve regeneration through paracrine effects of ADSCs rather than through in vitro nerve regeneration. The paracrine effects rely mainly, but not solely, on the elaboration of nerve growth factors and neurotrophic mediators that influence surrounding host cells to orchestrate in vivo nerve regeneration. Although this paradigm has been indirectly referred to in a host of publications, few major efforts for this type of neuromodulatory nerve regeneration have been forthcoming. The ADSCs are initially "primed" in vitro using specialized controlled medium (not for neuronal differentiation but for sustainability) and then incorporated into a hydrogel base matrix designed for this purpose. This core matrix is then introduced into a natural collagen-based nerve conduit. The prototype design concepts, evidence for paracrine influences, and regulatory hurdles that are avoided using this approach are discussed. Copyright © 2013 Wiley Periodicals, Inc.

  12. Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects.

    Science.gov (United States)

    Kitamura, Masahiro; Akamatsu, Motoki; Kawanami, Masamitsu; Furuichi, Yasushi; Fujii, Takeo; Mori, Mari; Kunimatsu, Kazushi; Shimauchi, Hidetoshi; Ogata, Yorimasa; Yamamoto, Matsuo; Nakagawa, Taneaki; Sato, Shuichi; Ito, Koichi; Ogasawara, Takefumi; Izumi, Yuichi; Gomi, Kazuhiro; Yamazaki, Kazuhisa; Yoshie, Hiromasa; Fukuda, Mitsuo; Noguchi, Toshihide; Takashiba, Shogo; Kurihara, Hidemi; Nagata, Toshihiko; Hamachi, Takafumi; Maeda, Katsumasa; Yokota, Makoto; Sakagami, Ryuji; Hara, Yoshitaka; Noguchi, Kazuyuki; Furuuchi, Toshi; Sasano, Takashi; Imai, Enyu; Ohmae, Masatoshi; Koizumi, Hayuru; Watanuki, Mitsuru; Murakami, Shinya

    2016-04-01

    We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multicenter, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4-mm and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co-primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval [CI], 32.7502 to 41.5123; n = 208) than it was in the placebo group at 21.579% (95% CI, 16.3571 to 26.8011; n = 100; p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multicenter, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6-mm and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks, was 1.927 mm (95% CI, 1.6615 to 2.1920; n = 108) in the rhFGF-2 group and 1.359 mm (95% CI, 1.0683 to 1.6495; n = 109) in the EMD group, showing non-inferiority (a prespecified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in either study. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony

  13. Three-dimensional aligned nanofibers-hydrogel scaffold for controlled non-viral drug/gene delivery to direct axon regeneration in spinal cord injury treatment

    Science.gov (United States)

    Nguyen, Lan Huong; Gao, Mingyong; Lin, Junquan; Wu, Wutian; Wang, Jun; Chew, Sing Yian

    2017-01-01

    Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment. A hemi-incision model at cervical level 5 in the rat spinal cord was chosen to evaluate the efficacy of this scaffold design. Specifically, aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered. Taken together, our results demonstrate the potential of our scaffold for neural tissue engineering applications. PMID:28169354

  14. Perfluorodecalin and bone regeneration

    Directory of Open Access Journals (Sweden)

    F Tamimi

    2013-01-01

    Full Text Available Perfluorodecalin (PFD is a chemically and biologically inert biomaterial and, as many perfluorocarbons, is also hydrophobic, radiopaque and has a high solute capacity for gases such as oxygen. In this article we have demonstrated, both in vitro and in vivo, that PFD may significantly enhance bone regeneration. Firstly, the potential benefit of PFD was demonstrated by prolonging the survival of bone marrow cells cultured in anaerobic conditions. These findings translated in vivo, where PFD incorporated into bone-marrow-loaded 3D-printed scaffolds substantially improved their capacity to regenerate bone. Secondly, in addition to biological applications, we have also shown that PFD improves the radiopacity of bone regeneration biomaterials, a key feature required for the visualisation of biomaterials during and after surgical implantation. Finally, we have shown how the extreme hydrophobicity of PFD enables the fabrication of highly cohesive self-setting injectable biomaterials for bone regeneration. In conclusion, perfluorocarbons would appear to be highly beneficial additives to a number of regenerative biomaterials, especially those for bone regeneration.

  15. Bioelectricity and epimorphic regeneration.

    Science.gov (United States)

    Stewart, Scott; Rojas-Muñoz, Agustin; Izpisúa Belmonte, Juan Carlos

    2007-11-01

    All cells have electric potentials across their membranes, but is there really compelling evidence to think that such potentials are used as instructional cues in developmental biology? Numerous reports indicate that, in fact, steady, weak bioelectric fields are observed throughout biology and function during diverse biological processes, including development. Bioelectric fields, generated upon amputation, are also likely to play a key role during vertebrate regeneration by providing the instructive cues needed to direct migrating cells to form a wound epithelium, a structure unique to regenerating animals. However, mechanistic insight is still sorely lacking in the field. What are the genes required for bioelectric-dependent cell migration during regeneration? The power of genetics combined with the use of zebrafish offers the best opportunity for unbiased identification of the molecular players in bioelectricity.

  16. Correlated response of in vitro regeneration capacity from different source of explants inCucumis melo.

    Science.gov (United States)

    Molina, R V; Nuez, F

    1995-01-01

    The variation among and within different populations of the regeneration ability from leaf, cotyledon and hypocotyl explants has been studied. A control population and two lines selected by their regeneration capacity from leaf explants were used. Significant differences among the plants of the control population,for the organogenic response, were detected. The regeneration capacity varies depending on the type of explant. Selection in order to improve the regeneration frequency from leaf explants also raises the organogenic response in the other explant types. This result suggests the presence of a partial common genetic system controlling the regeneration frequency of the diverse types of explants.

  17. Fgf and Sdf-1 pathways interact during zebrafish fin regeneration.

    Science.gov (United States)

    Bouzaffour, Mohamed; Dufourcq, Pascale; Lecaudey, Virginie; Haas, Petra; Vriz, Sophie

    2009-06-08

    The chemokine stromal cell-derived factor-1 (SDF1) was originally identified as a pre-B cell stimulatory factor but has been recently implicated in several other key steps in differentiation and morphogenesis. In addition, SDF1 as well as FGF signalling pathways have recently been shown to be involved in the control of epimorphic regeneration. In this report, we address the question of a possible interaction between the two signalling pathways during adult fin regeneration in zebrafish. Using a combination of pharmaceutical and genetic tools, we show that during epimorphic regeneration, expression of sdf1, as well as of its cognate receptors, cxcr4a, cxcr4b and cxcr7 are controlled by FGF signalling. We further show that, Sdf1a negatively regulates the expression of fgf20a. Together, these results lead us to propose that: 1) the function of Fgf in blastema formation is, at least in part, relayed by the chemokine Sdf1a, and that 2) Sdf1 exerts negative feedback on the Fgf pathway, which contributes to a transient expression of Fgf20a downstream genes at the beginning of regeneration. However this feedback control can be bypassed since the Sdf1 null mutants regenerate their fin, though slower. Very few mutants for the regeneration process were isolated so far, illustrating the difficulty in identifying genes that are indispensable for regeneration. This observation supports the idea that the regeneration process involves a delicate balance between multiple pathways.

  18. Fgf and Sdf-1 pathways interact during zebrafish fin regeneration.

    Directory of Open Access Journals (Sweden)

    Mohamed Bouzaffour

    Full Text Available The chemokine stromal cell-derived factor-1 (SDF1 was originally identified as a pre-B cell stimulatory factor but has been recently implicated in several other key steps in differentiation and morphogenesis. In addition, SDF1 as well as FGF signalling pathways have recently been shown to be involved in the control of epimorphic regeneration. In this report, we address the question of a possible interaction between the two signalling pathways during adult fin regeneration in zebrafish. Using a combination of pharmaceutical and genetic tools, we show that during epimorphic regeneration, expression of sdf1, as well as of its cognate receptors, cxcr4a, cxcr4b and cxcr7 are controlled by FGF signalling. We further show that, Sdf1a negatively regulates the expression of fgf20a. Together, these results lead us to propose that: 1 the function of Fgf in blastema formation is, at least in part, relayed by the chemokine Sdf1a, and that 2 Sdf1 exerts negative feedback on the Fgf pathway, which contributes to a transient expression of Fgf20a downstream genes at the beginning of regeneration. However this feedback control can be bypassed since the Sdf1 null mutants regenerate their fin, though slower. Very few mutants for the regeneration process were isolated so far, illustrating the difficulty in identifying genes that are indispensable for regeneration. This observation supports the idea that the regeneration process involves a delicate balance between multiple pathways.

  19. [Regeneration of airway epithelium].

    Science.gov (United States)

    Adam, D; Perotin, J-M; Lebargy, F; Birembaut, P; Deslée, G; Coraux, C

    2014-04-01

    Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis. The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult. Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  20. Heterogeneous scaffold designs for selective neural regeneration

    NARCIS (Netherlands)

    Wieringa, P.A.

    2014-01-01

    Over the past 5 decades, there has been a drive to apply technology to enhance neural regeneration in order to improve patient recovery after disease or injury. This has evolved into the field of Neural Engineering, with the aim to understand, control and exploit the development and function of neur

  1. Periodontal Regeneration of 1-, 2-, and 3-Walled Intrabony Defects Using Accell Connexus Versus Demineralized Freeze-Dried Bone Allograft: A Randomized Parallel Arm Clinical Control Trial

    Science.gov (United States)

    2013-06-01

    PERIODONTAL  REGENERATION  OF  1-­‐,  2-­‐,  AND  3-­‐WALLED  INTRABONY  DEFECTS  USING  ACCELL   CONNEXUS... Periodontics  Graduate  Program   Naval  Postgraduate  Dental  School   Uniformed  Services  University  of  the...Peter Bertrand, CAPT (ret), DC, USN Chairman, Periodontics Department Director, Periodontics Dept Glenn Munro, CAPT, DC, USN Dean, Naval Postgraduate

  2. Infection and Pulp Regeneration

    Directory of Open Access Journals (Sweden)

    Sahng G. Kim

    2016-03-01

    Full Text Available The regeneration of the pulp-dentin complex has been a great challenge to both scientists and clinicians. Previous work has shown that the presence of prior infection may influence the characteristics of tissues formed in the root canal space after regenerative endodontic treatment. The formation of ectopic tissues such as periodontal ligament, bone, and cementum has been observed in the root canal space of immature necrotic teeth with apical periodontitis, while the regeneration of dentin and pulp has been identified in previously non-infected teeth. The current regenerative endodontic therapy utilizes disinfection protocols, which heavily rely on chemical irrigation using conventional disinfectants. From a microbiological point of view, the current protocols may not allow a sufficiently clean root canal microenvironment, which is critical for dentin and pulp regeneration. In this article, the significance of root canal disinfection in regenerating the pulp-dentin complex, the limitations of the current regenerative endodontic disinfection protocols, and advanced disinfection techniques designed to reduce the microorganisms and biofilms in chronic infection are discussed.

  3. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  4. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat

    Directory of Open Access Journals (Sweden)

    Juan Felipe Diaz Quiroz

    2014-06-01

    Full Text Available Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal’s functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander’s regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries.

  5. Limb regeneration: a new development?

    Science.gov (United States)

    Nacu, Eugen; Tanaka, Elly M

    2011-01-01

    Salamander limb regeneration is a classical model of tissue morphogenesis and patterning. Through recent advances in cell labeling and molecular analysis, a more precise, mechanistic understanding of this process has started to emerge. Long-standing questions include to what extent limb regeneration recapitulates the events observed in mammalian limb development and to what extent are adult- or salamander- specific aspects deployed. Historically, researchers studying limb development and limb regeneration have proposed different models of pattern formation. Here we discuss recent data on limb regeneration and limb development to argue that although patterning mechanisms are likely to be similar, cell plasticity and signaling from nerves play regeneration-specific roles.

  6. Regenerative endodontics: regeneration or repair?

    Science.gov (United States)

    Simon, Stéphane R J; Tomson, Phillip L; Berdal, Ariane

    2014-04-01

    Recent advances in biotechnology and translational research have made it possible to provide treatment modalities that protect the vital pulp, allow manipulation of reactionary and reparative dentinogenesis, and, more recently, permit revascularization of an infected root canal space. These approaches are referred to as regenerative procedures. The method currently used to determine the origin of the tissue secreted during the repair/regeneration process is largely based on the identification of cellular markers (usually proteins) left by cells that were responsible for this tissue production. The presence of these proteins in conjunction with other indicators of cellular behavior (especially biomineralization) and analysis of the structure of the newly generated tissue allow conclusions to be made of how it was formed. Thus far, it has not been possible to truly establish the biological mechanism controlling tertiary dentinogenesis. This article considers current therapeutic techniques to treat the dentin-pulp complex and contextualize them in terms of reparative and regenerative processes. Although it may be considered a semantic argument rather than a biological one, the definitions of regeneration and repair are explored to clarify our position in this era of regenerative endodontics. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists.

    Science.gov (United States)

    Raffa, Robert B; Cavallo, Federica; Capasso, Anna

    2007-06-14

    Two benzodiazepine (midazolam and clorazepate) and one non-benzodiazepine (zolpidem) benzodiazepine-receptor agonists produced dose-related physical dependence, as evidenced by abstinence-induced decrease in planarian locomotor velocity (pLMV) when drug-exposed planarians were placed into drug-free water, but not when they were placed into drug-containing water (i.e., an abstinence-induced withdrawal, since the effect was only obtained in the removal of drug and not in the continued presence of drug). We have previously shown that the decrease in pLMV is associated with specific and transient withdrawal signs. In the present study, the selective benzodiazepine-receptor antagonist flumazenil significantly antagonized (Pbenzodiazepine-receptor agonists, for two different chemical categories, produce dose-related physical dependence manifested as abstinence-induced withdrawal in this simple and convenient model, and (2) in the absence of cloning or radioligand binding literature, suggest a possible specific interaction site (receptor?) for these compounds in planarians.

  8. Skin shedding and tissue regeneration in African spiny mice (Acomys).

    Science.gov (United States)

    Seifert, Ashley W; Kiama, Stephen G; Seifert, Megan G; Goheen, Jacob R; Palmer, Todd M; Maden, Malcolm

    2012-09-27

    Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.

  9. Regenerate augmentation with bone marrow concentrate after traumatic bone loss.

    Science.gov (United States)

    Gessmann, Jan; Köller, Manfred; Godry, Holger; Schildhauer, Thomas Armin; Seybold, Dominik

    2012-01-01

    Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC) for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64) with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders) were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15) months. With a mean healing index (HI) of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23). No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  10. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  11. Tissue regeneration with photobiomodulation

    Science.gov (United States)

    Tang, Elieza G.; Arany, Praveen R.

    2013-03-01

    Low level light therapy (LLLT) has been widely reported to reduce pain and inflammation and enhance wound healing and tissue regeneration in various settings. LLLT has been noted to have both stimulatory and inhibitory biological effects and these effects have been termed Photobiomodulation (PBM). Several elegant studies have shown the key role of Cytochrome C oxidase and ROS in initiating this process. The downstream biological responses remain to be clearly elucidated. Our work has demonstrated activation of an endogenous latent growth factor complex, TGF-β1, as one of the major biological events in PBM. TGF-β1 has critical roles in various biological processes especially in inflammation, immune responses, wound healing and stem cell biology. This paper overviews some of the studies demonstrating the efficacy of PBM in promoting tissue regeneration.

  12. Bionanomaterials for skin regeneration

    CERN Document Server

    Leonida, Mihaela D

    2016-01-01

    This book gives a concise overview of bionanomaterials with applications for skin regeneration. The advantages and challenges of nanoscale materials are covered in detail, giving a basic view of the skin structure and conditions that require transdermal or topical applications. Medical applications, such as wound healing, care for burns, skin disease, and cosmetic care, such as aging of the skin and photodamage, and how they benefit from bionanomaterials, are described in detail. A final chapter is devoted to the ethical and social issues related to the use of bionanomaterials for skin regeneration. This is an ideal book for researchers in materials science, medical scientists specialized in dermatology, and cosmetic chemists working in formulations. It can also serve as a reference for nanotechnologists, dermatologists, microbiologists, engineers, and polymer chemists, as well as students studying in these fields.

  13. Acute toxic responses of the freshwater planarian, Dugesia dorotocephala, to methylmercury

    Energy Technology Data Exchange (ETDEWEB)

    Best, J.B.; Morita, M.; Ragin, J.; Best, J. Jr.

    1981-07-01

    Toxic responses of planaria to various aquatic habitat concentrations of methylmercury chloride (MMC) were investigated. One hundred percent lethality occurred within 5 h in 2 ppM MMC, 24 h in 1 ppM MMC, and 5 days in 0.5 ppM MMC. No deaths occurred in 0.2 ppM MMC over a 10 day period, however, non-lethal toxic responses were observed. Varying degrees of head resorption, progressing caudally from the snout were observed. With continuing exposure, partial head regeneration and recovery toward more normal appearance occurred by 10 days. Teratogenic effects were observed in surgical decapitation experiments. Head regeneration was retarded in 0.1 and 0.2 ppM MMC. Malformations, visible lesions, or gross behavioral abnormalities were produced by 2 week exposure of planaria to concentrations of 20 ppB MMC or lower. (RJC)

  14. 生长因子智能控释与牙周组织再生%Intellectualized controlled release of growth factors in periodontal tissue regeneration

    Institute of Scientific and Technical Information of China (English)

    刘海燕; 孙海花; 薛蓓蕾; 陈发明

    2006-01-01

    牙周骨移植、引导组织再生术(guided tissue regeneration,GTR)为牙周病的治疗和牙周缺损的修复带来了新的希望,但在恢复牙周组织的结构和功能方面还远不能达到理想的目标.组织工程和基因技术才刚刚起步,离临床应用还有较远的距离;药物控释技术的迅猛发展和活性牙周生物材料的研制与开发,为损害牙周组织结构功能的修复重建开辟了新的研究空间.

