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Sample records for model organism stem

  1. Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

    Science.gov (United States)

    Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

    2010-06-01

    Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

  2. An "age"-structured model of hematopoietic stem cell organization with application to chronic myeloid leukemia.

    Science.gov (United States)

    Roeder, Ingo; Herberg, Maria; Horn, Matthias

    2009-04-01

    Previously, we have modeled hematopoietic stem cell organization by a stochastic, single cell-based approach. Applications to different experimental systems demonstrated that this model consistently explains a broad variety of in vivo and in vitro data. A major advantage of the agent-based model (ABM) is the representation of heterogeneity within the hematopoietic stem cell population. However, this advantage comes at the price of time-consuming simulations if the systems become large. One example in this respect is the modeling of disease and treatment dynamics in patients with chronic myeloid leukemia (CML), where the realistic number of individual cells to be considered exceeds 10(6). To overcome this deficiency, without losing the representation of the inherent heterogeneity of the stem cell population, we here propose to approximate the ABM by a system of partial differential equations (PDEs). The major benefit of such an approach is its independence from the size of the system. Although this mean field approach includes a number of simplifying assumptions compared to the ABM, it retains the key structure of the model including the "age"-structure of stem cells. We show that the PDE model qualitatively and quantitatively reproduces the results of the agent-based approach.

  3. Stem cell organization in Arabidopsis

    NARCIS (Netherlands)

    Wendrich, J.R.

    2016-01-01

    Growth of plant tissues and organs depends on continuous production of new cells, by niches of stem cells. Stem cells typically divide to give rise to one differentiating daughter and one non-differentiating daughter. This constant process of self-renewal ensures that the niches of stem cells or

  4. Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

    Directory of Open Access Journals (Sweden)

    Martin Hoffmann

    Full Text Available Therapeutic application of mesenchymal stem cells (MSC requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

  5. Stem Cell Lineages: Between Cell and Organism

    Directory of Open Access Journals (Sweden)

    Melinda Bonnie Fagan

    2017-01-01

    Full Text Available Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells.

  6. Stem-cell-activated organ following ultrasound exposure: better transplant option for organ transplantation.

    Science.gov (United States)

    Wang, Sen; Li, Yu; Ji, Ying-Chang; Lin, Chang-Min; Man, Cheng; Zheng, Xiao-Xuan

    2010-01-01

    Although doctors try their best to protect transplants during surgery, there remain great challenges for the higher survival rate and less rejection of transplants after organ transplantation. Growing evidence indicates that the stem cells could function after injury rather than aging, implying that suitable injury may activate the stem cells of damaged organs. Furthermore, it has been revealed that stem cells can be used to induce tolerance in transplantation and the ultrasound has great biological effects on organs. Basing on these facts, we hypothesize that the stem cells within the transplants can be activated by ultrasound with high-frequency and medium-intensity. Therefore, the stem-cell-activated organs (SCAO) can be derived, and the SCAO will be better transplant option for organ transplantation. We postulate the ultrasound can change the molecular activity and/or quantity of the stem cells, the membrane permeability, the cell-cell junctions, and their surrounding microenvironments. As a result, the stem cells are activated, and the SCAO will acquire more regenerative capacity and less rejection. In the paper, we also discuss the process, methods and models for verifying the theory, and the consequences. We believe the theory may provide a practical method for the clinical application of the ultrasound and stem cells in organ transplantation.

  7. Nucleosome Organization in Human Embryonic Stem Cells.

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    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  8. Organizing Organoids: Stem Cells Branch Out.

    Science.gov (United States)

    Davies, Jamie A

    2017-12-07

    In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a carefully optimized method for making a branch-competent ureteric bud, a tissue fundamental to kidney development, from mouse embryonic stem cells and human induced pluripotent stem cells. The work illuminates embryology and has important implications for making more realistic kidney organoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Stem Cell Models: A Guide to Understand and Mitigate Aging?

    Science.gov (United States)

    Brunauer, Regina; Alavez, Silvestre; Kennedy, Brian K

    2017-01-01

    Aging is studied either on a systemic level using life span and health span of animal models, or on the cellular level using replicative life span of yeast or mammalian cells. While useful in identifying general and conserved pathways of aging, both approaches provide only limited information about cell-type specific causes and mechanisms of aging. Stem cells are the regenerative units of multicellular life, and stem cell aging might be a major cause for organismal aging. Using the examples of hematopoietic stem cell aging and human pluripotent stem cell models, we propose that stem cell models of aging are valuable for studying tissue-specific causes and mechanisms of aging and can provide unique insights into the mammalian aging process that may be inaccessible in simple model organisms. © 2016 S. Karger AG, Basel.

  10. Extinction models for cancer stem cell therapy

    Science.gov (United States)

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  11. Mathematical Modeling: A Bridge to STEM Education

    Science.gov (United States)

    Kertil, Mahmut; Gurel, Cem

    2016-01-01

    The purpose of this study is making a theoretical discussion on the relationship between mathematical modeling and integrated STEM education. First of all, STEM education perspective and the construct of mathematical modeling in mathematics education is introduced. A review of literature is provided on how mathematical modeling literature may…

  12. Empowering Effective STEM Role Models to Promote STEM Equity in Local Communities

    Science.gov (United States)

    Harte, T.; Taylor, J.

    2017-12-01

    Empowering Effective STEM Role Models, a three-hour training developed and successfully implemented by NASA Langley Research Center's Science Directorate, is an effort to encourage STEM professionals to serve as role models within their community. The training is designed to help participants reflect on their identity as a role model and provide research-based strategies to effectively engage youth, particularly girls, in STEM (science, technology, engineering, and mathematics). Research shows that even though girls and boys do not demonstrate a significant difference in their ability to be successful in mathematics and science, there is a significant difference in their confidence level when participating in STEM subject matter and pursuing STEM careers. The Langley training model prepares professionals to disrupt this pattern and take on the habits and skills of effective role models. The training model is based on other successful models and resources for role modeling in STEM including SciGirls; the National Girls Collaborative; and publications by the American Association of University Women and the National Academies. It includes a significant reflection component, and participants walk through situation-based scenarios to practice a focused suite of research-based strategies. These strategies can be implemented in a variety of situations and adapted to the needs of groups that are underrepresented in STEM fields. Underpinning the training and the discussions is the fostering of a growth mindset and promoting perseverance. "The Power of Yet" becomes a means whereby role models encourage students to believe in themselves, working toward reaching their goals and dreams in the area of STEM. To provide additional support, NASA Langley role model trainers are available to work with a champion at other organizations to facilitate the training. This champion helps recruit participants, seeks leadership buy-in, and helps provide valuable insights for needs and

  13. Stem/progenitor cells in pituitary organ homeostasis and tumourigenesis

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    Manshaei, Saba

    2018-01-01

    Evidence for the presence of pituitary gland stem cells has been provided over the last decade using a combination of approaches including in vitro clonogenicity assays, flow cytometric side population analysis, immunohistochemical analysis and genetic approaches. These cells have been demonstrated to be able to self-renew and undergo multipotent differentiation to give rise to all hormonal lineages of the anterior pituitary. Furthermore, evidence exists for their contribution to regeneration of the organ and plastic responses to changing physiological demand. Recently, stem-like cells have been isolated from pituitary neoplasms raising the possibility that a cytological hierarchy exists, in keeping with the cancer stem cell paradigm. In this manuscript, we review the evidence for the existence of pituitary stem cells, their role in maintaining organ homeostasis and the regulation of their differentiation. Furthermore, we explore the emerging concept of stem cells in pituitary tumours and their potential roles in these diseases. PMID:28855316

  14. Genome engineering of stem cell organoids for disease modeling.

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    Sun, Yingmin; Ding, Qiurong

    2017-05-01

    Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.

  15. A MODEL FOR POSTRADIATION STEM CELL KINETICS,

    Science.gov (United States)

    In polycythemic rats observed for 17 days postradiation (300 R, 250 KVP X-rays) it was noted that stem cell release diminished to 8 percent of the...correlate these findings with a kinetic model of erythropoiesis. It was suggested that the initial depression in stem cell release might be due to cellular

  16. Human pluripotent stem cells: an emerging model in developmental biology.

    Science.gov (United States)

    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

  17. Modeling human infertility with pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Di Chen

    2017-05-01

    Full Text Available Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse. However, recent work using next generation sequencing, gene editing and differentiation of germline cells from pluripotent stem cells has revealed that the core molecular mechanisms that regulate human germline development are different from rodents. Here, we will discuss the major molecular pathways required for human germline differentiation and how pluripotent stem cells have revolutionized our ability to study the earliest steps in human embryonic lineage specification in order to understand human fertility.

  18. Queer in STEM Organizations: Workplace Disadvantages for LGBT Employees in STEM Related Federal Agencies

    Directory of Open Access Journals (Sweden)

    Erin A. Cech

    2017-02-01

    Full Text Available Lesbian, gay, bisexual, and transgender (LGBT individuals in U.S. workplaces often face disadvantages in pay, promotion, and inclusion and emergent research suggests that these disadvantages may be particularly pernicious within science and engineering environments. However, no research has systematically examined whether LGBT employees indeed encounter disadvantages in science, technology, engineering and math (STEM organizations. Using representative data of over 30,000 workers employed in six STEM-related federal agencies (the Department of Energy, the Environmental Protection Agency, the National Science Foundation, NASA, the Nuclear Regulatory Commission, and the Department of Transportation, over 1000 of whom identify as LGBT, we compare the workplace experiences of LGBT employees in STEM-related federal agencies with those of their non-LGBT colleagues. Across numerous measures along two separate dimensions of workplace experiences—perceived treatment as employees and work satisfaction—LGBT employees in STEM agencies report systematically more negative workplace experiences than their non-LGBT colleagues. Exploring how these disadvantages vary by agency, supervisory status, age cohort, and gender, we find that LGBT persons have more positive experiences in regulatory agencies but that supervisory status does not improve LGBT persons’ experiences, nor do the youngest LGBT employees fare better than their older LGBT colleagues. LGBT-identifying men and women report similar workplace disadvantages. We discuss the implications of these findings for STEM organizations and STEM inequality more broadly.

  19. The Stem Cell Club: a model for unrelated stem cell donor recruitment.

    Science.gov (United States)

    Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

    2017-12-01

    Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

  20. Stem biomass and volume models of selected tropical tree species ...

    African Journals Online (AJOL)

    Stem biomass and stem volume were modelled as a function of diameter (at breast height; Dbh) and stem height (height to the crown base). Logarithmic models are presented that utilise Dbh and height data to predict tree component biomass and stem volumes. Alternative models are given that afford prediction based on ...

  1. A quantitative and dynamic model for plant stem cell regulation.

    Directory of Open Access Journals (Sweden)

    Florian Geier

    Full Text Available Plants maintain pools of totipotent stem cells throughout their entire life. These stem cells are embedded within specialized tissues called meristems, which form the growing points of the organism. The shoot apical meristem of the reference plant Arabidopsis thaliana is subdivided into several distinct domains, which execute diverse biological functions, such as tissue organization, cell-proliferation and differentiation. The number of cells required for growth and organ formation changes over the course of a plants life, while the structure of the meristem remains remarkably constant. Thus, regulatory systems must be in place, which allow for an adaptation of cell proliferation within the shoot apical meristem, while maintaining the organization at the tissue level. To advance our understanding of this dynamic tissue behavior, we measured domain sizes as well as cell division rates of the shoot apical meristem under various environmental conditions, which cause adaptations in meristem size. Based on our results we developed a mathematical model to explain the observed changes by a cell pool size dependent regulation of cell proliferation and differentiation, which is able to correctly predict CLV3 and WUS over-expression phenotypes. While the model shows stem cell homeostasis under constant growth conditions, it predicts a variation in stem cell number under changing conditions. Consistent with our experimental data this behavior is correlated with variations in cell proliferation. Therefore, we investigate different signaling mechanisms, which could stabilize stem cell number despite variations in cell proliferation. Our results shed light onto the dynamic constraints of stem cell pool maintenance in the shoot apical meristem of Arabidopsis in different environmental conditions and developmental states.

  2. Local stem cell depletion model for radiation myelitis

    International Nuclear Information System (INIS)

    Yaes, R.J.; Kalend, A.

    1988-01-01

    We propose a model for normal tissue damage based on the assumption that adult mammalian stem cells have limited mobility and, consequently, for each organ, there is a maximum volume (the critical volume, Vc), that can be repopulated and repaired by a single surviving stem cell. This concept is applied to a simple, 1-dimensional model of the spinal cord, where the critical volume is a slice of thickness, t, assumed to be small compared to lengths of spinal cord usually irradiated clinically. The probability of myelitis is explicitly obtained as a function of the dose, dose per fraction, length of cord irradiated, slice thickness, number of stem cells per slice and parameters alpha and beta of the stem cell survival curve. The complication probability is expressed as a triple negative exponential function of dose analogous to the double negative exponential function for tumor control, resulting in a steep dose-response curve with short tails in both the high dose and low dose regions. We show that the model predictions are compatible with the experimental data for radiation myelitis in the rat. We discuss how this concept can be applied to other organs such as skin and to organs composed of structurally and functionally distinct subunits, such as the kidney

  3. Genome organization, instabilities, stem cells, and cancer

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    Senthil Kumar Pazhanisamy

    2009-01-01

    Full Text Available It is now widely recognized that advances in exploring genome organization provide remarkable insights on the induction and progression of chromosome abnormalities. Much of what we know about how mutations evolve and consequently transform into genome instabilities has been characterized in the spatial organization context of chromatin. Nevertheless, many underlying concepts of impact of the chromatin organization on perpetuation of multiple mutations and on propagation of chromosomal aberrations remain to be investigated in detail. Genesis of genome instabilities from accumulation of multiple mutations that drive tumorigenesis is increasingly becoming a focal theme in cancer studies. This review focuses on structural alterations evolve to raise a variety of genome instabilities that are manifested at the nucleotide, gene or sub-chromosomal, and whole chromosome level of genome. Here we explore an underlying connection between genome instability and cancer in the light of genome architecture. This review is limited to studies directed towards spatial organizational aspects of origin and propagation of aberrations into genetically unstable tumors.

  4. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  5. The Effect of STEM Learning through the Project of Designing Boat Model toward Student STEM Literacy

    Science.gov (United States)

    Tati, T.; Firman, H.; Riandi, R.

    2017-09-01

    STEM Learning focusses on development of STEM-literate society, the research about implementation of STEM learning to develope students’ STEM literacy is still limited. This study is aimed to examine the effect of implementation STEM learning through the project of designing boat model on students STEM literacy in energy topic. The method of this study was a quasi-experiment with non-randomized pretest-posttest control group design. There were two classes involved, the experiment class used Project Based Learning with STEM approach and control class used Project-Based Learning without STEM approach. A STEM Literacy test instrument was developed to measure students STEM literacy which consists of science literacy, mathematics literacy, and technology-engineering literacy. The analysis showed that there were significant differences on improvement science literacy, mathematics technology-engineering between experiment class and control class with effect size more than 0.8 (large effect). The difference of improvement of STEM literacy between experiment class and control class is caused by the existence of design engineering activity which required students to apply the knowledge from every field of STEM. The challenge that was faced in STEM learning through design engineering activity was how to give the students practice to integrate STEM field in solving the problems. In additional, most of the students gave positive response toward implementation of STEM learning through design boat model project.

  6. Promoting Strategic STEM Education Outreach Programming Using a Systems-Based STEM-EO Model

    Science.gov (United States)

    Ward, Annmarie R.

    2015-01-01

    In this paper a STEM Education Outreach (STEM-EO) Model for promoting strategic university outreach programming at Penn State University to the benefit of university, school district and community stakeholders is described. The model considers STEM-EO as a complex system involving overarching learning goals addressed within four outreach domains…

  7. Queer in STEM Organizations: Workplace Disadvantages for LGBT Employees in STEM Related Federal Agencies

    OpenAIRE

    Erin A. Cech; Michelle V. Pham

    2017-01-01

    Lesbian, gay, bisexual, and transgender (LGBT) individuals in U.S. workplaces often face disadvantages in pay, promotion, and inclusion and emergent research suggests that these disadvantages may be particularly pernicious within science and engineering environments. However, no research has systematically examined whether LGBT employees indeed encounter disadvantages in science, technology, engineering and math (STEM) organizations. Using representative data of over 30,000 workers employed i...

  8. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

    Full Text Available Abstract Background Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.. A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells. Results We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a

  9. Self-organization of human embryonic stem cells on micropatterns

    Science.gov (United States)

    Deglincerti, Alessia; Etoc, Fred; Guerra, M. Cecilia; Martyn, Iain; Metzger, Jakob; Ruzo, Albert; Simunovic, Mijo; Yoney, Anna; Brivanlou, Ali H.; Siggia, Eric; Warmflash, Aryeh

    2018-01-01

    Fate allocation in the gastrulating embryo is spatially organized as cells differentiate to specialized cell types depending on their positions with respect to the body axes. There is a need for in vitro protocols that allow the study of spatial organization associated with this developmental transition. While embryoid bodies and organoids can exhibit some spatial organization of differentiated cells, these methods do not yield consistent and fully reproducible results. Here, we describe a micropatterning approach where human embryonic stem cells are confined to disk-shaped, sub-millimeter colonies. After 42 hours of BMP4 stimulation, cells form self-organized differentiation patterns in concentric radial domains, which express specific markers associated with the embryonic germ layers, reminiscent of gastrulating embryos. Our protocol takes 3 days; it uses commercial microfabricated slides (CYTOO), human laminin-521 (LN-521) as extra-cellular matrix coating, and either conditioned or chemically-defined medium (mTeSR). Differentiation patterns within individual colonies can be determined by immunofluorescence and analyzed with cellular resolution. Both the size of the micropattern and the type of medium affect the patterning outcome. The protocol is appropriate for personnel with basic stem cell culture training. This protocol describes a robust platform for quantitative analysis of the mechanisms associated with pattern formation at the onset of gastrulation. PMID:27735934

  10. Desensitization for solid organ and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zachary, Andrea A; Leffell, Mary S

    2014-03-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  11. Organization of haemopoietic stem cells: the generation-age hypothesis

    International Nuclear Information System (INIS)

    Rosendaal, M.; Hodgson, G.S.; Bradley, T.R.

    1978-01-01

    This paper proposes that the previous division history of each stem cell is one determinant of the functional organisation of the haemopoietic stem cell population. Older stem cell are used to form blood before younger ones. The stem cells generating capacity of a lineage is finite, and cells are eventually lost to the system by forming two committed precursors of the cell lines, and the next oldest stem cell takes over. Hence the proposed term 'generation-age hypothesis', supported by experimental evidence. Older stem cells from normal bone marrow and 13 day foetal liver were stripped away with phase-specific drugs revealing a younger population of stem cells with three-to four-fold greater stem cell generating capacity. Normal stem cells aged by continuous irradiation and serial retransplantation had eight-fold reduced generating capacity. That of stem cells in the bloodstream was half to a quarter that of normal bone marrow stem cells. There were some circulating stem cells, identified by reaction to brain-associated antigen, positive for 75% of normal femoral stem cells but not their progeny, whose capacity for stem cell generation was an eighth to one fortieth that of normal cells. (U.K.)

  12. Conditioning a segmented stem profile model for two diameter measurements

    Science.gov (United States)

    Raymond L. Czaplewski; Joe P. Mcclure

    1988-01-01

    The stem profile model of Max and Burkhart (1976) is conditioned for dbh and a second upper stem measurement. This model was applied to a loblolly pine data set using diameter outside bark at 5.3m (i.e., height of 17.3 foot Girard form class) as the second upper stem measurement, and then compared to the original, unconditioned model. Variance of residuals was reduced...

  13. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    Science.gov (United States)

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  14. Covalent growth factor tethering to direct neural stem cell differentiation and self-organization.

    Science.gov (United States)

    Ham, Trevor R; Farrag, Mahmoud; Leipzig, Nic D

    2017-04-15

    Tethered growth factors offer exciting new possibilities for guiding stem cell behavior. However, many of the current methods present substantial drawbacks which can limit their application and confound results. In this work, we developed a new method for the site-specific covalent immobilization of azide-tagged growth factors and investigated its utility in a model system for guiding neural stem cell (NSC) behavior. An engineered interferon-γ (IFN-γ) fusion protein was tagged with an N-terminal azide group, and immobilized to two different dibenzocyclooctyne-functionalized biomimetic polysaccharides (chitosan and hyaluronan). We successfully immobilized azide-tagged IFN-γ under a wide variety of reaction conditions, both in solution and to bulk hydrogels. To understand the interplay between surface chemistry and protein immobilization, we cultured primary rat NSCs on both materials and showed pronounced biological effects. Expectedly, immobilized IFN-γ increased neuronal differentiation on both materials. Expression of other lineage markers varied depending on the material, suggesting that the interplay of surface chemistry and protein immobilization plays a large role in nuanced cell behavior. We also investigated the bioactivity of immobilized IFN-γ in a 3D environment in vivo and found that it sparked the robust formation of neural tube-like structures from encapsulated NSCs. These findings support a wide range of potential uses for this approach and provide further evidence that adult NSCs are capable of self-organization when exposed to the proper microenvironment. For stem cells to be used effectively in regenerative medicine applications, they must be provided with the appropriate cues and microenvironment so that they integrate with existing tissue. This study explores a new method for guiding stem cell behavior: covalent growth factor tethering. We found that adding an N-terminal azide-tag to interferon-γ enabled stable and robust Cu-free 'click

  15. Total tree, merchantable stem and branch volume models for ...

    African Journals Online (AJOL)

    Total tree, merchantable stem and branch volume models for miombo woodlands of Malawi. Daud J Kachamba, Tron Eid. Abstract. The objective of this study was to develop general (multispecies) models for prediction of total tree, merchantable stem and branch volume including options with diameter at breast height (dbh) ...

  16. Bong-Han Corpuscles as Possible Stem Cell Niches on the Organ-Surfaces

    Directory of Open Access Journals (Sweden)

    Min Su Kim

    2008-03-01

    Full Text Available Objectives : Showing that Bong-Han corpuscles(BHC are suppliers of the stem cells in adulthood, and the Bong-Han ducts(BHD are transportation routes of stem cells. Methods : BHC and BHD were obtained from the internal organ-surfaces of rats. The sliced BHC and BHD were immunostained with various stem cell markers. Extracellular matrices were also analyzed by immunohistochemistry. Result : The presence of mesenchymal stem cells was confirmed by the expression of Integrin beta 1, Collagen type 1 and Fibronectin. But CD54 was not expressed. The hematopoietic stem cell marker, Thy 1 was strongly expressed. BHDs showed Collagen type 1, Fibronectin, and vWF expression. Conclusion : Both hematopoietic and mesenchymal stem cell markers were expressed strongly in BHC similarly as in bone marrow. An endothelial cell marker(vWF demonstrated the possibility of the stem cell transportation routes of BHD.

  17. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction

    International Nuclear Information System (INIS)

    Francois, S.

    2006-01-01

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  18. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  19. 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.

  20. FireStem2D — A two-dimensional heat transfer model for simulating tree stem injury in fires

    Science.gov (United States)

    Efthalia K. Chatziefstratiou; Gil Bohrer; Anthony S. Bova; Ravishankar Subramanian; Renato P.M. Frasson; Amy Scherzer; Bret W. Butler; Matthew B. Dickinson

    2013-01-01

    FireStem2D, a software tool for predicting tree stem heating and injury in forest fires, is a physically-based, two-dimensional model of stem thermodynamics that results from heating at the bark surface. It builds on an earlier one-dimensional model (FireStem) and provides improved capabilities for predicting fire-induced mortality and injury before a fire occurs by...

  1. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  2. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  3. Nuclear organization during in vitro differentiation of porcine mesenchymal stem cells (MSCs) into adipocytes.

    Science.gov (United States)

    Stachecka, Joanna; Walczak, Agnieszka; Kociucka, Beata; Ruszczycki, Błażej; Wilczyński, Grzegorz; Szczerbal, Izabela

    2018-02-01

    Differentiation of progenitor cells into adipocytes is accompanied by remarkable changes in cell morphology, cytoskeletal organization, and gene expression profile. Mature adipocytes are filled with a large lipid droplet and the nucleus tends to move to the cell periphery. It was hypothesized that the differentiation process is also associated with changes of nuclear organization. The aim of this study was to determine the number and distribution of selected components of nuclear architecture during porcine in vitro adipogenesis. The pig is an important animal model sharing many similarities to humans at the anatomical, physiological, and genetic levels and has been recognized as a good model for human obesity. Thus, understanding how cellular structures important for fundamental nuclear processes may be altered during adipocyte differentiation is of great importance. Mesenchymal stem cells (MSCs) were derived from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) and were cultured for 7 days in the adipogenic medium. A variable differentiation potential of these cell populations towards adipogenic lineage was observed, and for further study, a comparative characteristic of the nuclear organization in BM-MSCs and AD-MSCs was performed. Nuclear substructures were visualized by indirect immunofluorescence (nucleoli, nuclear speckles, PML bodies, lamins, and HP1α) or fluorescence in situ hybridization (telomeres) on fixed cells at 0, 3, 5, and 7 days of differentiation. Comprehensive characterization of these structures, in terms of their number, size, dynamics, and arrangement in three-dimensional space of the nucleus, was performed. It was found that during differentiation of porcine MSCs into adipocytes, changes of nuclear organization occurred and concerned: (1) the nuclear size and shape; (2) reduced lamin A/C expression; and (3) reorganization of chromocenters. Other elements of nuclear architecture such as nucleoli, SC-35 nuclear speckles, and telomeres

  4. Stem Cell Fate Determination during Development and Regeneration of Ectodermal Organs

    Science.gov (United States)

    Jiménez-Rojo, Lucía; Granchi, Zoraide; Graf, Daniel; Mitsiadis, Thimios A.

    2012-01-01

    The development of ectoderm-derived appendages results in a large variety of highly specialized organs such as hair follicles, mammary glands, salivary glands, and teeth. Despite varying in number, shape, and function, all these ectodermal organs develop through continuous and reciprocal epithelial–mesenchymal interactions, sharing common morphological and molecular features especially during their embryonic development. Diseases such as ectodermal dysplasias can affect simultaneously these organs, suggesting that they may arise from common multipotent precursors residing in the embryonic ectoderm. During embryogenesis, these putative ectodermal stem cells may adopt different fates and consequently be able to generate a variety of tissue-specific stem cells, which are the sources for the various cell lineages that form the diverse organs. The specification of those common epithelial precursors, as well as their further lineage commitment to tissue-specific stem cells, might be controlled by specific signals. It has been well documented that Notch, Wnt, bone morphogenetic protein, and fibroblast growth factor signaling pathways regulate cell fate decisions during the various stages of ectodermal organ development. However, the in vivo spatial and temporal dynamics of these signaling pathways are not yet well understood. Improving the current knowledge on the mechanisms involved in stem cell fate determination during organogenesis and homeostasis of ectodermal organs is crucial to develop effective stem cell-based therapies in order to regenerate or replace pathological and damaged tissues. PMID:22539926

  5. Chimeric animal models in human stem cell biology.

    Science.gov (United States)

    Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

    2009-01-01

    The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

  6. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Science.gov (United States)

    Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

    2016-01-01

    Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  7. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

    Science.gov (United States)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

    2017-04-01

    Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  8. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

    2014-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

  9. Mesenchymal Stem Cell Therapy for Protection and Repair of Injured Vital Organs

    NARCIS (Netherlands)

    van Poll, D.; Parekkadan, B.; Rinkes, I. H. M. Borel; Tilles, A. W.; Yarmush, M. L.

    Recently there has been a paradigm shift in what is considered to be the therapeutic promise of mesenchymal stem cells (MSCs) in diseases of vital organs. Originally, research focused on MSCs as a source of regenerative cells by differentiation of transplanted cells into lost cell types. It is now

  10. Virtual Organizations: Trends and Models

    Science.gov (United States)

    Nami, Mohammad Reza; Malekpour, Abbaas

    The Use of ICT in business has changed views about traditional business. With VO, organizations with out physical, geographical, or structural constraint can collaborate with together in order to fulfill customer requests in a networked environment. This idea improves resource utilization, reduces development process and costs, and saves time. Virtual Organization (VO) is always a form of partnership and managing partners and handling partnerships are crucial. Virtual organizations are defined as a temporary collection of enterprises that cooperate and share resources, knowledge, and competencies to better respond to business opportunities. This paper presents an overview of virtual organizations and main issues in collaboration such as security and management. It also presents a number of different model approaches according to their purpose and applications.

  11. Impact of HLA Diversity on Donor Selection in Organ and Stem Cell Transplantation

    OpenAIRE

    Tiercy Jean-Marie; Claas Frans

    2013-01-01

    The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation pre transplant anti HLA antibodies nee...

  12. Organ-level quorum sensing directs regeneration in hair stem cell populations

    Science.gov (United States)

    Chen, Chih-Chiang; Wang, Lei; Plikus, Maksim V.; Jiang, Ting Xin; Murray, Philip J.; Ramos, Raul; Guerrero-Juarez, Christian F.; Hughes, Michael W; Lee, Oscar K.; Shi, Songtao; Widelitz, Randall B.; Lander, Arthur D.; Chuong, Cheng Ming

    2015-01-01

    SUMMARY Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair removal, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Removing hair at different densities leads to a regeneration of up to 5 times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells. PMID:25860610

  13. STEM based learning to facilitate middle school students’ conceptual change, creativity and collaboration in organization of living system topic

    Science.gov (United States)

    Rustaman, N. Y.; Afianti, E.; Maryati, S.

    2018-05-01

    A study using one group pre-post-test experimental design on Life organization system topic was carried out to investigate student’s tendency in learning abstract concept, their creativity and collaboration in designing and producing cell models through STEM-based learning. A number of seventh grade students in Cianjur district were involved as research subjects (n=34). Data were collected using two tier test for tracing changes in student conception before and after the application of STEM-based learning, and rubrics in creativity design (adopted from Torrance) and product on cell models (individually, in group), and rubric for self-assessment and observed skills on collaboration adapted from Marzano’s for life-long learning. Later the data obtained were analyzed qualitatively by interpreting the tendency of data presented in matrix sorted by gender. Research findings showed that the percentage of student’s scientific concept mastery is moderate in general. Their creativity in making a cell model design varied in category (expressing, emergent, excellent, not yet evident). Student’s collaboration varied from excellent, fair, good, less once, to less category in designing cell model. It was found that STEM based learning can facilitate students conceptual change, creativity and collaboration.

  14. Modelling of tomato stem diameter growth rate based on physiological responses

    International Nuclear Information System (INIS)

    Li, L.; Tan, J.; Lv, T.

    2017-01-01

    The stem diameter is an important parameter describing the growth of tomato plant during vegetative growth stage. A stem diameter growth model was developed to predict the response of plant growth under different conditions. By analyzing the diurnal variations of stem diameter in tomato (Solanum lycopersicum L.), it was found that the stem diameter measured at 3:00 am was the representative value as the daily basis of tomato stem diameter. Based on the responses of growth rate in stem diameter to light and temperature, a linear regression relationship was applied to establish the stem diameter growth rate prediction model for the vegetative growth stage in tomato and which was further validated by experiment. The root mean square error (RMSE) and relative error (RE) were used to test the correlation between measured and modeled stem diameter variations. Results showed that the model can be used in prediction for stem diameter growth rate at vegetative growth stage in tomato. (author)

  15. Мodification of Mechanical Limbal Stem Cell Deficiency Model

    Directory of Open Access Journals (Sweden)

    A. V. Bezushko

    2018-01-01

    Full Text Available Introduction. Ocular surface diseases related with limbal epithelial stem cells dysfunction were united in term “limbal stem cell  deficiency” (LSCD. For experimental study of the regenerative processes and evaluation of the success of new LSCD treatingmethods LSCD model is required. Various LSCD models were proposed in the experiment to study: mechanical, thermal, chemical,medicamental. The main lack of these models were the relative high cost and complexity of execution. The mechanical model allows forthe guaranteed removal of tissues containing LESCs, and therefore seems to be the most acceptable. We offered a modification of themechanical LSCD model in rabbits. Purpose to create a standardized modification of the mechanical limbal stem cell deficiency modelin the experiment. Material and methods. The experimental study was performed in 10 mature Chinchilla rabbits (20 eyes with anaverage weight 2.5–3.5 kg. With the local anesthesia, after a 40-second application of the filter paper impregnated with 20% ethanol,the corneal epithelium was removed. With microsurgical diamond blade we metered limb portion of 4 mm width, 0.2 mm deep, andit was removed along the 360° rim. Results. On the 30th day we discovered corneal opacity and neovascularization with conjunctivalpannus extending to the optical zone of the cornea. Histological examination revealed tissue edema, inflammatory infiltration, andnewly formed vessels. In some places, thinning of epithelium to one row of flattened cells was observed. The Bowman membrane wasdeformed and practically not detected. Histological examination and impression cytology confirmed the presence of goblet cells in thecorneal epithelium. Conclusions. Our modification of the mechanical limbal stem cell deficiency model is devoid of the main lacks ofprevious models, such as the high cost and complexity of execution, provides intraoperative limbal tissue resection depth control andexcludes the possibility of the

  16. [Activation of nucleolar organizers during in vitro cultivation of mouse R1 embryonic stem cells].

    Science.gov (United States)

    Kunafina, E R; Chaplina, M V; Filiasova, E I; Gibanova, N V; Khodarovich, Iu M; Larionov, O A; Zatsepina, O V

    2005-01-01

    We studies the activities of ribosomal genes (nucleolus forming regions of chromosomes) at successive stages of cultivation of the mouse R1 embryonic stem cells. The total number and number of active nucleolar organizers were estimated by means of in situ hybridization with mouse rDNA probes and argentophilic staining of nucleolus forming chromosomes regions from the 16th until the 32nd passages. The data we obtained suggest that the total number of nucleolar organizers per metaphase plate was constant (as a rule, eight), while the mean number of active nucleolar organizers progressively increased from the early (16th) to the late (32nd) passages: 5.2 +/- 0.4 versus 7.4 +/- 0.9 argentophilic organizers per cell. Cell heterogeneity by the number of active nucleolar organizers also increased during the late passages. Taken together, these data suggest activation of DNA transcription and synthesis of ribosomes during cultivation of mouse R1 embryonic stem cells. Based on the experimental and published data, it has been proposed that activation of ribosomal genes correlates in time with a decreased capacity of embryonic stem cells for pluripotent differentiation.

  17. Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Yang, Chunbo; Al-Aama, Jumana; Stojkovic, Miodrag; Keavney, Bernard; Trafford, Andrew; Lako, Majlinda; Armstrong, Lyle

    2015-09-01

    Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient-specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC-based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC-derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC-derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC-derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC-based disease modeling. © AlphaMed Press.

  18. Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond.

    Science.gov (United States)

    Liu, Chun; Oikonomopoulos, Angelos; Sayed, Nazish; Wu, Joseph C

    2018-03-08

    The advent of human induced pluripotent stem cells (iPSCs) presents unprecedented opportunities to model human diseases. Differentiated cells derived from iPSCs in two-dimensional (2D) monolayers have proven to be a relatively simple tool for exploring disease pathogenesis and underlying mechanisms. In this Spotlight article, we discuss the progress and limitations of the current 2D iPSC disease-modeling platform, as well as recent advancements in the development of human iPSC models that mimic in vivo tissues and organs at the three-dimensional (3D) level. Recent bioengineering approaches have begun to combine different 3D organoid types into a single '4D multi-organ system'. We summarize the advantages of this approach and speculate on the future role of 4D multi-organ systems in human disease modeling. © 2018. Published by The Company of Biologists Ltd.

  19. Mesenchymal Stem Cells in Organ Transplantation: Immunomodulatory properties of mesenchymal stem cells for application in organ transplantation

    OpenAIRE

    Crop, Meindert

    2010-01-01

    textabstractKidney transplantation is the only effective treatment for patients with end-stage renal disease. Transplantation of a donor organ, however, leads to recognition of the foreign donor antigens by the recipient’s immune system, resulting in rejection of the graft. In addition, ischemia-reperfusion injury leads to the initiation of immune responses. To prevent graft rejection, transplant recipients need to use life-long immunosuppressive medication. These drugs, however, can lead to ...

  20. Model of organ dose combination

    International Nuclear Information System (INIS)

    Valley, J.-F.; Lerch, P.

    1977-01-01

    The ICRP recommendations are based on the limitation of the dose to each organ. In the application and for a unique source the critical organ concept allows to limit the calculation and represents the irradiation status of an individuum. When several sources of radiation are involved the derivation of the dose contribution of each source to each organ is necessary. In order to represent the irradiation status a new parameter is to be defined. Propositions have been made by some authors, in particular by Jacobi introducing at this level biological parameters like the incidence rate of detriment and its severity. The new concept is certainly richer than a simple dose notion. However, in the actual situation of knowledge about radiation effects an intermediate parameter, using only physical concepts and the maximum permissible doses to the organs, seems more appropriate. The model, which is a generalization of the critical organ concept and shall be extended in the future to take the biological effects into account, will be presented [fr

  1. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...... for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT....

  2. Modeling TSC and LAM Using Patient Derived Induced Pluripotent Stem Cells

    Science.gov (United States)

    2016-10-01

    drug screens . We have now made TSC2 deficient human cells using patient induced pluripotent stem cells (iPSCs...Therapeutics.” Canadian Association of Research in Regenerative Medicine (CARRM), Ottawa, ON, CANADA March 7, 2015 • “ Stem cell approaches to model human... Stem cell approaches to model human development and disease.” Australian Regenerative Medicine Institute, Melbourne, Victoria, AUSTRALIA November

  3. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    International Nuclear Information System (INIS)

    Gross, Emilie; Quillet-Mary, Anne; Ysebaert, Loic; Laurent, Guy; Fournie, Jean-Jacques

    2011-01-01

    The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity

  4. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Fournie

    2011-03-01

    Full Text Available The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

  5. Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids

    Directory of Open Access Journals (Sweden)

    Lam-Phuong Nguyen DO

    2016-04-01

    Full Text Available Acute fibrinous and organizing pneumonia (AFOP is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

  6. Cardiomyocyte differentiation of embryonic stem cells on the surface of organic semiconductors.

    Science.gov (United States)

    Caserta, Sergio; Barra, Mario; Manganelli, Genesia; Tomaiuolo, Giovanna; Filosa, Stefania; Cassinese, Antonio; Guido, Stefano

    2013-06-25

    Electrically active supports provide new horizons for bio-sensing and artificial organ design. Cell-based electrochemical biosensors can be used as bio-microactuators, applied to the biorobotics. Microchip-based bioassay systems can provide real-time cell analysis for preclinical drug design or for intelligent drug delivery devices. In regenerative medicine, electrically active supports can be used as bio-reactors to monitor cell activity, optimize the stem cell differentiation and control cell and tissue morphology. Biocompatibility and direct interaction of the electrically active surface with the cell surface is a critical aspect of this technology.
 In this work embryonic stem cells (AK7 ES) have been cultivated on the surface of thin films achieved through the evaporation of two aromatic compounds (T6 and PDI-8CN2 ) of particular interest for the fabrication of organic field-effect transistors (OFET). One of the potential advantages offered by the application of OFETs as bio-electronic supports is that they represent a powerful tool for the detection of bio-signals because their electrically active surface is an organic film.
 The cell morphology on T6 and PDI-8CN2 surface shows to be similar to the usual cell appearance, as obtained when standard culture support (petri dish) are employed. Moreover, our experimental results demonstrate that stem cells can be lead to differentiation up to "beating" cardiomyocytes even on these electrically-active organic films.
 This investigation encourages the perspective to develop OFET-based biosensors in order to accurately characterize stem cells during the cardiac differentiation process and eventually increase their differentiation efficiency.

  7. Evaluation of alginate microspheres for mesenchymal stem cell engraftment on solid organ

    OpenAIRE

    Trouche, E.; Girod Fullana, S.; Mias, C.; Ceccaldi, C.; Tortosa, F.; Seguelas, M. H.; Calise, D.; Parini, A.; Cussac, D.; Sallerin, B.

    2010-01-01

    Mesenchymal stem cells (MSCs) may be used as a cell source for cell therapy of solid organs due to their differentiation potential and paracrine effect. Nevertheless, optimization of MSC-based therapy needs to develop alternative strategies to improve cell administration and efficiency. One option is the use of alginate microencapsulation, which presents an excellent biocompatibility and an in vivo stability. As MSCs are hypoimmunogenic, it was conceivable to produce microparticles with [algi...

  8. The Alpha Stem Cell Clinic: a model for evaluating and delivering stem cell-based therapies.

    Science.gov (United States)

    Trounson, Alan; DeWitt, Natalie D; Feigal, Ellen G

    2012-01-01

    Cellular therapies require the careful preparation, expansion, characterization, and delivery of cells in a clinical environment. There are major challenges associated with the delivery of cell therapies and high costs that will limit the companies available to fully evaluate their merit in clinical trials, and will handicap their application at the present financial environment. Cells will be manufactured in good manufacturing practice or near-equivalent facilities with prerequisite safety practices in place, and cell delivery systems will be specialized and require well-trained medical and nursing staff, technicians or nurses trained to handle cells once delivered, patient counselors, as well as statisticians and database managers who will oversee the monitoring of patients in relatively long-term follow-up studies. The model proposed for Alpha Stem Cell Clinics will initially use the capacities and infrastructure that exist in the most advanced tertiary medical clinics for delivery of established bone marrow stem cell therapies. As the research evolves, they will incorporate improved procedures and cell preparations. This model enables commercialization of medical devices, reagents, and other products required for cell therapies. A carefully constructed cell therapy clinical infrastructure with the requisite scientific, technical, and medical expertise and operational efficiencies will have the capabilities to address three fundamental and critical functions: 1) fostering clinical trials; 2) evaluating and establishing safe and effective therapies, and 3) developing and maintaining the delivery of therapies approved by the Food and Drug Administration, or other regulatory agencies.

  9. Impact of HLA diversity on donor selection in organ and stem cell transplantation.

    Science.gov (United States)

    Tiercy, Jean-Marie; Claas, Frans

    2013-01-01

    The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

  10. Self-organization of spatial patterning in human embryonic stem cells

    Science.gov (United States)

    Deglincerti, Alessia; Etoc, Fred; Ozair, M. Zeeshan; Brivanlou, Ali H.

    2017-01-01

    The developing embryo is a remarkable example of self-organization, where functional units are created in a complex spatio-temporal choreography. Recently, human embryonic stem cells (ESCs) have been used to recapitulate in vitro the self-organization programs that are executed in the embryo in vivo. This represents a unique opportunity to address self-organization in humans that is otherwise not addressable with current technologies. In this essay, we review the recent literature on self-organization of human ESCs, with a particular focus on two examples: formation of embryonic germ layers and neural rosettes. Intriguingly, both activation and elimination of TGFβ signaling can initiate self-organization, albeit with different molecular underpinnings. We discuss the mechanisms underlying the formation of these structures in vitro and explore future challenges in the field. PMID:26970615

  11. Self-Organization of Spatial Patterning in Human Embryonic Stem Cells.

    Science.gov (United States)

    Deglincerti, Alessia; Etoc, Fred; Ozair, M Zeeshan; Brivanlou, Ali H

    2016-01-01

    The developing embryo is a remarkable example of self-organization, where functional units are created in a complex spatiotemporal choreography. Recently, human embryonic stem cells (ESCs) have been used to recapitulate in vitro the self-organization programs that are executed in the embryo in vivo. This represents an unique opportunity to address self-organization in humans that is otherwise not addressable with current technologies. In this chapter, we review the recent literature on self-organization of human ESCs, with a particular focus on two examples: formation of embryonic germ layers and neural rosettes. Intriguingly, both activation and elimination of TGFβ signaling can initiate self-organization, albeit with different molecular underpinnings. We discuss the mechanisms underlying the formation of these structures in vitro and explore future challenges in the field. © 2016 Elsevier Inc. All rights reserved.

  12. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Directory of Open Access Journals (Sweden)

    Sandeep N Shah

    Full Text Available Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  13. Confronting Color-Blind STEM Talent Development: Toward a Contextual Model for Black Student STEM Identity

    Science.gov (United States)

    Collins, Kristina Henry

    2018-01-01

    What is Black student's science, technology, engineering, and mathematics (STEM) identity? The author addresses this question through a synthesis of the literature that includes studies that explore Black student identity. Background information regarding STEM achievement and persistence followed by empirical studies that explore STEM attitudes…

  14. Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation.

    Science.gov (United States)

    Kobayashi, Toshihiro; Kato-Itoh, Megumi; Nakauchi, Hiromitsu

    2015-01-15

    Generation of functional organs from patients' own cells is one of the ultimate goals of regenerative medicine. As a novel approach to creation of organs from pluripotent stem cells (PSCs), we employed blastocyst complementation in organogenesis-disabled animals and successfully generated PSC-derived pancreas and kidneys. Blastocyst complementation, which exploits the capacity of PSCs to participate in forming chimeras, does not, however, exclude contribution of PSCs to the development of tissues-including neural cells or germ cells-other than those specifically targeted by disabling of organogenesis. This fact provokes ethical controversy if human PSCs are to be used. In this study, we demonstrated that forced expression of Mix-like protein 1 (encoded by Mixl1) can be used to guide contribution of mouse embryonic stem cells to endodermal organs after blastocyst injection. We then succeeded in applying this method to generate functional pancreas in pancreatogenesis-disabled Pdx1 knockout mice using a newly developed tetraploid-based organ-complementation method. These findings hold promise for targeted organ generation from patients' own PSCs in livestock animals.

  15. A functional model for adult stem cells in epithelial tissues.

    NARCIS (Netherlands)

    Verstappen, J.; Katsaros, C.; Torensma, R.; Hoff, J.W. Von den

    2009-01-01

    Tissue turnover, regeneration, and repair take place throughout life. Stem cells are key players in these processes. The characteristics and niches of the stem cell populations in different tissues, and even in related tissues, vary extensively. In this review, stem cell differentiation and stem

  16. Stem cells in skin regeneration: biomaterials and computational models

    Directory of Open Access Journals (Sweden)

    Daniele eTartarini

    2016-01-01

    Full Text Available The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles, has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells have been proposed for the treatment of these wounds, thanks to the ability of stem cells to self-renew and specifically differentiate in response to the target bimolecular environment. Here we discuss how advanced biomedical devices can be developed by combining stem cells with properly engineered biomaterials and computational models. Examples include composite skin substitutes and bioactive dressings with controlled porosity and surface topography for controlling the infiltration and differentiation of the cells. In this scenario, mathematical frameworks for the simulation of cell population growth can provide support for the design of bio-constructs, reducing the need of expensive, time-consuming and ethically controversial animal experimentation.

  17. Colonic stem cell data are consistent with the immortal model of stem cell division under non-random strand segregation.

    Science.gov (United States)

    Walters, K

    2009-06-01

    Colonic stem cells are thought to reside towards the base of crypts of the colon, but their numbers and proliferation mechanisms are not well characterized. A defining property of stem cells is that they are able to divide asymmetrically, but it is not known whether they always divide asymmetrically (immortal model) or whether there are occasional symmetrical divisions (stochastic model). By measuring diversity of methylation patterns in colon crypt samples, a recent study found evidence in favour of the stochastic model, assuming random segregation of stem cell DNA strands during cell division. Here, the effect of preferential segregation of the template strand is considered to be consistent with the 'immortal strand hypothesis', and explore the effect on conclusions of previously published results. For a sample of crypts, it is shown how, under the immortal model, to calculate mean and variance of the number of unique methylation patterns allowing for non-random strand segregation and compare them with those observed. The calculated mean and variance are consistent with an immortal model that incorporates non-random strand segregation for a range of stem cell numbers and levels of preferential strand segregation. Allowing for preferential strand segregation considerably alters previously published conclusions relating to stem cell numbers and turnover mechanisms. Evidence in favour of the stochastic model may not be as strong as previously thought.

  18. Modeling Neuropsychiatric and Neurodegenerative Diseases With Induced Pluripotent Stem Cells.

    Science.gov (United States)

    LaMarca, Elizabeth A; Powell, Samuel K; Akbarian, Schahram; Brennand, Kristen J

    2018-01-01

    Human-induced pluripotent stem cells (hiPSCs) have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional "mini-brains" and clustered, regularly interspersed short palindromic repeats (CRISPR)-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson's disease, and consider the future of this groundbreaking research.

  19. Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

    Science.gov (United States)

    Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

    2016-03-31

    The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

  20. Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

    Science.gov (United States)

    Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

    2017-02-01

    Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324. © 2016 AlphaMed Press.

  1. Advances in stem cells and regenerative medicine: single-cell dynamics, new models and translational perspectives.

    Science.gov (United States)

    Twigger, Alecia-Jane; Scheel, Christina H

    2017-09-01

    An international cohort of over 300 stem cell biologists came together in Heidelberg, Germany in May 2017 as delegates of the 'Advances in Stem Cells and Regenerative Medicine' conference run through the European Molecular Biology Organization. This Meeting Review highlights the novel insights into stem cell regulation, new technologies aiding in discovery and exciting breakthroughs in the field of regenerative medicine that emerged from the meeting. © 2017. Published by The Company of Biologists Ltd.

  2. Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective

    Science.gov (United States)

    Heffernan, John M.; Sirianni, Rachael W.

    2018-02-01

    Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.

  3. The potential of the combination of CRISPR/Cas9 and pluripotent stem cells to provide human organs from chimaeric pigs.

    Science.gov (United States)

    Feng, Wanyou; Dai, Yifan; Mou, Lisha; Cooper, David K C; Shi, Deshun; Cai, Zhiming

    2015-03-23

    Clinical organ allotransplantation is limited by the availability of deceased human donors. However, the transplantation of human organs produced in other species would provide an unlimited number of organs. The pig has been identified as the most suitable source of organs for humans as organs of any size would be available. Genome editing by RNA-guided endonucleases, also known as clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), in combination with induced pluripotent stem cells (iPSC), may have the potential to enable the creation of human organs from genetically-modified chimaeric pigs. These could potentially provide an unlimited supply of organs that would not be rejected by the recipient's immune system. However, substantial research is needed to prove that this approach will work. Genetic modification of chimaeric pigs could also provide useful models for developing therapies for various human diseases, especially in relation to drug development.

  4. Using Stem Cells to Model Diseases of the Outer Retina

    Directory of Open Access Journals (Sweden)

    Camille Yvon

    2015-01-01

    Full Text Available Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE. It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP, Usher syndrome (USH, Leber congenital amaurosis (LCA, gyrate atrophy (GA, juvenile neuronal ceroid lipofuscinosis (NCL, Best vitelliform macular dystrophy (BVMD and age related macular degeneration (AMD.

  5. Using Stem Cells to Model Diseases of the Outer Retina.

    Science.gov (United States)

    Yvon, Camille; Ramsden, Conor M; Lane, Amelia; Powner, Michael B; da Cruz, Lyndon; Coffey, Peter J; Carr, Amanda-Jayne F

    2015-01-01

    Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE). It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC)-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP), Usher syndrome (USH), Leber congenital amaurosis (LCA), gyrate atrophy (GA), juvenile neuronal ceroid lipofuscinosis (NCL), Best vitelliform macular dystrophy (BVMD) and age related macular degeneration (AMD).

  6. Adjusting the Stems Regional Forest Growth Model to Improve Local Predictions

    Science.gov (United States)

    W. Brad Smith

    1983-01-01

    A simple procedure using double sampling is described for adjusting growth in the STEMS regional forest growth model to compensate for subregional variations. Predictive accuracy of the STEMS model (a distance-independent, individual tree growth model for Lake States forests) was improved by using this procedure

  7. Modeling human neurological disorders with induced pluripotent stem cells.

    Science.gov (United States)

    Imaizumi, Yoichi; Okano, Hideyuki

    2014-05-01

    Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained

  8. Stem Photosynthesis of Twig and Its Contribution to New Organ Development in Cutting Seedlings of Salix Matsudana Koidz.