  15. Low Temperature Regenerator Study.

    Science.gov (United States)

    1979-08-01

    effect. The idealized cycle achieves the same theoretical coefficient of performance (COP) as the theoretical Carnot cycle , whose limiting performance...DISTRIBUTION STATEMENT (of the abstract *irt.,ed in Block 20, iI different it oe) I8. SUPPLEMENTARY NOTES I9. KEY WORDS (Continute on reverse @do of noco*oy...PERFORMANCE ............ 64 3.1 Introduction ..... 0 ... . ......... ... . 64 3.2 Stirling Cycle Analysis ................. 71 3.2.1 Simple Regenerator Model

  16. [Periodontitis and tissue regeneration].

    Science.gov (United States)

    Yamazaki, Kazuhisa

    2005-08-01

    Chronic periodontitis is a destructive disease that affects the supporting structures of the teeth including periodontal ligament, cementum, and alveolar bone. If left untreated, patients may lose multiple teeth and extensive prosthetic treatment will be required. In order to re-engineer lost tooth-supporting tissues, various therapeutic modalities have been used clinically. Periodontal regeneration procedures including guided tissue regeneration have achieved substantial effects. However, there are several issues to be solved. They are highly technique-sensitive, applicable to limited cases which are susceptible to treatment, and supposed to have relatively low predictability. Therefore, it is necessary to develop new approaches to improve the predictability and effectiveness of regenerative therapies for periodontal tissues. Recently, the concept of tissue engineering has been introduced to restore lost tissues more effectively where the biological process of healing is mimicked. To achieve this, integration of three key elements is required: progenitor/stem cells, growth factors and the extracellular matrix scaffold. Although it has been shown that implantation of bone marrow-derived mesenchymal stem cells into periodontal osseous defects induced regeneration of cementum, periodontal ligament and alveolar bone in dogs, further extensive preclinical studies are required. On the other hand, application of growth factors, particularly basic fibroblast growth factor in the treatment of human periodontitis, is promising and is now in clinical trial. Furthermore, the rate of release of growth factor from the scaffold also can profoundly affect the results of tissue engineering strategies and the development of new materials is expected. In addition, as tissue regenerative potential is negatively regulated by aging, the effects of aging have to be clarified to gain complete regeneration.

  17. Regeneration of Optic Nerve

    Directory of Open Access Journals (Sweden)

    Kwok-Fai So

    2011-05-01

    Full Text Available The optic nerve is part of the central nervous system (CNS and has a structure similar to other CNS tracts. The axons that form the optic nerve originate in the ganglion cell layer of the retina and extend through the optic tract. As a tissue, the optic nerve has the same organization as the white matter of the brain in regard to its glia. There are three types of glial cells: Oligodendrocytes, astrocytes, and microglia. Little structural and functional regeneration of the CNS takes place spontaneously following injury in adult mammals. In contrast, the ability of the mammalian peripheral nervous system (PNS to regenerate axons after injury is well documented. A number of factors are involved in the lack of CNS regeneration, including: (i the response of neuronal cell bodies against the damage; (ii myelin-mediated inhibition by oligodendrocytes; (iii glial scarring, by astrocytes; (iv macrophage infiltration; and (v insufficient trophic factor support. The fundamental difference in the regenerative capacity between CNS and PNS neuronal cell bodies has been the subject of intensive research. In the CNS the target normally conveys a retrograde trophic signal to the cell body. CNS neurons die because of trophic deprivation. Damage to the optic nerve disconnects the neuronal cell body from its target-derived trophic peptides, leading to the death of retinal ganglion cells. Furthermore, the axontomized neurons become less responsive to the peptide trophic signals they do receive. On the other hand, adult PNS neurons are intrinsically responsive to neurotrophic factors and do not lose trophic responsiveness after axotomy. In this talk different strategies to promote optic-nerve regeneration in adult mammals are reviewed. Much work is still needed to resolve many issues. This is a very important area of neuroregeneration and neuroprotection, as currently there is no cure after traumatic optic nerve injury or retinal disease such as glaucoma, which

  18. ISLET FORMATION AND REGENERATION

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration. Methods Human embryonic pancreatic tissue at 7-14 weeks of gestation was collected. Diabetes mellitus rat model was induced with 65 mg/kg of streptozotocin. Insulin, glucagon, somatostatin, nestin, and cytokeratin 19 (CK19)of pancreatic tissues were observed by immunohistochemistry. Results At 9 weeks of gestation, pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin, and CK19 before migration. Islet cells gradually congregated along with the increase of aging, and at 14 weeks of gestation histological examination showed islet formation. At 12 weeks of gestation, nestin-positive cells could be seen in the pancreatic mesenchyme. During early embryogenesis, islet cells of pancreatic ducts co-expressed insulin, glucagon, and somatostatin. During pancreatic regeneration after damage, nestin expression of islet cells increased. Conclusion In the early stage of embryogenesis, islet cells of primary pancreatic ducts can be differentiated to multipotential endocrine cells before migration. During tissue regeneration, pancreatic stem cells may differentiate and proliferate to form pancreatic islet.

  19. Embryonic origin of adult stem cells required for tissue homeostasis and regeneration

    Science.gov (United States)

    Davies, Erin L; Lei, Kai; Seidel, Christopher W; Kroesen, Amanda E; McKinney, Sean A; Guo, Longhua; Robb, Sofia MC; Ross, Eric J; Gotting, Kirsten; Alvarado, Alejandro Sánchez

    2017-01-01

    Planarian neoblasts are pluripotent, adult somatic stem cells and lineage-primed progenitors that are required for the production and maintenance of all differentiated cell types, including the germline. Neoblasts, originally defined as undifferentiated cells residing in the adult parenchyma, are frequently compared to embryonic stem cells yet their developmental origin remains obscure. We investigated the provenance of neoblasts during Schmidtea mediterranea embryogenesis, and report that neoblasts arise from an anarchic, cycling piwi-1+ population wholly responsible for production of all temporary and definitive organs during embryogenesis. Early embryonic piwi-1+ cells are molecularly and functionally distinct from neoblasts: they express unique cohorts of early embryo enriched transcripts and behave differently than neoblasts in cell transplantation assays. Neoblast lineages arise as organogenesis begins and are required for construction of all major organ systems during embryogenesis. These subpopulations are continuously generated during adulthood, where they act as agents of tissue homeostasis and regeneration. DOI: http://dx.doi.org/10.7554/eLife.21052.001 PMID:28072387

  20. Fiber soliton-form 3R regenerator and its performance analysis

    Institute of Scientific and Technical Information of China (English)

    ZHU Bo; YANG XiangLin

    2007-01-01

    A novel fiber optical 3R regenerator based on optical soliton-effect using highly nonlinear fiber is constructed and investigated for the needs of the high rate and long-haul optical communications. The propagation equation of the pulses in the proposed optical 3R regenerator with the control of optical modulator and filter is established. By the use of the variational approach, the evolution of the distorted optical pulses in the regenerator and the functions of reamplification, reshaping,and retiming are investigated. The relation between the construction parameters and the output performance of the regenerator is discussed. The stable operation condition of the regenerator is revealed.

  1. Yap1, transcription regulator in the Hippo signaling pathway, is required for Xenopus limb bud regeneration.

    Science.gov (United States)

    Hayashi, Shinichi; Tamura, Koji; Yokoyama, Hitoshi

    2014-04-01

    The Hippo signaling pathway is conserved from insects to mammals and is important for multiple processes, including cell proliferation, apoptosis and tissue homeostasis. Hippo signaling is also crucial for regeneration, including intercalary regeneration, of the whole body in the flatworm and of the leg in the cricket. However, its role in vertebrate epimorphic regeneration is unknown. Therefore, to identify principles of regeneration that are conserved among bilaterians, we investigated the role of Hippo signaling in the limb bud regeneration of an anuran amphibian, Xenopus laevis. We found that a transcription factor, Yap1, an important downstream effector of Hippo signaling, is upregulated in the regenerating limb bud. To evaluate Yap1׳s function in limb bud regeneration, we made transgenic animals that expressed a dominant-negative form of Yap under a heat-shock promoter. Overexpression of a dominant-negative form of Yap in tadpoles reduced cell proliferation, induced ectopic apoptosis, perturbed the expression domains of limb-patterning genes including hoxa13, hoxa11, and shh in the regenerating limb bud. Transient expression of a dominant-negative Yap in transgenic tadpoles also caused limb bud regeneration defects, and reduced intercalary regeneration. These results indicate that Yap1 has a crucial role in controlling the limb regenerative capacity in Xenopus, and suggest that the involvement of Hippo signaling in regeneration is conserved between vertebrates and invertebrates. This finding provides molecular evidence that common principles underlie regeneration across phyla, and may contribute to the development of new therapies in regenerative medicine.

  2. Analysis of basic pulse-tube refrigerator with regenerator

    Science.gov (United States)

    de Boer, P. C. T.

    A previously presented thermodynamic analysis of the basic pulse-tube refrigerator is extended to the case with a regenerator. In this case there is a heat exchanger at the warm end of the regenerator, in addition to the cold and warm heat exchangers at the ends of the pulse tube. The analysis is based on a four-step cycle: adiabatic compression of the gas in the pulse tube; isobaric heat transfer from the gas to the wall of the pulse tube; adiabatic expansion of the gas in the pulse tube; and isobaric heat transfer from the wall of the pulse tube to the gas. The pressure is taken to be uniform during the entire cycle. Gas elements inside the regenerator are assumed to be at the local temperature of the regenerator. The performance of the regenerator and its adjacent heat exchangers is investigated using control volume analysis to determine enthalpy flows, and by control mass analysis to determine heat flows associated with individual gas elements. The mechanism by which heat is transported from the cold end to the warm end of the regenerator is discussed. The addition of the regenerator is found to yield significant improvements in the heat removed per cycle, the coefficient of performance and the refrigeration efficiency. Detailed results for these quantities are presented as a function of the temperature ratio of the heat exchangers.

  3. Biomaterial Selection for Tooth Regeneration

    OpenAIRE

    2011-01-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or s...

  4. Understanding Urban Regeneration in Turkey

    Science.gov (United States)

    Candas, E.; Flacke, J.; Yomralioglu, T.

    2016-06-01

    In Turkey, rapid population growth, informal settlements, and buildings and infrastructures vulnerable to natural hazards are seen as the most important problems of cities. Particularly disaster risk cannot be disregarded, as large parts of various cities are facing risks from earthquakes, floods and landslides and have experienced loss of lives in the recent past. Urban regeneration is an important planning tool implemented by local and central governments in order to reduce to disaster risk and to design livable environments for the citizens. The Law on the Regeneration of Areas under Disaster Risk, commonly known as the Urban Regeneration Law, was enacted in 2012 (Law No.6306, May 2012). The regulation on Implementation of Law No. 6306 explains the fundamental steps of the urban regeneration process. The relevant institutions furnished with various authorities such as expropriation, confiscation and changing the type and place of your property which makes urban regeneration projects very important in terms of property rights. Therefore, urban regeneration projects have to be transparent, comprehensible and acceptable for all actors in the projects. In order to understand the urban regeneration process, the legislation and projects of different municipalities in Istanbul have been analyzed. While some steps of it are spatial data demanding, others relate to land values. In this paper an overview of the urban regeneration history and activities in Turkey is given. Fundamental steps of the urban regeneration process are defined, and particularly spatial-data demanding steps are identified.

  5. Regenerated Cellulose Capsules for Controlled Drug Delivery, Part 2: Modulating Membrane Permeability by Incorporation of Depolymerized Cellulose and Altering Membrane Thickness.

    Science.gov (United States)

    Bhatt, Bhavik; Kumar, Vijay

    2015-12-01

    For application of regenerated cellulose (RC) membranes in capsule dosage forms, the methods to modify drug release from these membranes are described. Membranes were fabricated by blending native and depolymerized celluloses dissolved in dimethyl sulfoxide and paraformaldehyde solvent system, prior to casting on molds, precipitation in water, and thermal annealing. The effect of laminating layers of RC to fabricate membranes with increasing thickness was also investigated. Solute diffusion studies using ionic and hydrophobic solutes, as well as large protein molecules, were conducted in side-by-side diffusion cells. Microscopic as well as physiological evaluation of these membranes indicated that pore size, porosity, and water uptake decreased as the fraction of depolymerized cellulose increased in the membranes. Permeability analysis of small ionic and hydrophobic solutes indicated that the solute transport across the hydrated membrane occurs through diffusion in the water-filled pores that are formed in situ. The apparent path for solute diffusion increases as the fraction of depolymerized cellulose increases. Permeability analysis of large protein molecules indicated that the pore sizes and distribution in these membranes is heterogeneous. Increasing the membrane thickness by lamination of RC does not influence porosity but causes formation of dead-end pores because of blocking by subsequent laminate layers.

  6. Regenerable solid imine sorbents

    Science.gov (United States)

    Gray, McMahan; Champagne, Kenneth J.; Fauth, Daniel; Beckman, Eric

    2013-09-10

    Two new classes of amine-based sorbents are disclosed. The first class comprises new polymer-immobilized tertiary amine sorbents; the second class new polymer-bound amine sorbents. Both classes are tailored to facilitate removal of acid anhydrides, especially carbon dioxide (CO.sub.2), from effluent gases. The amines adsorb acid anhydrides in a 1:1 molar ratio. Both classes of amine sorbents adsorb in the temperature range from about 20.degree. C. upwards to 90.degree. C. and can be regenerated by heating upwards to 100.degree. C.

  7. Gene transfer to promote cardiac regeneration.

    Science.gov (United States)

    Collesi, Chiara; Giacca, Mauro

    2016-12-01

    There is an impelling need to develop new therapeutic strategies for patients with myocardial infarction and heart failure. Leading from the large quantity of new information gathered over the last few years on the mechanisms controlling cardiomyocyte proliferation during embryonic and fetal life, it is now possible to devise innovative therapies based on cardiac gene transfer. Different protein-coding genes controlling cell cycle progression or cardiomyocyte specification and differentiation, along with microRNA mimics and inhibitors regulating pre-natal and early post-natal cell proliferation, are amenable to transformation in potential therapeutics for cardiac regeneration. These gene therapy approaches are conceptually revolutionary, since they are aimed at stimulating the intrinsic potential of differentiated cardiac cells to proliferate, rather than relying on the implantation of exogenously expanded cells to achieve tissue regeneration. For efficient and prolonged cardiac gene transfer, vectors based on the Adeno-Associated Virus stand as safe, efficient and reliable tools for cardiac gene therapy applications.

  8. Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

    Science.gov (United States)

    Jolivalt, Corinne G.; Vu, Yvonne; Mizisin, Leah M.; Mizisin, Andrew P.; Calcutt, Nigel A.

    2009-01-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) following sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats and that prosaptide TX14(A) can improve aspects of nerve regeneration. PMID:18596543

  9. Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide.

    Science.gov (United States)

    Jolivalt, Corinne G; Vu, Yvonne; Mizisin, Leah M; Mizisin, Andrew P; Calcutt, Nigel A

    2008-07-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) after sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia, and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats, and that prosaptide TX14(A) can improve aspects of nerve regeneration.

  10. Beneficial effect of hyperbaric oxygenation on liver regeneration in cirrhosis.

    Science.gov (United States)

    Ozdogan, Mehmet; Ersoy, Eren; Dundar, Kadir; Albayrak, Levent; Devay, Seda; Gundogdu, Haldun

    2005-12-01

    Underlying hepatic injury and cirrhosis are leading factors that interfere with the post-operative liver regeneration and function. Hyperbaric oxygenation (HBO) has been reported to ameliorate the ischemia-reperfusion injury of the liver, to induce compensatory hypertrophy of the predicted remnant liver in rats after portal vein ligation and to augment liver regeneration after hepatectomy in non-cirrhotic rats. Our aim was to determine the effect of HBO treatment on liver regeneration after partial hepatectomy in normal and cirrhotic mice in this experimental study. The effect of HBO on liver regeneration was studied in a mice model combining carbon tetrachloride induced cirrhosis and partial hepatectomy. Mice were divided into four groups: Control, cirrhotic, non-cirrhotic HBO-treated, and cirrhotic HBO-treated. All animals underwent 40% hepatectomy. Liver regeneration was evaluated by the proliferating cell nuclear antigen-labeling index. Serum aspartate aminotransferase and alanine aminotransferase levels were measured to evaluate liver injury. Serum alanine aminotransferase and aspartate aminotransferase levels were significantly decreased in HBO-treated cirrhotic group compared to cirrhosis group after hepatectomy (P = 0.001 and P = 0.014, respectively). The proliferating cell nuclear antigen labeling index was significantly higher in HBO treated cirrhotic group than in cirrhotic group after hepatectomy (P = 0.022). Our results suggest that HBO treatment improves liver functions and augments hepatocyte regeneration in cirrhotic mice after hepatectomy. Post-operative HBO treatment may have a beneficial effect on post-operative liver function and regeneration in cirrhotic patients.

  11. Atmospheric pressure plasma accelerates tail regeneration in tadpoles Xenopus laevis

    Science.gov (United States)

    Rivie, A.; Martus, K.; Menon, J.

    2017-08-01

    Atmospheric pressure plasma is a partially ionized gas composed of neutral and charged particles, including electrons and ions, as well as reactive oxygen species (ROS). Recently, it is utilized as possible therapy in oncology, sterilization, skin diseases, wound healing and tissue regeneration. In this study we focused on effect of plasma exposure on tail regeneration of tadpoles, Xenopus leavis with special emphasis on role of ROS, antioxidant defenses and morphological features of the regenerate. When amputated region of the tail was exposed to the helium plasma it resulted in a faster rate of growth, elevated ROS and increase in antioxidant enzymes in the regenerate compared to that of untreated control. An increase in nitric oxide (free radical) as well as activity of nitric oxide synthase(s) were observed once the cells of the regeneration blastema - a mass of proliferating cells are ready for differentiation. Microscopically the cells of the regenerate of plasma treated tadpoles show altered morphology and characteristics of cellular hypoxia and oxidative stress. We summarize that plasma exposure accelerates the dynamics of wound healing and tail regeneration through its effects on cell proliferation and differentiation as well as angiogenesis mediated through ROS signaling.