    Directory of Open Access Journals (Sweden)

    Junxiang Liu

    2018-04-01

    Full Text Available The objective of this study was to illustrate the photosynthetic characteristics of current twigs of Salix matsudana Koidz., and clarify the effect of stem photosynthesis on the new organ development in cutting seedlings. Excised twigs were taken as the experimental samples. The response of the stem photosynthesis rate to increasing light intensity and the effective photochemical efficiency of the cross section of the twig were determined. Then, twigs were used as cuttings and exposed to 0, 20, and 100 μmol m−2 s−1 light intensities, respectively, to achieve distinctive stem photosynthetic rates. After 14 days of treatment, stem water and non-structural carbohydrate (NSC content, as well as the biomass and carbon isotopic composition, of new organs in the cutting seedlings under different light treatments were examined. The results showed that the gross photosynthetic rate significantly increased within 400 μmol m−2 s−1 of light intensity, and the maximum rate was approximately 1.27 μmol m−2 s−1. The effective photochemical efficiency of the PSⅡ of the cortex was significantly higher than the inner tissues in the cross section of the twig. When twig cuttings were exposed to different light intensities, stem water and starch content, as well as bud and root biomass, were significantly higher in the cutting seedling subjected to 100 μmol m−2 s−1 than the case treated in darkness; however, the bud δ13C trend was the opposite. Stem photosynthesis played a positive role in the maintenance of stem water and starch supply for the cutting seedlings, and 13C depleted assimilates produced by stem photosynthesis contributed to bud biomass, revealing that stem photosynthesis promotes organ development in cutting seedlings of Salix matsudana.

  9. using stereochemistry models in teaching organic compounds

    African Journals Online (AJOL)

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    The purpose of the study was to find out the effect of stereochemistry models on students' ... consistent with the names given to organic compounds. Some of ... Considering class level, what is the performance of the students in naming organic.

  10. Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres [Oslo University Hospital-Rikshospitalet, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); Bargallo, Nuria [Universitat de Barcelona, Section of Neuroradiology, Department of Radiology, Hospital Clinic, Barcelona (Spain); Institut d' investigacions Biomediques August Pi i Sunyer (IDIBARS), Resonance Magnetic Image Core Facility, Barcelona (Spain); Floeisand, Yngvar [Oslo University Hospital-Rikshospitalet, Department of Hematology, Oslo (Norway); Sponheim, Jon [Oslo University Hospital-Rikshospitalet, Section of Gastroenterology, Department of Transplantation Medicine, Oslo (Norway); Graus, Francesc [Universitat de Barcelona, Department of Neurology, Hospital Clinic, Barcelona (Spain); Institut d' investigacions Biomediques August Pi i Sunyer (IDIBARS), Neuroimmunology Program, Barcelona (Spain); Hald, John K. [Oslo University Hospital-Rikshospitalet, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Faculty of Medicine, Oslo (Norway)

    2017-02-15

    Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months. Further differentiation will be based on etiology: infections, drug toxicity, metabolic derangements, cerebrovascular complications, and posttransplantation malignancies. In addition, differentiation will be based on complications specific to the type of transplantation: allogeneic and autologous hematopoietic stem cells (HSC), heart, lung, kidney, pancreas, and liver. Thus, in this article we emphasize the strategic role of neuroradiology in the diagnosis and response to treatment by utilizing a methodical approach in the work up of patients with neurologic complications after transplantation. (orig.)

  11. Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation

    International Nuclear Information System (INIS)

    Server, Andres; Bargallo, Nuria; Floeisand, Yngvar; Sponheim, Jon; Graus, Francesc; Hald, John K.

    2017-01-01

    Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months. Further differentiation will be based on etiology: infections, drug toxicity, metabolic derangements, cerebrovascular complications, and posttransplantation malignancies. In addition, differentiation will be based on complications specific to the type of transplantation: allogeneic and autologous hematopoietic stem cells (HSC), heart, lung, kidney, pancreas, and liver. Thus, in this article we emphasize the strategic role of neuroradiology in the diagnosis and response to treatment by utilizing a methodical approach in the work up of patients with neurologic complications after transplantation. (orig.)

  12. Breaking Down the Door: A Nonprofit Model Creating Pathways for Non-Traditional STEM Student Engagement

    Science.gov (United States)

    Pelaez, C.; Pelaez, J.

    2015-12-01

    Blueprint Earth was created as a nonprofit scientific research organization dedicated to conducting micro-scale interdisciplinary environmental investigations to generate macroscopic, system-level environmental understanding. The field data collection and analysis process was conceived to be dependent on student participation and collaboration with more senior scientists, effecting knowledge transfer and emphasizing the critical nature of interdisciplinary research in investigating complex, macroscopic questions. Recruiting for student volunteer researchers is conducted in academic institutions, and to date has focused primarily on the Los Angeles area. Self-selecting student participation has run contrary to traditional STEM demographics. The vast majority of research participants in Blueprint Earth's work are female and/or from a minority (non-white) background, and most are first-generation college students or from low-income, Pell grant-eligible households. Traditional field research programs for students often come at a high cost, creating barriers to access for field-based STEM opportunities. The nonprofit model employed by Blueprint Earth provides zero-cost access to opportunity for students that the STEM world is currently targeting for future professional development.

  13. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan

    2012-07-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  14. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan; Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  15. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    Science.gov (United States)

    Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O2 pressure (pO2) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2 to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases. PMID:22224628

  16. Which bank? A guardian model for regulation of embryonic stem cell research in Australia.

    Science.gov (United States)

    McLennan, A

    2007-08-01

    In late 2005 the Legislation Review: Prohibition of Human Cloning Act 2002 (Cth) and the Research Involving Human Embryos Act 2002 (Cth) recommended the establishment of an Australian stem cell bank. This article aims to address a lack of discussion of issues surrounding stem cell banking by suggesting possible answers to the questions of whether Australia should establish a stem cell bank and what its underlying philosophy and functions should be. Answers are developed through an analysis of regulatory, scientific and intellectual property issues relating to embryonic stem cell research in the United Kingdom, United States and Australia. This includes a detailed analysis of the United Kingdom Stem Cell Bank. It is argued that a "guardian" model stem cell bank should be established in Australia. This bank would aim to promote the maximum public benefit from human embryonic stem cell research by providing careful regulatory oversight and addressing ethical issues, while also facilitating research by addressing practical scientific concerns and intellectual property issues.

  17. Generation of organized germ layers from a single mouse embryonic stem cell.

    Science.gov (United States)

    Poh, Yeh-Chuin; Chen, Junwei; Hong, Ying; Yi, Haiying; Zhang, Shuang; Chen, Junjian; Wu, Douglas C; Wang, Lili; Jia, Qiong; Singh, Rishi; Yao, Wenting; Tan, Youhua; Tajik, Arash; Tanaka, Tetsuya S; Wang, Ning

    2014-05-30

    Mammalian inner cell mass cells undergo lineage-specific differentiation into germ layers of endoderm, mesoderm and ectoderm during gastrulation. It has been a long-standing challenge in developmental biology to replicate these organized germ layer patterns in culture. Here we present a method of generating organized germ layers from a single mouse embryonic stem cell cultured in a soft fibrin matrix. Spatial organization of germ layers is regulated by cortical tension of the colony, matrix dimensionality and softness, and cell-cell adhesion. Remarkably, anchorage of the embryoid colony from the 3D matrix to collagen-1-coated 2D substrates of ~1 kPa results in self-organization of all three germ layers: ectoderm on the outside layer, mesoderm in the middle and endoderm at the centre of the colony, reminiscent of generalized gastrulating chordate embryos. These results suggest that mechanical forces via cell-matrix and cell-cell interactions are crucial in spatial organization of germ layers during mammalian gastrulation. This new in vitro method could be used to gain insights on the mechanisms responsible for the regulation of germ layer formation.

  18. Tree-Structured Digital Organisms Model

    Science.gov (United States)

    Suzuki, Teruhiko; Nobesawa, Shiho; Tahara, Ikuo

    Tierra and Avida are well-known models of digital organisms. They describe a life process as a sequence of computation codes. A linear sequence model may not be the only way to describe a digital organism, though it is very simple for a computer-based model. Thus we propose a new digital organism model based on a tree structure, which is rather similar to the generic programming. With our model, a life process is a combination of various functions, as if life in the real world is. This implies that our model can easily describe the hierarchical structure of life, and it can simulate evolutionary computation through mutual interaction of functions. We verified our model by simulations that our model can be regarded as a digital organism model according to its definitions. Our model even succeeded in creating species such as viruses and parasites.

  19. Modeling Neuropsychiatric and Neurodegenerative Diseases With Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth A. LaMarca

    2018-04-01

    Full Text Available Human-induced pluripotent stem cells (hiPSCs have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional “mini-brains” and clustered, regularly interspersed short palindromic repeats (CRISPR-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson’s disease, and consider the future of this groundbreaking research.

  20. Incorporating additional tree and environmental variables in a lodgepole pine stem profile model

    Science.gov (United States)

    John C. Byrne

    1993-01-01

    A new variable-form segmented stem profile model is developed for lodgepole pine (Pinus contorta) trees from the northern Rocky Mountains of the United States. I improved estimates of stem diameter by predicting two of the model coefficients with linear equations using a measure of tree form, defined as a ratio of dbh and total height. Additional improvements were...

  1. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

  2. Stem Cells as In Vitro Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Patricia L. Martínez-Morales

    2012-01-01

    Full Text Available Progress in understanding neurodegenerative cell biology in Parkinson's disease (PD has been hampered by a lack of predictive and relevant cellular models. In addition, the lack of an adequate in vitro human neuron cell-based model has been an obstacle for the uncover of new drugs for treating PD. The ability to generate induced pluripotent stem cells (iPSCs from PD patients and a refined capacity to differentiate these iPSCs into DA neurons, the relevant disease cell type, promises a new paradigm in drug development that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSC that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSC can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling PD “in a dish” and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets, and enhance the probability of clinical success of new drugs.

  3. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Rishindra M., E-mail: reddyrm@med.umich.edu [Medical Center, University of Michigan, 1500 E. Medical Center Drive, 2120 Taubman Center, Ann Arbor, MI 48109 (United States); Kakarala, Madhuri; Wicha, Max S. [Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (United States)

    2011-06-20

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples.

  4. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    International Nuclear Information System (INIS)

    Reddy, Rishindra M.; Kakarala, Madhuri; Wicha, Max S.

    2011-01-01

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples

  5. Modelling organic particles in the atmosphere

    International Nuclear Information System (INIS)

    Couvidat, Florian

    2012-01-01

    Organic aerosol formation in the atmosphere is investigated via the development of a new model named H 2 O (Hydrophilic/Hydrophobic Organics). First, a parameterization is developed to take into account secondary organic aerosol formation from isoprene oxidation. It takes into account the effect of nitrogen oxides on organic aerosol formation and the hydrophilic properties of the aerosols. This parameterization is then implemented in H 2 O along with some other developments and the results of the model are compared to organic carbon measurements over Europe. Model performance is greatly improved by taking into account emissions of primary semi-volatile compounds, which can form secondary organic aerosols after oxidation or can condense when temperature decreases. If those emissions are not taken into account, a significant underestimation of organic aerosol concentrations occurs in winter. The formation of organic aerosols over an urban area was also studied by simulating organic aerosols concentration over the Paris area during the summer campaign of Megapoli (July 2009). H 2 O gives satisfactory results over the Paris area, although a peak of organic aerosol concentrations from traffic, which does not appear in the measurements, appears in the model simulation during rush hours. It could be due to an underestimation of the volatility of organic aerosols. It is also possible that primary and secondary organic compounds do not mix well together and that primary semi volatile compounds do not condense on an organic aerosol that is mostly secondary and highly oxidized. Finally, the impact of aqueous-phase chemistry was studied. The mechanism for the formation of secondary organic aerosol includes in-cloud oxidation of glyoxal, methylglyoxal, methacrolein and methylvinylketone, formation of methyltetrols in the aqueous phase of particles and cloud droplets, and the in-cloud aging of organic aerosols. The impact of wet deposition is also studied to better estimate the

  6. Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Ho, Beatrice Xuan; Pek, Nicole Min Qian; Soh, Boon-Seng

    2018-03-21

    The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo. This review serves to highlight recent advances in the 3D organoid technology for use in modeling complex hereditary diseases, cancer, host-microbe interactions, and possible use in translational and personalized medicine where organoid cultures were used to uncover diagnostic biomarkers for early disease detection via high throughput pharmaceutical screening. In addition, this review also aims to discuss the advantages and shortcomings of utilizing organoids in disease modeling. In summary, studying human diseases using hiPSC-derived organoids may better illustrate the processes involved due to similarities in the architecture and microenvironment present in an organoid, which also allows drug responses to be properly recapitulated in vitro.

  7. Development of a tree shrew metabolic syndrome model and use of umbilical cord mesenchymal stem cell transplantation for treatment.

    Science.gov (United States)

    Pan, Xing-Hua; Zhu, Lu; Yao, Xiang; Liu, Ju-Fen; Li, Zi-An; Yang, Jian-Yong; Pang, Rong-Qing; Ruan, Guang-Ping

    2016-12-01

    The aim of this study was to establish a tree shrew metabolic syndrome model and demonstrate the utility of MSCs in treating metabolic syndrome. We used tree shrew umbilical cord mesenchymal stem cell (TS-UC-MSC) transplantation for the treatment of metabolic syndrome to demonstrate the clinical application of these stem cells and to provide a theoretical basis and reference methods for this treatment. Tree shrew metabolic syndrome model showed significant insulin resistance, high blood sugar, lipid metabolism disorders, and hypertension, consistent with the diagnostic criteria. TS-UC-MSC transplantation at 16 weeks significantly reduced blood sugar and lipid levels, improved insulin resistance and the regulation of insulin secretion, and reduced the expression levels of the pro-inflammatory cytokines IL-1 and IL-6 (P metabolic syndrome model and showed that MSC migrate in diseased organs and can attenuate metabolic syndrome severity in a tree shrew model.

  8. Transcriptional regulation by histone modifications: towards a theory of chromatin re-organization during stem cell differentiation

    International Nuclear Information System (INIS)

    Binder, Hans; Steiner, Lydia; Przybilla, Jens; Rohlf, Thimo; Prohaska, Sonja; Galle, Jörg

    2013-01-01

    Chromatin-related mechanisms, as e.g. histone modifications, are known to be involved in regulatory switches within the transcriptome. Only recently, mathematical models of these mechanisms have been established. So far they have not been applied to genome-wide data. We here introduce a mathematical model of transcriptional regulation by histone modifications and apply it to data of trimethylation of histone 3 at lysine 4 (H3K4me3) and 27 (H3K27me3) in mouse pluripotent and lineage-committed cells. The model describes binding of protein complexes to chromatin which are capable of reading and writing histone marks. Molecular interactions of the complexes with DNA and modified histones create a regulatory switch of transcriptional activity. The regulatory states of the switch depend on the activity of histone (de-) methylases, the strength of complex-DNA-binding and the number of nucleosomes capable of cooperatively contributing to complex-binding. Our model explains experimentally measured length distributions of modified chromatin regions. It suggests (i) that high CpG-density facilitates recruitment of the modifying complexes in embryonic stem cells and (ii) that re-organization of extended chromatin regions during lineage specification into neuronal progenitor cells requires targeted de-modification. Our approach represents a basic step towards multi-scale models of transcriptional control during development and lineage specification. (paper)

  9. Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

    Science.gov (United States)

    Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

    2015-10-01

    Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

  10. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Directory of Open Access Journals (Sweden)

    Adam S Zeiger

    Full Text Available Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs via immunocytochemistry, atomic force microscopy (AFM, and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  11. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Science.gov (United States)

    Zeiger, Adam S; Loe, Felicia C; Li, Ran; Raghunath, Michael; Van Vliet, Krystyn J

    2012-01-01

    Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  12. Research progress in animal models and stem cell therapy for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Han F

    2014-12-01

    Full Text Available Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the treatment of AD. We first review the advances in molecular pathogenesis and animal models of AD and then discuss recent clinical studies using small molecules and immunoglobulins to target amyloid-beta plaques for AD therapy. Finally, we discuss stem cell therapy for AD using neural stem cells, olfactory ensheathing cells, embryonic stem cells, and mesenchymal stem cell from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific induced pluripotent stem cells are proposed as a future treatment for AD. Keywords: amyloid-beta plaque, neurofibrillary tangle, neural stem cell, olfactory ensheathing cell, mesenchymal stem cell, induced pluripotent stem cell

  13. Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells.

    Science.gov (United States)

    Salmasi, Shima; Kalaskar, Deepak M; Yoon, Wai-Weng; Blunn, Gordon W; Seifalian, Alexander M

    2015-03-26

    Recent regenerative medicine and tissue engineering strategies (using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional (3D) organs, such as bone, skin, liver, kidney and ear, using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nano-surface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.

  14. Cellular therapy by mesenchymal stem cells in the gamma radiation-induced multi organ dysfunction syndrome

    International Nuclear Information System (INIS)

    Francois, S.; Mouiseddine, M.; Semont, A.; Frick, J.; Sache, A.; Thierry, D.; Voisin, P.; Gourmelon, P.; Chapel, A.; Gorin, N.C.

    2007-01-01

    Mesenchymal stem cells (M.S.C.) have been shown to migrate to various tissues. There is little information on the fate and potential therapeutic efficacy of the re infusion of M.S.C. following total body irradiation (T.B.I.). We addressed this question using human M.S.C. (h.M.S.C.) infused to non obese diabetic/severe combined immuno-deficient (N.O.D./S.C.I.D.) mice submitted to T.B.I.. Further, we tested the impact of additional local irradiation (A.L.I.) superimposed to T.B.I., as a model of accidental irradiation. N.O.D./S.C.I.D. mice were transplanted with h.M.S.C.. Group 1 was not irradiated before receiving h.M.S.C. infusion. Group 2 received only T.B.I. at a dose of 3.5 Gy, group 3 received local irradiation to the abdomen at a dose of 4.5 Gy in addition to T.B.I., and group 4 received local irradiation to the leg at 26.5 Gy in addition to T.B.I.. Fifteen days after gamma irradiation, quantitative and spatial distribution of the h.M.S.C. were studied. Histological analysis of mouse tissues confirmed the presence of radio-induced lesions in the irradiated fields. Following their infusion into nonirradiated animals, h.M.S.C. homed at a very low level to various tissues (lung, bone marrow, and muscles) and no significant engraftment was found in other organs. T.B.I. induced an increase of engraftment levels of h.M.S.C. in the brain, heart, bone marrow, and muscles. Abdominal irradiation (A.I.) as compared with leg irradiation (L.I.) increased h.M.S.C. engraftment in the exposed area (the gut, liver, and spleen). Comparison of two local irradiations has shown that (L.I.) as compared with (A.I.) increased h.M.S.C. engraftment in the exposed area. An increase of h.M.S.C. engraftment in organs outside the fields of the A.L.I. was also observed. Conversely, following L.I., h.M.S.C. engraftment was increased in the brain as compared with A.I.. This study shows that engraftment of h.M.S.C. in N.O.D./ S.C.I.D. mice with significantly increased in response to tissue

  15. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    International Nuclear Information System (INIS)

    Winkler, Sandra; Borkham-Kamphorst, Erawan; Stock, Peggy; Brückner, Sandra; Dollinger, Matthias; Weiskirchen, Ralf; Christ, Bruno

    2014-01-01

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH

  16. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig (Germany)

    2014-08-15

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.

  17. Sustainability Transdisciplinary Education Model: Interface of Arts, Science, and Community (STEM)

    Science.gov (United States)

    Clark, Barbara; Button, Charles

    2011-01-01

    Purpose: The purpose of this paper is to describe the components of a sustainability transdisciplinary education model (STEM), a contemporary approach linking art, science, and community, that were developed to provide university and K-12 students, and society at large shared learning opportunities. The goals and application of the STEM curriculum…

  18. Inactivation of Salmonella in tomato stem scars by organic acid wash and chitosan-allyl isothiocyanate coating

    Science.gov (United States)

    The objective of this study was to evaluate inactivation of inoculated Salmonella enterica on tomato stem scars exploiting integrated treatment of organic acid wash (AW) followed by chitosan-allyl isothiocyanate (CT-AIT) coating. The treatment effect on microbial loads and fruit quality during 21 d...

  19. Organic production in a dynamic CGE model

    DEFF Research Database (Denmark)

    Jacobsen, Lars Bo

    2004-01-01

    for conventional production into land for organic production, a period of two years must pass before the land being transformed can be used for organic production. During that time, the land is counted as land of the organic industry, but it can only produce the conventional product. To handle this rule, we make......Concerns about the impact of modern agriculture on the environment have in recent years led to an interest in supporting the development of organic farming. In addition to environmental benefits, the aim is to encourage the provision of other “multifunctional” properties of organic farming...... such as rural amenities and rural development that are spillover benefit additional to the supply of food. In this paper we further develop an existing dynamic general equilibrium model of the Danish economy to specifically incorporate organic farming. In the model and input-output data each primary...

  20. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  1. Pluripotent stem cells: An in vitro model for nanotoxicity assessments.

    Science.gov (United States)

    Handral, Harish K; Tong, Huei Jinn; Islam, Intekhab; Sriram, Gopu; Rosa, Vinicus; Cao, Tong

    2016-10-01

    The advent of technology has led to an established range of engineered nanoparticles that are used in diverse applications, such as cell-cell interactions, cell-material interactions, medical therapies and the target modulation of cellular processes. The exponential increase in the utilization of nanomaterials and the growing number of associated criticisms has highlighted the potential risks of nanomaterials to human health and the ecosystem. The existing in vivo and in vitro platforms show limitations, with fluctuations being observed in the results of toxicity assessments. Pluripotent stem cells (PSCs) are viable source of cells that are capable of developing into specialized cells of the human body. PSCs can be efficiently used to screen new biomaterials/drugs and are potential candidates for studying impairments of biophysical morphology at both the cellular and tissue levels during interactions with nanomaterials and for diagnosing toxicity. Three-dimensional in vitro models obtained using PSC-derived cells would provide a realistic, patient-specific platform for toxicity assessments and in drug screening applications. The current review focuses on PSCs as an alternative in vitro platform for assessing the hazardous effects of nanomaterials on health systems and highlights the importance of PSC-derived in vitro platforms. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Multiscale grooved titanium processed with femtosecond laser influences mesenchymal stem cell morphology, adhesion, and matrix organization.

    Science.gov (United States)

    Dumas, Virginie; Rattner, Aline; Vico, Laurence; Audouard, Eric; Dumas, Jean Claude; Naisson, Pierre; Bertrand, Philippe

    2012-11-01

    The femtosecond laser processing enabled the structuring of six types of surfaces on titanium-6aluminium-4vanadium (Ti-6Al-4V) plates. The obtained hierarchical features consisted of a combination of microgrooves and oriented nanostructures. By adjusting beam properties such as laser polarization, the width of the microgrooves (20 or 60 μm) and the orientation of the nanostructures (parallel or perpendicular to the microgrooves) can be precisely controlled. Mesenchymal stem cells (MSCs) grown on these structured surfaces produced cytoplasmic extensions with focal contacts, while on the smooth titanium, the cells were found to be well spread and without any focal contact 12 h postseeding. The 600-nm wide nanostructures on their own were sufficient to orient the MSCs. For the multiscale structured areas, when the orientation of the nanostructures was orthogonal in relation to the microgrooves, there was an important decrease in or even a loss of cell alignment signifying that cells were sensitive to the directional nanostructures in the microgrooves. At 7 days, cell proliferation was not affected but the direction of nanostructures controlled the matrix organization. The ultrafast laser, as a new method for producing micro-nanohybrid surfaces, is a promising approach to promote desired tissue organization for tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

  3. Young at Heart: Pioneering Approaches to Model Nonischaemic Cardiomyopathy with Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Aoife Gowran

    2016-01-01

    Full Text Available A mere 9 years have passed since the revolutionary report describing the derivation of induced pluripotent stem cells from human fibroblasts and the first in-patient translational use of cells obtained from these stem cells has already been achieved. From the perspectives of clinicians and researchers alike, the promise of induced pluripotent stem cells is alluring if somewhat beguiling. It is now evident that this technology is nascent and many areas for refinement have been identified and need to be considered before induced pluripotent stem cells can be routinely used to stratify, treat and cure patients, and to faithfully model diseases for drug screening purposes. This review specifically addresses the pioneering approaches to improve induced pluripotent stem cell based models of nonischaemic cardiomyopathy.

  4. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  5. The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

    OpenAIRE

    Muller-Sieburg, C.E.; Sieburg, H.B.

    2006-01-01

    Hematopoietic stem cells (HSC) show heterogeneous behavior even when isolated as phenotypically homogeneous populations. The cellular and molecular mechanisms that control the generation of diversity (GOD) in the HSC compartment are not well understood, but have been the focus of much debate. There is increasing evidence that the most important HSC functions, self-renewal and differentiation, are epigenetically preprogrammed and therefore predictable. Indeed, recent data show that the adult H...

  6. Stem thrust prediction model for Westinghouse wedge gate valves with linkage type stem-to-disk connection

    International Nuclear Information System (INIS)

    Wang, J.K.; Sharma, V.; Kalsi, M.S.

    1996-01-01

    The Electric Power Research Institute (EPRI) conducted a comprehensive research program with the objective of providing nuclear utilities with analytical methods to predict motor operated valve (MOV) performance under design basis conditions. This paper describes the stem thrust calculation model developed for evaluating the performance of one such valve, the Westinghouse flexible wedge gate valve. These procedures account for the unique functional characteristics of this valve design. In addition, model results are compared to available flow loop and in situ test data as a basis for evaluating the performance of the valve model

  7. Stem thrust prediction model for Westinghouse wedge gate valves with linkage type stem-to-disk connection

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.K.; Sharma, V.; Kalsi, M.S. [Kalsi Engineering, Inc., Sugar Land, TX (United States)] [and others

    1996-12-01

    The Electric Power Research Institute (EPRI) conducted a comprehensive research program with the objective of providing nuclear utilities with analytical methods to predict motor operated valve (MOV) performance under design basis conditions. This paper describes the stem thrust calculation model developed for evaluating the performance of one such valve, the Westinghouse flexible wedge gate valve. These procedures account for the unique functional characteristics of this valve design. In addition, model results are compared to available flow loop and in situ test data as a basis for evaluating the performance of the valve model.

  8. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova

    2011-08-01

    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  9. Project-matrix models of marketing organization

    Directory of Open Access Journals (Sweden)

    Gutić Dragutin

    2009-01-01

    Full Text Available Unlike theory and practice of corporation organization, in marketing organization numerous forms and contents at its disposal are not reached until this day. It can be well estimated that marketing organization today in most of our companies and in almost all its parts, noticeably gets behind corporation organization. Marketing managers have always been occupied by basic, narrow marketing activities as: sales growth, market analysis, market growth and market share, marketing research, introduction of new products, modification of products, promotion, distribution etc. They rarely found it necessary to focus a bit more to different aspects of marketing management, for example: marketing planning and marketing control, marketing organization and leading. This paper deals with aspects of project - matrix marketing organization management. Two-dimensional and more-dimensional models are presented. Among two-dimensional, these models are analyzed: Market management/products management model; Products management/management of product lifecycle phases on market model; Customers management/marketing functions management model; Demand management/marketing functions management model; Market positions management/marketing functions management model. .