  12. Regulation of p53 is critical for vertebrate limb regeneration.

    Science.gov (United States)

    Yun, Maximina H; Gates, Phillip B; Brockes, Jeremy P

    2013-10-22

    Extensive regeneration of the vertebrate body plan is found in salamander and fish species. In these organisms, regeneration takes place through reprogramming of differentiated cells, proliferation, and subsequent redifferentiation of adult tissues. Such plasticity is rarely found in adult mammalian tissues, and this has been proposed as the basis of their inability to regenerate complex structures. Despite their importance, the mechanisms underlying the regulation of the differentiated state during regeneration remain unclear. Here, we analyzed the role of the tumor-suppressor p53 during salamander limb regeneration. The activity of p53 initially decreases and then returns to baseline. Its down-regulation is required for formation of the blastema, and its up-regulation is necessary for the redifferentiation phase. Importantly, we show that a decrease in the level of p53 activity is critical for cell cycle reentry of postmitotic, differentiated cells, whereas an increase is required for muscle differentiation. In addition, we have uncovered a potential mechanism for the regulation of p53 during limb regeneration, based on its competitive inhibition by ΔNp73. Our results suggest that the regulation of p53 activity is a pivotal mechanism that controls the plasticity of the differentiated state during regeneration.

  13. The Involvement of Heat Shock Proteins in Murine Liver Regeneration

    Institute of Scientific and Technical Information of China (English)

    Qing Shi; Zhongjun Dong; Haiming Wei

    2007-01-01

    Partial hepatectomy (PHx) in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins (HSPs) were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitior of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration.

  14. Nanofibrous nerve conduit-enhanced peripheral nerve regeneration.

    Science.gov (United States)

    Jiang, Xu; Mi, Ruifa; Hoke, Ahmet; Chew, Sing Yian

    2014-05-01

    Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15-mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (ε-caprolactone) (PCL) microfibers (981 ± 83 nm, Microfiber) or nanofibers (251 ± 32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non-porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10(3) vs. 0.98 ± 0.30 × 10(3) in Microfiber, p regeneration. These results could provide useful insights for future nerve guide designs.

  15. Diamex solvent regeneration studies

    Energy Technology Data Exchange (ETDEWEB)

    Nicol, C.; Cames, B.; Margot, L.; Ramain, L. [CEA/VALRHO - site de Marcoule, Dept. de Recherche en Retraitement et en Vitrification, DRRV, 30 - Marcoule (France)

    2000-07-01

    The CEA has undertaken the development of the DIAMEX process as the first step in the strategy aiming at recovering minor actinides which could then be transmuted or separately conditioned. The scientific feasibility of this process was demonstrated during counter current hot tests operated in 1993. Then experimental works were conducted, on one hand to optimise the extractant formula, on the other hand to improve the flowsheet. Reference extractant and flowsheet were then chosen, respectively in 1995 and 1996. The next step, still in progress, is the demonstration of the DIAMEX technical feasibility (in 2002); this means that the flowsheet should include solvent regeneration treatments. In this aim, degradation studies were performed to quantify main degradation products, and identify those which could be disturbing in the process. This paper deals with experimental studies performed with intend to propose a regeneration treatment, included in the flowsheet, so that the solvent could be recycled. It comprises: - Quantification of the main degradation products issued from radiolysis or hydrolysis, which are methyl octyl amine (MOA) and carboxylic acids; - Effects of these products on extracting and hydrodynamics performances of the process; - Study of methods able to remove mainly disturbing degradation products. Acidic scrubbing, which are performed in the scrubbing and stripping sections of the DIAMEX process, should allow the quantitative removal of methyl octyl amine. Then basic scrubbings, which were more especially studied, should eliminate at least 80% of carboxylic acids, and part of the cations remaining in the solvent. (authors)

  16. Nanobiomaterials for neural regeneration

    Institute of Scientific and Technical Information of China (English)

    Nuan Chen; Lingling Tian; Liumin He; Seeram Ramakrishna

    2016-01-01

    Diseases and disorders associated with nervous system such as injuries by trauma and neurodegeneration are shown to be one of the most serious problems in medicine, requiring innovative strategies to trigger and enhance the nerve regeneration. Tissue engineering aims to provide a highly biomimetic environment by using a combination of cells, materials and suitable biological cues, by which the lost body part may be regenerated or even fully rebuilt. Electrospinning, being able to produce extracellular matrix (ECM)-like nanostructures with great lfexibility in design and choice of materials, have demonstrated their great po-tential for fabrication of nerve tissue engineered scaffolds. The review here begins with a brief description of the anatomy of native nervous system, which provides basic knowledge and ideas for the design of nerve tissue scaffolds, followed by ifve main parts in the design of electrospun nerve tissue engineered scaffolds including materials selection, structural design,in vitro bioreactor, functionalization and cellular support. Performances of biomimetic electrospun nanofibrous nerve implant devices are also reviewed. Finally, future directions for advanced electrospun nerve tissue engineered scaffolds are discussed.

  17. Progesterone and peripheral nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Fei Fan; Haichao Li; Yuwei Wang; Yanglin Zheng; Lianjun Jia; Zhihui Wang

    2006-01-01

    OBJECTIVE: To explore the effect of progesterone on peripheral nerve regeneration.DATA SOURCES: An online search of Medline and OVID databases was under taken to identify articles about progesterone and peripheral nerve regeneration published in English between January 1990 and June 2004 by using the keywords of "peripheral nerve, injury, progesterone, regeneration".STUDY SELECTION: The data were primarily screened, those correlated with progesterone and peripheral nerve regeneration were involved, and their original articles were further searched, the repetitive studies or reviews were excluded.DATA EXTRACTION: Totally 59 articles about progesterone and peripheral nerve regeneration were collected, and 26 of them were involved, the other 33 excluded ones were the repetitive studies or reviews.DATA SYNTHESIS: Recent researches found that certain amount of progesterone could be synthetized in peripheral nervous system, and the expression of progesterone receptor could be found in sensory neurons and Schwann cells. After combined with the receptor, endogenous and exogenous progesterone can accelerate the formation of peripheral nerve myelin sheath, also promote the axonal regeneration.CONCLUSION: Progesterone plays a role in protecting neurons, increasing the sensitivity of nerve tissue to nerve growth factor, and accelerating regeneration of nerve in peripheral nerve regeneration, which provides theoretical references for the treatment of demyelinated disease and nerve injury, as well as the prevention of neuroma, especially that the in vivo level of progesterone should be considered for the elderly people accompanied by neuropathy and patients with congenital luteal phase defect, which is of positive significance in guiding the treatment.

  18. Molecular approach to echinoderm regeneration.

    Science.gov (United States)

    Thorndyke, M C; Chen, W C; Beesley, P W; Patruno, M

    2001-12-15

    Until very recently echinoderm regeneration research and indeed echinoderm research in general has suffered because of the lack of critical mass. In terms of molecular studies of regeneration, echinoderms in particular have lagged behind other groups in this respect. This is in sharp contrast to the major advances achieved with molecular and genetic techniques in the study of embryonic development in echinoderms. The aim of our studies has been to identify genes involved in the process of regeneration and in particular neural regeneration in different echinoderm species. Our survey included the asteroid Asterias rubens and provided evidence for the expression of Hox gene homologues in regenerating radial nerve cords. Present evidence suggests: 1) ArHox1 expression is maintained in intact radial nerve cord and may be upregulated during regeneration. 2) ArHox1 expression may contribute to the dedifferentiation and/or cell proliferation process during epimorphic regeneration. From the crinoid Antedon bifida, we have been successful in cloning a fragment of a BMP2/4 homologue (AnBMP2/4) and analysing its expression during arm regeneration. Here, we discuss the importance of this family of growth factors in several regulatory spheres, including maintaining the identity of pluripotent blastemal cells or as a classic skeletal morphogenic regulator. There is clearly substantial scope for future echinoderm research in the area of molecular biology and certain aspects are discussed in this review.

  19. Acoustic field modulation in regenerators

    Science.gov (United States)

    Hu, J. Y.; Wang, W.; Luo, E. C.; Chen, Y. Y.

    2016-12-01

    The regenerator is a key component that transfers energy between heat and work. The conversion efficiency is significantly influenced by the acoustic field in the regenerator. Much effort has been spent to quantitatively determine this influence, but few comprehensive experimental verifications have been performed because of difficulties in modulating and measuring the acoustic field. In this paper, a method requiring two compressors is introduced and theoretically investigated that achieves acoustic field modulation in the regenerator. One compressor outputs the acoustic power for the regenerator; the other acts as a phase shifter. A RC load dissipates the acoustic power out of both the regenerator and the latter compressor. The acoustic field can be modulated by adjusting the current in the two compressors and opening the RC load. The acoustic field is measured with pressure sensors instead of flow-field imaging equipment, thereby greatly simplifying the experiment.

  20. Retinoid antagonists inhibit normal patterning during limb regeneration in the axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Del Rincón, Sonia V; Scadding, Steven R

    2002-04-01

    Retinoic acid (RA) has been detected in the regenerating limb of the axolotl, and exogenous RA can proximalize, posteriorize, and ventralize blastemal cells. Thus, RA may be an endogenous regulatory factor during limb regeneration. We have investigated whether endogenous retinoids are essential for patterning during axolotl (Ambystoma mexicanum) limb regeneration by using retinoid antagonists that bind to specific RAR (retinoic acid receptor) or RXR (retinoid X receptor) retinoid receptor subtypes. Retinoid antagonists (Ro41-5253, Ro61-8431, LE135, and LE540) were administered to regenerating limbs using implanted silastin blocks loaded with each antagonist. The skeletal pattern of regenerated limbs treated with Ro41-5253 or Ro61-8431 differed only slightly from control limbs. Treatment with LE135 inhibited limb regeneration, while treatment with LE540 allowed relatively normal limb regeneration. When LE135 and LE540 were implanted together, regeneration was not completely inhibited and a hand-like process regenerated. These results demonstrate that interfering with retinoid receptors can modify pattern in the regenerating limb indicating that endogenous retinoids are important during patterning of the regenerating limb.

  1. Cell- and gene- based therapeutics for periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Keshava Abbayya

    2015-01-01

    Full Text Available Periodontitis is a disease of the periodontium, characterized by loss of connective tissue attachment and supporting the alveolar bone. Therefore, to regenerate these lost tissues of the periodontium researchers have included a variety of surgical procedures including grafting materials growth factors and the use of barrier membranes, ultimately resulting into regeneration that is biologically possible but clinically unpredictable. Recently a newer approach of delivering DNA plasmids as therapeutic agents is gaining special attention and is called gene delivery method. Gene therapy being considered a novel approach have a potential to channel their signals in a very systematic and controlled manner thereby providing encoded proteins at all stages of tissue regeneration. The aim of this review was to enlighten a view on the application involving gene delivery and tissue engineering in periodontal regeneration.

  2. Mechanisms of hyperpolarization in regenerated mature motor axons in cat

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian

    2004-01-01

    We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared...... the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na(+)-K(+) pump function: polarization, cooling to 20 degrees C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation...... at 200 Hz. The abnormalities in excitability of regenerated nerves were reduced by depolarization and cooling and increased by hyperpolarization and during postischaemia. Moreover, the time course of recovery of excitability from repetitive stimulation and ischaemia was prolonged in regenerated nerves...

  3. Photon Regeneration Plans

    CERN Document Server

    Ringwald, A

    2006-01-01

    Precision experiments exploiting low-energy photons may yield information on particle physics complementary to experiments at high-energy colliders, in particular on new very light and very weakly interacting particles, predicted in many extensions of the standard model. Such particles may be produced by laser photons send along a transverse magnetic field. The laser polarization experiment PVLAS may have seen the first indirect signal of such particles by observing an anomalously large rotation of the polarization plane of photons after the passage through a magnetic field. This can be interpreted as evidence for photon disappearance due to particle production. There are a number of experimental proposals to test independently the particle interpretation of PVLAS. Many of them are based on the search for photon reappearance or regeneration, i.e. for ``light shining through a wall''. At DESY, the Axion-Like Particle Search (ALPS) collaboration is currently setting up such an experiment.

  4. Photon regeneration plans

    Energy Technology Data Exchange (ETDEWEB)

    Ringwald, A.

    2006-12-15

    Precision experiments exploiting low-energy photons may yield information on particle physics complementary to experiments at high-energy colliders, in particular on new very light and very weakly interacting particles, predicted in many extensions of the standard model. Such particles may be produced by laser photons send along a transverse magnetic field. The laser polarization experiment PVLAS may have seen the first indirect signal of such particles by observing an anomalously large rotation of the polarization plane of photons after the passage through a magnetic field. This can be interpreted as evidence for photon disappearance due to particle production. There are a number of experimental proposals to test independently the particle interpretation of PVLAS. Many of them are based on the search for photon reappearance or regeneration, i.e. for ''light shining through a wall''. At DESY, the Axion-Like Particle Search (ALPS) collaboration is currently setting up such an experiment. (orig.)

  5. A regenerable bitumen composition

    Energy Technology Data Exchange (ETDEWEB)

    Sudzuki, K.; Asakava, Y.; Matsui, A.; Ogava, A.

    1982-10-18

    The regenerable bitumin composition includes the bitumen material (asphalt, oxidized bitumen, petroleum or asphalt pitch) emulsified by an cation emulsifier (alkylamine or an imidazole derivative) and additionally by a noniononic emulsifier (polyoxyethylenamine), an amide, which contains greater than 1 amide groups per molecule (amide derivative, imidazoline), an epoxide compound with greater than 1 epoxide group per molecule (preferably with an epoxy equivalent of 180 to 500), an inorganic compound which hardens in water (Portland cement or silicate cement) and additionally, water. The total content of the second third components is 1 to 200 parts per million to 100 parts of the first component, while the content of the fourth component is from 1 to 400 parts. The water content in the composition is 5 to 1,000 percent of the total content of the first three components. The patented composition is characterized by high stability, strength, chemical stability, resistance to water and good adhesion properties.

  6. Acellular nerve allograft promotes selective regeneration

    Institute of Scientific and Technical Information of China (English)

    Haili Xin; Guanjun Wang; Xinrong He; Jiang Peng; Quanyi Guo; Wenjing Xu

    2011-01-01

    Acellular nerve allograft preserves the basilar membrane tube and extracellular matrix, which pro-motes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetyl-choline esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive senso-ry nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.

  7. Cellular Players in Skeletal Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    Laura Cristina Ceafalan

    2014-01-01

    Full Text Available Skeletal muscle, a tissue endowed with remarkable endogenous regeneration potential, is still under focused experimental investigation mainly due to treatment potential for muscle trauma and muscular dystrophies. Resident satellite cells with stem cell features were enthusiastically described quite a long time ago, but activation of these cells is not yet controlled by any medical interventions. However, after thorough reports of their existence, survival, activation, and differentiation there are still many questions to be answered regarding the intimate mechanism of tissue regeneration. This review delivers an up-to-date inventory of the main known key players in skeletal muscle repair, revealed by various models of tissue injuries in mechanical trauma, toxic lesions, and muscular dystrophy. A better understanding of the spatial and temporal relationships between various cell populations, with different physical or paracrine interactions and phenotype changes induced by local or systemic signalling, might lead to a more efficient approach for future therapies.

  8. Amphibian tail regeneration in space: effect on the pigmentation of the blastema

    Science.gov (United States)

    Grinfeld, S.; Foulquier, F.; Mitashov, V.; Bruchlinskaia, N.; Duprat, A. M.

    In Urodele amphibians, the tail regenerates after section. This regeneration, including tissues as different as bone (vertebrae), muscle, epidermis and central nervous system (spinal cord), was studied in adult Pleurodeles sent aboard the russian satellite Bion 10 and compared with tail regeneration in synchronous controls. Spinal cord, muscle and cartilage regeneration occurred in space animals as in synchronous controls. One of the most important differences between the two groups was the pigmentation of the blastemas: it was shown in laboratory, to be not due to a difference in light intensity.

  9. Somaclonal variation in Asparagus officinalis plants regenerated by organogenesis from long-term callus cultures

    Directory of Open Access Journals (Sweden)

    Pontaroli Ana Clara

    2005-01-01

    Full Text Available Somaclonal variation in plants regenerated by organogenesis from long-term cultured calluses of two diploid staminate genotypes of Asparagus officinalis cv. Argenteuil was characterized by plant phenotype, ploidy, meiotic behavior, pollen viability, fruit and seed set, and AFLP profiles. Phenotypic deviations from the donors were detected in foliage color, flower size, and cladode and flower morphology. Ploidy changes were observed in 37.8% of the 37 regenerants studied. Meiotic alterations in 12 out of 21 regenerants included laggards, dicentric bridges, micronuclei, restitution nuclei and polyads. Of the 408 AFLP markers screened in 43 regenerants and the donors, 2.94% showed polymorphism. High pollen viability was observed in the 22 regenerants analyzed. All crosses between one pistillate plant and 35 regenerants, as well as the controls, produced fruits and seeds; however, no plump seeds resulted in 35.3% of the crosses with regenerants, and no seeds germinated in 12.5% of those with apparently normal seeds. Fruit and seed set was similar in crosses with diploid regenerants with normal meiosis and the controls but was lower in crosses with diploid and polyploid regenerants with abnormal meiosis. Our results show that the regenerated plants exhibited conspicuous somaclonal variation that could be eventually exploited for in vitro selection systems.

  10. Cardiac Regeneration and Stem Cells.

    Science.gov (United States)

    Zhang, Yiqiang; Mignone, John; MacLellan, W Robb

    2015-10-01

    After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.

  11. Biomaterial selection for tooth regeneration.

    Science.gov (United States)

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y; Zhou, Hong; Chen, Lili; Mao, Jeremy J

    2011-10-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth.

  12. Rabbit facial nerve regeneration in NGF-containing silastic tubes.

    Science.gov (United States)

    Spector, J G; Lee, P; Derby, A; Frierdich, G E; Neises, G; Roufa, D G

    1993-05-01

    Previous reports suggest that exogenous nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. Rabbit facial nerve regeneration in 10-mm Silastic tubes prefilled with NGF was compared to cytochrome C (Cyt. C), bridging an 8-mm nerve gap. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than cytochrome-C-treated controls. Morphometric analysis at the midtube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and cytochrome-C-treated implants. However, when the number of myelinated fibers in 5-week regenerates were compared to their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than cytochrome-C--treated implants (46% vs. 18%, respectively). In addition, NGF-containing chambers reinnervated a higher percentage of myelinated axons in the distal transected neural stumps (49% vs. 34%). Behavioral and electrophysiologic studies demonstrated spontaneous and induced activities in the target muscles when approximately one third of the myelinated axons were recovered in the midchamber (1280 axons). Horseradish peroxidase (HRP) studies demonstrated retrograde axonal transport to the midchamber and proximal transected neural stump. PC12 bioassay demonstrated persistent NGF activity in the intrachamber fluids at 3 (5:1 dilution) and 5 (2:1 dilution) weeks of entubation. Electrophysiologic tests demonstrated a slow conduction velocity of a propagated electrical impulse (43.5 m/s-1 vs. 67 m/s-1) and shallow wide compound action potential. In wider defects (15-mm chambers) and longer entubation periods (7 weeks), no regeneration or NGF activity was seen. Therefore, exogenous NGF provides an early but limited neurotrophic effect on the regeneration of the rabbit buccal division of the facial nerve and a

  13. 催化裂化装置待生立管磨损原因分析及处理措施%Reason Analysis and Treatment Control on Regeneration Standpipe Wear of FCC

    Institute of Scientific and Technical Information of China (English)

    刘金超

    2012-01-01

    对催化裂化装置同轴式沉降再生器待生立管磨损原因进行分析,认为原设计不合理是主要原因,对待生立管及密封结构进行了改进。%The wear reasons were analyzed of the regeneration standpipe in the coaxial settler and regenerator in the FCC unit.Original design unreasonable was the major cause,and the regeneration standpipe and sealing structure were reformed.

  14. An experimental study of passive regenerator geometries

    DEFF Research Database (Denmark)

    Engelbrecht, Kurt; Nielsen, Kaspar Kirstein; Pryds, Nini

    2011-01-01

    this article studies the effects of regenerator geometry on performance for flat plate regenerators. This paper investigates methods of improving the performance of flat plate regenerators for use in AMR systems and studies how manufacturing variation affects regenerator performance. In order to eliminate...... experimental uncertainty associated with magnetocaloric material properties, all regenerators are made of aluminum. The performance of corrugated plates and dimpled plates are compared to traditional flat plate regenerators for a range of cycle times and utilizations. Each regenerator is built using 18...

  15. Regenerable Contaminant Removal System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Regenerable Contaminant Removal System (RCRS) is an innovative method to remove sulfur and halide compounds from contaminated gas streams to part-per-billion...

  16. Instructive composites for bone regeneration

    NARCIS (Netherlands)

    Barbieri, D.

    2012-01-01

    Developing new biomaterials for tissue regeneration requires careful balance between many factors, which is challenging because, on one side, such materials must provide complex information, through their physicochemical properties to actively interact with the biological surroundings and induce tis

  17. Stem cells sources for intervertebral disc regeneration

    Institute of Scientific and Technical Information of China (English)

    Gianluca; Vadalà; Fabrizio; Russo; Luca; Ambrosio; Mattia; Loppini; Vincenzo; Denaro

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

  18. Retinal synaptic regeneration via microfluidic guiding channels.

    Science.gov (United States)

    Su, Ping-Jung; Liu, Zongbin; Zhang, Kai; Han, Xin; Saito, Yuki; Xia, Xiaojun; Yokoi, Kenji; Shen, Haifa; Qin, Lidong

    2015-08-28

    In vitro culture of dissociated retinal neurons is an important model for investigating retinal synaptic regeneration (RSR) and exploring potentials in artificial retina. Here, retinal precursor cells were cultured in a microfluidic chip with multiple arrays of microchannels in order to reconstruct the retinal neuronal synapse. The cultured retinal cells were physically connected through microchannels. Activation of electric signal transduction by the cells through the microchannels was demonstrated by administration of glycinergic factors. In addition, an image-based analytical method was used to quantify the synaptic connections and to assess the kinetics of synaptic regeneration. The rate of RSR decreased significantly below 100 μM of inhibitor glycine and then approached to a relatively constant level at higher concentrations. Furthermore, RSR was enhanced by chemical stimulation with potassium chloride. Collectively, the microfluidic synaptic regeneration chip provides a novel tool for high-throughput investigation of RSR at the cellular level and may be useful in quality control of retinal precursor cell transplantation.

  19. Protein phosphorylation: Localization in regenerating optic axons

    Energy Technology Data Exchange (ETDEWEB)

    Larrivee, D. (Cornell Univ. Medical College, New York, NY (USA))

    1990-09-01

    A number of axonal proteins display changes in phosphorylation during goldfish optic nerve regeneration. (1) To determine whether the phosphorylation of these proteins was closely linked to their synthesis in the retinal ganglion cell body, cycloheximide was injected intraocularly into goldfish whose optic nerves had been regenerating for 3 weeks. Cycloheximide reduced the incorporation of (3H)proline and 32P orthophosphate into total nerve protein by 84% and 46%, respectively. Of the 20 individual proteins examined, 17 contained less than 15% of the (3H)proline label measured in corresponding controls, whereas 18 proteins contained 50% or more of the 32P label, suggesting that phosphorylation was largely independent of synthesis. (2) To determine whether the proteins were phosphorylated in the ganglion cell axons, axonal transport of proteins was blocked by intraocular injection of vincristine. Vincristine reduced (3H)proline labeling of total protein by 88% and 32P labeling by 49%. Among the individual proteins (3H)proline labeling was reduced by 90% or more in 18 cases but 32P labeling was reduced only by 50% or less. (3) When 32P was injected into the cranial cavity near the ends of the optic axons, all of the phosphoproteins were labeled more intensely in the optic tract than in the optic nerve. These results suggest that most of the major phosphoproteins that undergo changes in phosphorylation in the course of regeneration are phosphorylated in the optic axons.

  20. Ozone promotes regeneration by regulating the inflammatory response in zebrafish.

    Science.gov (United States)

    Hao, Kenan; Li, Yanhao; Feng, Jianyu; Zhang, Wenqing; Zhang, Yiyue; Ma, Ning; Zeng, Qingle; Pang, Huajin; Wang, Chunyan; Xiao, Lijun; He, Xiaofeng

    2015-09-01

    Ozone is thought to advance wound healing by inhibiting inflammation, but the mechanism of this phenomenon has not been determined. Although the zebrafish is often used in regeneration experiments, there has been no report of zebrafish treated with ozonated water. We successfully established a zebrafish model of ozonated water treatment and demonstrate that ozonated water stimulates the regeneration of the zebrafish caudal fin, its mechanism, and time dependence. The growth rate of the caudal fin and the number of neutrophils migrating to the caudal fin wound after resection were higher in the experimental (ozonated) group than in the control group, preliminarily confirming that ozone-promoted regeneration is related to the stimulation of an early inflammatory response by ozone. Ozone modulated the expression of tumor necrosis factor-α (TNF-α) in two ways by regulating interleukin 10 (IL-10) expression. Therefore, ozone promotes tissue regeneration by regulating the inflammatory pathways. This effect of ozone in an experimental zebrafish model is demonstrated for the first time, confirming its promotion of wound healing and the mechanism of its effect in tissue regeneration. These results will open up new directions for ozone and regeneration research.

  1. Guided bone regeneration using a flexible hydroxyapatite patch.

    Science.gov (United States)

    Sun, Fangfang; Kang, Hyun Gu; Ryu, Su-Chak; Kim, Ji Eun; Park, Enoch Y; Hwang, Dae Youn; Lee, Jaebeom

    2013-11-01

    Guided bone regeneration (GBR) is a new method of promoting new bone formation by blocking the proliferation of regenerated connective tissue or providing additional interventions such as direct drug delivery and mechanical support. This in vivo study of bone regeneration in radius compound fractures in rabbits was conducted using a highly flexible scaffold of nanoscale hydroxyapatite (nHAp)/chitosan, termed a "bone patch". A solidification-assisted compression (SAC) method was utilized to fabricate the bone patch, and its in vivo cytotoxicity, bio-absorption, and bone regeneration capacity were evaluated. Four weeks after implantation, new bone formation with abundant active osteoblasts and incompleted degradation of chitosan in the patch were observed without any regeneration of connective tissue, compared with the corresponding implant without a patch. X-ray images showed that the radius with the bone patch had higher opacity than that of the control, which was consistent with the results obtained via histological analysis. Evidently, the nHAp-embedded bone-patch scaffold has considerable potential for application in the field of orthopedics of bone regeneration.

  2. Cementum proteins: role in cementogenesis, biomineralization, periodontium formation and regeneration.

    Science.gov (United States)

    Arzate, Higinio; Zeichner-David, Margarita; Mercado-Celis, Gabriela

    2015-02-01

    Destruction of the periodontium is normally associated with periodontal disease, although many other factors, such as trauma, aging, infections, orthodontic tooth movement and systemic and genetic diseases, can contribute to this process. Strategies (such as guided tissue regeneration) have been developed to guide and control regeneration using bioresorbable membranes and bone grafts. Although effective to a certain point, these strategies have the problem that they are not predictable and do not completely restore the architecture of the original periodontium. To achieve complete repair and regeneration it is necessary to recapitulate the developmental process with complete formation of cementum, bone and periodontal ligament fibers. Detailed knowledge of the biology of cementum is key for understanding how the periodontium functions, identifying pathological issues and for developing successful therapies for repair and regeneration of damaged periodontal tissue. It is the purpose of this review to focus on the role of cementum and its specific components in the formation, repair and regeneration of the periodontium. As cementum is a matrix rich in growth factors that could influence the activities of various periodontal cell types, this review will examine the characteristics of cementum, its composition and the role of cementum components, especially the cementum protein-1, during the process of cementogenesis, and their potential usefulness for regeneration of the periodontal structures in a predictable therapeutic manner.

  3. Tissue engineering for periodontal regeneration.

    Science.gov (United States)

    Kao, Richard T; Conte, Greg; Nishimine, Dee; Dault, Scott

    2005-03-01

    As a result of periodontal regeneration research, a series of clinical techniques have emerged that permit tissue engineering to be performed for more efficient regeneration and repair of periodontal defects and improved implant site development. Historically, periodontal regeneration research has focused on a quest for "magic filler" material. This search has led to the development of techniques utilizing autologous bone and bone marrow, allografts, xenografts, and various man-made bone substitutes. Though these techniques have had limited success, the desire for a more effective regenerative approach has resulted in the development of tissue engineering techniques. Tissue engineering is a relatively new field of reconstructive biology which utilizes mechanical, cellular, or biologic mediators to facilitate reconstruction/regeneration of a particular tissue. In periodontology, the concept of tissue engineering had its beginnings with guided tissue regeneration, a mechanical approach utilizing nonresorbable membranes to obtain regeneration in defects. In dental implantology, guided bone regeneration membranes +/- mechanical support are used for bone augmentation of proposed implant placement sites. With the availability of partially purified protein mixture from developing teeth and growth factors from recombinant technology, a new era of tissue engineering whereby biologic mediators can be used for periodontal regeneration. The advantage of recombinant growth factors is this tissue engineering device is consistent in its regenerative capacity, and variations in regenerative response are due to individual healing response and/or poor surgical techniques. In this article, the authors review how tissue engineering has advanced and discuss its impact on the clinical management of both periodontal and osseous defects in preparation for implant placement. An understanding of these new tissue engineering techniques is essential for comprehending today's ever

  4. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  5. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration

    OpenAIRE

    Mahmoud, Ahmed I.; O’Meara, Caitlin C.; Gemberling, Matthew; Zhao, Long; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F.; Burns, Caroline E.; Burns, C. Geoffrey; MacRae, Calum A.; Poss, Kenneth D.; Lee, Richard T.

    2015-01-01

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte...

  6. Tissue Regeneration: A Silk Road

    Science.gov (United States)

    Jao, Dave; Mou, Xiaoyang; Hu, Xiao

    2016-01-01

    Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world’s best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration. PMID:27527229

  7. Tissue Regeneration: A Silk Road.

    Science.gov (United States)

    Jao, Dave; Mou, Xiaoyang; Hu, Xiao

    2016-01-01

    Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world's best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration.

  8. A small molecule screen identifies in vivo modulators of peripheral nerve regeneration in zebrafish

    Science.gov (United States)

    Skinner, Julianne; Granato, Michael

    2017-01-01

    Adult vertebrates have retained the ability to regenerate peripheral nerves after injury, although regeneration is frequently incomplete, often leading to functional impairments. Small molecule screens using whole organisms have high potential to identify biologically relevant targets, yet currently available assays for in vivo peripheral nerve regeneration are either very laborious and/or require complex technology. Here we take advantage of the optical transparency of larval zebrafish to develop a simple and fast pectoral fin removal assay that measures peripheral nerve regeneration in vivo. Twenty-four hours after fin amputation we observe robust and stereotyped nerve regrowth at the fin base. Similar to laser mediated nerve transection, nerve regrowth after fin amputation requires Schwann cells and FGF signaling, confirming that the fin amputation assay identifies pathways relevant for peripheral nerve regeneration. From a library of small molecules with known targets, we identified 21 compounds that impair peripheral nerve regeneration. Several of these compounds target known regulators of nerve regeneration, further validating the fin removal assay. Twelve of the identified compounds affect targets not previously known to control peripheral nerve regeneration. Using a laser-mediated nerve transection assay we tested ten of those compounds and confirmed six of these compounds to impair peripheral nerve regeneration: an EGFR inhibitor, a glucocorticoid, prostaglandin D2, a retinoic acid agonist, an inhibitor of calcium channels and a topoisomerase I inhibitor. Thus, we established a technically simple assay to rapidly identify valuable entry points into pathways critical for vertebrate peripheral nerve regeneration. PMID:28575069

  9. Hybrid-assisted DPF regeneration in distribution trucks

    NARCIS (Netherlands)

    Foster, D.L.; Kessels, J.T.B.A.; Aneke, N.P.I.; Rojer, C.

    2009-01-01

    TNO Automotive is developing an Integrated Powertrain Control (IPC) concept for powertrain controls that focuses on integration of the engine, aftertreatment and parallel hybrid electric system. One of the first steps is the focus on hybrid assisted Diesel Particulate Filter (DPF) regeneration. For

  10. Sex-inducing effect of a hydrophilic fraction on reproductive switching in the planarian Dugesia ryukyuensis (Seriata, Tricladida

    Directory of Open Access Journals (Sweden)

    Hoshi Motonori

    2011-10-01

    Full Text Available Abstract Background The mechanisms underlying the switching from an asexual to a sexual mode of reproduction, and vice versa, remain unknown in metazoans. In planarians, asexual worms acquire cryptic sexuality when fed with sexual worms, indicating that sexual worms contain a sex-inducing substance. Although such a chemical compound will provide clues about the mechanisms underlying the switching, information on the sex-inducing substance is poor. In order to identify this substance, we have established an assay system for sexual induction in asexual worms of Dugesia ryukyuensis by feeding them with sexual worms. Here, we carried out an isolation study on the sex-inducing substance using this assay system. Results After centrifugation of sexual worms homogenised in saline solution, we found that not only did the precipitate have a sex-inducing effect on the asexual worms, which has been shown previously, but the cytosolic fraction did as well. We confirmed that the sex-inducing activity in the cytosolic fraction was recovered in a hydrophilic fraction separated on an octadecylsilane (ODS column. We showed that the sex-inducing substance in the hydrophilic fraction is papain-resistant and a putative low-molecular-weight compound of less than 500. We also suggest the presence of an enhancer of sexual induction with a molecular weight (MW of more than 5 K in the hydrophilic fraction. Conclusion Our experiments showed the existence of a sex-inducing substance and an enhancer of sex-induction in a hydrophilic fraction, and a putative hydrophobic sex-inducing substance in the precipitate. Sexual induction in the asexual worms might be triggered by additive or synergistic effects of these chemical compounds.

  11. High multiple paternity and low last-male sperm precedence in a hermaphroditic planarian flatworm: consequences for reciprocity patterns.

    Science.gov (United States)

    Pongratz, N; Michiels, N K

    2003-06-01

    It is difficult to predict a priori how mating success translates into fertilization success in simultaneous hermaphrodites with internal fertilization. Whereas insemination decisions will be determined by male interests, fertilization will depend on female interests, possibly leading to discrepancies between insemination and fertilization patterns. The planarian flatworm Schmidtea polychroa, a simultaneous hermaphrodite in which mating partners trade sperm was studied. Sperm can be stored for months yet individuals mate frequently. Using microsatellites, maternity and paternity data were obtained from 748 offspring produced in six groups of 10 individuals during four weeks. Adults produced young from four mates on average. Reciprocal fertilization between two mates was found in only 41 out of 110 registered mate combinations, which is clearly less than what is predicted from insemination patterns. Multiple paternity was high: > 80% of all cocoons had two to five fathers for only three to five offspring per cocoon. Because animals were collected from a natural population, 28% of all hatchlings were sired by unknown sperm donors in the field, despite a 10-day period of acclimatization and within-group mating. This percentage decreased only moderately throughout the experiment, showing that sperm can be stored and used for at least a month, despite frequent mating and sperm digestion. The immediate paternity a sperm donor could expect to obtain was only about 25%. Male reproductive success increased linearly with the number of female partners, providing support for Bateman's principle in hermaphrodites. Our results suggest that hermaphrodites do not trade fertilizations when trading sperm during insemination, lending support to the view that such conditional sperm exchange is driven by exchange of resources.

  12. Regenerated soleus muscle shows reduced creatine kinase efflux after contractile activity in vitro.

    Science.gov (United States)

    Baltusnikas, Juozas; Kilikevicius, Audrius; Venckunas, Tomas; Fokin, Andrej; Lionikas, Arimantas; Ratkevicius, Aivaras

    2015-02-01

    Regenerated skeletal muscles show less muscle damage after strenuous muscle exercise. The aim of the studies was to investigate if the regeneration is associated with reduced muscle creatine kinase (CK) efflux immediately after the exercise. Cryolesion was applied to the soleus muscle of 3-month-old C57BL/6J male mice. Then total CK efflux was assessed in vitro in the regenerated muscles without exercise or after 100 eccentric contractions. The same measurements were performed in the control muscles, which were not exposed to cryolesion. Regenerated muscles generated weaker (P resistance to damage after eccentric exercise.

  13. Defective bursa regeneration after irradiation of young thymectomized chickens

    Energy Technology Data Exchange (ETDEWEB)

    Bhogal, B.S.; Chi, D.S.; Galton, J.E.; Bell, M.K.; Thorbecke, G.J.