  10. The Zebrafish Model Organism Database (ZFIN)

    Data.gov (United States)

    U.S. Department of Health & Human Services — ZFIN serves as the zebrafish model organism database. It aims to: a) be the community database resource for the laboratory use of zebrafish, b) develop and support...

  11. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

    Energy Technology Data Exchange (ETDEWEB)

    Francois, S

    2006-01-15

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  12. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

    Energy Technology Data Exchange (ETDEWEB)

    Francois, S

    2006-01-15

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  13. Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

    Directory of Open Access Journals (Sweden)

    Navin Gupta

    2017-08-01

    Full Text Available The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

  14. Complex Systems and Self-organization Modelling

    CERN Document Server

    Bertelle, Cyrille; Kadri-Dahmani, Hakima

    2009-01-01

    The concern of this book is the use of emergent computing and self-organization modelling within various applications of complex systems. The authors focus their attention both on the innovative concepts and implementations in order to model self-organizations, but also on the relevant applicative domains in which they can be used efficiently. This book is the outcome of a workshop meeting within ESM 2006 (Eurosis), held in Toulouse, France in October 2006.

  15. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

    Science.gov (United States)

    Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

    2015-06-05

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging. Copyright © 2015, American Association for the Advancement of Science.

  16. The U.S. STEM Undergraduate Model: Applying System Dynamics to Help Meet President Obama's Goals for One Million STEM Graduates and the U.S. Navy's Civilian STEM Workforce Needs

    Science.gov (United States)

    Business-Higher Education Forum, 2013

    2013-01-01

    This report shows how insights gained from system dynamics modeling and the U.S. STEM Undergraduate Model® can help inform the Navy's strategy to grow a robust civilian workforce that is strongly invested with Navy-relevant STEM skills and ready to contribute to the next generation of Naval innovation. This work positions the Navy to serve a…

  17. Cell-based Therapy for Acute Organ Injury: Preclinical Evidence and On-going Clinical Trials Using Mesenchymal Stem Cells

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W.

    2014-01-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver or brain. Genomic, proteomic and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of pro-mitotic, anti-apoptotic, anti-inflammatory and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, we review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. PMID:25211170

  18. Stem breakage of salt marsh vegetation under wave forcing: A field and model study

    Science.gov (United States)

    Vuik, Vincent; Suh Heo, Hannah Y.; Zhu, Zhenchang; Borsje, Bas W.; Jonkman, Sebastiaan N.

    2018-01-01

    One of the services provided by coastal ecosystems is wave attenuation by vegetation, and subsequent reduction of wave loads on flood defense structures. Therefore, stability of vegetation under wave forcing is an important factor to consider. This paper presents a model which determines the wave load that plant stems can withstand before they break or fold. This occurs when wave-induced bending stresses exceed the flexural strength of stems. Flexural strength was determined by means of three-point-bending tests, which were carried out for two common salt marsh species: Spartina anglica (common cord-grass) and Scirpus maritimus (sea club-rush), at different stages in the seasonal cycle. Plant stability is expressed in terms of a critical orbital velocity, which combines factors that contribute to stability: high flexural strength, large stem diameter, low vegetation height, high flexibility and a low drag coefficient. In order to include stem breakage in the computation of wave attenuation by vegetation, the stem breakage model was implemented in a wave energy balance. A model parameter was calibrated so that the predicted stem breakage corresponded with the wave-induced loss of biomass that occurred in the field. The stability of Spartina is significantly higher than that of Scirpus, because of its higher strength, shorter stems, and greater flexibility. The model is validated by applying wave flume tests of Elymus athericus (sea couch), which produced reasonable results with regards to the threshold of folding and overall stem breakage percentage, despite the high flexibility of this species. Application of the stem breakage model will lead to a more realistic assessment of the role of vegetation for coastal protection.

  19. Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

    Directory of Open Access Journals (Sweden)

    Nikolce Gjorevski

    2017-01-01

    Full Text Available Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

  20. Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

    Science.gov (United States)

    Qu, Bo; Xin, Guo-Rong; Zhao, Li-Xia; Xing, Hui; Lian, Li-Ying; Jiang, Hai-Yan; Tong, Jia-Zhao; Wang, Bei-Bei; Jin, Shi-Zhu

    2014-01-01

    The gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD). BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

  1. A Model of Factors Contributing to STEM Learning and Career Orientation

    Science.gov (United States)

    Nugent, Gwen; Barker, Bradley; Welch, Greg; Grandgenett, Neal; Wu, ChaoRong; Nelson, Carl

    2015-05-01

    The purpose of this research was to develop and test a model of factors contributing to science, technology, engineering, and mathematics (STEM) learning and career orientation, examining the complex paths and relationships among social, motivational, and instructional factors underlying these outcomes for middle school youth. Social cognitive career theory provided the foundation for the research because of its emphasis on explaining mechanisms which influence both career orientations and academic performance. Key constructs investigated were youth STEM interest, self-efficacy, and career outcome expectancy (consequences of particular actions). The study also investigated the effects of prior knowledge, use of problem-solving learning strategies, and the support and influence of informal educators, family members, and peers. A structural equation model was developed, and structural equation modeling procedures were used to test proposed relationships between these constructs. Results showed that educators, peers, and family-influenced youth STEM interest, which in turn predicted their STEM self-efficacy and career outcome expectancy. STEM career orientation was fostered by youth-expected outcomes for such careers. Results suggest that students' pathways to STEM careers and learning can be largely explained by these constructs, and underscore the importance of youth STEM interest.

  2. Immunosuppressive and remodelling properties of mesenchymal stem cells in a model of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Patricia Semedo

    2009-12-01

    Full Text Available Objective: To investigate the role of mesenchymal stem cells in fibrogenesis using a model of chronic renal insufficiency. Methods: Mesenchymal stem cells  were obtained from tibias and femurs of Wistar-EPM rats. After three to five passages, the cells were submitted to phenotypic analyses and differentiation. Wistar rats were submitted to the 5/6 nephrectomy model, and 2.105 mesenchymal stem cells  were administered intravenously to each rat every two weeks until the eighth week. Rresults: Sex-determining region Y was observed in female rats treated with stem cells. Serum and urine analyses showed improvement of functional parameters in mesenchymal stem cells treated animals, such as creatinine, serum urea, and proteinuria. Moreover, hemocrit analysis showed improvement of anemia in mesenchymal stem cells treated animals. Masson’s Trichromium and Picrosirius Red staining demonstrated reduced levels of fibrosis in mesenchymal stem cells treated in animals. These results were corroborated by reduced vimentin, collagen I, TGFβ, FSP-1, MCP-1 and Smad3 mRNA expression. Renal IL-6 and TNFα mRNA expression levels were significantly decreased after mesenchymal stem cells treatment, while IL-4 and IL-10 expression were increased. Serum expression of IL-1α, IL-1β, IL-6, IFN-γ, TNF-α, and IL-10 was decreased in mesenchymal cell-treated animals. Cconclusions: Altogether, these results suggest that mesenchymal stem cells therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal lesion. The immunosuppresive and remodeling properties of the mesenchymal stem cells  may be involved in the improved fibrotic outcome.

  3. Stem cells: a model for screening, discovery and development of drugs

    Directory of Open Access Journals (Sweden)

    Kitambi SS

    2011-09-01

    Full Text Available Satish Srinivas Kitambi1, Gayathri Chandrasekar21Department of Medical Biochemistry and Biophysics; 2Department of Biosciences, Karolinska Institutet, Stockholm, SwedenAbstract: The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.Keywords: therapeutics, stem cells, cancer stem cells, screening models, drug development, high throughput screening

  4. The retention of first-generation college students in STEM: An extension of Tinto's longitudinal model

    Science.gov (United States)

    Uche, Ada Rosemary

    In the current technologically advanced global economy, the role of human capital and education cannot be over-emphasized. Since almost all great inventions in the world have a scientific or technological foundation, having a skilled workforce is imperative for any nation's economic growth. Currently, large segments of the United States' population are underrepresented in the attainment of science, technology, engineering, and math (STEM) degrees, and in the STEM professions. Scholars, educators, policy-makers, and employers are concerned about the decline in student enrollment and graduation from STEM disciplines. This trend is especially problematic for first-generation college students. This study uses both quantitative and qualitative methods to assess the factors that predict the retention of first-generation college students in the STEM majors. It employs Tinto's longitudinal model (1993) as a conceptual framework to predict STEM retention for first-generation college students. The analysis uses the Beginning Post-secondary Students study (BPS 04/09) data and Roots of STEM qualitative data to investigate the role of first-generation status in STEM major retention. Results indicate that upper levels of achievement in high school math have a significant effect on first-generation status in STEM outcomes.

  5. Modeling self-organization of novel organic materials

    Science.gov (United States)

    Sayar, Mehmet

    In this thesis, the structural organization of oligomeric multi-block molecules is analyzed by computational analysis of coarse-grained models. These molecules form nanostructures with different dimensionalities, and the nanostructured nature of these materials leads to novel structural properties at different length scales. Previously, a number of oligomeric triblock rodcoil molecules have been shown to self-organize into mushroom shaped noncentrosymmetric nanostructures. Interestingly, thin films of these molecules contain polar domains and a finite macroscopic polarization. However, the fully polarized state is not the equilibrium state. In the first chapter, by solving a model with dipolar and Ising-like short range interactions, we show that polar domains are stable in films composed of aggregates as opposed to isolated molecules. Unlike classical molecular systems, these nanoaggregates have large intralayer spacings (a ≈ 6 nm), leading to a reduction in the repulsive dipolar interactions that oppose polar order within layers. This enables the formation of a striped pattern with polar domains of alternating directions. The energies of the possible structures at zero temperature are computed exactly and results of Monte Carlo simulations are provided at non-zero temperatures. In the second chapter, the macroscopic polarization of such nanostructured films is analyzed in the presence of a short range surface interaction. The surface interaction leads to a periodic domain structure where the balance between the up and down domains is broken, and therefore films of finite thickness have a net macroscopic polarization. The polarization per unit volume is a function of film thickness and strength of the surface interaction. Finally, in chapter three, self-organization of organic molecules into a network of one dimensional objects is analyzed. Multi-block organic dendron rodcoil molecules were found to self-organize into supramolecular nanoribbons (threads) and

  6. Diagnosis and treatment of fungal infections in allogeneic stem cell and solid organ transplant recipients.

    Science.gov (United States)

    Vehreschild, Jörg J; Rüping, Maria J G T; Steinbach, Angela; Cornely, Oliver A

    2010-01-01

    Invasive fungal diseases (IFD) are severe complications in patients receiving immunosuppression after solid organ or allogeneic stem cell transplantation. Extensive study has been conducted on therapeutic strategies for IFD in neutropenic patients, mostly those with hematological malignancy. There is an ongoing discussion on whether these studies may be applied to transplant patients as well. We have reviewed relevant literature on transplantation and clinical mycology of the last 20 years and selected articles relevant for today's treatment decisions. This article reports on the epidemiology of IFD in transplant recipients and current antifungal drugs in the context of tansplantation medicine. For invasive aspergillosis and invasive candidiasis, we give a detailed report of current clinical evidence. This review is intended as a quick-start for clinicians and other care providers new to transplant care and as an update for experienced transplant physicians. In a field in which evidence is scarce and conflicting, we provide evidence-based strategies for diagnosing and treating the most relevant IFD in transplant recipients. Physicians treating transplant patients should maintain a high level of awareness towards IFD. They should know the local epidemiology of IFD to make the optimal decision between current diagnostic and therapeutic strategies. Prophylaxis or early treatment should be considered given the high mortality of IFD.

  7. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.

    Directory of Open Access Journals (Sweden)

    Andrea Sottoriva

    2011-05-01

    Full Text Available The cancer stem cell (CSC concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.

  8. Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model.

    Science.gov (United States)

    Takagi, Ryoji; Ishimaru, Junko; Sugawara, Ayaka; Toyoshima, Koh-Ei; Ishida, Kentaro; Ogawa, Miho; Sakakibara, Kei; Asakawa, Kyosuke; Kashiwakura, Akitoshi; Oshima, Masamitsu; Minamide, Ryohei; Sato, Akio; Yoshitake, Toshihiro; Takeda, Akira; Egusa, Hiroshi; Tsuji, Takashi

    2016-04-01

    The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bioengineered 3D integumentary organ system was fully functional following transplantation into nude mice and could be properly connected to surrounding host tissues, such as the epidermis, arrector pili muscles, and nerve fibers, without tumorigenesis. The bioengineered hair follicles in the 3D integumentary organ system also showed proper hair eruption and hair cycles, including the rearrangement of follicular stem cells and their niches. Potential applications of the 3D integumentary organ system include an in vitro assay system, an animal model alternative, and a bioengineered organ replacement therapy.

  9. The sagittal stem alignment and the stem version clearly influence the impingement-free range of motion in total hip arthroplasty: a computer model-based analysis.

    Science.gov (United States)

    Müller, Michael; Duda, Georg; Perka, Carsten; Tohtz, Stephan

    2016-03-01

    The component alignment in total hip arthroplasty influences the impingement-free range of motion (ROM). While substantiated data is available for the cup positioning, little is known about the stem alignment. Especially stem rotation and the sagittal alignment influence the position of the cone in relation to the edge of the socket and thus the impingement-free functioning. Hence, the question arises as to what influence do these parameters have on the impingement-free ROM? With the help of a computer model the influence of the sagittal stem alignment and rotation on the impingement-free ROM were investigated. The computer model was based on the CT dataset of a patient with a non-cemented THA. In the model the stem version was set at 10°/0°/-10° and the sagittal alignment at 5°/0°/-5°, which resulted in nine alternative stem positions. For each position, the maximum impingement-free ROM was investigated. Both stem version and sagittal stem alignment have a relevant influence on the impingement-free ROM. In particular, flexion and extension as well as internal and external rotation capability present evident differences. In the position intervals of 10° sagittal stem alignment and 20° stem version a difference was found of about 80° in the flexion and 50° in the extension capability. Likewise, differences were evidenced of up to 72° in the internal and up to 36° in the external rotation. The sagittal stem alignment and the stem torsion have a relevant influence on the impingement-free ROM. To clarify the causes of an impingement or accompanying problems, both parameters should be examined and, if possible, a combined assessment of these factors should be made.

  10. Monte Carlo modelling of damage to haemopoietic stem cells from internally deposited alpha-emitters

    International Nuclear Information System (INIS)

    Utteridge, T.D.; University of South Australia, Pooraka, SA; Charlton, D.E.; Turner, M.S.; Beddoe, A.H.; Leong, A. S-Y.; Milios, J.; Fazzalari, N.; To, L.B.

    1996-01-01

    Full text: Monte Carlo modelling of alpha particle radiation dose to haemopoietic stem cells from radon decay in human marrow fat cells was undertaken following Richardson et al's (Brit J Radiol, 64, 608-624, 1991) proposition that such exposure could induce leukaemia, and epidemiological observations that uranium miners have not developed an excess of leukaemia (Tomasek L. et al, Lancet, 341, 919-923, 1993). The dose to haemopoietic stem cells from alpha emitting radiopharmaceuticals proposed for radiotherapy is also important in risk assessment. Haemopoietic stem cells (presumed to be the targets for leukaemia) were identified as CD34+CD38- mononuclear cells (Terstappen LWMM et al, Blood, 77, 1218-1227, 1991) and their diameters measured using image analysis. The distribution of stem cell distances from fat cells was also measured. The model was used with Monte Carlo treatment of the alpha particle flux from radon and its short lived decay products to estimate (a) the dose and LET distributions for the three stem cell diameters; (b) the number of passages per hit; and (c) stem cell survival. The stem cell population exhibited a trimodal distribution, with mean diameters of 5.7, 11.6 and 14.8 μm; a trimodal distribution has previously been identified in mice (Visser J et al, Exper Hematol Today, 21-27, 1977). At 40% fat in a human lumbar vertebra 3 section, approximately half the stem cells were located on, or very close to the edge, of fat cells in marrow sections. This agrees with the predicted distribution of distances between fat and stem cells obtained using a 3-D model with randomly distributed stem cells. At an air activity of 20 Bq m -3 (ie the UK average indoor radon concentration used by Richardson et al mentioned above) about 0.1 stem cells per person-year were hit and survived; at 100 Bq m -3 about 1 stem cell per person-year was hit and survived. Across the range of radon concentrations encountered in residential and underground miner exposures

  11. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  12. Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

    Directory of Open Access Journals (Sweden)

    Sriram Chandrasekaran

    2017-12-01

    Full Text Available Summary: Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates. The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells. Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive and primed cells. Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate. : Chandrasekaran et al. use computational modeling, metabolomics, and metabolic inhibitors to discover metabolic differences between various pluripotent stem cell states and infer their impact on stem cell fate decisions. Keywords: systems biology, stem cell biology, metabolism, genome-scale modeling, pluripotency, histone methylation, naive (ground state, primed state, cell fate, metabolic network

  13. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem

  14. Stem cells regenerative properties on new rat spinal fusion model

    Czech Academy of Sciences Publication Activity Database

    Klíma, K.; Vaněček, Václav; Kohout, A.; Jiroušek, Ondřej; Foltán, R.; Štulík, J.; Machoň, V.; Pavlíková, G.; Jendelová, Pavla; Syková, Eva; Šedý, Jiří

    2015-01-01

    Roč. 64, č. 1 (2015), s. 119-128 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT13477; GA ČR(CZ) GAP304/10/0320 Institutional support: RVO:67985823 ; RVO:68378297 ; RVO:68378041 Keywords : mesenchymal stem cells * bone graft substitute * spinal fusion Subject RIV: FH - Neurology Impact factor: 1.643, year: 2015

  15. Exploring Student Persistence in STEM Programs: A Motivational Model

    Science.gov (United States)

    Simon, Rebecca A.; Aulls, Mark W.; Dedic, Helena; Hubbard, Kyle; Hall, Nathan C.

    2015-01-01

    To address continually decreasing enrollment and rising attrition in post-secondary STEM degree (science, technology, engineering, and mathematics) programs, particularly for women, the present study examines the utility of motivation and emotion variables to account for persistence and achievement in science in male and female students…

  16. The conceptual model of organization social responsibility

    OpenAIRE

    LUO, Lan; WEI, Jingfu

    2014-01-01

    With the developing of the research of CSR, people more and more deeply noticethat the corporate should take responsibility. Whether other organizations besides corporatesshould not take responsibilities beyond their field? This paper puts forward theconcept of organization social responsibility on the basis of the concept of corporate socialresponsibility and other theories. And the conceptual models are built based on theconception, introducing the OSR from three angles: the types of organi...

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

    Science.gov (United States)

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

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

  18. Numerical Model of Streaming DEP for Stem Cell Sorting

    Directory of Open Access Journals (Sweden)

    Rucha Natu

    2016-11-01

    Full Text Available Neural stem cells are of special interest due to their potential in neurogenesis to treat spinal cord injuries and other nervous disorders. Flow cytometry, a common technique used for cell sorting, is limited due to the lack of antigens and labels that are specific enough to stem cells of interest. Dielectrophoresis (DEP is a label-free separation technique that has been recently demonstrated for the enrichment of neural stem/progenitor cells. Here we use numerical simulation to investigate the use of streaming DEP for the continuous sorting of neural stem/progenitor cells. Streaming DEP refers to the focusing of cells into streams by equilibrating the dielectrophoresis and drag forces acting on them. The width of the stream should be maximized to increase throughput while the separation between streams must be widened to increase efficiency during retrieval. The aim is to understand how device geometry and experimental variables affect the throughput and efficiency of continuous sorting of SC27 stem cells, a neurogenic progenitor, from SC23 cells, an astrogenic progenitor. We define efficiency as the ratio between the number of SC27 cells over total number of cells retrieved in the streams, and throughput as the number of SC27 cells retrieved in the streams compared to their total number introduced to the device. The use of cylindrical electrodes as tall as the channel yields streams featuring >98% of SC27 cells and width up to 80 µm when using a flow rate of 10 µL/min and sample cell concentration up to 105 cells/mL.

  19. Putting "Organizations" into an Organization Theory Course: A Hybrid CAO Model for Teaching Organization Theory

    Science.gov (United States)

    Hannah, David R.; Venkatachary, Ranga

    2010-01-01

    In this article, the authors present a retrospective analysis of an instructor's multiyear redesign of a course on organization theory into what is called a hybrid Classroom-as-Organization model. It is suggested that this new course design served to apprentice students to function in quasi-real organizational structures. The authors further argue…

  20. Growth dynamics and cytoskeleton organization during stem maturation and gravity-induced stem bending in Zea mays L

    Science.gov (United States)

    Collings, D. A.; Winter, H.; Wyatt, S. E.; Allen, N. S.; Davies, E. (Principal Investigator)

    1998-01-01

    Characterization of gravitropic bending in the maize stem pulvinus, a tissue that functions specifically in gravity responses, demonstrates that the pulvinus is an ideal system for studying gravitropism. Gravistimulation during the second of three developmental phases of the pulvinus induces a gradient of cell elongation across the non-growing cells of the pulvinus, with the most elongation occurring on the lower side. This cell elongation is spatially and temporally separated from normal internodal cell elongation. The three characterized growth phases in the pulvinus correspond closely to a specialized developmental sequence in which structural features typical of cells not fully matured are retained while cell maturation occurs in surrounding internodal and nodal tissue. For example, the lignification of supporting tissue and rearrangement of transverse microtubules to oblique that occur in the internode when cell elongation ceases are delayed for up to 10 d in the adjacent cells of the pulvinus, and only occurs as a pulvinus loses its capacity to respond to gravistimulation. Gravistimulation does not modify this developmental sequence. Neither wall lignification nor rearrangement of transverse microtubules occurs in the rapidly elongating lower side or non-responsive upper side of the pulvinus until the pulvinus loses the capacity to bend further. Gravistimulation does, however, lead to the formation of putative pit fields within the expanding cells of the pulvinus.

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

    OpenAIRE

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

    2013-01-01

    Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epiderm...

  2. A role for topographic cues in the organization of collagenous matrix by corneal fibroblasts and stem cells.

    Directory of Open Access Journals (Sweden)

    Dimitrios Karamichos

    Full Text Available Human corneal fibroblasts (HCF and corneal stromal stem cells (CSSC each secrete and organize a thick stroma-like extracellular matrix in response to different substrata, but neither cell type organizes matrix on tissue-culture polystyrene. This study compared cell differentiation and extracellular matrix secreted by these two cell types when they were cultured on identical substrata, polycarbonate Transwell filters. After 4 weeks in culture, both cell types upregulated expression of genes marking differentiated keratocytes (KERA, CHST6, AQP1, B3GNT7. Absolute expression levels of these genes and secretion of keratan sulfate proteoglycans were significantly greater in CSSC than HCF. Both cultures produced extensive extracellular matrix of aligned collagen fibrils types I and V, exhibiting cornea-like lamellar structure. Unlike HCF, CSSC produced little matrix in the presence of serum. Construct thickness and collagen organization was enhanced by TGF-ß3. Scanning electron microscopic examination of the polycarbonate membrane revealed shallow parallel grooves with spacing of 200-300 nm, similar to the topography of aligned nanofiber substratum which we previously showed to induce matrix organization by CSSC. These results demonstrate that both corneal fibroblasts and stromal stem cells respond to a specific pattern of topographical cues by secreting highly organized extracellular matrix typical of corneal stroma. The data also suggest that the potential for matrix secretion and organization may not be directly related to the expression of molecular markers used to identify differentiated keratocytes.

  3. Methods in Molecular Biology: Germline Stem Cells | Center for Cancer Research

    Science.gov (United States)

    The protocols in Germline Stem Cells are intended to present selected genetic, molecular, and cellular techniques used in germline stem cell research. The book is divided into two parts. Part I covers germline stem cell identification and regulation in model organisms. Part II covers current techniques used in in vitro culture and applications of germline stem cells.

  4. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    Directory of Open Access Journals (Sweden)

    Melissa Lo Monaco

    2018-01-01

    Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  5. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

    Science.gov (United States)

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  6. Safety Cultural Competency Modeling in Nuclear Organizations

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sa Kil; Oh, Yeon Ju; Luo, Meiling; Lee, Yong Hee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The nuclear safety cultural competency model should be supplemented through a bottom-up approach such as behavioral event interview. The developed model, however, is meaningful for determining what should be dealt for enhancing safety cultural competency of nuclear organizations. The more details of the developing process, results, and applications will be introduced later. Organizational culture include safety culture in terms of its organizational characteristics.

  7. A STRATEGIC MANAGEMENT MODEL FOR SERVICE ORGANIZATIONS

    OpenAIRE

    Andreea ZAMFIR

    2013-01-01

    This paper provides a knowledge-based strategic management of services model, with a view to emphasise an approach to gaining competitive advantage through knowledge, people and networking. The long-term evolution of the service organization is associated with the way in which the strategic management is practised.

  8. Expanding on Successful Concepts, Models, and Organization

    Science.gov (United States)

    If the goal of the AEP framework was to replace existing exposure models or databases for organizing exposure data with a concept, we would share Dr. von Göetz concerns. Instead, the outcome we promote is broader use of an organizational framework for exposure science. The f...

  9. The Hippo pathway: key interaction and catalytic domains in organ growth control, stem cell self-renewal and tissue regeneration.

    Science.gov (United States)

    Cherrett, Claire; Furutani-Seiki, Makoto; Bagby, Stefan

    2012-01-01

    The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homoeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), consequently disabling their transcriptional co-activation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins.

  10. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  11. Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model

    OpenAIRE

    Takagi, Ryoji; Ishimaru, Junko; Sugawara, Ayaka; Toyoshima, Koh-ei; Ishida, Kentaro; Ogawa, Miho; Sakakibara, Kei; Asakawa, Kyosuke; Kashiwakura, Akitoshi; Oshima, Masamitsu; Minamide, Ryohei; Sato, Akio; Yoshitake, Toshihiro; Takeda, Akira; Egusa, Hiroshi

    2016-01-01

    The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bio...