    1984-08-01

    The ability of the bursa of Fabricius to regenerate after gamma-irradiation and bone marrow reconstitution was examined in chickens thymectomized (TX) immediately after hatching. Irradiation (2 X 500 R) 3 weeks after hatching was followed by impaired bursa regeneration, as judged both by bursa/body weight ratios and by bursa follicle development 3-6 weeks later in TX as compared to control birds. Germinal center formation in the spleen was deficient, and immune responses to sheep erythrocytes (SRBC) and B. abortus (BA) were moderately reduced in the TX as compared to control birds irradiated at 3 weeks but not in TX birds irradiated at 5 weeks of age.

  14. The effect of hypergravity on the lens, cornea and tail regeneration in Urodela

    Science.gov (United States)

    Grigoryan, E. N.; Dvorochkin, N.; Poplinskaya, V. A.; Yousuf, R.; Radugina, E. A.; Almeida, E. A.

    2017-09-01

    In previous experiments onboard Russian Bion/Foton satellites it was found that exposure to microgravity causes changes in eye lens regeneration of Urodela. The changes included higher rate of regeneration, increased cell proliferation in lens anlage, and synchronization of lens restoration. Similar changes were observed regarding tail regeneration. Recently, investigations were performed to find out whether exposure to hypergravity could also alter lens, cornea and tail regeneration in the newt P. waltl. Nine days prior to exposure the left lens was surgically removed through corneal incision and distal 1/3 of the tail was amputated, thus initiating regeneration. The experimental animals were allowed to recover for 9 days at 1 g and then exposed to 2 g for 12 days in an 8 ft diameter centrifuge at NASA Ames Research Center. The experimental animals were divided into 1 g controls, 2 g centrifugation animals, basal controls, and aquarium controls. Lens and corneal regeneration appeared to be inhibited in 2 g group compared to 1 g animals. In all 1 g controls, lens regeneration reached stages VII-IX in a synchronous fashion and corneal regeneration was nearly complete. In the 2 g newts, neural retinal detachment from the pigmented epithelium was seen in most operated eyes. It was also observed in the non-operated (right) eyes of the animals exposed to 2 g. The level of retinal detachment varied and could have been caused by hypergravity-induced high intraocular pressure. Regeneration (when it could be assessed) proceeded asynchronously, reaching stages from II to IX. Corneal restoration was also noticeably delayed and corneal morphology changed. Cell proliferation was measured using BrdU; the results were not comparable to the 1 g data because of retinal detachment. Previous investigations demonstrated that lens regeneration was controlled by the neural retina; therefore, lower regeneration rate at 2 g was, at least in part, associated with retinal detachment. FGF2

  15. Cementum and Periodontal Ligament Regeneration.

    Science.gov (United States)

    Menicanin, Danijela; Hynes, K; Han, J; Gronthos, S; Bartold, P M

    2015-01-01

    The unique anatomy and composition of the periodontium make periodontal tissue healing and regeneration a complex process. Periodontal regeneration aims to recapitulate the crucial stages of wound healing associated with periodontal development in order to restore lost tissues to their original form and function and for regeneration to occur, healing events must progress in an ordered and programmed sequence both temporally and spatially, replicating key developmental events. A number of procedures have been employed to promote true and predictable regeneration of the periodontium. Principally, the approaches are based on the use of graft materials to compensate for the bone loss incurred as a result of periodontal disease, use of barrier membranes for guided tissue regeneration and use of bioactive molecules. More recently, the concept of tissue engineering has been integrated into research and applications of regenerative dentistry, including periodontics, to aim to manage damaged and lost oral tissues, through reconstruction and regeneration of the periodontium and alleviate the shortcomings of more conventional therapeutic options. The essential components for generating effective cellular based therapeutic strategies include a population of multi-potential progenitor cells, presence of signalling molecules/inductive morphogenic signals and a conductive extracellular matrix scaffold or appropriate delivery system. Mesenchymal stem cells are considered suitable candidates for cell-based tissue engineering strategies owing to their extensive expansion rate and potential to differentiate into cells of multiple organs and systems. Mesenchymal stem cells derived from multiple tissue sources have been investigated in pre-clinical animal studies and clinical settings for the treatment and regeneration of the periodontium.

  16. Transforming growth factor: beta signaling is essential for limb regeneration in axolotls.

    Directory of Open Access Journals (Sweden)

    Mathieu Lévesque

    Full Text Available Axolotls (urodele amphibians have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-beta. In the present study, the full length sequence of the axolotl TGF-beta1 cDNA was isolated. The spatio-temporal expression pattern of TGF-beta1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-beta signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-beta type I receptor, SB-431542, we show that TGF-beta signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-beta signaling are down-regulated. These data directly implicate TGF

  17. a Low Temperature Regenerator Test Facility

    Science.gov (United States)

    Kashani, A.; Helvensteijn, B. P. M.; Feller, J. R.; Salerno, L. J.; Kittel, P.

    2008-03-01

    Testing regenerators presents an interesting challenge. When incorporated into a cryocooler, a regenerator is intimately coupled to the other components: expander, heat exchangers, and compressor. It is difficult to isolate the performance of any single component. We have developed a low temperature test facility that will allow us to separate the performance of the regenerator from the rest of the cryocooler. The purpose of the facility is the characterization of test regenerators using novel materials and/or geometries in temperature ranges down to 15 K. It consists of the following elements: The test column has two regenerators stacked in series. The coldest stage regenerator is the device under test. The warmer stage regenerator contains a stack of stainless steel screen, a well-characterized material. A commercial cryocooler is used to fix the temperatures at both ends of the test regenerator, cooling both heat exchangers flanging the regenerator stack. Heaters allow varying the temperatures and allow measurement of the remaining cooling power, and thus, regenerator effectiveness. A linear compressor delivers an oscillating pressure to the regenerator assembly. An inertance tube and reservoir provide the proper phase difference between mass flow and pressure. This phase shift, along with the imposed temperature differential, simulates the conditions of the test regenerator when used in an actual pulse tube cryocooler. This paper presents development details of the regenerator test facility, and test results on a second stage, stainless steel screen test regenerator.

  18. Pancreatic regeneration: basic research and gene regulation.

    Science.gov (United States)

    Okita, Kenji; Mizuguchi, Toru; Shigenori, Ota; Ishii, Masayuki; Nishidate, Toshihiko; Ueki, Tomomi; Meguro, Makoto; Kimura, Yasutoshi; Tanimizu, Naoki; Ichinohe, Norihisa; Torigoe, Toshihiko; Kojima, Takashi; Mitaka, Toshihiro; Sato, Noriyuki; Sawada, Norimasa; Hirata, Koichi

    2016-06-01

    Pancreatic regeneration (PR) is an interesting phenomenon that could provide clues as to how the control of diabetes mellitus might be achieved. Due to the different regenerative abilities of the pancreas and liver, the molecular mechanism responsible for PR is largely unknown. In this review, we describe five representative murine models of PR and thirteen humoral mitogens that stimulate β-cell proliferation. We also describe pancreatic ontogenesis, including the molecular transcriptional differences between α-cells and β-cells. Furthermore, we review 14 murine models which carry defects in genes related to key transcription factors for pancreatic ontogenesis to gain further insight into pancreatic development.

  19. Stem cell death and survival in heart regeneration and repair.

    Science.gov (United States)

    Abdelwahid, Eltyeb; Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

    2016-03-01

    Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

  20. Tissue engineering in periodontal regeneration: A brief review

    Directory of Open Access Journals (Sweden)

    Sarita Dabra

    2012-01-01

    Full Text Available Periodontal disease is a major public health issue and the development of effective therapies to treat the disease and regenerate periodontal tissue is an important goal of today′s medicine. Regeneration of periodontal tissue is perhaps one of the most complex process to occur in the body. Langer and colleagues proposed tissue engineering as a possible technique for regenerating the lost periodontal tissues. Tissue engineering is a multidisciplinary field, which involves the application of the principles and methods of engineering and life sciences to help in the development of biological substitutes to restore, maintain or improve the function of damaged tissues and organs. A Google/Medline search was conducted and relevant literature evaluating the potential role of the tissue engineering in periodontal regeneration, which included histological studies and controlled clinical trials, was reviewed. A comprehensive search was designed. The articles were independently screened for eligibility. Articles with authentic controls and proper randomization and pertaining specifically to their role in periodontal regeneration were included. The available literature was analyzed and compiled. The analysis indicate tissue engineering to be a promising, as well as an effective novel approach to reconstruct and engineer the periodontal apparatus. Here, we represent several articles, as well as recent texts that make up a special and an in-depth review on the subject. The purpose behind writing this brief review has been to integrate the evidence of research related to tissue engineering so as to implement them in our daily practice.

  1. Tissue engineering in periodontal regeneration: A brief review.

    Science.gov (United States)

    Dabra, Sarita; Chhina, Kamalpreet; Soni, Nitin; Bhatnagar, Rakhi

    2012-11-01

    Periodontal disease is a major public health issue and the development of effective therapies to treat the disease and regenerate periodontal tissue is an important goal of today's medicine. Regeneration of periodontal tissue is perhaps one of the most complex process to occur in the body. Langer and colleagues proposed tissue engineering as a possible technique for regenerating the lost periodontal tissues. Tissue engineering is a multidisciplinary field, which involves the application of the principles and methods of engineering and life sciences to help in the development of biological substitutes to restore, maintain or improve the function of damaged tissues and organs. A Google/Medline search was conducted and relevant literature evaluating the potential role of the tissue engineering in periodontal regeneration, which included histological studies and controlled clinical trials, was reviewed. A comprehensive search was designed. The articles were independently screened for eligibility. Articles with authentic controls and proper randomization and pertaining specifically to their role in periodontal regeneration were included. The available literature was analyzed and compiled. The analysis indicate tissue engineering to be a promising, as well as an effective novel approach to reconstruct and engineer the periodontal apparatus. Here, we represent several articles, as well as recent texts that make up a special and an in-depth review on the subject. The purpose behind writing this brief review has been to integrate the evidence of research related to tissue engineering so as to implement them in our daily practice.

  2. Bone morphogenetic proteins: Periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Subramaniam M Rao

    2013-01-01

    Full Text Available Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search. All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP.

  3. Contemporaryperspective on endogenous myocardial regeneration

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Considering the complex nature of the adult heart,it is no wonder that innate regenerative processes,while maintaining adequate cardiac function, fall shortin myocardial jeopardy. In spite of these enchaining limitations, cardiac rejuvenation occurs as well asrestricted regeneration. In this review, the backgroundas well as potential mechanisms of endogenousmyocardial regeneration are summarized. We presentand analyze the available evidence in three subsequentsteps. First, we examine the experimental researchdata that provide insights into the mechanisms andorigins of the replicating cardiac myocytes, includingcell populations referred to as cardiac progenitor cells(i.e. , c-kit+ cells). Second, we describe the role ofclinical settings such as acute or chronic myocardialischemia, as initiators of pathways of endogenousmyocardial regeneration. Third, the hitherto conductedclinical studies that examined different approachesof initiating endogenous myocardial regeneration infailing human hearts are analyzed. In conclusion, wepresent the evidence in support of the notion thatregaining cardiac function beyond cellular replacementof dysfunctional myocardium via initiation of innateregenerative pathways could create a new perspectiveand a paradigm change in heart failure therapeutics.Reinitiating cardiac morphogenesis by reintroducingdevelopmental pathways in the adult failing heart mightprovide a feasible way of tissue regeneration. Basedon our hypothesis "embryonic recall", we present firstsupporting evidence on regenerative impulses in themyocardium, as induced by developmental processes.

  4. Advanced sulfur control concepts in hot-gas desulfurization technology: Phase 2. Exploratory studies on the direct production of elemental sulfur during the regeneration of high temperature desulfurization sorbents. Topical report

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, A.; Huang, W.; White, J. [and others

    1997-07-01

    The topical report describes the results of Phase 2 research to determine the feasibility of the direct production of elemental sulfur during the regeneration of high temperature desulfurization sorbents. Many of the contaminants present in coal emerge from the gasification process in the product gas. Much effort has gone into the development of high temperature metal oxide sorbents for removal of H{sub 2}S from coal gas. The oxides of zinc, iron, manganese, and others have been studied. In order for high temperature desulfurization to be economical it is necessary that the sorbents be regenerated to permit multicycle operation. Current methods of sorbent regeneration involve oxidation of the metal sulfide to reform the metal oxide and free the sulfur as SO{sub 2}. An alternate regeneration process in which the sulfur is liberated in elemental form is desired. Elemental sulfur, which is the typical feed to sulfuric acid plants, may be easily separated, stored, and transported. Although research to convert SO{sub 2} produced during sorbent regeneration to elemental sulfur is on-going, additional processing steps are required and the overall process will be more complex. Clearly, the direct production of elemental sulfur is preferred. Desulfurization utilizing a cerium oxide based sorbent is discussed.

  5. Regenerator cross arm seal assembly

    Science.gov (United States)

    Jackman, Anthony V.

    1988-01-01

    A seal assembly for disposition between a cross arm on a gas turbine engine block and a regenerator disc, the seal assembly including a platform coextensive with the cross arm, a seal and wear layer sealingly and slidingly engaging the regenerator disc, a porous and compliant support layer between the platform and the seal and wear layer porous enough to permit flow of cooling air therethrough and compliant to accommodate relative thermal growth and distortion, a dike between the seal and wear layer and the platform for preventing cross flow through the support layer between engine exhaust and pressurized air passages, and air diversion passages for directing unregenerated pressurized air through the support layer to cool the seal and wear layer and then back into the flow of regenerated pressurized air.

  6. Muscle regeneration in mitochondrial myopathies

    DEFF Research Database (Denmark)

    Krag, T O; Hauerslev, S; Jeppesen, T D

    2013-01-01

    Mitochondrial myopathies cover a diverse group of disorders in which ragged red and COX-negative fibers are common findings on muscle morphology. In contrast, muscle degeneration and regeneration, typically found in muscular dystrophies, are not considered characteristic features of mitochondrial...... myopathies. We investigated regeneration in muscle biopsies from 61 genetically well-defined patients affected by mitochondrial myopathy. Our results show that the perturbed energy metabolism in mitochondrial myopathies causes ongoing muscle regeneration in a majority of patients, and some were even affected...... by a dystrophic morphology. The results add to the complexity of the pathogenesis underlying mitochondrial myopathies, and expand the knowledge about the impact of energy deficiency on another aspect of muscle structure and function....

  7. Natural regeneration processes in big sagebrush (Artemisia tridentata)

    Science.gov (United States)

    Schlaepfer, Daniel R.; Lauenroth, William K.; Bradford, John B.

    2014-01-01

    Big sagebrush, Artemisia tridentata Nuttall (Asteraceae), is the dominant plant species of large portions of semiarid western North America. However, much of historical big sagebrush vegetation has been removed or modified. Thus, regeneration is recognized as an important component for land management. Limited knowledge about key regeneration processes, however, represents an obstacle to identifying successful management practices and to gaining greater insight into the consequences of increasing disturbance frequency and global change. Therefore, our objective is to synthesize knowledge about natural big sagebrush regeneration. We identified and characterized the controls of big sagebrush seed production, germination, and establishment. The largest knowledge gaps and associated research needs include quiescence and dormancy of embryos and seedlings; variation in seed production and germination percentages; wet-thermal time model of germination; responses to frost events (including freezing/thawing of soils), CO2 concentration, and nutrients in combination with water availability; suitability of microsite vs. site conditions; competitive ability as well as seedling growth responses; and differences among subspecies and ecoregions. Potential impacts of climate change on big sagebrush regeneration could include that temperature increases may not have a large direct influence on regeneration due to the broad temperature optimum for regeneration, whereas indirect effects could include selection for populations with less stringent seed dormancy. Drier conditions will have direct negative effects on germination and seedling survival and could also lead to lighter seeds, which lowers germination success further. The short seed dispersal distance of big sagebrush may limit its tracking of suitable climate; whereas, the low competitive ability of big sagebrush seedlings may limit successful competition with species that track climate. An improved understanding of the

  8. Characterization of Optic Nerve Regeneration using transgenic Zebrafish

    Directory of Open Access Journals (Sweden)

    Heike eDiekmann

    2015-04-01

    Full Text Available In contrast to the adult mammalian central nervous system (CNS, fish are able to functionally regenerate severed axons upon injury. Although the zebrafish is a well-established model vertebrate for genetic and developmental studies, its use for anatomical studies of axon regeneration has been hampered by the paucity of appropriate tools to visualize re-growing axons in the adult CNS. On this account, we used transgenic zebrafish that express enhanced green fluorescent protein (GFP under the control of a GAP-43 promoter. In adult, naïve retinae, GFP was restricted to young retinal ganglion cells (RGCs and their axons. Within the optic nerve, these fluorescent axons congregated in a distinct strand at the nerve periphery, indicating age-related order. Upon optic nerve crush, GFP expression was markedly induced in RGC somata and intra-retinal axons at 4 to at least 14 days post injury. Moreover, individual axons were visualized in their natural environment of the optic nerve using wholemount tissue clearing and confocal microscopy. With this novel approach, regenerating axons were clearly detectable beyond the injury site as early as 2 days after injury and grew past the optic chiasm by 4 days. Regenerating axons in the entire optic nerve were labelled from 6 to at least 14 days after injury, thereby allowing detailed visualization of the complete regeneration process. Therefore, this new approach could now be used in combination with expression knockdown or pharmacological manipulations to analyze the relevance of specific proteins and signaling cascades for axonal regeneration in vivo. In addition, the RGC-specific GFP expression facilitated accurate evaluation of neurite growth in dissociated retinal cultures. This fast in vitro assay now enables the screening of compound and expression libraries. Overall, the presented methodologies provide exciting possibilities to investigate the molecular mechanisms underlying successful CNS regeneration in

  9. Repair and regeneration in endodontics.

    Science.gov (United States)

    Lin, L M; Rosenberg, P A

    2011-10-01

    The ideal objective of treatment of established diseases, including irreversible pulpitis and apical periodontitis, is to achieve wound healing. Wound healing can result in repair or regeneration. The ultimate goal of wound healing is to restore the original architecture and biological function of the injured tissue or organ. Although humans are equipped with powerful innate and adaptive immune defence mechanisms, many intrinsic and extrinsic factors can affect wound healing. Complete regeneration following injury in humans can occur only in the pre-natal foetus within 24 weeks of gestation. Post-natal wounds including irreversible pulpitis or apical periodontitis always heal by repair or by a combination of repair and regeneration. Somatic cells, such as fibroblasts, macrophages, cementoblasts and osteoblasts, in the pulp and periapical tissues have limited potential for regeneration following injury and lack of telomerase. Wound healing of irreversible pulpitis and apical periodontitis requires recruitment and differentiation of progenitor/stem cells into tissue-committed somatic cells. Stem cell differentiation is regulated by intrinsic factors and extrinsic micro-environmental cues. Functionality of stem cells appears to show an age-related decline because of the change in intrinsic properties and diminished signals within the extrinsic local and systemic environment that modulate the function of stem cells or their progeny. Infection induces an immuno-inflammatory response and tissue destruction, which hinders the potential of tissue regeneration. Therefore, prevention, early detection and treatment of inflammation/infection of pulpal and periapical disease can enhance regeneration and minimize the repair of pulpal and periapical tissues after endodontic therapy. © 2011 International Endodontic Journal.