  12. Effect of wine inhibitors on free pineapple stem bromelain activity in a model wine system.

    Science.gov (United States)

    Esti, Marco; Benucci, Ilaria; Liburdi, Katia; Garzillo, Anna Maria Vittoria

    2011-04-13

    The influence of potential inhibitors, naturally present in wine, on the activity of stem bromelain was investigated in order to evaluate the applicability of this enzyme for protein stabilization in white wine. Bromelain proteolytic activity was tested against a synthetic substrate (Bz-Phe-Val-Arg-pNA) in a model wine system after adding ethanol, sulfur dioxide (SO(2)), skin, seed, and gallic and ellagic tannins at the average range of their concentration in wine. All the inhibitors of stem bromelain activity tested turned out to be reversible. Ethanol was a competitive inhibitor with a rather limited effect. Gallic and ellagic tannins have no inhibitory effect on stem bromelain activity, while both seed and skin tannins were uncompetitive inhibitors. The strongest inhibition effect was revealed for sulfur dioxide, which was a mixed-type inhibitor for the enzyme activity. This study provides useful information relative to a future biotechnological application of stem bromelain in winemaking.

  13. Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells.

    Science.gov (United States)

    Johari, Behrooz; Ebrahimi-Rad, Mina; Maghsood, Faezeh; Lotfinia, Majid; Saltanatpouri, Zohreh; Teimoori-Toolabi, Ladan; Sharifzadeh, Zahra; Karimipoor, Morteza; Kadivar, Mehdi

    2017-01-01

    Myc (c-Myc) alone activates the embryonic stem cell-like transcriptional module in both normal and transformed cells. Its dysregulation might lead to increased cancer stem cells (CSCs) population in some tumor cells. In order to investigate the potential of Myc decoy oligodeoxynucleotides for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of CSCs. To our best of knowledge this is the first report outlining the application of Myc decoy in transcription factor decoy "TFD" strategy for inducing differentiation in mESCs. A 20-mer double-stranded Myc transcription factor decoy and scrambled oligodeoxynucleotides (ODNs) were designed, analyzed by electrophoretic mobility shift (EMSA) assay and transfected into the mESCs under 2 inhibitors (2i) condition. Further investigations were carried out using fluorescence and confocal microscopy, cell proliferation and apoptosis analysis, alkaline phosphatase and embryoid body formation assay, real-time PCR and western blotting. EMSA data showed that Myc decoy ODNs bound specifically to c-Myc protein. They were found to be localized in both cytoplasm and nucleus of mESCs. Our results revealed the potential capability of Myc decoy ODNs to decrease cell viability by (16.1±2%), to increase the number of cells arrested in G0/G1 phases and apoptosis by (14.2±3.1%) and (12.1±3.2%), respectively regarding the controls. Myc decoy could also modulate differentiation in mESCs despite the presence of 2i/LIF in our medium the presence of 2i/LIF in our medium. The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Emergent organization in a model market

    Science.gov (United States)

    Yadav, Avinash Chand; Manchanda, Kaustubh; Ramaswamy, Ramakrishna

    2017-09-01

    We study the collective behaviour of interacting agents in a simple model of market economics that was originally introduced by Nørrelykke and Bak. A general theoretical framework for interacting traders on an arbitrary network is presented, with the interaction consisting of buying (namely consumption) and selling (namely production) of commodities. Extremal dynamics is introduced by having the agent with least profit in the market readjust prices, causing the market to self-organize. In addition to examining this model market on regular lattices in two-dimensions, we also study the cases of random complex networks both with and without community structures. Fluctuations in an activity signal exhibit properties that are characteristic of avalanches observed in models of self-organized criticality, and these can be described by power-law distributions when the system is in the critical state.

  15. Role model and prototype matching: Upper-secondary school students’ meetings with tertiary STEM students

    DEFF Research Database (Denmark)

    Lykkegaard, Eva; Ulriksen, Lars

    2016-01-01

    concerning STEM students and attending university. The regular self-to-prototype matching process was shown in real-life role-models meetings to be extended to a more complex three-way matching process between students’ self-perceptions, prototype images and situation-specific conceptions of role models...

  16. Integrated modelling of two xenobiotic organic compounds

    DEFF Research Database (Denmark)

    Lindblom, Erik Ulfson; Gernaey, K.V.; Henze, Mogens

    2006-01-01

    This paper presents a dynamic mathematical model that describes the fate and transport of two selected xenobiotic organic compounds (XOCs) in a simplified representation. of an integrated urban wastewater system. A simulation study, where the xenobiotics bisphenol A and pyrene are used as reference...... compounds, is carried out. Sorption and specific biological degradation processes are integrated with standardised water process models to model the fate of both compounds. Simulated mass flows of the two compounds during one dry weather day and one wet weather day are compared for realistic influent flow...... rate and concentration profiles. The wet weather day induces resuspension of stored sediments, which increases the pollutant load on the downstream system. The potential of the model to elucidate important phenomena related to origin and fate of the model compounds is demonstrated....

  17. Cardiac regeneration using pluripotent stem cells—Progression to large animal models

    Directory of Open Access Journals (Sweden)

    James J.H. Chong

    2014-11-01

    Full Text Available Pluripotent stem cells (PSCs have indisputable cardiomyogenic potential and therefore have been intensively investigated as a potential cardiac regenerative therapy. Current directed differentiation protocols are able to produce high yields of cardiomyocytes from PSCs and studies in small animal models of cardiovascular disease have proven sustained engraftment and functional efficacy. Therefore, the time is ripe for cardiac regenerative therapies using PSC derivatives to be tested in large animal models that more closely resemble the hearts of humans. In this review, we discuss the results of our recent study using human embryonic stem cell derived cardiomyocytes (hESC-CM in a non-human primate model of ischemic cardiac injury. Large scale remuscularization, electromechanical coupling and short-term arrhythmias demonstrated by our hESC-CM grafts are discussed in the context of other studies using adult stem cells for cardiac regeneration.

  18. [STEM on Station Education

    Science.gov (United States)

    Lundebjerg, Kristen

    2016-01-01

    The STEM on Station team is part of Education which is part of the External Relations organization (ERO). ERO has traditional goals based around BHAG (Big Hairy Audacious Goal). The BHAG model is simplified to a saying: Everything we do stimulates actions by others to advance human space exploration. The STEM on Station education initiate is a project focused on bringing off the earth research and learning into classrooms. Educational resources such as lesson plans, activities to connect with the space station and STEM related contests are available and hosted by the STEM on Station team along with their partners such as Texas Instruments. These educational activities engage teachers and students in the current happenings aboard the international space station, inspiring the next generation of space explorers.

  19. Predicting stem borer density in maize using RapidEye data and generalized linear models

    Science.gov (United States)

    Abdel-Rahman, Elfatih M.; Landmann, Tobias; Kyalo, Richard; Ong'amo, George; Mwalusepo, Sizah; Sulieman, Saad; Ru, Bruno Le

    2017-05-01

    Average maize yield in eastern Africa is 2.03 t ha-1 as compared to global average of 6.06 t ha-1 due to biotic and abiotic constraints. Amongst the biotic production constraints in Africa, stem borers are the most injurious. In eastern Africa, maize yield losses due to stem borers are currently estimated between 12% and 21% of the total production. The objective of the present study was to explore the possibility of RapidEye spectral data to assess stem borer larva densities in maize fields in two study sites in Kenya. RapidEye images were acquired for the Bomet (western Kenya) test site on the 9th of December 2014 and on 27th of January 2015, and for Machakos (eastern Kenya) a RapidEye image was acquired on the 3rd of January 2015. Five RapidEye spectral bands as well as 30 spectral vegetation indices (SVIs) were utilized to predict per field maize stem borer larva densities using generalized linear models (GLMs), assuming Poisson ('Po') and negative binomial ('NB') distributions. Root mean square error (RMSE) and ratio prediction to deviation (RPD) statistics were used to assess the models performance using a leave-one-out cross-validation approach. The Zero-inflated NB ('ZINB') models outperformed the 'NB' models and stem borer larva densities could only be predicted during the mid growing season in December and early January in both study sites, respectively (RMSE = 0.69-1.06 and RPD = 8.25-19.57). Overall, all models performed similar when all the 30 SVIs (non-nested) and only the significant (nested) SVIs were used. The models developed could improve decision making regarding controlling maize stem borers within integrated pest management (IPM) interventions.

  20. Stem cell potency and the ability to contribute to chimeric organisms.

    Science.gov (United States)

    Polejaeva, Irina; Mitalipov, Shoukhrat

    2013-03-01

    Mouse embryonic chimeras are a well-established tool for studying cell lineage commitment and pluripotency. Experimental chimeras were successfully produced by combining two or more preimplantation embryos or by introducing into host embryo cultured pluripotent embryonic stem cells (ESCs). Chimera production using genetically modified ESCs became the method of choice for the generation of knockout or knockin mice. Although the derivation of ESCs or ESC-like cells has been reported for other species, only mouse and rat pluripotent stem cells have been shown to contribute to germline-competent chimeras, which is the defining feature of ESCs. Herein, we describe different approaches employed for the generation of embryonic chimeras, define chimera-competent cell types, and describe cases of spontaneous chimerism in humans. We also review the current state of derivation of pluripotent stem cells in several species and discuss outcomes of various chimera studies when such cells are used.

  1. Role model and prototype matching: Upper-secondary school students’ meetings with tertiary STEM students

    Directory of Open Access Journals (Sweden)

    Eva Lykkegaard

    2016-04-01

    Full Text Available Previous research has found that young people’s prototypes of science students and scientists affect their inclination to choose tertiary STEM programs (Science, Technology, Engineering and Mathematics. Consequently, many recruitment initiatives include role models to challenge these prototypes. The present study followed 15 STEM-oriented upper-secondary school students from university-distant backgrounds during and after their participation in an 18-months long university-based recruitment and outreach project involving tertiary STEM students as role models. The analysis focusses on how the students’ meetings with the role models affected their thoughts concerning STEM students and attending university. The regular self-to-prototype matching process was shown in real-life role-models meetings to be extended to a more complex three-way matching process between students’ self-perceptions, prototype images and situation-specific conceptions of role models. Furthermore, the study underlined the positive effect of prolonged role-model contact, the importance of using several role models and that traditional school subjects catered more resistant prototype images than unfamiliar ones did.

  2. Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model.

    Science.gov (United States)

    Chong, Alphonsus K S; Ang, Abel D; Goh, James C H; Hui, James H P; Lim, Aymeric Y T; Lee, Eng Hin; Lim, Beng Hai

    2007-01-01

    A repaired tendon needs to be protected for weeks until it has accrued enough strength to handle physiological loads. Tissue-engineering techniques have shown promise in the treatment of tendon and ligament defects. The present study tested the hypothesis that bone marrow-derived mesenchymal stem cells can accelerate tendon-healing after primary repair of a tendon injury in a rabbit model. Fifty-seven New Zealand White rabbits were used as the experimental animals, and seven others were used as the source of bone marrow-derived mesenchymal stem cells. The injury model was a sharp complete transection through the midsubstance of the Achilles tendon. The transected tendon was immediately repaired with use of a modified Kessler suture and a running epitendinous suture. Both limbs were used, and each side was randomized to receive either bone marrow-derived mesenchymal stem cells in a fibrin carrier or fibrin carrier alone (control). Postoperatively, the rabbits were not immobilized. Specimens were harvested at one, three, six, and twelve weeks for analysis, which included evaluation of gross morphology (sixty-two specimens), cell tracing (twelve specimens), histological assessment (forty specimens), immunohistochemistry studies (thirty specimens), morphometric analysis (forty specimens), and mechanical testing (sixty-two specimens). There were no differences between the two groups with regard to the gross morphology of the tendons. The fibrin had degraded by three weeks. Cell tracing showed that labeled bone marrow-derived mesenchymal stem cells remained viable and present in the intratendinous region for at least six weeks, becoming more diffuse at later time-periods. At three weeks, collagen fibers appeared more organized and there were better morphometric nuclear parameters in the treatment group (p tendon repair can improve histological and biomechanical parameters in the early stages of tendon-healing.

  3. Identification of Novel Targets for Lung Cancer Therapy Using an Induced Pluripotent Stem Cell Model.

    Science.gov (United States)

    Shukla, Vivek; Rao, Mahadev; Zhang, Hongen; Beers, Jeanette; Wangsa, Darawalee; Wangsa, Danny; Buishand, Floryne O; Wang, Yonghong; Yu, Zhiya; Stevenson, Holly; Reardon, Emily; McLoughlin, Kaitlin C; Kaufman, Andrew; Payabyab, Eden; Hong, Julie A; Zhang, Mary; Davis, Sean R; Edelman, Daniel C; Chen, Guokai; Miettinen, Markku; Restifo, Nicholas; Ried, Thomas; Meltzer, Paul S; Schrump, David S

    2018-04-01

    small cell lung cancer lines and specimens. Overexpression of the additional sex combs like-3 gene correlated with increased genomic copy number in small cell lung cancer lines. Knock-down of the additional sex combs like-3 gene inhibited proliferation, clonogenicity, and teratoma formation by lung induced pluripotent stem cells and significantly diminished in vitro clonogenicity and growth of small cell lung cancer cells in vivo. Collectively, these studies highlight the potential utility of this lung induced pluripotent stem cell model for elucidating epigenetic mechanisms contributing to pulmonary carcinogenesis and suggest that additional sex combs like-3 is a novel target for small cell lung cancer therapy.

  4. The small GTPase RhoA is required to maintain spinal cord neuroepithelium organization and the neural stem cell pool

    DEFF Research Database (Denmark)

    Herzog, Dominik; Loetscher, Pirmin; van Hengel, Jolanda

    2011-01-01

    ablation. We show that, in the spinal cord neuroepithelium, RhoA is essential to localize N-cadherin and ß-catenin to AJs and maintain apical-basal polarity of neural progenitor cells. Ablation of RhoA caused the loss of AJs and severe abnormalities in the organization of cells within the neuroepithelium......Dia1), does not localize to apical AJs in which it likely stabilizes intracellular adhesion by promoting local actin polymerization and microtubule organization. Furthermore, expressing a dominant-negative form of mDia1 in neural stem/progenitor cells results in a similar phenotype compared...... with that of the RhoA conditional knock-out, namely the loss of AJs and apical polarity. Together, our data show that RhoA signaling is necessary for AJ regulation and for the maintenance of mammalian neuroepithelium organization preventing precocious cell-cycle exit and differentiation....

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Transplant of Hepatocytes, Undifferentiated Mesenchymal Stem Cells, and In Vitro Hepatocyte-Differentiated Mesenchymal Stem Cells in a Chronic Liver Failure Experimental Model: A Comparative Study.

    Science.gov (United States)

    El Baz, Hanan; Demerdash, Zeinab; Kamel, Manal; Atta, Shimaa; Salah, Faten; Hassan, Salwa; Hammam, Olfat; Khalil, Heba; Meshaal, Safa; Raafat, Inas

    2018-02-01

    Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group. Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

  8. Protein regulation of induced pluripotent stem cells by transplanting in a Huntington's animal model.

    Science.gov (United States)

    Mu, S; Han, L; Zhou, G; Mo, C; Duan, J; He, Z; Wang, Z; Ren, L; Zhang, J

    2016-10-01

    The purpose of this study was to determine the functional recovery and protein regulation by transplanted induced pluripotent stem cells in a rat model of Huntington's disease (HD). In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle 10 days after the quinolinic acid injection. At 8 weeks after transplantation, fluorodeoxyglucose-PET/CT scan and balance-beam test were performed to evaluate the functional recovery of experimental rats. In addition, immunofluorescence and protein array analysis were used to investigate the regulation of stimulated protein expression in the striatum. At 8 weeks after induced pluripotent stem cell transplantation, motor function was improved in comparison with the quinolinic acid-treated rats. High fluorodeoxyglucose accumulation in the injured striatum was also observed by PET/CT scans. In addition, immunofluorescence analysis demonstrated that implanted cells migrated from the lateral ventricle into the lesioned striatum and differentiated into striatal projection neurons. Array analysis showed a significant upregulation of GFR (Glial cell line-derived neurotrophic factor receptor) alpha-1, Adiponectin/Acrp30, basic-fibroblast growth factors, MIP-1 (Macrophage-inflammatory protein) alpha and leptin, as well as downregulation of cytokine-induced neutrophil chemoattractant-3 in striatum after transplantatation of induced pluripotent stem cells in comparison with the quinolinic acid -treated rats. The findings in this work indicate that transplantation of induced pluripotent stem cells is a promising therapeutic candidate for HD. © 2016 British Neuropathological Society.

  9. Nucleosome organizations in induced pluripotent stem cells reprogrammed from somatic cells belonging to three different germ layers.

    Science.gov (United States)

    Tao, Yu; Zheng, Weisheng; Jiang, Yonghua; Ding, Guitao; Hou, Xinfeng; Tang, Yitao; Li, Yueying; Gao, Shuai; Chang, Gang; Zhang, Xiaobai; Liu, Wenqiang; Kou, Xiaochen; Wang, Hong; Jiang, Cizhong; Gao, Shaorong

    2014-12-21

    Nucleosome organization determines the chromatin state, which in turn controls gene expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it is still unclear to what degree the re-established nucleosome organization of induced pluripotent stem cells (iPSCs) resembles embryonic stem cells (ESCs), and whether the iPSCs inherit some residual gene expression from the parental fibroblast cells. We generated genome-wide nucleosome maps in mouse ESCs and in iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons showed that the nucleosome organizations in the iPSCs, regardless of the iPSCs' tissue of origin, were nearly identical to the ESCs, but distinct from mouse embryonic fibroblasts (MEF). There is a canonical nucleosome arrangement of -1, nucleosome depletion region, +1, +2, +3, and so on nucleosomes around the transcription start sites of active genes whereas only a nucleosome occupies silent transcriptional units. Transcription factor binding sites possessed characteristic nucleosomal architecture, such that their access was governed by the rotational and translational settings of the nucleosome. Interestingly, the tissue-specific genes were highly expressed only in the parental somatic cells of the corresponding iPS cell line before reprogramming, but had a similar expression level in all the resultant iPSCs and ESCs. The re-established nucleosome landscape during nuclear reprogramming provides a conserved setting for accessibility of DNA sequences in mouse pluripotent stem cells. No persistent residual expression program or nucleosome positioning of the parental somatic cells that reflected their tissue of origin was passed on to the resulting mouse iPSCs.

  10. Modelling the behaviour of organic degradation products

    International Nuclear Information System (INIS)

    Cross, J.E.; Ewart, F.T.; Greenfield, B.F.

    1989-03-01

    Results are presented from recent studies at Harwell which show that the degradation products which are formed when certain organic waste materials are exposed to the alkaline conditions typical of a cementitious environment, can enhance the solubility of plutonium, even at pH values as high as 12, by significant factors. Characterisation of the degradation products has been undertaken but the solubility enhancement does not appear to be related to the concentration of any of the major organic species that have been identified in the solutions. While it has not been possible to identify by analysis the organic ligand responsible for the increased solubility of plutonium, the behaviour of D-Saccharic acid does approach the behaviour of the degradation products. The PHREEQE code has been used to simulate the solubility of plutonium in the presence of D-Saccharic acid and other model degradation products, in order to explain the solubility enhancement. The extrapolation of the experimental conditions to the repository is the major objective, but in this work the ability of a model to predict the behaviour of plutonium over a range of experimental conditions has been tested. (author)

  11. Dynamic root uptake model for neutral lipophilic organics

    DEFF Research Database (Denmark)

    Trapp, Stefan

    2002-01-01

    and output to stem with the transpiration stream plus first-order metabolism and dilution by exponential growth. For chemicals with low or intermediate lipophilicity (log Kow , 2), there was no relevant difference between dynamic model and equilibrium approach. For lipophilic compounds, the dynamic model...

  12. Pathways to Tumorigenesis—Modeling Mutation Acquisition in Stem Cells and Their Progeny

    Directory of Open Access Journals (Sweden)

    Rina Ashkenazi

    2008-11-01

    Full Text Available Most adult tissues consist of stem cells, progenitors, and mature cells, and this hierarchical architecture may play an important role in the multistep process of carcinogenesis. Here, we develop and discuss the important predictions of a simple mathematical model of cancer initiation and early progression within a hierarchically structured tissue. This work presents a model that incorporates both the sequential acquisition of phenotype altering mutations and tissue hierarchy. The model simulates the progressive effect of accumulating mutations that lead to an increase in fitness or the induction of genetic instability. A novel aspect of the model is that symmetric self-renewal, asymmetric division, and differentiation are all incorporated, and this enables the quantitative study of the effect of mutations that deregulate the normal, homeostatic stem cell division pattern. The model is also capable of predicting changes in both tissue composition and in the progression of cells along their lineage at any given time and for various sequences of mutations. Simulations predict that the specific order in which mutations are acquired is crucial for determining the pace of cancer development. Interestingly, we find that the importance of genetic stability differs significantly depending on the physiological expression of mutations related to symmetric self-renewal and differentiation of stem and progenitor cells. In particular, mutations that lead to the alteration of the stem cell division pattern or the acquisition of some degree of immortality in committed progenitors lead to an early onset of cancer and diminish the impact of genetic instability.

  13. Skin-derived mesenchymal stem cells help restore function to ovaries in a premature ovarian failure mouse model.

    Directory of Open Access Journals (Sweden)

    Dongmei Lai

    Full Text Available Skin-derived mesenchymal stem cells (SMSCs can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs and male skin-derived mesenchymal stem cells (M-SMSCs from red fluorescence protein (RFP transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.

  14. Stem cells for amyotrophic lateral sclerosis modeling and therapy: myth or fact?

    Science.gov (United States)

    Coatti, G C; Beccari, M S; Olávio, T R; Mitne-Neto, M; Okamoto, O K; Zatz, M

    2015-03-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose pathophysiology is poorly understood. Aiming to better understand the cause of motor neuron death, the use of experimental cell-based models increased significantly over the past years. In this scenario, much knowledge has been generated from the study of motor neurons derived from embryonic stem cells and induced pluripotent stem cells. These methods, however, have advantages and disadvantages, which must be balanced on experimental design. Preclinical studies provide valuable information, making it possible to combine diverse methods to build an expanded knowledge of ALS pathophysiology. In addition to using stem cells as experimental models for understanding disease mechanism, these cells had been quoted for therapy in ALS. Despite ethical issues involved in its use, cell therapy with neural stem cells stands out. A phase I clinical trial was recently completed and a phase II is on its way, attesting the method's safety. In another approach, mesenchymal stromal cells capable of releasing neuroregulatory and anti-inflammatory factors have also been listed as candidates for cell therapy for ALS, and have been admitted as safe in a phase I trial. Despite recent advances, application of stem cells as an actual therapy for ALS patients is still in debate. Here, we discuss how stem cells have been useful in modeling ALS and address critical topics concerning their therapeutic use, such as administration protocols, injection site, cell type to be administered, type of transplantation (autologous vs. allogeneic) among other issues with particular implications for ALS therapy. © 2015 International Society for Advancement of Cytometry.

  15. Investigating and modeling the pyrolysis kinetic of leaves and stems of pistachio trees for biofuel production

    Directory of Open Access Journals (Sweden)

    M Ostad Hoseini

    2016-09-01

    500°C with 30 minutes residence time. The instantaneous amount (in decimal of the produced gas (M and char (Ms as a function of time (t was modeled using the following equations: For each experiment B is a constant value and is represented by: Where Ea is the activation energy, R is universal gas constant, T is the temperature of the experiment and A is the pre-exponential constant. By having M or Ms at different times (t, the parameters of A, B and Ea were estimated using the curve fitting tool box of the MATLAB® software. Results and Discussion The results of chemical analysis indicated that the leaves powders contained 1.5% N, 42.1% C, 5.5% H, 0.4% S and 48.3% O while the stem samples contained 0.5% N, 46.5% C, 6.1% H, 0.2% S and 44.6% O. Higher amount of carbon and hydrogen in the stem leaves indicates that the stem should have higher energy content. In fact, the calculated high and low heating values for leaves were 17.23 and 16.03 MJ.kg-1, and for the stems were 18.91 and 17.59 MJ.kg-1, respectively which comply with the predicted results from chemical analysis of the powders. The TGA test results indicated that the initial weight loss took place up to 270°C for the stems powder and up to 220°C for leaves powders. This weight loss was due to loss of moisture and volatile compounds. The actual degradation temperature for the stem powders ranged from 300 to 500°C while for the leaves was from 350 to 600°C. The results of pyrolysis experiments indicated that the pyrolysis of stems took place faster than leaves. The pyrolysis time was 10 to 15 min for leaves and 5 to 10 min for stems. The resulting char for pyrolysis of stem was 30% and for stems were 40% of the original materials. The kinetic of pyrolysis was modeled using one-step global model for production of char and gas. The experimental data were fitted to the used model with high degrees of accuracy (R2>0.99. The model parameters, namely activation energy and frequency factors were 10.70 kJ.mol-1, and

  16. Stem cell proliferation and differentiation a multitype branching process model

    CERN Document Server

    Macken, Catherine A

    1988-01-01

    The body contains many cellular systems that require the continuous production of new, fully functional, differentiated cells to replace cells lacking or having limited self-renewal capabilities that die or are damaged during the lifetime of an individual. Such systems include the epidermis, the epithelial lining of the gut, and the blood. For example, erythrocytes (red blood cells) lack nuclei and thus are incapable of self-replication. They have a life span in the circulation of about 120 days. Mature granulocytes, which also lack proliferative capacity, have a much shorter life span - typically 12 hours, though this may be reduced to only two or three hours in times of serious tissue infection. Perhaps a more familiar example is the outermost layer of the skin. This layer is composed of fully mature, dead epidermal cells that must be replaced by the descendants of stem cells lodged in lower layers of the epidermis (cf. Alberts et al. , 1983). In total, to supply the normal steady-state demands of cells, an...

  17. Embryonic stem cells as an ectodermal cellular model of human p63-related dysplasia syndromes.

    NARCIS (Netherlands)

    Rostagno, P.; Wolchinsky, Z.; Vigano, A.M.; Shivtiel, S.; Zhou, Huiqing; Bokhoven, J.H.L.M. van; Ferone, G.; Missero, C.; Mantovani, R.; Aberdam, D.; Virolle, T.

    2010-01-01

    Heterozygous mutations in the TP63 transcription factor underlie the molecular basis of several similar autosomal dominant ectodermal dysplasia (ED) syndromes. Here we provide a novel cellular model derived from embryonic stem (ES) cells that recapitulates in vitro the main steps of embryonic skin

  18. PIRPOSAL Model of Integrative STEM Education: Conceptual and Pedagogical Framework for Classroom Implementation

    Science.gov (United States)

    Wells, John G.