  10. Peculiarities of lens and tail regeneration detected in newts after spaceflight aboard Foton M3

    Science.gov (United States)

    Grigoryan, Eleonora N.; Almeida, Eduardo; Poplinskaya, Valentina; Novikova, Julia; Domaratskaya, Elena; Aleinikova, Karina; Souza, Kenneth; Skidmore, Mike; Grigoryan, Eleonora N.

    In September 2007 the joint, 12 day long experiment was carried out aboard Russian satellite Foton M3. The goal of the experiment was to study eye lens, tail and forelimb toe regeneration in adult 16 newts (Pl. waltl.) operated 10 days before taking-off. In spaceflight and synchronous ground control we used video recording, temperature and irradiation control, as well as constant availability of thymidine analog BrdU for its absorption via animals' skin. New techniques allowed us to analyze animals' behavior in hyperand microgravity periods of time, to take proper account of spaceflight factors, and measure accumulated pools of DNA-synthesizing cells in regenerating tissues. All tissue specimens obtained from animals were isolated in the day of landing and then prepared for morphological, immunochemical and molecular investigations. Synchronous control was shifted for two days and reproduced flight conditions except changes of gravity influence. As a result in flown animals as compared with synchronous ground control we found lens regeneration of 0.5-1 stage speeded up and an increased BrdU+ (S-phase) cell number in eye cornea, growth zone, limbus and newly forming lens. These features of regeneration were accompanied by an increase of FGF2 expression in eye growth zone and heat shock protein (HSP90) induction purely in retinal macroglial cells of regenerating eyes. Toe regeneration rate was equal and achieved the stage of accomplished healing of amputation area in both groups - "flown" and control animals. We found no essential differences in tail regeneration rate and tail regenerate sizes in the newts exposed to space and on ground. In both groups tail regeneration reached the stage IV-V when tail length and square were around 4.4 mm and 15.5 mm2, correspondingly. However we did observe remarkable changes of tail regenerate form and some of pigmentation. Computer morphometrical analysis showed that only in ground control animals the evident dorso

  11. Antler regrowth as a form of epimorphic regeneration in vertebrates - a comparative view.

    Science.gov (United States)

    Kierdorf, Uwe; Kierdorf, Horst

    2012-01-01

    The annual regrowth of deer antlers is a unique case of extensive appendage regeneration in mammals. This review compares basic aspects of antler regeneration with epimorphic regeneration in other vertebrate taxa. The mesenchymal cells that build up the regenerating antler are not derived from dedifferentiated cells in the pedicle stump, but from the proliferation of cells of the pedicle periosteum; and based on different lines of evidence it has more recently been suggested that the pedicle periosteum contains stem cells that are periodically activated to produce a new antler. This constitutes a difference to urodele limb regeneration, where the blastema is (largely) formed from dedifferentiated cells. Antler regeneration involves healing of the large casting wound with no or only minor scarring, making the antler an interesting model for the control of scarring in mammals. Contrary to urodele limb regeneration, antler regrowth does not depend on a functional nerve supply. In our view, a comparative analysis of different regeneration phenomena, including antler regeneration, probably offers the best chance for achieving significant progress in regenerative medicine.

  12. Incomplete bone regeneration of rabbit calvarial defects using different membranes

    DEFF Research Database (Denmark)

    Aaboe, M; Pinholt, E M; Schou, S

    1998-01-01

    of the membrane. The calvarial defects of 2 groups were covered by an outer expanded polytetrafluoroethylene (ePTFE) membrane respectively by a Polyglactin 910 membrane. Bicortical ePTFE membranes or Polyglactin 910 membranes were used in 2 other groups. The defects were not covered by membranes in the control...... herniation into the defects. Subsequently, bone regeneration was impaired. The cellular reactions due to degradation of the material were minor and did not interfere with bone healing. Defects covered bicortically by ePTFE membranes revealed the largest amount of regenerated bone. The ePTFE membrane induced...

  13. Heat Saturation Time of Solid Spherical Regenerator of HTAC

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to control the heat saturation time, the temperature field of the regenerators of high temperature air combustion (HTAC) technology after reheating furnace was studied. A one-dimensional unsteady mathematical model was established and discretized through finite difference method. The relationship between the heat saturation time and some factors was determined through the calculation of a program developed by language C. The heat saturation time decreases with the increase of heat convection coefficient, however, the increase of heat capacity,density and radius of regenerator all increase the heat saturation time approximately linearly.

  14. Use of electrospinning to construct biomaterials for peripheral nerve regeneration.

    Science.gov (United States)

    Quan, Qi; Chang, Biao; Meng, Hao Ye; Liu, Ruo Xi; Wang, Yu; Lu, Shi Bi; Peng, Jiang; Zhao, Qing

    2016-10-01

    A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

  15. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  16. [Morphogenetic changes during newt tail regeneration under changed gravity conditions].

    Science.gov (United States)

    Radugina, E A; Grigorian, É N

    2012-01-01

    Gravity-dependent shape alterations in newt tail regenerates are described, which were previously noticed in experiments onboard satellites Foton M2, M3 and in corresponding laboratory controls. Laboratory conditions were developed that allow reproducing this phenomenon persistently in the adult newts Pleurodeles waltl (Michahelles, 1830). The newts kept in an aquarium (in partial weightlessness) after 1/3 tail amputation developed normal lanceolate regenerates, while those that stayed on a moist mat (exposed to greater gravity than in aquarium) developed curved tail regenerates. Dynamics of the shape alterations were described using computer morphometric analysis. The curve was shown to develop at stage III of regeneration and to be caused by bending of the developing axial structures: the ependymal tube and the cartilage rode. Cellular processes were described that accompany the tail shape changes, such as cell migration and formation of dense aggregates. Unequal proliferation throughout the wound epidermis and blastema was revealed using BrdU assay. Proliferation increased within dorsal and apical regions of the regenerates in the newts kept on the mat cell compared with the aquarian animals.

  17. Regulation of tissue repair and regeneration by electric fields

    Institute of Scientific and Technical Information of China (English)

    WANG En-tong; ZHAO Min

    2010-01-01

    Endogenous electric fields(Efs)have been detected at wounds and damaged tissues.The potential roles of Efs in tissue repair and regeneration have been an intriguing topic for centuries.Recent researches have provided significant insights into how naturally occurring Efs may participate in the control of tissue repair and regeneration.Applied Efs equivalent to the size of fields measured in vivo direct cell migration,cell proliferation and nerve sprouting at wounds.More remarkably,physiological Efs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation,wound void,contact inhibition release,population pressure and chemotaxis.Efs activate many intracellular signaling pathways in a directional manner.Modulation of endogenous wound Efs affects epithelial cell migration,cell proliferation,and nerve growth at cornea wounds in vivo.Electric stimulation is being tested clinically for the treatments of bone fracture,wound healing and spinal cord injury.Efs thus may represent a novel type of signaling paradigm in tissue repair and regeneration.Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration.This review introduces experimental evidence for the existence of endogenous Efs and discusses their roles in tissue repair and regeneration.

  18. Regulation of tissue repair and regeneration by electric fields.

    Science.gov (United States)

    Wang, En-tong; Zhao, Min

    2010-02-01

    Endogenous electric fields (EFs) have been detected at wounds and damaged tissues. The potential roles of EFs in tissue repair and regeneration have been an intriguing topic for centuries. Recent researches have provided significant insights into how naturally occurring EFs may participate in the control of tissue repair and regeneration. Applied EFs equivalent to the size of fields measured in vivo direct cell migration, cell proliferation and nerve sprouting at wounds. More remarkably, physiological EFs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation, wound void, contact inhibition release, population pressure and chemotaxis. EFs activate many intracellular signaling pathways in a directional manner. Modulation of endogenous wound EFs affects epithelial cell migration, cell proliferation, and nerve growth at cornea wounds in vivo. Electric stimulation is being tested clinically for the treatments of bone fracture, wound healing and spinal cord injury. EFs thus may represent a novel type of signaling paradigm in tissue repair and regeneration. Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration. This review introduces experimental evidence for the existence of endogenous EFs and discusses their roles in tissue repair and regeneration.

  19. In vitro regeneration of 'Feizixiao' litchi (Litchi chinensis Sonn.)

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    of the leaf blade and eventually obtained regenerated plants. By „Heli‟ ... design with 10 replications (0.1 g of fresh callus per replicate) for each treatment was ... root tip of air layering seedlings were used as a diploid control. Histograms of ...

  20. The invasive land planarian Platydemus manokwari (Platyhelminthes, Geoplanidae: records from six new localities, including the first in the USA

    Directory of Open Access Journals (Sweden)

    Jean-Lou Justine

    2015-06-01

    Full Text Available The land planarian Platydemus manokwari de Beauchamp, 1963 or “New Guinea flatworm” is a highly invasive species, mainly in the Pacific area, and recently in Europe (France. We report specimens from six additional countries and territories: New Caledonia (including mainland and two of the Loyalty Islands, Lifou and Maré, Wallis and Futuna Islands, Singapore, Solomon Islands, Puerto Rico, and Florida, USA. We analysed the COI gene (barcoding in these specimens with two sets of primers and obtained 909 bp long sequences. In addition, specimens collected in Townsville (Australia were also sequenced. Two haplotypes of the COI sequence, differing by 3.7%, were detected: the “World haplotype” found in France, New Caledonia, French Polynesia, Singapore, Florida and Puerto Rico; and the “Australian haplotype” found in Australia. The only locality with both haplotypes was in the Solomon Islands. The country of origin of Platydemus manokwari is New Guinea, and Australia and the Solomon Islands are the countries closest to New Guinea from which we had specimens. These results suggest that two haplotypes exist in the area of origin of the species, but that only one of the two haplotypes (the “World haplotype” has, through human agency, been widely dispersed. However, since P. manokwari is now recorded from 22 countries in the world and we have genetic information from only 8 of these, with none from New Guinea, this analysis provides only partial knowledge of the genetic structure of the invasive species. Morphological analysis of specimens from both haplotypes has shown some differences in ratio of the genital structures but did not allow us to interpret the haplotypes as different species. The new reports from Florida and Puerto Rico are firsts for the USA, for the American continent, and the Caribbean. P. manokwari is a known threat for endemic terrestrial molluscs and its presence is a matter of concern. While most of the infected

  1. Nanostructured Mesoporous Silicas for Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Isabel Izquierdo-Barba

    2008-01-01

    Full Text Available The research on the development of new biomaterials that promote bone tissue regeneration is receiving great interest by the biomedical scientific community. Recent advances in nanotechnology have allowed the design of materials with nanostructure similar to that of natural bone. These materials can promote new bone formation by inducing the formation of nanocrystalline apatites analogous to the mineral phase of natural bone onto their surfaces, i.e. they are bioactive. They also stimulate osteoblast proliferation and differentiation and, therefore, accelerate the healing processes. Silica-based ordered mesoporous materials are excellent candidates to be used as third generation bioceramics that enable the adsorption and local control release of biological active agents that promote bone regeneration. This local delivery capability together with the bioactive behavior of mesoporous silicas opens up promising expectations in the bioclinical field. In this review, the last advances in nanochemistry aimed at designing and tailoring the chemical and textural properties of mesoporous silicas for biomedical applications are described. The recent developed strategies to synthesize bioactive glasses with ordered mesopore arrangements are also summarized. Finally, a deep discussion about the influence of the textural parameters and organic modification of mesoporous silicas on molecules adsorption and controlled release is performed.

  2. Adsorption of Ammonia on Regenerable Carbon Sorbents

    Science.gov (United States)

    Wójtowicz, Marek A.; Cosgrove, Jesph E.; Serio, Michael A..; Wilburn, Monique

    2015-01-01

    Results are presented on the development of reversible sorbents for the combined carbon dioxide, moisture, and trace-contaminant (TC) removal for use in Extravehicular Activities (EVAs), and more specifically in the Primary Life Support System (PLSS). The currently available life support systems use separate units for carbon dioxide, trace contaminants, and moisture control, and the long-term objective is to replace the above three modules with a single one. Data on sorption and desorption of ammonia, which is a major TC of concern, are presented in this paper. The current TC-control technology involves the use of a packed bed of acid-impregnated granular charcoal, which is non-regenerable, and the carbon-based sorbent under development in this project can be regenerated by exposure to vacuum at room temperature. In this study, several carbon sorbents were fabricated and tested for ammonia sorption. Ammonia-sorption capacity was related to carbon pore structure characteristics, and the temperature of oxidative carbon-surface treatment was optimized for enhanced ammonia-sorption performance.

  3. Environmental conditions influence tissue regeneration rates in scleractinian corals.

    Science.gov (United States)

    Sabine, Alexis M; Smith, Tyler B; Williams, Dana E; Brandt, Marilyn E

    2015-06-15

    Natural and anthropogenic factors may influence corals' ability to recover from partial mortality. To examine how environmental conditions affect lesion healing, we assessed several water quality parameters and tissue regeneration rates in corals at six reefs around St. Thomas, US Virgin Islands. We hypothesized that sites closer to developed areas would have poor water quality due to proximity to anthropogenic stresses, which would impede tissue regeneration. We found that water flow and turbidity most strongly influenced lesion recovery rates. The most impacted site, with high turbidity and low flow, recovered almost three times slower than the least impacted site, with low turbidity, high flow, and low levels of anthropogenic disturbance. Our results illustrate that in addition to lesion-specific factors known to affect tissue regeneration, environmental conditions can also control corals' healing rates. Resource managers can use this information to protect low-flow, turbid nearshore reefs by minimizing sources of anthropogenic stress.

  4. Pancreatic beta cell protection/regeneration with phytotherapy

    Directory of Open Access Journals (Sweden)

    Azar Hosseini

    2015-03-01

    Full Text Available Although currently available drugs are useful in controlling early onset complications of diabetes, serious late onset complications appear in a large number of patients. Considering the physiopathology of diabetes, preventing beta cell degeneration and stimulating the endogenous regeneration of islets will be essential approaches for the treatment of insulin-dependent diabetes mellitus. The current review focused on phytochemicals, the antidiabetic effect of which has been proved by pancreatic beta cell protection/regeneration. Among the hundreds of plants that have been investigated for diabetes, a small fraction has shown the regenerative property and was described in this paper. Processes of pancreatic beta cell degeneration and regeneration were described. Also, the proposed mechanisms for the protective/regenerative effects of such phytochemicals and their potential side effects were discussed.

  5. [Cytoskeletal reorganization in hepatocytes of the regenerating mouse liver].

    Science.gov (United States)

    Gleĭberman, A S; Troianovskiĭ, S M; Bannikov, G A

    1984-12-01

    The intracellular pattern of prekeratin and actin filaments has been studied on sections of mouse livers regenerating after CCl4 injury. Monoclonal antibodies against one of liver prekeratins and monospecific polyclonal actin antibodies were used in the indirect immunofluorescent test. The presence of alpha-fetoprotein and bile canaliculi antigen was also monitored during regeneration. In control livers, prekeratin and actin filaments formed thick bundles adjacent to plasma membranes. The cytoplasmic prekeratin network was unmarked. In contrast to the latter, the bright well developed intracytoplasmic prekeratin network and intracytoplasmic actin fibers were identified in the perinecrotic hepatocytes by the 3d-4th day of regeneration. This rearrangement of the cytoskeleton coincided in time with the appearance of alpha-fetoprotein and the loss of the bile canaliculi antigen in the perinecrotic hepatocytes.

  6. Semiconductor devices for all-optical regeneration

    DEFF Research Database (Denmark)

    Öhman, Filip; Bischoff, Svend; Tromborg, Bjarne

    2003-01-01

    We review different implementations of semiconductor devices for all-optical regeneration. A general model will be presented for all-optical regeneration in fiber links, taking into consideration the trade-off between non-linearity and noise. Furthermore we discuss a novel regenerator type, based...

  7. REGENERATION OF DRY DEBRIS-CONTAMINATED LUBRICATION

    Directory of Open Access Journals (Sweden)

    T. A. Ahmetov

    2011-01-01

    Full Text Available Industrial testing of regenerated lubricant in the process of wire drawing showed satisfactory quality (absence of gloss. It is determined that consumption of regenerated lubricant does not differ from consumption of new lubricant. Regenerated lubricant corresponds to the requirements of normative documents.

  8. Deer antler regeneration: cells, concepts, and controversies.

    Science.gov (United States)

    Kierdorf, Uwe; Kierdorf, Horst; Szuwart, Thomas

    2007-08-01

    The periodic replacement of antlers is an exceptional regenerative process in mammals, which in general are unable to regenerate complete body appendages. Antler regeneration has traditionally been viewed as an epimorphic process closely resembling limb regeneration in urodele amphibians, and the terminology of the latter process has also been applied to antler regeneration. More recent studies, however, showed that, unlike urodele limb regeneration, antler regeneration does not involve cell dedifferentiation and the formation of a blastema from these dedifferentiated cells. Rather, these studies suggest that antler regeneration is a stem-cell-based process that depends on the periodic activation of, presumably neural-crest-derived, periosteal stem cells of the distal pedicle. The evidence for this hypothesis is reviewed and as a result, a new concept of antler regeneration as a process of stem-cell-based epimorphic regeneration is proposed that does not involve cell dedifferentiation or transdifferentiation. Antler regeneration illustrates that extensive appendage regeneration in a postnatal mammal can be achieved by a developmental process that differs in several fundamental aspects from limb regeneration in urodeles.

  9. All optical regeneration using semiconductor devices

    DEFF Research Database (Denmark)

    Mørk, Jesper; Öhman, Filip; Tromborg, Bjarne

    All-optical regeneration is a key functionality for implementing all-optical networks. We present a simple theory for the bit-error-rate in links employing all-optical regenerators, which elucidates the interplay between the noise and and nonlinearity of the regenerator. A novel device structure ...... is analyzed, emphasizing general aspects of active semiconductor waveguides....

  10. DECOLORIZATION AND CHEMICAL REGENERATION OF ...

    African Journals Online (AJOL)

    Preferred Customer

    Citric acid is an important chemical product which wildly used in the food and ... activated carbon (PAC) decoloring process is batch operation and has to be filtered to .... adsorbates adsorbed from solution per unit weight of regenerated GAC at the ..... Achaerandio, I.; Guell, C.; Lopez, F. J. Food Engineering 2002, 51, 311. 9.

  11. Skeletal muscle development and regeneration.

    NARCIS (Netherlands)

    Grefte, S.; Kuijpers-Jagtman, A.M.; Torensma, R.; Hoff, J.W. Von den

    2007-01-01

    In the late stages of muscle development, a unique cell population emerges that is a key player in postnatal muscle growth and muscle regeneration. The location of these cells next to the muscle fibers triggers their designation as satellite cells. During the healing of injured muscle tissue, satell

  12. Bone regeneration and stem cells

    DEFF Research Database (Denmark)

    Arvidson, K; Abdallah, B M; Applegate, L A

    2011-01-01

    cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed....

  13. MECHANICAL REGENERATION OF SAND WASTE

    Directory of Open Access Journals (Sweden)

    D. I. Gnir

    2005-01-01

    Full Text Available The experimental activation of the sand regenerator of the firm SINTO is carried out at ОАО “MZOO". It is shown that sand grains are cleared from films of binding agents, that allows to use the treated sand for preparation of agglutinant and core sands.

  14. Bone regeneration during distraction osteogenesis

    NARCIS (Netherlands)

    Amir, L.R.; Everts, V.; Bronckers, A.L.J.J.

    2009-01-01

    Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connec- tive tissues in the gap area between two separated bone segments. This procedure has received much clinical atten- tion as a way to co

  15. Skeletal muscle development and regeneration.

    NARCIS (Netherlands)

    Grefte, S.; Kuijpers-Jagtman, A.M.; Torensma, R.; Hoff, J.W. Von den

    2007-01-01

    In the late stages of muscle development, a unique cell population emerges that is a key player in postnatal muscle growth and muscle regeneration. The location of these cells next to the muscle fibers triggers their designation as satellite cells. During the healing of injured muscle tissue,

  16. Mechanical device for tissue regeneration

    NARCIS (Netherlands)

    Herder, J.L.; Maij, E.

    2010-01-01

    The invention relates to a mechanical device for tissue- regeneration inside a patient, comprising means (2, 3) to place a scaffold for the tissue under mechanical stress. Said means comprise a first device-part (2) and a second device-part (3) which parts are arranged to be movable with respect to

  17. Novel RNAi-mediated approach to G protein-coupled receptor deorphanization: proof of principle and characterization of a planarian 5-HT receptor.

    Directory of Open Access Journals (Sweden)

    Mostafa Zamanian

    Full Text Available G protein-coupled receptors (GPCRs represent the largest known superfamily of membrane proteins extending throughout the Metazoa. There exists ample motivation to elucidate the functional properties of GPCRs given their role in signal transduction and their prominence as drug targets. In many target organisms, these efforts are hampered by the unreliable nature of heterologous receptor expression platforms. We validate and describe an alternative loss-of-function approach for ascertaining the ligand and G protein coupling properties of GPCRs in their native cell membrane environment. Our efforts are focused on the phylum Platyhelminthes, given the heavy health burden exacted by pathogenic flatworms, as well as the role of free-living flatworms as model organisms for the study of developmental biology. RNA interference (RNAi was used in conjunction with a biochemical endpoint assay to monitor cAMP modulation in response to the translational suppression of individual receptors. As proof of principle, this approach was used to confirm the neuropeptide GYIRFamide as the cognate ligand for the planarian neuropeptide receptor GtNPR-1, while revealing its endogenous coupling to Gα(i/o. The method was then extended to deorphanize a novel Gα(s-coupled planarian serotonin receptor, DtSER-1. A bioinformatics protocol guided the selection of receptor candidates mediating 5-HT-evoked responses. These results provide functional data on a neurotransmitter central to flatworm biology, while establishing the great potential of an RNAi-based deorphanization protocol. Future work can help optimize and adapt this protocol for higher-throughput platforms as well as other phyla.

  18. Optical Regeneration and Noise in Semiconductor Devices

    DEFF Research Database (Denmark)

    Öhman, Filip

    2005-01-01

    In this report all-optical 2R-regeneration in optical communication systems is investigated. A simple regenerator device based on concatenated semiconductor optical amplifiers (SOAs) and electro absorbers (EAs) is introduced and examined. Experiments show that the monolithic SOA-EA 2R-regenerator......In this report all-optical 2R-regeneration in optical communication systems is investigated. A simple regenerator device based on concatenated semiconductor optical amplifiers (SOAs) and electro absorbers (EAs) is introduced and examined. Experiments show that the monolithic SOA-EA 2R...

  19. How sex hormones promote skeletal muscle regeneration.

    Science.gov (United States)

    Velders, Martina; Diel, Patrick

    2013-11-01

    Skeletal muscle regeneration efficiency declines with age for both men and women. This decline impacts on functional capabilities in the elderly and limits their ability to engage in regular physical activity and to maintain independence. Aging is associated with a decline in sex hormone production. Therefore, elucidating the effects of sex hormone substitution on skeletal muscle homeostasis and regeneration after injury or disuse is highly relevant for the aging population, where sarcopenia affects more than 30 % of individuals over 60 years of age. While the anabolic effects of androgens are well known, the effects of estrogens on skeletal muscle anabolism have only been uncovered in recent times. Hence, the purpose of this review is to provide a mechanistic insight into the regulation of skeletal muscle regenerative processes by both androgens and estrogens. Animal studies using estrogen receptor (ER) antagonists and receptor subtype selective agonists have revealed that estrogens act through both genomic and non-genomic pathways to reduce leukocyte invasion and increase satellite cell numbers in regenerating skeletal muscle tissue. Although animal studies have been more conclusive than human studies in establishing a role for sex hormones in the attenuation of muscle damage, data from a number of recent well controlled human studies is presented to support the notion that hormonal therapies and exercise induce added positive effects on functional measures and lean tissue mass. Based on the fact that aging human skeletal muscle retains the ability to adapt to exercise with enhanced satellite cell activation, combining sex hormone therapies with exercise may induce additive effects on satellite cell accretion. There is evidence to suggest that there is a 'window of opportunity' after the onset of a hypogonadal state such as menopause, to initiate a hormonal therapy in order to achieve maximal benefits for skeletal muscle health. Novel receptor subtype selective

  20. Prolonged target deprivation reduces the capacity of injured motoneurons to regenerate.

    Science.gov (United States)

    Furey, Matthew J; Midha, Rajiv; Xu, Qing-Gui; Belkas, Jason; Gordon, Tessa

    2007-04-01

    To investigate whether or not it is the frustrated growth state (no axon growth) that reduces regenerative capacity or the inability of axotomized motoneurons to remake muscle connections (axon growth-no muscle contact) that accounts for poor regenerative capacity of chronically axotomized motoneurons. We chronically axotomized rat femoral motoneurons for 2 months by cutting the nerve and either capping the proximal nerve to prevent axon regeneration (Group 1, no axon growth for 2 mo) or encouraging axon regeneration but not target reinnervation by suture to the distal stump of cut saphenous nerve (Group 2, axon growth with no muscle contact). In the control fresh axotomy group (axon growth with muscle contact), femoral nerve stumps were resutured immediately. Two months later, the femoral nerve was recut and sutured immediately to encourage regeneration in a freshly cut saphenous nerve stump for 6 weeks. Regenerating axons in the saphenous nerve were back-labeled with fluorogold for enumeration of the femoral motoneurons that regenerated their axons into the distal nerve stump. We found that significantly fewer chronically axotomized motoneurons regenerated their axons than freshly axotomized motoneurons that regenerated their axons to reform nerve-muscle connections in the same length of time. The number of motoneurons that regenerated their axons was reduced in both the conditions of no axon growth and axon growth with no muscle contact; thus chronic axotomy for a 2-month period reduced regenerative success irrespective of whether the motoneurons were prevented from regenerating or encouraged to regenerate their axons in that same period of time. Axonal regeneration does not protect motoneurons from the negative effects of prolonged axotomy on regenerative capacity. It is the period of chronic axotomy, in which motoneurons remain without target nerve-muscle connection, and not simply a state of frustrated growth that accounts for the reduced regenerative

  1. Limb Regeneration in Xenopus laevis Froglet

    Directory of Open Access Journals (Sweden)

    Makoto Suzuki

    2006-01-01

    Full Text Available Limb regeneration in amphibians is a representative process of epimorphosis. This type of organ regeneration, in which a mass of undifferentiated cells referred to as the “blastema” proliferate to restore the lost part of the amputated organ, is distinct from morphallaxis as observed, for instance, in Hydra, in which rearrangement of pre-existing cells and tissues mainly contribute to regeneration. In contrast to complete limb regeneration in urodele amphibians, limb regeneration in Xenopus, an anuran amphibian, is restricted. In this review of some aspects regarding adult limb regeneration in Xenopus laevis, we suggest that limb regeneration in adult Xenopus, which is pattern/tissue deficient, also represents epimorphosis.

  2. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    Science.gov (United States)

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

  3. New responsabilities: rethinking regeneration

    Directory of Open Access Journals (Sweden)

    Alessandra Focà

    2015-11-01

    Full Text Available “Regenerative Design, Green Strategy” is a research placed within the debate on the management of construction projects in urban areas with the aim of providing a scientific methodology of control of the effects (taking into consideration the relations among buildings, the environment and non-material elements of an urban area; this is also useful to reevaluate the pri- orities of construction projects, considering all the environmental, social, economic and technological aspects of the place; in other words, it represents a framework that gives same value to both the control of the transformation of the elements within the urban area and to the linkages among those elements. The testing phase takes place in the creation of design guidelines, structured at different levels, for regenerative interventions on the environmental system of the axis of the “Torrente Calopinace”, in the southern part of Reggio Calabria. 

  4. Bioceramics: from bone regeneration to cancer nanomedicine.

    Science.gov (United States)

    Vallet-Regí, María; Ruiz-Hernández, Eduardo

    2011-11-23

    Research on biomaterials has been growing in the last few years due to the clinical needs in organs and tissues replacement and regeneration. In addition, cancer nanomedicine has recently appeared as an effective means to combine nanotechnology developments towards a clinical application. Ceramic materials are suitable candidates to be used in the manufacturing of bone-like scaffolds. Bioceramic materials may also be designed to deliver biologically active substances aimed at repairing, maintaining, restoring or improving the function of organs and tissues in the organism. Several materials such as calcium phosphates, glasses and glass ceramics able to load and subsequently release in a controlled fashion drugs, hormones, growth factors, peptides or nucleic acids have been developed. In particular, to prevent post surgical infections bioceramics may be surface modified and loaded with certain antibiotics, thus preventing the formation of bacterial biofilms. Remarkably, mesoporous bioactive glasses have shown excellent characteristics as drug carrying bone regeneration materials. These bioceramics are not only osteoconductive and osteoproductive, but also osteoinductive, and have therefore been proposed as ideal components for the fabrication of scaffolds for bone tissue engineering. A recent promising development of bioceramic materials is related to the design of magnetic mediators against tumors. Magnetic composites are suitable thermoseeds for cancer treatment by hyperthermia. Moreover, magnetic nanomaterials offer a wide range of possibilities for diagnosis and therapy. These nanoparticles may be conjugated with therapeutic agents and heat the surrounding tissue under the action of alternating magnetic fields, enabling hyperthermia of cancer as an effective adjunct to chemotherapy regimens.

  5. Innovative Approaches to Regenerate Enamel and Dentin

    Directory of Open Access Journals (Sweden)

    Xanthippi Chatzistavrou

    2012-01-01

    Full Text Available The process of tooth mineralization and the role of molecular control of cellular behavior during embryonic tooth development have attracted much attention the last few years. The knowledge gained from the research in these fields has improved the general understanding about the formation of dental tissues and the entire tooth and set the basis for teeth regeneration. Tissue engineering using scaffold and cell aggregate methods has been considered to produce bioengineered dental tissues, while dental stem/progenitor cells, which can differentiate into dental cell lineages, have been also introduced into the field of tooth mineralization and regeneration. Some of the main strategies for making enamel, dentin, and complex tooth-like structures are presented in this paper. However, there are still significant barriers that obstruct such strategies to move into the regular clinic practice, and these should be overcome in order to have the regenerative dentistry as the important mean that can treat the consequences of tooth-related diseases.

  6. Germline Transgenic Methods for Tracking Cells and Testing Gene Function during Regeneration in the Axolotl

    Science.gov (United States)

    Khattak, Shahryar; Schuez, Maritta; Richter, Tobias; Knapp, Dunja; Haigo, Saori L.; Sandoval-Guzmán, Tatiana; Hradlikova, Kristyna; Duemmler, Annett; Kerney, Ryan; Tanaka, Elly M.

    2013-01-01

    The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum (axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we inducibly overexpress the cell-cycle inhibitor p16INK4a, which negatively regulates spinal cord regeneration. These tissue-specific germline axolotl lines and tightly inducible Cre drivers and LoxP reporter lines render this classical regeneration model molecularly accessible. PMID:24052945

  7. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    to large neurons after crush and regeneration than in controls, indicating that regeneration of small neurons was less complete than that of large ones. This contrasted with the fact that unmyelinated axons in the regenerated sural nerve after 74 days were only slightly reduced....... of axons. Axonal counts do not reflect the number of regenerated neurons because of axonal branching and because myelinated axons form unmyelinated sprouts. Two days to 10 weeks after crushing, the distal sural or peroneal nerves were cut and exposed to fluoro-dextran. Large and small dorsal root ganglion...... cells that had been labelled, i.e., that had regenerated axons towards or beyond the injection site, were counted in serial sections. Large and small neurons with presumably myelinated and unmyelinated axons, respectively, were classified by immunostaining for neurofilaments. The axonal growth rate...

  8. Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Ping Li

    2016-01-01

    Full Text Available Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes’ expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord.

  9. Effect of JNK inhibitor SP600125 on hair cell regeneration in zebrafish (Danio rerio) larvae

    Science.gov (United States)

    Sun, Shaoyang; Wang, Xu; Li, Wenyan; Li, Huawei

    2016-01-01

    The c-Jun amino-terminal kinase (JNK) proteins are a subgroup of the mitogen-activated protein kinase family. They play a complex role in cell proliferation, survival, and apoptosis. Here, we report a novel role of JNK signalling in hair cell regeneration. We eliminated hair cells of 5-day post-fertilization zebrafish larvae using neomycin followed by JNK inhibition with SP600125. JNK inhibition strongly decreased the number of regenerated hair cells in response to neomycin damage. These changes were associated with reduced proliferation. JNK inhibition also increased cleaved caspase-3 activity and induced apoptosis in regenerating neuromasts. Finally, JNK inhibition with SP600125 decreased the expression of genes related to Wnt. Over-activation of the Wnt signalling pathway partly rescued the hair cell regeneration defects induced by JNK inhibition. Together, our findings provide novel insights into the function of JNK and show that JNK inhibition blocks hair cell regeneration by controlling the Wnt signalling pathway. PMID:27438150

  10. Preliminary Results from Simulations of Temperature Oscillations in Stirling Engine Regenerator Matrices

    DEFF Research Database (Denmark)

    Andersen, Stig Kildegård; Carlsen, Henrik; Thomsen, Per Grove

    2006-01-01

    The objective of this study has been to create a Stirling engine model for studying the effects of regenerator matrix temperature oscillations on Stirling engine performance. A one-dimensional model with axial discretisation of engine components has been formulated using the control volume method....... The model contains a system of ordinary differential equations (ODEs) derived from mass and energy balances for gas filled control volumes and energy balances for regenerator matrix control masses. Interpolation methods with filtering properties are used for state variables at control volume interfaces...... shooting method. It has been found possible to accurately solve the stiff ODE system that describes the coupled thermodynamics of the gas and the regenerator matrix and to reliably find periodic steady state solutions to the model. Preliminary results indicate that the regenerator matrix temperature...

  11. Nutrient regeneration by mussel Mytilus edulis spat assemblages in a macrotidal system

    NARCIS (Netherlands)

    Broekhoven, van W.; Troost, K.; Jansen, H.M.; Smaal, A.C.

    2014-01-01

    Besides exercising grazing control over phytoplankton populations, suspension-feeding bivalves can also stimulate carrying capacity by regeneration of nutrients. This study provides new data on nutrient uptake and release dynamics, and potential implications for availability and stoichiometry of nut

  12. Research of Energy Regeneration Technology in Electric Vehicle%电动车能量再生技术

    Institute of Scientific and Technical Information of China (English)

    陈家新; 江建中; 汪信尧

    2003-01-01

    The theory of energy regeneration in electric vehicle (EV) has been introduced in most papers, but the mathematic modelof EV energy regeneration system was little studied. In this paper the mathematic model of EV energy regeneration system is studied,and then the system ability under four control strategies is analyzed. In the end the system reliability is researched, and the calcula-tion model of system reliability is proposed.