    2016-01-01

    The PIRPOSAL model is both a conceptual and pedagogical framework intended for use as a pragmatic guide to classroom implementation of Integrative STEM Education. Designerly questioning prompted by a "need to know" serves as the basis for transitioning student designers within and among multiple phases while they progress toward an…

  19. Modeling Niemann Pick type C1 using human embryonic and induced pluripotent stem cells.

    Science.gov (United States)

    Ordoñez, M Paulina; Steele, John W

    2017-02-01

    Data generated in Niemann Pick type C1 (NPC1) human embryonic and human induced pluripotent stem cell derived neurons complement on-going studies in animal models and provide the first example, in disease-relevant human cells, of processes that underlie preferential neuronal defects in a NPC1. Our work and that of other investigators in human neurons derived from stem cells highlight the importance of performing rigorous mechanistic studies in relevant cell types to guide drug discovery and therapeutic development, alongside of existing animal models. Through the use of human stem cell-derived models of disease, we can identify and discover or repurpose drugs that revert early events that lead to neuronal failure in NPC1. Together with the study of disease pathogenesis and efficacy of therapies in animal models, these strategies will fulfill the promise of stem cell technology in the development of new treatments for human diseases. This article is part of a Special Issue entitled SI: Exploiting human neurons. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. STEM Engagement with NASA's Solar System Treks Portals for Lunar and Planetary Mapping and Modeling

    Science.gov (United States)

    Law, E. S.; Day, B. H.

    2018-01-01

    This presentation will provide an overview of the uses and capabilities of NASA's Solar System Treks family of online mapping and modeling portals. While also designed to support mission planning and scientific research, this presentation will focus on the Science, Technology, Engineering, and Math (STEM) engagement and public outreach capabilities of these web based suites of data visualization and analysis tools.

  1. The Burden of Being "Model": Racialized Experiences of Asian STEM College Students

    Science.gov (United States)

    McGee, Ebony O.; Thakore, Bhoomi K.; LaBlance, Sandra S.

    2017-01-01

    This qualitative study used narrative methodology to investigate what becoming a scientist or engineer entails for Asian and Asian American college students stereotyped as "model minorities." We present the narratives of 23 high-achieving science, technology, engineering, and mathematics (STEM) college students who self-identified as…

  2. Stem cell therapy for joint problems using the horse as a clinically relevant animal model

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Betts, Dean H.

    2007-01-01

    of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

  3. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Ivana Antonucci

    2016-04-01

    Full Text Available In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

  4. Biogovernance Beyond the State: The Shaping of Stem Cell Therapy by Patient Organizations in India.

    Science.gov (United States)

    Heitmeyer, Carolyn

    2017-04-01

    Public engagement through government-sponsored "public consultations" in biomedical innovation, specifically stem cell research and therapy, has been relatively limited in India. However, patient groups are drawing upon collaborations with medical practitioners to gain leverage in promoting biomedical research and the conditions under which patients can access experimental treatments. Based on qualitative fieldwork conducted between 2012 and 2015, I examine the ways in which two patient groups engaged with debates around how experimental stem cell therapy should be regulated, given the current lack of legally binding research guidelines. Such processes of engagement can be seen as an alternative form of biomedical governance which responds to the priorities and exigencies of Indian patients, contrasting with the current measures taken by the Indian state which, instead, are primarily directed at the global scientific and corporate world.

  5. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  6. Tracking stem cells in tissue-engineered organs using magnetic nanoparticles

    OpenAIRE

    Hachani, R.; Lowdell, M.; Birchall, M.; Thanh, N. T.

    2013-01-01

    The use of human stem cells (SCs) in tissue engineering holds promise in revolutionising the treatment of numerous diseases. There is a pressing need to comprehend the distribution, movement and role of SCs once implanted onto scaffolds. Nanotechnology has provided a platform to investigate this through the development of inorganic magnetic nanoparticles (MNPs). MNPs can be used to label and track SCs by magnetic resonance imaging (MRI) since this clinically available imaging modality has hig...

  7. Virtuous organization: A structural equation modeling approach

    Directory of Open Access Journals (Sweden)

    Majid Zamahani

    2013-02-01

    Full Text Available For years, the idea of virtue was unfavorable among researchers and virtues were traditionally considered as culture-specific, relativistic and they were supposed to be associated with social conservatism, religious or moral dogmatism, and scientific irrelevance. Virtue and virtuousness have been recently considered seriously among organizational researchers. The proposed study of this paper examines the relationships between leadership, organizational culture, human resource, structure and processes, care for community and virtuous organization. Structural equation modeling is employed to investigate the effects of each variable on other components. The data used in this study consists of questionnaire responses from employees in Payam e Noor University in Yazd province. A total of 250 questionnaires were sent out and a total of 211 valid responses were received. Our results have revealed that all the five variables have positive and significant impacts on virtuous organization. Among the five variables, organizational culture has the most direct impact (0.80 and human resource has the most total impact (0.844 on virtuous organization.

  8. Study on the Occurrence and Epidemic Model of Rape Sclerotinia Stem Rot of ‘Zheyou 50’

    OpenAIRE

    Xu Sen-fu; Wang Hui-fu; Yu Shanhong; Wang En-guo

    2013-01-01

    In order to investigate invading and epidemic rules of rape sclerotinia stem rot of ‘Zheyou 50’ and promote the development of brassica campestris industry, this paper studied the outbreak regularity and epidemic model of rape sclerotinia stem rot according to field investigation and infection. The result showed that machinery direct seeding rape was good for the occurrence of sclerotinia stem rot for the reason of late seeding and high density. The period from water damage appeared to wiltin...

  9. Models relevant to radiation effects on stem cell pools

    Energy Technology Data Exchange (ETDEWEB)

    Lajtha, L G

    1971-04-01

    The available evidence clearly indicates the existence of a pluripotential primitive stem cell population (CFU). In the normal animal a large proportion of this population will 'sit' in the G{sub 0} state. At any time a small proportion of these cells will differentiate into one or more 'precursor' populations. One such precursor population is the erythropoietin responsive cell (ERC) and it is important to realize that this population has a significant number of mitoses in it, i.e. it is capable of considerable, although not indefinite proliferation. This is indicated by the colony growth during which, from a single colony former, large numbers of differentiated cells can be formed, in excess of several millions, at a time when the CFU numbers in the colony are still very small. To understand then the effects of radiation on this complex series of populations the following will have to be borne in mind. The ultimate stem cells are, at least in the small rodent, the CFU. It is their quantity that is essential for regeneration. However, the normal rate of differentiation of CFU in the small rodent is very low. This is because this rate of differentiation gives rise to a possibly committed precursor cell population such as the ERC, or possibly the agar forming 'GRC', the precursor populations with considerable proliferative potential in them. Therefore, after relatively small doses of radiation, or even during a regime of continuous irradiation, the proliferative potential of these transit precursor populations will be able to cope with near normal haemopoiesis at a time when the number of colony formers is gradually depleted. It is also significant that the rate of seeding of the primitive colony former is not related to its numbers and, therefore, under conditions of partial irradiation, at least in the small rodent, greatly increased relative migration and to some extent increased absolute migration of the CFU is possible, with consequent enhancement of the

  10. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    Directory of Open Access Journals (Sweden)

    Daniel R. Bayzigitov

    2016-01-01

    Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

  11. The influence of female social models in corporate STEM initiatives on girls' math and science attitudes

    Science.gov (United States)

    Medeiros, Donald J.

    The United States' Science, Technology, Engineering, and Mathematics (STEM) workforce is growing slower than in the past, in comparison to demand, and in comparison to other countries. Competitive talent conditions require the United States to develop a strong pipeline of STEM talent within its own citizens. Given the number of female college graduates and their underrepresentation in the STEM workforce, women provide the greatest opportunity for fulfilling this need. The term social model represents the individuals and media that shape children's self-perceptions. Social models have been shown to positively influence girl's perceptions of the value of math and science as well as their expectations of success. This study examined differences in attitudes towards math and science among student participants in corporate STEM programs. Differences were measured based on participant gender and ethnicity, their mentor's gender and ethnicity, and program design differences. The research purpose was to inform the design of corporate STEM programs to improve female participants' attitudes towards math and science and eventually increase the number of women in the STEM workforce. Over three hundred students in differing corporate STEM programs completed math and science attitudinal scales at the start and end of their programs. Study results revealed, prior to program start, female participants had a better attitude towards math and science than male participants. Analysis of the Trends in International Mathematics and Science Study data showed similar results. Overall program results demonstrated higher post program math and science attitudes with no differences based on gender, age, or ethnicity of the participant or mentor. Participants with high program or mentor satisfaction were found to have higher attitudes towards math and science. These results may suggest improving female academic choice requires more focus on their expectations of success than perceived task

  12. iSTEM: Promoting Fifth Graders' Mathematical Modeling

    Science.gov (United States)

    Yanik, H. Bahadir; Karabas, Celil

    2014-01-01

    Modeling requires that people develop representations or procedures to address particular problem situations (Lesh et al. 2000). Mathematical modeling is used to describe essential characteristics of a phenomenon or a situation that one intends to study in the real world through building mathematical objects. This article describes how fifth-grade…

  13. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

  14. NASA GISS Climate Change Research Initiative: A Multidisciplinary Vertical Team Model for Improving STEM Education by Using NASA's Unique Capabilities.

    Science.gov (United States)

    Pearce, M. D.

    2017-12-01

    CCRI is a year-long STEM education program designed to bring together teams of NASA scientists, graduate, undergraduate and high school interns and high school STEM educators to become immersed in NASA research focused on atmospheric and climate changes in the 21st century. GISS climate research combines analysis of global datasets with global models of atmospheric, land surface, and oceanic processes to study climate change on Earth and other planetary atmospheres as a useful tool in assessing our general understanding of climate change. CCRI interns conduct research, gain knowledge in assigned research discipline, develop and present scientific presentations summarizing their research experience. Specifically, CCRI interns write a scientific research paper explaining basic ideas, research protocols, abstract, results, conclusion and experimental design. Prepare and present a professional presentation of their research project at NASA GISS, prepare and present a scientific poster of their research project at local and national research symposiums along with other federal agencies. CCRI Educators lead research teams under the direction of a NASA GISS scientist, conduct research, develop research based learning units and assist NASA scientists with the mentoring of interns. Educators create an Applied Research STEM Curriculum Unit Portfolio based on their research experience integrating NASA unique resources, tools and content into a teacher developed unit plan aligned with the State and NGSS standards. STEM Educators also Integrate and implement NASA unique units and content into their STEM courses during academic year, perform community education STEM engagement events, mentor interns in writing a research paper, oral research reporting, power point design and scientific poster design for presentation to local and national audiences. The CCRI program contributes to the Federal STEM Co-STEM initiatives by providing opportunities, NASA education resources and

  15. Reconstruction of 3D tree stem models from low-cost terrestrial laser scanner data

    Science.gov (United States)

    Kelbe, Dave; Romanczyk, Paul; van Aardt, Jan; Cawse-Nicholson, Kerry

    2013-05-01

    With the development of increasingly advanced airborne sensing systems, there is a growing need to support sensor system design, modeling, and product-algorithm development with explicit 3D structural ground truth commensurate to the scale of acquisition. Terrestrial laser scanning is one such technique which could provide this structural information. Commercial instrumentation to suit this purpose has existed for some time now, but cost can be a prohibitive barrier for some applications. As such we recently developed a unique laser scanning system from readily-available components, supporting low cost, highly portable, and rapid measurement of below-canopy 3D forest structure. Tools were developed to automatically reconstruct tree stem models as an initial step towards virtual forest scene generation. The objective of this paper is to assess the potential of this hardware/algorithm suite to reconstruct 3D stem information for a single scan of a New England hardwood forest site. Detailed tree stem structure (e.g., taper, sweep, and lean) is recovered for trees of varying diameter, species, and range from the sensor. Absolute stem diameter retrieval accuracy is 12.5%, with a 4.5% overestimation bias likely due to the LiDAR beam divergence.

  16. Health consumers and stem cell therapy innovation: markets, models and regulation.

    Science.gov (United States)

    Salter, Brian; Zhou, Yinhua; Datta, Saheli

    2014-05-01

    Global health consumer demand for stem cell therapies is vibrant, but the supply of treatments from the conventional science-based model of innovation is small and unlikely to increase in the near future. At the same time, several models of medical innovation have emerged that can respond to the demand, often employing a transnational value chain to deliver the product. Much of the commentary has approached the issue from a supply side perspective, demonstrating the extent to which national and transnational regulation fails to impose what are regarded as appropriate standards on the 'illicit' supply of stem cell therapies characterized by little data and poor outcomes. By contrast, this article presents a political economic analysis with a strong demand side perspective, arguing that the problem of what is termed 'stem cell tourism' is embedded in the demand-supply relationship of the health consumer market and its engagement with different types of stem cell therapy innovation. To be meaningful, discussions of regulation must recognize that analysis or risk being sidelined by a market, which ignores their often wishful thinking.

  17. The potential of induced pluripotent stem cells in models of neurological disorders: implications on future therapy.

    Science.gov (United States)

    Crook, Jeremy Micah; Wallace, Gordon; Tomaskovic-Crook, Eva

    2015-03-01

    There is an urgent need for new and advanced approaches to modeling the pathological mechanisms of complex human neurological disorders. This is underscored by the decline in pharmaceutical research and development efficiency resulting in a relative decrease in new drug launches in the last several decades. Induced pluripotent stem cells represent a new tool to overcome many of the shortcomings of conventional methods, enabling live human neural cell modeling of complex conditions relating to aberrant neurodevelopment, such as schizophrenia, epilepsy and autism as well as age-associated neurodegeneration. This review considers the current status of induced pluripotent stem cell-based modeling of neurological disorders, canvassing proven and putative advantages, current constraints, and future prospects of next-generation culture systems for biomedical research and translation.

  18. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    2015-08-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use.

  19. Human pluripotent stem cells in modeling human disorders: the case of fragile X syndrome.

    Science.gov (United States)

    Vershkov, Dan; Benvenisty, Nissim

    2017-01-01

    Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS. In this review we summarize the methodologies for generation of FXS-PSCs, discuss their advantages and disadvantages compared with existing modeling systems and describe their utilization in the study of FXS pathogenesis and in the development of targeted treatment.

  20. An Organization's Extended (Soft) Competencies Model

    Science.gov (United States)

    Rosas, João; Macedo, Patrícia; Camarinha-Matos, Luis M.

    One of the steps usually undertaken in partnerships formation is the assessment of organizations’ competencies. Typically considered competencies of a functional or technical nature, which provide specific outcomes can be considered as hard competencies. Yet, the very act of collaboration has its specific requirements, for which the involved organizations must be apt to exercise other type of competencies that affect their own performance and the partnership success. These competencies are more of a behavioral nature, and can be named as soft-competencies. This research aims at addressing the effects of the soft competencies on the performance of the hard ones. An extended competencies model is thus proposed, allowing the construction of adjusted competencies profiles, in which the competency levels are adjusted dynamically according to the requirements of collaboration opportunities.

  1. Modeling photocurrent transients in organic solar cells

    International Nuclear Information System (INIS)

    Hwang, I; Greenham, N C

    2008-01-01

    We investigate the transient photocurrents of organic photovoltaic devices in response to a sharp turn-on of illumination, by numerical modeling of the drift-diffusion equations. We show that the photocurrent turn-on dynamics are determined not only by the transport dynamics of free charges, but also by the time required for the population of geminate charge pairs to reach its steady-state value. The dissociation probability of a geminate charge pair is found to be a key parameter in determining the device performance, not only by controlling the efficiency at low intensities, but also in determining the fate of charge pairs formed by bimolecular recombination at high intensities. Bimolecular recombination is shown to reduce the turn-on time at high intensities, since the typical distance traveled by a charge pair is reduced.

  2. Computational modeling of Metal-Organic Frameworks

    Science.gov (United States)

    Sung, Jeffrey Chuen-Fai

    In this work, the metal-organic frameworks MIL-53(Cr), DMOF-2,3-NH 2Cl, DMOF-2,5-NH2Cl, and HKUST-1 were modeled using molecular mechanics and electronic structure. The effect of electronic polarization on the adsorption of water in MIL-53(Cr) was studied using molecular dynamics simulations of water-loaded MIL-53 systems with both polarizable and non-polarizable force fields. Molecular dynamics simulations of the full systems and DFT calculations on representative framework clusters were utilized to study the difference in nitrogen adsorption between DMOF-2,3-NH2Cl and DMOF-2,5-NH 2Cl. Finally, the control of proton conduction in HKUST-1 by complexation of molecules to the Cu open metal site was investigated using the MS-EVB methodology.

  3. International Society for Stem Cell Research

    Science.gov (United States)

    ... renowned stem cell and regenerative medicine community. More stem cell research Take a closer look Recent Blogs View ... story independent nonprofit organization & the voice of the stem cell research community The International Society for Stem Cell ...

  4. Disease modeling using human induced pluripotent stem cells: lessons from the liver.

    Science.gov (United States)

    Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

    2015-01-01

    Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  5. Modeling of desorption of Alfalfa (Medicago sativa) stems and leaves.

    NARCIS (Netherlands)

    ArabHosseini, A.; Huisman, W.; Müller, J.

    2011-01-01

    The equilibrium moisture content of agricultural products is necessary to optimize drying process and helps to keep the quality of the product during the period of storage. The main aim of this research was to find the best model which could define well, the exchange of moisture between alfalfa

  6. Model for Railway Infrastructure Management Organization

    Directory of Open Access Journals (Sweden)

    Gordan Stojić

    2012-03-01

    Full Text Available The provision of appropriate quality rail services has an important role in terms of railway infrastructure: quality of infrastructure maintenance, regulation of railway traffic, line capacity, speed, safety, train station organization, the allowable lines load and other infrastructure parameters.The analysis of experiences in transforming the railway systems points to the conclusion that there is no unique solution in terms of choice for institutional rail infrastructure management modes, although more than nineteen years have passed from the beginning of the implementation of the Directive 91/440/EEC. Depending on the approach to the process of restructuring the national railway company, adopted regulations and caution in its implementation, the existence or absence of a clearly defined transport strategy, the willingness to liberalize the transport market, there are several different ways for institutional management of railway infrastructure.A hybrid model for selection of modes of institutional rail infrastructure management was developed based on the theory of artificial intelligence, theory of fuzzy sets and theory of multicriteria optimization.KEY WORDSmanagement, railway infrastructure, organizational structure, hybrid model

  7. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  8. Project-matrix models of marketing organization

    OpenAIRE

    Gutić Dragutin; Rudelj Siniša

    2009-01-01

    Unlike theory and practice of corporation organization, in marketing organization numerous forms and contents at its disposal are not reached until this day. It can be well estimated that marketing organization today in most of our companies and in almost all its parts, noticeably gets behind corporation organization. Marketing managers have always been occupied by basic, narrow marketing activities as: sales growth, market analysis, market growth and market share, marketing research, introdu...

  9. Cell of Origin and Cancer Stem Cells in Tumor Suppressor Mouse Models of Glioblastoma.

    Science.gov (United States)

    Alcantara Llaguno, Sheila R; Xie, Xuanhua; Parada, Luis F

    2016-01-01

    The cellular origins and the mechanisms of progression, maintenance of tumorigenicity, and therapeutic resistance are central questions in the glioblastoma multiforme (GBM) field. Using tumor suppressor mouse models, our group recently reported two independent populations of adult GBM-initiating central nervous system progenitors. We found different functional and molecular subtypes depending on the tumor-initiating cell lineage, indicating that the cell of origin is a driver of GBM subtype diversity. Using an in vivo model, we also showed that GBM cancer stem cells (CSCs) or glioma stem cells (GSCs) contribute to resistance to chemotherapeutic agents and that genetic ablation of GSCs leads to a delay in tumor progression. These studies are consistent with the cell of origin and CSCs as critical regulators of the pathogenesis of GBM. © 2016 Alcantara Llaguno et al; Published by Cold Spring Harbor Laboratory Press.

  10. Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering.

    Science.gov (United States)

    Paim, Ágata; Tessaro, Isabel C; Cardozo, Nilo S M; Pranke, Patricia

    2018-03-05

    Tissue engineering is a multidisciplinary field of research in which the cells, biomaterials, and processes can be optimized to develop a tissue substitute. Three-dimensional (3D) architectural features from electrospun scaffolds, such as porosity, tortuosity, fiber diameter, pore size, and interconnectivity have a great impact on cell behavior. Regarding tissue development in vitro, culture conditions such as pH, osmolality, temperature, nutrient, and metabolite concentrations dictate cell viability inside the constructs. The effect of different electrospun scaffold properties, bioreactor designs, mesenchymal stem cell culture parameters, and seeding techniques on cell behavior can be studied individually or combined with phenomenological modeling techniques. This work reviews the main culture and scaffold factors that affect tissue development in vitro regarding the culture of cells inside 3D matrices. The mathematical modeling of the relationship between these factors and cell behavior inside 3D constructs has also been critically reviewed, focusing on mesenchymal stem cell culture in electrospun scaffolds.

  11. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  12. Water transport through tall trees: A vertically-explicit, analytical model of xylem hydraulic conductance in stems.

    Science.gov (United States)

    Couvreur, Valentin; Ledder, Glenn; Manzoni, Stefano; Way, Danielle A; Muller, Erik B; Russo, Sabrina E

    2018-05-08

    Trees grow by vertically extending their stems, so accurate stem hydraulic models are fundamental to understanding the hydraulic challenges faced by tall trees. Using a literature survey, we showed that many tree species exhibit continuous vertical variation in hydraulic traits. To examine the effects of this variation on hydraulic function, we developed a spatially-explicit, analytical water transport model for stems. Our model allows Huber ratio, stem-saturated conductivity, pressure at 50% loss of conductivity, leaf area, and transpiration rate to vary continuously along the hydraulic path. Predictions from our model differ from a matric flux potential model parameterized with uniform traits. Analyses show that cavitation is a whole-stem emergent property resulting from nonlinear pressure-conductivity feedbacks that, with gravity, cause impaired water transport to accumulate along the path. Because of the compounding effects of vertical trait variation on hydraulic function, growing proportionally more sapwood and building tapered xylem with height, as well as reducing xylem vulnerability only at branch tips while maintaining transport capacity at the stem base, can compensate for these effects. We therefore conclude that the adaptive significance of vertical variation in stem hydraulic traits is to allow trees to grow tall and tolerate operating near their hydraulic limits. This article is protected by copyright. All rights reserved.

  13. Self-organization phenomena in embryonic stem cell-derived embryoid bodies: axis formation and breaking of symmetry during cardiomyogenesis.

    Science.gov (United States)

    Fuchs, Christiane; Scheinast, Matthias; Pasteiner, Waltraud; Lagger, Sabine; Hofner, Manuela; Hoellrigl, Alexandra; Schultheis, Martina; Weitzer, Georg

    2012-01-01

    Aggregation of embryonic stem cells gives rise to embryoid bodies (EBs) which undergo developmental processes reminiscent of early eutherian embryonic development. Development of the three germ layers suggests that gastrulation takes place. In vivo, gastrulation is a highly ordered process but in EBs only few data support the hypothesis that self-organization of differentiating cells leads to morphology, reminiscent of the early gastrula. Here we demonstrate that a timely implantation-like process is a prerequisite for the breaking of the radial symmetry of suspended EBs. Attached to a surface, EBs develop a bilateral symmetry and presumptive mesodermal cells emerge between the center of the EBs and a horseshoe-shaped ridge of cells. The development of an epithelial sheet of cells on one side of the EBs allows us to define an 'anterior' and a 'posterior' end of the EBs. In the mesodermal area, first cardiomyocytes (CMCs) develop mainly next to this epithelial sheet of cells. Development of twice as many CMCs at the 'left' side of the EBs breaks the bilateral symmetry and suggests that cardiomyogenesis reflects a local or temporal asymmetry in EBs. The asymmetric appearance of CMCs but not the development of mesoderm can be disturbed by ectopic expression of the muscle-specific protein Desmin. Later, the bilateral morphology becomes blurred by an apparently chaotic differentiation of many cell types. The absence of comparable structures in aggregates of cardiovascular progenitor cells isolated from the heart demonstrates that the self-organization of cells during a gastrulation-like process is a unique feature of embryonic stem cells. Copyright © 2011 S. Karger AG, Basel.

  14. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    Energy Technology Data Exchange (ETDEWEB)

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  15. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

    Science.gov (United States)

    Kanani, S.; Pumir, A.; Krinsky, V.

    2008-01-01

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  16. Impact of tissue surface properties on the desorption electrospray ionization imaging of organic acids in grapevine stem.

    Science.gov (United States)

    Dong, Yonghui; Guella, Graziano; Franceschi, Pietro

    2016-03-30

    Desorption electrospray ionization (DESI) imaging is a fast analytical technique used to assess spatially resolved biological processes over unmodified sample surfaces. Although DESI profiling experiments have demonstrated that the properties of the sample surface significantly affect the outcomes of DESI analyses, the potential implications of these phenomena in imaging applications have not yet been explored extensively. The distribution of endogenous and exogenous organic acids in pith and out pith region of grapevine stems was investigated by using DESI imaging, ion chromatography and direct infusion methods. Several common normalization strategies to account for the surface effect, including TIC normalization, addition of the internal standard in the spray solvent and deposition of the standard over the sample surface, were critically evaluated. DESI imaging results show that, in our case, the measured distributions of these small organic acids are not consistent with their 'true' localizations within the tissues. Furthermore, our results indicate that the common normalization strategies are not able to completely compensate for the observed surface effect. Variations in the tissue surface properties across the tissue sample can greatly affect the semi-quantitative detection of organic acids. Attention should be paid when interpreting DESI imaging results and an independent analytical validation step is important in untargeted DESI imaging investigations. Copyright © 2016 John Wiley & Sons, Ltd.