  13. Expressed genes in regenerating rat liver after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Cun-Shuan Xu; Salman Rahrnan; Jing-Bo Zhang; Cui-Fang Chang; Jin-Yun Yuan; Wen-Qiang Li; Hong-Peng Han; Ke-Jin Yang; Li-Feng Zhao; Yu-Chang Li; Hui-Yong Zhang

    2005-01-01

    AIM: To reveal the liver regeneration (LR) and its controlas well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers.METHODS: Five hundred and fifty-one expressed sequence tags screened by suppression subtractive hybridization were made into an in-house cDNA microarray, and the expressive genes and their expressive profiles in regenerating rat livers were analyzed by microarray and bioinformatics. RESULTS: Three hundred of the analyzed 551 genes were up- or downregulated more than twofolds at one or more time points during LR. Most of the genes were up- or downregulated 2-5 folds, but the highest reached 90 folds of the control. One hundred and thirty-nine of themshowed upregulation, 135 displayed downregulation, and up or down expression of 26 genes revealed a dependence on regenerating livers. The genes expressedin 24-h regenerating livers were much more than those in the others. Cluster analysis and generalization analysis showed that there were at least six distinct temporal patterns of gene expression in the regenerating livers, that is, genes were expressed in the immediate early phase, early phase, intermediate phase, early-late phase, late phase, terminal phase. CONCLUSION: In LR, the number of down-regulated genes was almost similar to that of the upregulated genes; the successively altered genes were more than the rapidly transient genes. The temporal patterns of gene expression were similar 2 and 4 h, 12 and 16 h, 48 and 96 h, 72 and 144 h after PH. Microarray combined with suppressive subtractive hybridization can effectively identify the genes related to LR.

  14. Regeneration of soft tissues is promoted by MMP1 treatment after digit amputation in mice.

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    Full Text Available The ratio of matrix metalloproteinases (MMPs to the tissue inhibitors of metalloproteinases (TIMPs in wounded tissues strictly control the protease activity of MMPs, and therefore regulate the progress of wound closure, tissue regeneration and scar formation. Some amphibians (i.e. axolotl/newt demonstrate complete regeneration of missing or wounded digits and even limbs; MMPs play a critical role during amphibian regeneration. Conversely, mammalian wound healing re-establishes tissue integrity, but at the expense of scar tissue formation. The differences between amphibian regeneration and mammalian wound healing can be attributed to the greater ratio of MMPs to TIMPs in amphibian tissue. Previous studies have demonstrated the ability of MMP1 to effectively promote skeletal muscle regeneration by favoring extracellular matrix (ECM remodeling to enhance cell proliferation and migration. In this study, MMP1 was administered to the digits amputated at the mid-second phalanx of adult mice to observe its effect on digit regeneration. Results indicated that the regeneration of soft tissue and the rate of wound closure were significantly improved by MMP1 administration, but the elongation of the skeletal tissue was insignificantly affected. During digit regeneration, more mutipotent progenitor cells, capillary vasculature and neuromuscular-related tissues were observed in MMP1 treated tissues; moreover, there was less fibrotic tissue formed in treated digits. In summary, MMP1 was found to be effective in promoting wound healing in amputated digits of adult mice.

  15. Nerve-dependent and -independent events in blastema formation during Xenopus froglet limb regeneration.

    Science.gov (United States)

    Suzuki, Makoto; Satoh, Akira; Ide, Hiroyuki; Tamura, Koji

    2005-10-01

    Blastema formation, the initial stage of epimorphic limb regeneration in amphibians, is an essential process to produce regenerates. In our study on nerve dependency of blastema formation, we used forelimb of Xenopus laevis froglets as a system and applied some histological and molecular approaches in order to determine early events during blastema formation. We also investigated the lateral wound healing in comparison to blastema formation in limb regeneration. Our study confirmed at the molecular level that there are nerve-dependent and -independent events during blastema formation after limb amputation, Tbx5 and Prx1, reliable markers of initiation of limb regeneration, that start to be expressed independently of nerve supply, although their expressions cannot be maintained without nerve supply. We also found that cell proliferation activity, cell survival and expression of Fgf8, Fgf10 and Msx1 in the blastema were affected by denervation, suggesting that these events specific for blastema outgrowth are controlled by the nerve supply. Wound healing, which is thought to be categorized into tissue regeneration, shares some nerve-independent events with epimorphic limb regeneration, although the healing process results in simple restoration of wounded tissue. Overall, our results demonstrate that dedifferentiated blastemal cells formed at the initial phase of limb regeneration must enter the nerve-dependent epimorphic phase for further processes, including blastema outgrowth, and that failure of entry results in a simple redifferentiation as tissue regeneration.

  16. Lagging and Its Kinetic Mechanism of Hydrocarbon Re-generation from Organic Matters in Coals

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Based on the composite analysis of the coal sample series with natural and artificial maturation, the lagging and its kinetic mechanism of the hydrocarbon re-generation from the organic matters in coals were studied using the Rock-Eval gas chromatogram (Py-GC) method. The results show that the maturation at the hydrocarbon re-generation peak shifts regularly forward with increasing the starting maturation and the deadline of the hydrocarbon re-generation lies about at 4. 0% Ro. The difference value between the peak and starting maturation of the hydrocarbon regeneration develops in a parabola-like pattern with increasing the starting maturation, and the resolute and relative laggings evolve in stage, from which the lagging depth could be predicted. The peak half-width of the hydrocarbon re-generation curve develops as the starting maturation increases, which might indicate that the hydrocarbon-derived rocks with the starting maturation lied about at oil-generated peak might be relatively high in the hydrocarbon-regenerated amount. In the meantime, the mean reactivated energy of the coal samples with starting maturation develops in four stages that are highly consistent with those of the hydrocarbon-regenerated amount and lagging, which indicated that the hydrocarbon re-generation is strictly controlled by the geochemical mechanism of the reactive kinetics.

  17. Regeneration of soft tissues is promoted by MMP1 treatment after digit amputation in mice.

    Science.gov (United States)

    Mu, Xiaodong; Bellayr, Ian; Pan, Haiying; Choi, Yohan; Li, Yong

    2013-01-01

    The ratio of matrix metalloproteinases (MMPs) to the tissue inhibitors of metalloproteinases (TIMPs) in wounded tissues strictly control the protease activity of MMPs, and therefore regulate the progress of wound closure, tissue regeneration and scar formation. Some amphibians (i.e. axolotl/newt) demonstrate complete regeneration of missing or wounded digits and even limbs; MMPs play a critical role during amphibian regeneration. Conversely, mammalian wound healing re-establishes tissue integrity, but at the expense of scar tissue formation. The differences between amphibian regeneration and mammalian wound healing can be attributed to the greater ratio of MMPs to TIMPs in amphibian tissue. Previous studies have demonstrated the ability of MMP1 to effectively promote skeletal muscle regeneration by favoring extracellular matrix (ECM) remodeling to enhance cell proliferation and migration. In this study, MMP1 was administered to the digits amputated at the mid-second phalanx of adult mice to observe its effect on digit regeneration. Results indicated that the regeneration of soft tissue and the rate of wound closure were significantly improved by MMP1 administration, but the elongation of the skeletal tissue was insignificantly affected. During digit regeneration, more mutipotent progenitor cells, capillary vasculature and neuromuscular-related tissues were observed in MMP1 treated tissues; moreover, there was less fibrotic tissue formed in treated digits. In summary, MMP1 was found to be effective in promoting wound healing in amputated digits of adult mice.

  18. Influences of antibiotics on plantlet regeneration via organogenesis in loblolly pine (Pinus taeda L.)

    Institute of Scientific and Technical Information of China (English)

    TANG Wei; Latoya Harris; Ronald J. Newton

    2003-01-01

    Three antibiotics ampicillin, carbenicillin, and cefotaxime were evaluated for their effects on induction, growth, and differentiation of organogenic calli, as well as rooting of regenerated shoots of three loblolly pine (Pinus taeda L.) genotypes. Of the antibiotics administered, cefotaxime maximally increased the frequency of callus formation and growth rate of organogenic calli, carbenicillin maximally increased the frequency of shoot regeneration and the average number of adventitious shoots per piece of organogenic callus, ampicillin maximally decreased the rooting frequency of regenerated shoots and mean number of roots per regenerated shoot, in comparison with antibiotic-free media. Compared with the control, ampicillin minimally increased the frequency of callus formation, cefotaxime minimally increased the frequency of shoot regeneration, and carbenicillin minimally decreased the rooting frequency of regenerated shoots in three loblolly pine genotypes tested. All three antibiotics increased the frequencies of callus formation and shoot regeneration, and reduced the rooting frequency of regenerated shoots suggested that the establishment of an efficient Agrobacterium tumefaciens-mediated transformation protocol for stable integration of foreign genes into loblolly pine need to select a suitable antibiotic. This investigation could be useful for optimizing genetic transformation of conifers.

  19. Prey-tracking behavior in the invasive terrestrial planarian Platydemus manokwari (Platyhelminthes, Tricladida)

    Science.gov (United States)

    Iwai, Noriko; Sugiura, Shinji; Chiba, Satoshi

    2010-11-01

    Platydemus manokwari is a broadly distributed invasive terrestrial flatworm that preys heavily on land snails and has been credited with the demise of numerous threatened island faunas. We examined whether P. manokwari tracks the mucus trails of land snail prey, investigated its ability to determine trail direction, and evaluated prey preference among various land snail species. A plastic treatment plate with the mucus trail of a single species and a control plate without the trail were placed side by side at the exit of cages housing P. manokwari. All trials were then videotaped overnight. The flatworms moved along plates with mucus trails, but did not respond to plates without trails, blank control (distilled water), or with conspecific flatworm trails. When presented at the midpoint of a snail mucus trail, the flatworms followed the trail in a random direction. The flatworms showed a preference when choosing between two plates, each with a mucus trail of different land snail species. Our results suggest that P. manokwari follows snail mucus trails based on chemical cues to increase the chance of encountering prey; however, trail-tracking behavior showed no directionality.

  20. Cardiac regeneration from activated epicardium.

    Directory of Open Access Journals (Sweden)

    Bram van Wijk

    Full Text Available In contrast to lower vertebrates, the mammalian heart has a very limited regenerative capacity. Cardiomyocytes, lost after ischemia, are replaced by fibroblasts. Although the human heart is able to form new cardiomyocytes throughout its lifespan, the efficiency of this phenomenon is not enough to substitute sufficient myocardial mass after an infarction. In contrast, zebrafish hearts regenerate through epicardial activation and initiation of myocardial proliferation. With this study we obtain insights into the activation and cellular contribution of the mammalian epicardium in response to ischemia. In a mouse myocardial infarction model we analyzed the spatio-temporal changes in expression of embryonic epicardial, EMT, and stem cell markers and the contribution of cells of the Wt1-lineage to the infarcted area. Though the integrity of the epicardial layer overlaying the infarct is lost immediately after the induction of the ischemia, it was found to be regenerated at three days post infarction. In this regenerated epicardium, the embryonic gene program is transiently re-expressed as well as proliferation. Concomitant with this activation, Wt1-lineage positive subepicardial mesenchyme is formed until two weeks post-infarction. These mesenchymal cells replace the cardiomyocytes lost due to the ischemia and contribute to the fibroblast population, myofibroblasts and coronary endothelium in the infarct, and later also to the cardiomyocyte population. We show that in mice, as in lower vertebrates, an endogenous, epicardium-dependent regenerative response to injury is induced. Although this regenerative response leads to the formation of new cardiomyocytes, their number is insufficient in mice but sufficient in lower vertebrates to replace lost cardiomyocytes. These molecular and cellular analyses provide basic knowledge essential for investigations on the regeneration of the mammalian heart aiming at epicardium-derived cells.

  1. Inducement of tissue regeneration of harvested hamstring tendons in a rabbit model

    Science.gov (United States)

    Soejima, T.; Murakami, H.; Noguchi, K.; Shiba, N.; Nagata, K.

    2016-01-01

    Objectives The objective of this study was to determine if the use of fascia lata as a tendon regeneration guide (placed into the tendon canal following harvesting the semitendinosus tendon) would improve the incidence of tissue regeneration and prevent fatty degeneration of the semitendinosus muscle. Materials and Methods Bilateral semitendinosus tendons were harvested from rabbits using a tendon stripper. On the inducing graft (IG) side, the tendon canal and semitendinosus tibial attachment site were connected by the fascia lata, which was harvested at the same width as the semitendinosus tendon. On the control side, no special procedures were performed. Two groups of six rabbits were killed at post-operative weeks 4 and 8, respectively. In addition, three healthy rabbits were killed to obtain normal tissue. We evaluated the incidence of tendon tissue regeneration, cross-sectional area of the regenerated tendon tissue and proportion of fatty tissue in the semitendinosus muscle. Results At post-operative week 8, the distal end of the regenerated tissue reached the vicinity of the tibial insertion on the control side in two of six specimens. On the IG side, the regenerated tissue maintained continuity with the tibial insertion in all specimens. The cross-sectional area of the IG side was significantly greater than that of the control side. The proportion of fatty tissue in the semitendinosus muscle on the IG side was comparable with that of the control side, but was significantly greater than that of the normal muscle. Conclusions Tendon tissue regenerated with the fascia lata graft was thicker than naturally occurring regenerated tissue. However, the proportion of fatty tissue in the semitendinosus muscle was greater than that of normal muscle. Cite this article: K. Tabuchi, T. Soejima, H. Murakami, K. Noguchi, N. Shiba, K. Nagata. Inducement of tissue regeneration of harvested hamstring tendons in a rabbit model. Bone Joint Res 2016;5:247–252. DOI: 10

  2. A study on the regeneration performance characteristics of an internally heated regenerator in a liquid desiccant system

    Energy Technology Data Exchange (ETDEWEB)

    Mun, Ji Hyun [Korea University of Science and Technology, Daejeon (Korea, Republic of); Jeon, Dong Soon; Kim, Young Lyoul; Kim, Seon Chang [Korea Institute of Industrial Technology, Cheonan (Korea, Republic of)

    2016-03-15

    This paper presents a study on the regeneration performance characteristics of an internally heated regenerator applicable to a liquid desiccant system. The internally heated regenerator used in this study was designed and manufactured to provide better regeneration performance. An experimental setup was established to examine the regeneration performance. LiCl aqueous solution was used as working fluid. Variables to evaluate regeneration performance characteristics of the internally heated regenerator were dry bulb temperature, relative humidity and velocity of regeneration air, mass flow rate, temperature and concentration of the LiCl aqueous solution. The experimental conditions were chosen by using a 1/2 fractional factorial DOE. Regeneration rate and regeneration effectiveness were taken as results. From the results, solution concentration and regeneration air relative humidity have strong effects on the regeneration rate. The regeneration effectiveness was affected mostly by regeneration air velocity.

  3. Growth and Scaling during Development and Regeneration

    CERN Document Server

    Werner, Steffen

    2016-01-01

    Life presents fascinating examples of self-organization and emergent phenomena. In multi-cellular organisms, a multitude of cells interact to form and maintain highly complex body plans of well-defined size. In this thesis, we investigate theoretical feedback mechanisms for both self-organized body plan patterning and size control. The thesis is inspired by the astonishing scaling and regeneration abilities of flatworms. These worms can perfectly regrow their entire body plan even from tiny amputation fragments like the tip of the tail. Moreover, they can grow and actively de-grow by more than a factor of 40 in length depending on feeding conditions. These capabilities prompt for remarkable physical mechanisms of self-organized pattern formation and scaling. First, we explore the basic principles and challenges of pattern scaling in mechanisms previously proposed to describe biological pattern formation. Next, we present a novel class of patterning mechanisms yielding entirely self-organized and self-scaling ...

  4. Regeneration in Macrostomum lignano (Platyhelminthes): cellular dynamics in the neoblast stem cell system.

    Science.gov (United States)

    Nimeth, Katharina Theresia; Egger, Bernhard; Rieger, Reinhard; Salvenmoser, Willi; Peter, Roland; Gschwentner, Robert

    2007-03-01

    Neoblasts are potentially totipotent stem cells and the only proliferating cells in adult Platyhelminthes. We have examined the cellular dynamics of neoblasts during the posterior regeneration of Macrostomum lignano. Double-labeling of neoblasts with bromodeoxyuridine and the anti-phospho histone H3 mitosis marker has revealed a complex cellular response in the first 48 h after amputation; this response is different from that known to occur during regeneration in triclad platyhelminths and in starvation/feeding experiments in M. lignano. Mitotic activity is reduced during the first 8 h of regeneration but, at 48 h after amputation, reaches almost twice the value of control animals. The total number of S-phase cells significantly increases after 1 day of regeneration. A subpopulation of fast-cycling neoblasts surprisingly shows the same dynamics during regeneration as those in control animals. Wound healing and regeneration are accompanied by the formation of a distinct blastema. These results present new insights, at the cellular level, into the early regeneration of rhabditophoran Platyhelminthes.

  5. Guiding tissue regeneration with ultrasound in vitro and in vivo

    Science.gov (United States)

    Dalecki, Diane; Comeau, Eric S.; Raeman, Carol H.; Child, Sally Z.; Hobbs, Laura; Hocking, Denise C.

    2015-05-01

    Developing new technologies that enable the repair or replacement of injured or diseased tissues is a major focus of regenerative medicine. This paper will discuss three ultrasound technologies under development in our laboratories to guide tissue regeneration both in vitro and in vivo. A critical obstacle in tissue engineering is the need for rapid and effective tissue vascularization strategies. To address this challenge, we are developing acoustic patterning techniques for microvascular tissue engineering. Acoustic radiation forces associated with ultrasound standing wave fields provide a rapid, non-invasive approach to spatially pattern cells in three dimensions without affecting cell viability. Acoustic patterning of endothelial cells leads to the rapid formation of microvascular networks throughout the volumes of three-dimensional hydrogels, and the morphology of the resultant microvessel networks can be controlled by design of the ultrasound field. A second technology under development uses ultrasound to noninvasively control the microstructure of collagen fibers within engineered tissues. The microstructure of extracellular matrix proteins provides signals that direct cell functions critical to tissue regeneration. Thus, controlling collagen microfiber structure with ultrasound provides a noninvasive approach to regulate the mechanical properties of biomaterials and control cellular responses. The third technology employs therapeutic ultrasound to enhance the healing of chronic wounds. Recent studies demonstrate increased granulation tissue thickness and collagen deposition in murine dermal wounds exposed to pulsed ultrasound. In summary, ultrasound technologies offer noninvasive approaches to control cell behaviors and extracellular matrix organization and thus hold great promise to advance tissue regeneration in vitro and in vivo.