  17. A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment

    Science.gov (United States)

    Nör, Jacques Eduardo

    2018-01-01

    Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics. By including the molecular details of IL-6 binding, we are able to quantify the temporal changes in fractional occupancies of bound receptors and their influence on tumor volume. There is a strong correlation between the model output and experimental data for primary tumor xenografts. We also used the model to predict tumor response to administration of the humanized IL-6R monoclonal antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ administered weekly for 7 weeks is sufficient to result in tumor reduction and a sustained deceleration of tumor growth. PMID:29351275

  18. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Piya Prajumwongs

    2016-01-01

    Full Text Available Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

  19. Advanced Good Cell Culture Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems.

    Science.gov (United States)

    Pamies, David; Bal-Price, Anna; Chesné, Christophe; Coecke, Sandra; Dinnyes, Andras; Eskes, Chantra; Grillari, Regina; Gstraunthaler, Gerhard; Hartung, Thomas; Jennings, Paul; Leist, Marcel; Martin, Ulrich; Passier, Robert; Schwamborn, Jens C; Stacey, Glyn N; Ellinger-Ziegelbauer, Heidrun; Daneshian, Mardas

    2018-04-13

    A major reason for the current reproducibility crisis in the life sciences is the poor implementation of quality control measures and reporting standards. Improvement is needed, especially regarding increasingly complex in vitro methods. Good Cell Culture Practice (GCCP) was an effort from 1996 to 2005 to develop such minimum quality standards also applicable in academia. This paper summarizes recent key developments in in vitro cell culture and addresses the issues resulting for GCCP, e.g. the development of induced pluripotent stem cells (iPSCs) and gene-edited cells. It further deals with human stem-cell-derived models and bioengineering of organo-typic cell cultures, including organoids, organ-on-chip and human-on-chip approaches. Commercial vendors and cell banks have made human primary cells more widely available over the last decade, increasing their use, but also requiring specific guidance as to GCCP. The characterization of cell culture systems including high-content imaging and high-throughput measurement technologies increasingly combined with more complex cell and tissue cultures represent a further challenge for GCCP. The increasing use of gene editing techniques to generate and modify in vitro culture models also requires discussion of its impact on GCCP. International (often varying) legislations and market forces originating from the commercialization of cell and tissue products and technologies are further impacting on the need for the use of GCCP. This report summarizes the recommendations of the second of two workshops, held in Germany in December 2015, aiming map the challenge and organize the process or developing a revised GCCP 2.0.

  20. The Time Is Right to Focus on Model Organism Metabolomes

    Directory of Open Access Journals (Sweden)

    Arthur S. Edison

    2016-02-01

    Full Text Available Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  1. Genetic Tools for Self-Organizing Culture of Mouse Embryonic Stem Cells via Small Regulatory RNA-Mediated Technologies, CRISPR/Cas9, and Inducible RNAi.

    Science.gov (United States)

    Takata, Nozomu; Sakakura, Eriko; Sakuma, Tetsushi; Yamamoto, Takashi

    2017-01-01

    Approaches to investigate gene functions in experimental biology are becoming more diverse and reliable. Furthermore, several kinds of tissues and organs that possess their original identities can be generated in petri dishes from stem cells including embryonic, adult and induced pluripotent stem cells. Researchers now have several choices of experimental methods and their combinations to analyze gene functions in various biological systems. Here, as an example we describe one of the better protocols, which combines three-dimensional embryonic stem cell culture with small regulatory RNA-mediated technologies, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), and inducible RNA interference (RNAi). This protocol allows investigation of genes of interest to better understand gene functions in target tissues (or organs) during in vitro development.

  2. Stem cells in pharmaceutical biotechnology.

    Science.gov (United States)

    Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

    2011-11-01

    Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All

  3. Models of care and organization of services.

    Science.gov (United States)

    Markova, Alina; Xiong, Michael; Lester, Jenna; Burnside, Nancy J

    2012-01-01

    This article examines the overall organization of services and delivery of health care in the United States. Health maintenance organization, fee-for-service, preferred provider organizations, and the Veterans Health Administration are discussed, with a focus on structure, outcomes, and areas for improvement. An overview of wait times, malpractice, telemedicine, and the growing population of physician extenders in dermatology is also provided. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Unique Organization of the Nuclear Envelope in the Post-natal Quiescent Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Arantxa Cebrián-Silla

    2017-07-01

    Full Text Available Neural stem cells (B1 astrocytes; NSCs in the adult ventricular-subventricular-zone (V-SVZ originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS, reported in certain lymphocytes and some cancer cells. Using molecular markers, [3H]thymidine birth-dating, and Ara-C, we found that B1 cells with ELCS correspond to quiescent NSCs. ELCS begin forming in embryonic radial glia cells and represent a specific nuclear compartment containing particular epigenetic modifications and telomeres. These results reveal a unique nuclear compartment in quiescent NSCs, which is useful for identifying these primary progenitors and study their gene regulation.

  5. Induced pluripotent stem cells as a cellular model for studying Down Syndrome

    Directory of Open Access Journals (Sweden)

    Brigida AL

    2016-11-01

    Full Text Available Down Syndrome (DS, or Trisomy 21 Syndrome, is one of the most common genetic diseases. It is a chromosomal abnormality caused by a duplication of chromosome 21. DS patients show the presence of a third copy (or a partial third copy of chromosome 21 (trisomy, as result of meiotic errors. These patients suffer of many health problems, such as intellectual disability, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, immune system deficiencies, muscle hypotonia and motor disorders. About one in 1000 babies born each year are affected by DS. Alterations in the dosage of genes located on chromosome 21 (also called HSA21 are responsible for the DS phenotype. However, the molecular pathogenic mechanisms of DS triggering are still not understood; newest evidences suggest the involvement of epigenetic mechanisms. For obvious ethical reasons, studies performed on DS patients, as well as on human trisomic tissues are limited. Some authors have proposed mouse models of this syndrome. However, not all the features of the syndrome are represented. Stem cells are considered the future of molecular and regenerative medicine. Several types of stem cells could provide a valid approach to offer a potential treatment for some untreatable human diseases. Stem cells also represent a valid system to develop new cell-based drugs and/or a model to study molecular disease pathways. Among stem cell types, patient-derived induced pluripotent stem (iPS cells offer some advantages for cell and tissue replacement, engineering and studying: self-renewal capacity, pluripotency and ease of accessibility to donor tissues. These cells can be reprogrammed into completely different cellular types. They are derived from adult somatic cells via reprogramming with ectopic expression of four transcription factors (Oct3/4, Sox2, c-Myc and Klf4; or, Oct3/4, Sox2, Nanog, and Lin28. By reprogramming cells from DS patients, it is possible to obtain new tissue with

  6. Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Pournasr, Behshad; Duncan, Stephen A

    2017-11-01

    Inborn errors of hepatic metabolism are because of deficiencies commonly within a single enzyme as a consequence of heritable mutations in the genome. Individually such diseases are rare, but collectively they are common. Advances in genome-wide association studies and DNA sequencing have helped researchers identify the underlying genetic basis of such diseases. Unfortunately, cellular and animal models that accurately recapitulate these inborn errors of hepatic metabolism in the laboratory have been lacking. Recently, investigators have exploited molecular techniques to generate induced pluripotent stem cells from patients' somatic cells. Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. In this mini-review, we present a brief overview of the state-of-the-art in using pluripotent stem cells for such studies. © 2017 American Heart Association, Inc.

  7. New lessons learned from disease modeling with induced Pluripotent Stem Cells

    Science.gov (United States)

    Onder, Tamer T.; Daley, George Q.

    2012-01-01

    Cellular reprogramming and generation of induced pluripotent stem cells (iPSCs) from adult cell types has enabled the creation of patient-specific stem cells for use in disease modeling. To date, many iPSC lines have been generated from a variety of disorders, which have then been differentiated into disease-relevant cell types. When a disease-specific phenotype is detectable in such differentiated cells, the reprogramming technology provides a new opportunity to identify aberrant disease-associated pathways and drugs that can block them. Here, we highlight recent progress as well as limitations in the use of iPSCs to recapitulate disease phenotypes and to screen for therapeutics in vitro. PMID:22749051

  8. Stem cell models of polyglutamine diseases and their use in cell-based therapies

    Directory of Open Access Journals (Sweden)

    Evangelia eSiska

    2015-07-01

    Full Text Available Polyglutamine diseases are fatal neurological disorders that affect the central nervous system. They are caused by mutations in disease genes that contain CAG trinucleotide expansions in their coding regions. These mutations are translated into expanded glutamine chains in pathological proteins. Mutant proteins induce cytotoxicity, form intranuclear aggregates and cause neuronal cell death in specific brain regions. At the moment there is no cure for these diseases and only symptomatic treatments are available. Here, we discuss novel therapeutic approaches that aim in neuronal cell replacement using induced pluripotent or adult stem cells. Additionally, we present the beneficial effect of genetically engineered mesenchymal stem cells and their use as disease models or RNAi/gene delivery vehicles. In combination with their paracrine and cell-trophic properties, such cells may prove useful for the development of novel therapies against polyglutamine diseases.

  9. Organization model and formalized description of nuclear enterprise information system

    International Nuclear Information System (INIS)

    Yuan Feng; Song Yafeng; Li Xudong

    2012-01-01

    Organization model is one of the most important models of Nuclear Enterprise Information System (NEIS). Scientific and reasonable organization model is the prerequisite that NEIS has robustness and extendibility, and is also the foundation of the integration of heterogeneous system. Firstly, the paper describes the conceptual model of the NEIS on ontology chart, which provides a consistent semantic framework of organization. Then it discusses the relations between the concepts in detail. Finally, it gives the formalized description of the organization model of NEIS based on six-tuple array. (authors)

  10. A Bridge to the Stars: A Model High School-to-College Pipeline to Improve Diversity in STEM

    Science.gov (United States)

    McIntosh, Daniel H.; Jennings, Derrick H.

    2017-01-01

    Increasing participation by historically underrepresented Americans in the STEM workforce remains a national priority. Existing strategies have failed to increase diversity especially in the physical sciences despite federal mandates. To meet this urgent challenge, it is imperative to immediately identify and support the expansion of effective high school-to-college STEM pipelines. A Bridge to the Stars (ABttS) is a creative and tested pipeline designed to steadily increase the numbers of disadvantaged 15-21 year-olds pursuing and completing 4-year STEM degrees. This unique program offers extended engagement in astronomy, arguably the most accessible window to science, through a 3-tier STEM immersion program of innovative learning (in a freshman science course), authentic research training (in a freshman science lab), and supportive near-peer mentoring at U.Missouri-Kansas City, an urban research university. Each tier of the ABttS pipeline by itself has the potential to broaden student aspirations for careers as technological innovators or STEM educators. Students who elect to transition through multiple tiers will substantially reinforce their successes with STEM activities, and significantly bolster their self-esteem necessary to personally manifest STEM aspirations. We will summarize the impact of this program after 5 years, and share our latest improvements. The long-term mission of ABttS is to see urban educational institutions across the U.S. adopt similar pipelines in all STEM disciplines built on the ABttS model.

  11. Systematic gene tagging using CRISPR/Cas9 in human stem cells to illuminate cell organization.

    Science.gov (United States)

    Roberts, Brock; Haupt, Amanda; Tucker, Andrew; Grancharova, Tanya; Arakaki, Joy; Fuqua, Margaret A; Nelson, Angelique; Hookway, Caroline; Ludmann, Susan A; Mueller, Irina A; Yang, Ruian; Horwitz, Rick; Rafelski, Susanne M; Gunawardane, Ruwanthi N

    2017-10-15

    We present a CRISPR/Cas9 genome-editing strategy to systematically tag endogenous proteins with fluorescent tags in human induced pluripotent stem cells (hiPSC). To date, we have generated multiple hiPSC lines with monoallelic green fluorescent protein tags labeling 10 proteins representing major cellular structures. The tagged proteins include alpha tubulin, beta actin, desmoplakin, fibrillarin, nuclear lamin B1, nonmuscle myosin heavy chain IIB, paxillin, Sec61 beta, tight junction protein ZO1, and Tom20. Our genome-editing methodology using Cas9/crRNA ribonuclear protein and donor plasmid coelectroporation, followed by fluorescence-based enrichment of edited cells, typically resulted in <0.1-4% homology-directed repair (HDR). Twenty-five percent of clones generated from each edited population were precisely edited. Furthermore, 92% (36/39) of expanded clonal lines displayed robust morphology, genomic stability, expression and localization of the tagged protein to the appropriate subcellular structure, pluripotency-marker expression, and multilineage differentiation. It is our conclusion that, if cell lines are confirmed to harbor an appropriate gene edit, pluripotency, differentiation potential, and genomic stability are typically maintained during the clonal line-generation process. The data described here reveal general trends that emerged from this systematic gene-tagging approach. Final clonal lines corresponding to each of the 10 cellular structures are now available to the research community. © 2017 Roberts, Haupt, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

    The human blood brain barrier has yet to be successfully replicated as an in vitro model. One of the more promising approaches has been to develop an in vitro model derived from human pluripotent stem cells. However, as promising as this model may be, a successful replication of the differentiation...... method on different kinds of pluripotent stem cell lines have yet to be accomplished. We try to approach the promising method as described by Stebbins et al. (2015) to differentiate human pluripotent stem cells into brain like endothelial cells (BECs). Five different human pluripotent stem cell lines...... configurations (mono culture, non-contact co-culture and contact co-culture) with primary rat astrocytes to induce barrier-like properties. Endothelial cell media supplemented with retinoic acid were then applied to the cells to ensure selective expansion of BECs. The different culture configurations were...

  13. 3D Bioprinting of Tissue/Organ Models.

    Science.gov (United States)

    Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

    2016-04-04

    In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Authentication in Virtual Organizations: A Reputation Based PKI Interconnection Model

    Science.gov (United States)

    Wazan, Ahmad Samer; Laborde, Romain; Barrere, Francois; Benzekri, Abdelmalek

    Authentication mechanism constitutes a central part of the virtual organization work. The PKI technology is used to provide the authentication in each organization involved in the virtual organization. Different trust models are proposed to interconnect the different PKIs in order to propagate the trust between them. While the existing trust models contain many drawbacks, we propose a new trust model based on the reputation of PKIs.

  15. The damaging effect of densely ionizing radiations on stem cells of mammalian critical organs

    International Nuclear Information System (INIS)

    Konoplyannikov, A.G.; Konoplyannikova, O.A.

    1985-01-01

    Literature and experimental data on foundation of conceptions for cell determinants of survival rate in irradiated animals are analysed. Experimental confirmation of conceptions for cell determinants for both CFU of hemopoietic organs and for cases of intestinal death after densely ionizing radiation effect is obtained. The explanation of causes for difference in interrelation of two types of radiation death of animals in such a case is suggested

  16. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    Science.gov (United States)

    Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  17. Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

    Science.gov (United States)

    Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

    2017-05-31

    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

  18. Stem thrust prediction model for W-K-M double wedge parallel expanding gate valves

    Energy Technology Data Exchange (ETDEWEB)

    Eldiwany, B.; Alvarez, P.D. [Kalsi Engineering Inc., Sugar Land, TX (United States); Wolfe, K. [Electric Power Research Institute, Palo Alto, CA (United States)

    1996-12-01

    An analytical model for determining the required valve stem thrust during opening and closing strokes of W-K-M parallel expanding gate valves was developed as part of the EPRI Motor-Operated Valve Performance Prediction Methodology (EPRI MOV PPM) Program. The model was validated against measured stem thrust data obtained from in-situ testing of three W-K-M valves. Model predictions show favorable, bounding agreement with the measured data for valves with Stellite 6 hardfacing on the disks and seat rings for water flow in the preferred flow direction (gate downstream). The maximum required thrust to open and to close the valve (excluding wedging and unwedging forces) occurs at a slightly open position and not at the fully closed position. In the nonpreferred flow direction, the model shows that premature wedging can occur during {Delta}P closure strokes even when the coefficients of friction at different sliding surfaces are within the typical range. This paper summarizes the model description and comparison against test data.

  19. Stem thrust prediction model for W-K-M double wedge parallel expanding gate valves

    International Nuclear Information System (INIS)

    Eldiwany, B.; Alvarez, P.D.; Wolfe, K.

    1996-01-01

    An analytical model for determining the required valve stem thrust during opening and closing strokes of W-K-M parallel expanding gate valves was developed as part of the EPRI Motor-Operated Valve Performance Prediction Methodology (EPRI MOV PPM) Program. The model was validated against measured stem thrust data obtained from in-situ testing of three W-K-M valves. Model predictions show favorable, bounding agreement with the measured data for valves with Stellite 6 hardfacing on the disks and seat rings for water flow in the preferred flow direction (gate downstream). The maximum required thrust to open and to close the valve (excluding wedging and unwedging forces) occurs at a slightly open position and not at the fully closed position. In the nonpreferred flow direction, the model shows that premature wedging can occur during ΔP closure strokes even when the coefficients of friction at different sliding surfaces are within the typical range. This paper summarizes the model description and comparison against test data

  20. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  1. Mesenchymal stem cells from human umbilical cord ameliorate testicular dysfunction in a male rat hypogonadism model

    Directory of Open Access Journals (Sweden)

    Zhi-Yuan Zhang

    2017-01-01

    Full Text Available Androgen deficiency is a physical disorder that not only affects adults but can also jeopardize children′s health. Because there are many disadvantages to using traditional androgen replacement therapy, we have herein attempted to explore the use of human umbilical cord mesenchymal stem cells for the treatment of androgen deficiency. We transplanted CM-Dil-labeled human umbilical cord mesenchymal stem cells into the testes of an ethane dimethanesulfonate (EDS-induced male rat hypogonadism model. Twenty-one days after transplantation, we found that blood testosterone levels in the therapy group were higher than that of the control group (P = 0.037, and using immunohistochemistry and flow cytometry, we observed that some of the CM-Dil-labeled cells expressed Leydig cell markers for cytochrome P450, family 11, subfamily A, polypeptide 1, and 3-β-hydroxysteroid dehydrogenase. We then recovered these cells and observed that they were still able to proliferate in vitro. The present study shows that mesenchymal stem cells from human umbilical cord may constitute a promising therapeutic modality for the treatment of male hypogonadism patients.

  2. Patient-Specific Induced Pluripotent Stem Cell Models: Generation and Characterization of Cardiac Cells.

    Science.gov (United States)

    Zanella, Fabian; Sheikh, Farah

    2016-01-01

    The generation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes has been of utmost interest for the study of cardiac development, cardiac disease modeling, and evaluation of cardiotoxic effects of novel candidate drugs. Several protocols have been developed to guide human stem cells toward the cardiogenic path. Pioneering work used serum to promote cardiogenesis; however, low cardiogenic throughputs, lack of chemical definition, and batch-to-batch variability of serum lots constituted a considerable impediment to the implementation of those protocols to large-scale cell biology. Further work focused on the manipulation of pathways that mouse genetics indicated to be fundamental in cardiac development to promote cardiac differentiation in stem cells. Although extremely elegant, those serum-free protocols involved the use of human recombinant cytokines that tend to be quite costly and which can also be variable between lots. The latest generation of cardiogenic protocols aimed for a more cost-effective and reproducible definition of the conditions driving cardiac differentiation, using small molecules to manipulate cardiogenic pathways overriding the need for cytokines. This chapter details methods based on currently available cardiac differentiation protocols for the generation and characterization of robust numbers of hiPSC-derived cardiomyocytes under chemically defined conditions.

  3. Intestinal stem cells in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Jiang, Huaqi; Edgar, Bruce A.

    2011-01-01

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

  4. Documentation on the development of the Swiss TIMES Electricity Model (STEM-E)

    International Nuclear Information System (INIS)

    Kannan, R.; Turton, H.

    2011-10-01

    This comprehensive report by the Paul Scherrer Institute PSI in Switzerland documents the development of the Swiss TIMES Electricity Model (STEM-E). This is a flexible model which explicitly depicts plausible pathways for the development of the Swiss electricity sector, while dealing with inter-temporal variations in demand and supply. TIMES is quoted as having the capability to portray the entire energy system from resource supply, through fuel processing, representation of infrastructures, conversion to secondary energy carriers, end-use technologies and energy service demands at end-use sectors. The background of the model's development and a reference energy system are described. Also, electricity end-use sectors and generating systems are examined, including hydropower, nuclear power, thermal generation and renewables. Environmental factors and the calibration of the model are discussed, as is the application of the model. The document is completed with an outlook, references and six appendices

  5. The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Nurfatin Asyikhin Kamaruzaman

    2013-01-01

    Full Text Available No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

  6. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    OpenAIRE

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain...

  7. A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

    Science.gov (United States)

    Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

    2013-04-01

    Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

  8. MODELING OF MANAGEMENT PROCESSES IN AN ORGANIZATION

    Directory of Open Access Journals (Sweden)

    Stefan Iovan

    2016-05-01

    Full Text Available When driving any major change within an organization, strategy and execution are intrinsic to a project’s success. Nevertheless, closing the gap between strategy and execution remains a challenge for many organizations [1]. Companies tend to focus more on execution than strategy for quick results, instead of taking the time needed to understand the parts that make up the whole, so the right execution plan can be put in place to deliver the best outcomes. A large part of this understands that business operations don’t fit neatly within the traditional organizational hierarchy. Business processes are often messy, collaborative efforts that cross teams, departments and systems, making them difficult to manage within a hierarchical structure [2]. Business process management (BPM fills this gap by redefining an organization according to its end-to-end processes, so opportunities for improvement can be identified and processes streamlined for growth, revenue and transformation. This white paper provides guidelines on what to consider when using business process applications to solve your BPM initiatives, and the unique capabilities software systems provides that can help ensure both your project’s success and the success of your organization as a whole. majority of medium and small businesses, big companies and even some guvermental organizations [2].

  9. Donor mesenchymal stem cells home to maternal wounds after transamniotic stem cell therapy (TRASCET) in a rodent model.

    Science.gov (United States)

    Graham, Christopher D; Shieh, Hester F; Brazzo, Joseph A; Zurakowski, David; Fauza, Dario O

    2017-06-01

    Transamniotic stem cell therapy (TRASCET) with amniotic fluid-derived MSCs (afMSCs) has emerged experimentally as a practical treatment strategy for congenital anomalies. In this study, we sought to determine whether afMSCs migrate to the mother following TRASCET. Pregnant rat dams were divided into three groups. Two groups received volume-matched injections into all amniotic cavities of either a suspension of afMSCs labeled with a luciferase reporter gene or the luciferase protein alone. In a third group, a suspension of labeled cells was aliquoted onto the serosal surface of the uterus. Maternal samples from the laparotomy scar (fascia and skin separately), bone marrow, and peripheral blood were procured, along with placenta and umbilical cord. Specimens were screened for luminescence via microplate luminometry. Luminescence was detected in 60% (9/15) of the fascial scars from the group receiving intraamniotic injection of afMSCs, but in none of the other groups (Pcells in the placenta and their presence in maternal fascia (Wald test=10.2; P=0.001). Amniotic mesenchymal stem cells migrate to maternal sites of injury after intraamniotic injection. Maternal homing of donor cells must be considered in the setting of transamniotic stem cell therapy. N/A (animal and laboratory study). Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Self-Organizing Map Models of Language Acquisition

    Directory of Open Access Journals (Sweden)

    Ping eLi

    2013-11-01

    Full Text Available Connectionist models have had a profound impact on theories of language. While most early models were inspired by the classic PDP architecture, recent models of language have explored various other types of models, including self-organizing models for language acquisition. In this paper we aim at providing a review of the latter type of models, and highlight a number of simulation experiments that we have conducted based on these models. We show that self-organizing connectionist models can provide significant insights into long-standing debates in both monolingual and bilingual language development.

  11. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

    OpenAIRE

    Hedges, Erin C.; Mehler, Vera J.; Nishimura, Agnes L.

    2016-01-01

    In recent years several genes have linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular ...

  12. A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.

    Science.gov (United States)

    Caron, Leslie; Kher, Devaki; Lee, Kian Leong; McKernan, Robert; Dumevska, Biljana; Hidalgo, Alejandro; Li, Jia; Yang, Henry; Main, Heather; Ferri, Giulia; Petek, Lisa M; Poellinger, Lorenz; Miller, Daniel G; Gabellini, Davide; Schmidt, Uli

    2016-09-01

    : Facioscapulohumeral muscular dystrophy (FSHD) represents a major unmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response, and cell adhesion. This cellular model will be a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies. This work describes an efficient and highly scalable monolayer system to differentiate human pluripotent stem cells (hPSCs) into skeletal muscle cells (SkMCs) and demonstrates disease-specific phenotypes in SkMCs derived from both embryonic and induced hPSCs affected with facioscapulohumeral muscular dystrophy. This study represents the first human stem cell-based cellular model for a muscular dystrophy that is suitable for high-throughput screening and drug development. ©AlphaMed Press.

  13. Two new initiatives to support STEM careers for women | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-11-15

    Nov 15, 2017 ... A new partnership with UNESCO's Organization for Women in Science for ... in STEM fields and role models for the next generation of female scientists. ... Linking research to urban planning at the ICLEI World Congress 2018.

  14. Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models.

    Science.gov (United States)

    Sproul, Andrew A

    2015-01-01

    Human pluripotent stem cells (PSCs) have the capacity to revolutionize medicine by allowing the generation of functional cell types such as neurons for cell replacement therapy. However, the more immediate impact of PSCs on treatment of Alzheimer's disease (AD) will be through improved human AD model systems for mechanistic studies and therapeutic screening. This review will first briefly discuss different types of PSCs and genome-editing techniques that can be used to modify PSCs for disease modeling or for personalized medicine. This will be followed by a more in depth analysis of current AD iPSC models and a discussion of the need for more complex multicellular models, including cell types such as microglia. It will finish with a discussion on current clinical trials using PSC-derived cells and the long-term potential of such strategies for treating AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The initiative on Model Organism Proteomes (iMOP) Session

    DEFF Research Database (Denmark)

    Schrimpf, Sabine P; Mering, Christian von; Bendixen, Emøke

    2012-01-01

    iMOP – the Initiative on Model Organism Proteomes – was accepted as a new HUPO initiative at the Ninth HUPO meeting in Sydney in 2010. A goal of iMOP is to integrate research groups working on a great diversity of species into a model organism community. At the Tenth HUPO meeting in Geneva...

  16. Modeling the Explicit Chemistry of Anthropogenic and Biogenic Organic Aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Madronich, Sasha [Univ. Corporation for Atmospheric Research, Boulder, CO (United States)

    2015-12-09

    The atmospheric burden of Secondary Organic Aerosols (SOA) remains one of the most important yet uncertain aspects of the radiative forcing of climate. This grant focused on improving our quantitative understanding of SOA formation and evolution, by developing, applying, and improving a highly detailed model of atmospheric organic chemistry, the Generation of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) model. Eleven (11) publications have resulted from this grant.

  17. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    Science.gov (United States)

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Induced pluripotent stem cells (iPSC)-derived retinal cells in disease modeling and regenerative medicine.

    Science.gov (United States)

    Rathod, Reena; Surendran, Harshini; Battu, Rajani; Desai, Jogin; Pal, Rajarshi

    2018-02-12

    Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction, lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies. We also provide an overview of the ongoing efforts towards developing a suitable in vitro model for modeling retinal degenerative diseases. This basic understanding in turn has contributed to advances in translational goals such as drug screening and cell-replacement therapies. Furthermore we discuss gene editing approaches for autologous repair of genetic disorders and allogeneic transplantation of stem cell-based retinal derivatives for degenerative disorders with an ultimate goal to restore vision. It is pertinent to note however, that these exciting new developments throw up several challenges that need to be overcome before their full clinical potential can be realized. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

    Science.gov (United States)

    Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

    2018-05-01

    Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

  20. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  1. Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Faye M. Drawnel

    2014-11-01

    Full Text Available Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.

  2. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  3. Importance of Nongovernmental Organizations for the Establishment of a Successful Hematopoietic Stem-Cell Transplantation Program in a Developing Country

    Directory of Open Access Journals (Sweden)

    Monica M. Rivera Franco

    2018-02-01

    Full Text Available Purpose: In low- and middle-income countries with limited resources, the success of a hematopoietic stem-cell transplantation (HSCT program relies directly on its affordability while obtaining similar outcomes to developed regions. The objective of this study was to describe the experience of a tertiary/referral center in Mexico City performing HSCT with the subsidy of a nongovernmental organization (NGO. Patients and Methods: We performed a retrospective analysis including 146 patients who underwent HSCT at the National Institutes of Health Sciences and Nutrition Salvador Zubiran and were subsidized by the NGO Unidos. Results: Seventy-five patients (51% and 71 patients (49% underwent autologous and allogeneic HSCT, respectively. The median age was 30 years, 56% did not obtain a bachelor’s degree, 79% had a low socioeconomic level, and 75% were unemployed. None had any health coverage. According to the real patient out-of-pocket expense, the subsidy by Unidos corresponded to 88% and 72% in autologous and allogeneic HSCT, respectively. Conclusion: Our results highlight that undergoing an HSCT was feasible for vulnerable patients because of the subsidy of medications and chemotherapy by Unidos. Therefore, creating NGOs in developing countries is important to provide complex medical procedures, such as HSCT, at limited-resource centers to underserved populations while obtaining good outcomes.

  4. Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

    Science.gov (United States)

    Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

    2016-01-01

    ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

  5. Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem cells: a model of molecular convergence for stemness.

    Science.gov (United States)

    Hong, Sung-Hyun; Yang, Seung-Jip; Kim, Tae-Min; Shim, Jae-Seung; Lee, Ho-Sun; Lee, Ga-Young; Park, Bo-Bae; Nam, Suk Woo; Ryoo, Zae Young; Oh, Il-Hoan

    2014-05-01

    The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells (HSCs) without overriding the normal stem cell pool size. A similar enhancement of HSC self-renewal occurs when signal transducer and activator of transcription 3 (STAT3) is activated in HSCs. In this study, to gain insight into the functional organization of individual transcription factors (TFs) that have similar effects on HSCs, we investigated the molecular interplay between HoxB4 and STAT3 in the regulation of HSC self-renewal. We found that while STAT3-C or HoxB4 similarly enhanced the in vitro self-renewal and in vivo repopulating activities of HSCs, simultaneous transduction of both TFs did not have additive effects, indicating their functional redundancy in HSCs. In addition, activation of STAT3 did not cause changes in the expression levels of HoxB4. In contrast, the inhibition of STAT3 activity in HoxB4-overexpressing hematopoietic cells significantly abrogated the enhancing effects of HoxB4, and the upregulation of HoxB4 caused a ligand-independent Tyr-phosphorylation of STAT3. Microarray analysis revealed a significant overlap of the transcriptomes regulated by STAT3 and HoxB4 in undifferentiated hematopoietic cells. Moreover, a gene set enrichment analysis showed significant overlap in the candidate TFs that can recapitulate the transcriptional changes induced by HoxB4 or STAT3. Interestingly, among these common TFs were the pluripotency-related genes Oct-4 and Nanog. These results indicate that tissue-specific TFs regulating HSC self-renewal are functionally organized to play an equivalent role in transcription and provide insights into the functional convergence of multiple entries of TFs toward a conserved transcription program for the stem cell state. © 2014 AlphaMed Press.

  6. Organizer-Derived WOX5 Signal Maintains Root Columella Stem Cells through Chromatin-Mediated Repression of CDF4 Expression.

    NARCIS (Netherlands)

    Pi, L.; Graaff, van der E.; Llavata Peris, C.I.; Weijers, D.; Henning, L.; Groot, de E.; Laux, T.

    2015-01-01

    Stem cells in plants and animals are maintained pluripotent by signals from adjacent niche cells. In plants, WUSCHEL HOMEOBOX (WOX) transcription factors are central regulators of stem cell maintenance in different meristem types, yet their molecular mode of action has remained elusive. Here we show

  7. Cell lineage identification and stem cell culture in a porcine model for the study of intestinal epithelial regeneration.

    Directory of Open Access Journals (Sweden)

    Liara M Gonzalez

    Full Text Available Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA, Minichromosome Maintenance Complex 2 (MCM2, Bromodeoxyuridine (BrdU and phosphorylated Histone H3 (pH3 distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/'reserve' stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2; enteroendocrine cells by Chromogranin A (CGA, Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII and sucrase isomaltase (SIM. Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease.

  8. Saccharomyces cerevisiae as a model organism: a comparative study.

    Directory of Open Access Journals (Sweden)

    Hiren Karathia

    Full Text Available BACKGROUND: Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes. CONCLUSIONS/SIGNIFICANCE: The method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.

  9. The System Dynamics Model for Development of Organic Agriculture

    Science.gov (United States)

    Rozman, Črtomir; Škraba, Andrej; Kljajić, Miroljub; Pažek, Karmen; Bavec, Martina; Bavec, Franci

    2008-10-01

    Organic agriculture is the highest environmentally valuable agricultural system, and has strategic importance at national level that goes beyond the interests of agricultural sector. In this paper we address development of organic farming simulation model based on a system dynamics methodology (SD). The system incorporates relevant variables, which affect the development of the organic farming. The group decision support system (GDSS) was used in order to identify most relevant variables for construction of causal loop diagram and further model development. The model seeks answers to strategic questions related to the level of organically utilized area, levels of production and crop selection in a long term dynamic context and will be used for simulation of different policy scenarios for organic farming and their impact on economic and environmental parameters of organic production at an aggregate level.

  10. Disruption of a Quorum Sensing mechanism triggers tumorigenesis: a simple discrete model corroborated by experiments in mammary cancer stem cells

    Directory of Open Access Journals (Sweden)

    Kirnasovsky Oleg U

    2010-04-01

    Full Text Available Abstract Background The balance between self-renewal and differentiation of stem cells is expected to be tightly controlled in order to maintain tissue homeostasis throughout life, also in the face of environmental hazards. Theory, predicting that homeostasis is maintained by a negative feedback on stem cell proliferation, implies a Quorum Sensing mechanism in higher vertebrates. Results Application of this theory to a cellular automata model of stem cell development in disrupted environments shows a sharply dichotomous growth dynamics: maturation within 50-400 cell cycles, or immortalization. This dichotomy is mainly driven by intercellular communication, low intensity of which causes perpetual proliferation. Another driving force is the cells' kinetic parameters. Reduced tissue life span of differentiated cells results in uncontrolled proliferation. Model's analysis, showing that under the Quorum Sensing control, stem cell fraction within a steady state population is fixed, is corroborated by experiments in breast carcinoma cells. Experimental results show that the plating densities of CD44+ cells and of CD44+/24lo/ESA+ cells do not affect stem cell fraction near confluence. Conclusions This study suggests that stem cell immortalization may be triggered by reduced intercellular communication, rather than exclusively result from somatic evolution, and implies that stem cell proliferation can be attenuated by signal manipulation, or enhanced by cytotoxics targeted to differentiated cells. In vivo verification and identification of the Quorum Sensing mediating molecules will pave the way to a higher level control of stem cell proliferation in cancer and in tissue engineering. Reviewers This article was reviewed by Glenn Webb and Marek Kimmel.

  11. Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies

    Directory of Open Access Journals (Sweden)

    Karina O. Brandão

    2017-09-01

    Full Text Available It is now a decade since human induced pluripotent stem cells (hiPSCs were first described. The reprogramming of adult somatic cells to a pluripotent state has become a robust technology that has revolutionised our ability to study human diseases. Crucially, these cells capture all the genetic aspects of the patient from which they were derived. Combined with advances in generating the different cell types present in the human heart, this has opened up new avenues to study cardiac disease in humans and investigate novel therapeutic approaches to treat these pathologies. Here, we provide an overview of the current state of the field regarding the generation of cardiomyocytes from human pluripotent stem cells and methods to assess them functionally, an essential requirement when investigating disease and therapeutic outcomes. We critically evaluate whether treatments suggested by these in vitro models could be translated to clinical practice. Finally, we consider current shortcomings of these models and propose methods by which they could be further improved.

  12. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

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    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  13. Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and Genome Engineering.

    Science.gov (United States)

    Jung, Moonjung; Dunbar, Cynthia E; Winkler, Thomas

    2015-12-01

    The combination of epigenetic reprogramming with advanced genome editing technologies opened a new avenue to study disease mechanisms, particularly of disorders with depleted target tissue. Bone marrow failure syndromes (BMFS) typically present with a marked reduction of peripheral blood cells due to a destroyed or dysfunctional bone marrow compartment. Somatic and germline mutations have been etiologically linked to many cases of BMFS. However, without the ability to study primary patient material, the exact pathogenesis for many entities remained fragmentary. Capturing the pathological genotype in induced pluripotent stem cells (iPSCs) allows studying potential developmental defects leading to a particular phenotype. The lack of hematopoietic stem and progenitor cells in these patients can also be overcome by differentiating patient-derived iPSCs into hematopoietic lineages. With fast growing genome editing techniques, such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or introduction of mutations in cells from healthy individuals enable comparative studies that may identify other genetic or epigenetic events contributing to a specific disease phenotype. In this review, we present recent progresses in disease modeling of inherited and acquired BMFS using reprogramming and genome editing techniques. We also discuss the challenges and potential shortcomings of iPSC-based models for hematological diseases.

  14. Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of neuroblastoma.

    Science.gov (United States)

    Kimura, Koseki; Kishida, Tsunao; Wakao, Junko; Tanaka, Tomoko; Higashi, Mayumi; Fumino, Shigehisa; Aoi, Shigeyoshi; Furukawa, Taizo; Mazda, Osam; Tajiri, Tatsuro

    2016-12-01

    Human mesenchymal stem cells (hMSCs) are multipotent stem-like cells that are reported to have tumor-suppression effects and migration ability toward damaged tissues or tumors. The aim of this study was to analyze the tumor-homing ability of hMSCs and antitumor potency in a transgenic TH-MYCN mouse model of neuroblastoma (NB). hMSCs (3×10 6 ) labeled with DiR, a lipophilic near-infrared dye, were intraperitoneally (i.p.) or intravenously (i.v.) administered to the TH-MYCN mice. hMSC in vivo kinetics were assayed using the IVIS® imaging system for 24h after injection. Immunohistochemistry using human CD90 antibody was also performed to confirm the location of hMSCs in various organs and tumors. Furthermore, the survival curve of TH-MYCN mice treated with hMSCs was compared to a control group administered PBS. i.p. hMSCs were recognized in the tumors of TH-MYCN mice by IVIS. hMSCs were also located inside the tumor tissue. Conversely, most of the i.v. hMSCs were captured by the lungs, and migration into the tumors was not noted. There was no significant difference in the survival between the hMSC and control groups. The present study suggested that hMSCs may be potential tumor-specific therapeutic delivery vehicles in NB according to their homing potential to tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A linear solvation energy relationship model of organic chemical partitioning to dissolved organic carbon.

    Science.gov (United States)

    Kipka, Undine; Di Toro, Dominic M

    2011-09-01

    Predicting the association of contaminants with both particulate and dissolved organic matter is critical in determining the fate and bioavailability of chemicals in environmental risk assessment. To date, the association of a contaminant to particulate organic matter is considered in many multimedia transport models, but the effect of dissolved organic matter is typically ignored due to a lack of either reliable models or experimental data. The partition coefficient to dissolved organic carbon (K(DOC)) may be used to estimate the fraction of a contaminant that is associated with dissolved organic matter. Models relating K(DOC) to the octanol-water partition coefficient (K(OW)) have not been successful for many types of dissolved organic carbon in the environment. Instead, linear solvation energy relationships are proposed to model the association of chemicals with dissolved organic matter. However, more chemically diverse K(DOC) data are needed to produce a more robust model. For humic acid dissolved organic carbon, the linear solvation energy relationship predicts log K(DOC) with a root mean square error of 0.43. Copyright © 2011 SETAC.

  16. Modelling the Stem Curve of a Palm in a Strong Wind

    DEFF Research Database (Denmark)

    Philipsen, Claus; Markvorsen, Steen; Kliem, Wolfhard

    1996-01-01

    Nonlinear differential equations governing the stem curve of a wind-loaded palm are derived and solved numerically.......Nonlinear differential equations governing the stem curve of a wind-loaded palm are derived and solved numerically....

  17. Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

    Directory of Open Access Journals (Sweden)

    Christian Bucher

    2013-01-01

    Full Text Available Intervertebral disc (IVD cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5 by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

  18. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Behre Gerhard

    2009-03-01

    Full Text Available Abstract Introduction We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. Case presentation A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. Conclusion As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  19. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report.

    Science.gov (United States)

    Behre, Gerhard; Theurich, Sebastian; Christopeit, Maximilian; Weber, Thomas

    2009-03-10

    We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  20. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Science.gov (United States)

    Ude, Chinedu C; Sulaiman, Shamsul B; Min-Hwei, Ng; Hui-Cheng, Chen; Ahmad, Johan; Yahaya, Norhamdan M; Saim, Aminuddin B; Idrus, Ruszymah B H

    2014-01-01

    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7) autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  1. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Directory of Open Access Journals (Sweden)

    Chinedu C Ude

    Full Text Available OBJECTIVES: In this study, Adipose stem cells (ADSC and bone marrow stem cells (BMSC, multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008. Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013. Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001. Fluorescence of the tracking dye (PKH26 in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  2. A Geoscience Workforce Model for Non-Geoscience and Non-Traditional STEM Students

    Science.gov (United States)

    Liou-Mark, J.; Blake, R.; Norouzi, H.; Vladutescu, D. V.; Yuen-Lau, L.

    2016-12-01

    The Summit on the Future of Geoscience Undergraduate Education has recently identified key professional skills, competencies, and conceptual understanding necessary in the development of undergraduate geoscience students (American Geosciences Institute, 2015). Through a comprehensive study involving a diverse range of the geoscience academic and employer community, the following professional scientist skills were rated highly important: 1) critical thinking/problem solving skills; 2) effective communication; 3) ability to access and integrate information; 4) strong quantitative skills; and 5) ability to work in interdisciplinary/cross cultural teams. Based on the findings of the study above, the New York City College of Technology (City Tech) has created a one-year intensive training program that focusses on the development of technical and non-technical geoscience skills for non-geoscience, non-traditional STEM students. Although City Tech does not offer geoscience degrees, the primary goal of the program is to create an unconventional pathway for under-represented minority STEM students to enter, participate, and compete in the geoscience workforce. The selected cohort of STEM students engage in year-round activities that include a geoscience course, enrichment training workshops, networking sessions, leadership development, research experiences, and summer internships at federal, local, and private geoscience facilities. These carefully designed programmatic elements provide both the geoscience knowledge and the non-technical professional skills that are essential for the geoscience workforce. Moreover, by executing this alternate, robust geoscience workforce model that attracts and prepares underrepresented minorities for geoscience careers, this unique pathway opens another corridor that helps to ameliorate the dire plight of the geoscience workforce shortage. This project is supported by NSF IUSE GEOPATH Grant # 1540721.

  3. Biomechanics of stem cells

    Science.gov (United States)

    Spector, A. A.; Yuan, D.; Somers, S.; Grayson, W. L.

    2018-04-01

    Stem cells play a key role in the healthy development and maintenance of organisms. They are also critically important in medical treatments of various diseases. It has been recently demonstrated that the mechanical factors such as forces, adhesion, stiffness, relaxation, etc. have significant effects on stem cell functions. Under physiological conditions, cells (stem cells) in muscles, heart, and blood vessels are under the action of externally applied strains. We consider the stem cell microenvironment and performance associated with their conversion (differentiation) into skeletal muscle cells. Two problems are studied by using mathematical models whose parameters are then optimized by fitting experiments. First, we present our analysis of the process of stem cell differentiation under the application of cyclic unidirectional strain. This process is interpreted as a transition through several (six) stages where each of them is defined in terms of expression of a set of factors typical to skeletal muscle cells. The stem cell evolution toward muscle cells is described by a system of nonlinear ODEs. The parameters of the model are determined by fitting the experimental data on the time course of expression of the factors under consideration. Second, we analyse the mechanical (relaxation) properties of a scaffold that serves as the microenvironment for stem cells differentiation into skeletal muscle cells. This scaffold (surrounded by a liquid solution) is composed of unidirectional fibers with pores between them. The relaxation properties of the scaffold are studied in an experiment where a long cylindrical specimen is loaded by the application of ramp displacement until the strain reaches a prescribed value. The magnitude of the corresponding load is recorded. The specimen is considered as transversely isotropic poroelastic cylinder whose force relaxation is associated with liquid diffusion through the pores. An analytical solution for the total force applied to

  4. Modeling the influence of organic acids on soil weathering

    Science.gov (United States)

    Lawrence, Corey R.; Harden, Jennifer W.; Maher, Kate

    2014-01-01

    Biological inputs and organic matter cycling have long been regarded as important factors in the physical and chemical development of soils. In particular, the extent to which low molecular weight organic acids, such as oxalate, influence geochemical reactions has been widely studied. Although the effects of organic acids are diverse, there is strong evidence that organic acids accelerate the dissolution of some minerals. However, the influence of organic acids at the field-scale and over the timescales of soil development has not been evaluated in detail. In this study, a reactive-transport model of soil chemical weathering and pedogenic development was used to quantify the extent to which organic acid cycling controls mineral dissolution rates and long-term patterns of chemical weathering. Specifically, oxalic acid was added to simulations of soil development to investigate a well-studied chronosequence of soils near Santa Cruz, CA. The model formulation includes organic acid input, transport, decomposition, organic-metal aqueous complexation and mineral surface complexation in various combinations. Results suggest that although organic acid reactions accelerate mineral dissolution rates near the soil surface, the net response is an overall decrease in chemical weathering. Model results demonstrate the importance of organic acid input concentrations, fluid flow, decomposition and secondary mineral precipitation rates on the evolution of mineral weathering fronts. In particular, model soil profile evolution is sensitive to kaolinite precipitation and oxalate decomposition rates. The soil profile-scale modeling presented here provides insights into the influence of organic carbon cycling on soil weathering and pedogenesis and supports the need for further field-scale measurements of the flux and speciation of reactive organic compounds.

  5. Plant stem cell niches.

    Science.gov (United States)

    Stahl, Yvonne; Simon, Rüdiger

    2005-01-01

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

  6. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  7. Modeling the effects of temperature and relative humidity on gas exchange of prickly pear cactus (Opuntia spp.) stems

    NARCIS (Netherlands)

    Guevara-Arauza, J.C.; Yahia, E.M.; Cedeno, L.; Tijskens, L.M.M.

    2006-01-01

    A model to estimate gas profile of modified atmosphere packaged (MAP) prickly pear cactus stems was developed and calibrated. The model describes the transient gas exchange taking in consideration the effect of temperature (T) and relative humidity (RH) on film permeability (FPgas), respiration rate

  8. Daphnia as an Emerging Epigenetic Model Organism

    Directory of Open Access Journals (Sweden)

    Kami D. M. Harris

    2012-01-01

    Full Text Available Daphnia offer a variety of benefits for the study of epigenetics. Daphnia’s parthenogenetic life cycle allows the study of epigenetic effects in the absence of confounding genetic differences. Sex determination and sexual reproduction are epigenetically determined as are several other well-studied alternate phenotypes that arise in response to environmental stressors. Additionally, there is a large body of ecological literature available, recently complemented by the genome sequence of one species and transgenic technology. DNA methylation has been shown to be altered in response to toxicants and heavy metals, although investigation of other epigenetic mechanisms is only beginning. More thorough studies on DNA methylation as well as investigation of histone modifications and RNAi in sex determination and predator-induced defenses using this ecologically and evolutionarily important organism will contribute to our understanding of epigenetics.

  9. CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.

    Science.gov (United States)

    Shi, Kaibin; Wang, Zhen; Liu, Yuanchu; Gong, Ye; Fu, Ying; Li, Shaowu; Wood, Kristofer; Hao, Junwei; Zhang, Guang-Xian; Shi, Fu-Dong; Yan, Yaping

    2016-11-01

    A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. Copyright © 2016 by The American Association of Immunologists, Inc.

  10. Nematodes: Model Organisms in High School Biology

    Science.gov (United States)

    Bliss, TJ; Anderson, Margery; Dillman, Adler; Yourick, Debra; Jett, Marti; Adams, Byron J.; Russell, RevaBeth

    2007-01-01

    In a collaborative effort between university researchers and high school science teachers, an inquiry-based laboratory module was designed using two species of insecticidal nematodes to help students apply scientific inquiry and elements of thoughtful experimental design. The learning experience and model are described in this article. (Contains 4…

  11. Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.

    Science.gov (United States)

    Santiago-Osorio, Edelmiro; Ledesma-Martínez, Edgar; Aguiñiga-Sánchez, Itzen; Poblano-Pérez, Ignacio; Weiss-Steider, Benny; Montesinos-Montesinos, Juan José; Mora-García, María de Lourdes

    2015-09-25

    BACKGROUND Hematopoietic stem cells transplantation has high clinical potential against a wide variety of hematologic, metabolic, and autoimmune diseases and solid tumors. Clinically, hematopoietic stem cells derived from peripheral blood are currently used more than those obtained from sources such as bone marrow. However, mobilizing agents used in the clinic tend to fail in high rates, making the number of mobilized cells insufficient for transplantation. We investigated whether sodium caseinate induces functional mobilization of hematopoietic stem cells into peripheral blood of Balb/c mice. MATERIAL AND METHODS Using a mouse model, we administrated sodium caseinate or Plerixafor, a commercial mobilizing agent, and analyzed counts of hematopoietic stem cells in peripheral blood, and then cells were transplanted into lethally irradiated mice to restore hematopoiesis. All assays were performed at least twice. RESULTS We found that sodium caseinate increases the number of mononuclear cells in peripheral blood with the immunophenotype of hematopoietic stem cells (0.2 to 0.5% LSK cells), allowing them to form colonies of various cell lineages in semisolid medium (psodium caseinate as a mobilizer of hematopoietic stem cells and its potential clinical application in transplantation settings.

  12. Collaboration of 3D context and extracellular matrix in the development of glioma stemness in a 3D model.

    Science.gov (United States)

    Ma, Nina K L; Lim, Jia Kai; Leong, Meng Fatt; Sandanaraj, Edwin; Ang, Beng Ti; Tang, Carol; Wan, Andrew C A

    2016-02-01

    A hierarchy of cellular stemness exists in certain cancers, and any successful strategy to treat such cancers would have to eliminate the self-renewing tumor-initiating cells at the apex of the hierarchy. The cellular microenvironment, in particular the extracellular matrix (ECM), is believed to have a role in regulating stemness. In this work, U251 glioblastoma cells are cultured on electrospun polystyrene (ESPS) scaffolds coated with an array of 7 laminin isoforms to provide a 3D model for stem cell-related genes and proteins expression studies. We observed collaboration between 3D context and laminins in promoting glioma stemness. Depending on the laminin isoform presented, U251 cells cultured on ESPS scaffolds (3D) exhibited increased expression of stemness markers compared to those cultured on tissue culture polystyrene (2D). Our results indicate the influence of 3D (versus 2D) context on integrin expression, specifically, the upregulation of the laminin-binding integrins alpha 6 and beta 4. By a colony forming assay, we showed enhanced clonogenicity of cells grown on ESPS scaffolds in collaboration with laminins 411, 421, 511 and 521. Evaluation of patient glioma databases demonstrated significant enrichment of integrin and ECM pathway networks in tumors of worse prognosis, consistent with our observations. The present results demonstrate how 3D versus 2D context profoundly affects ECM signaling, leading to stemness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. On the Relationship between Aquatic Plant Stem Characteristics and Drag Force: Is a Modeling Application Possible?

    Directory of Open Access Journals (Sweden)

    Anna Maria Łoboda

    2018-04-01

    Full Text Available This paper presents a basic model that shows the relationship between the diameter of a stem and its flexural rigidity. The model was developed from experimental measurements of biomechanical traits (i.e., tensile and bending traits like maximum forces, stresses, moduli of elasticity, flexural rigidity, strain of three freshwater macrophyte species (Elodea canadensis Michx., Potamogeton pectinatus L., and P. crispus L., reflecting the seasonal changes in plant biomechanics throughout the vegetative season. These were obtained with the use of a bench-top testing machine in 2016 and 2017. The presented calculations are based on the ratio of drag-to-bending forces, in which the flexural rigidity plays a key role. The proposed model has the form EI = adb, and two approaches based on a regression analysis were applied to determine the parameters of the model—a and b. In the first method, the parameters were identified separately for each day of measurement, while in the second method, the coefficient b was calculated for all data from all days as a unified number for individual plants. The results suggest that coefficient b may provide information about the proportion of changes in drag forces depending on plant stiffness. The values of this coefficient were associated with the shape of the stem cross-section. The more circular the cross-section, the closer the value of the parameter was to 1. The parameter values were 1.60 for E. canadensis, 1.98 for P. pectinatus, and 2.46 for P. crispus. Moreover, this value also depended on the density of the cross-section structure. Most of the results showed that with an increase in stem diameter, the ratio between the drag and bending forces decreased, which led to fewer differences between these two forces. The model application may be introduced in many laboratory measurements of flow–biota interactions as well as in aquatic plant management applications. The implementation of these results in control

  14. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Science.gov (United States)

    Monteagudo, Ángel; Santos, José

    2015-01-01

    Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  15. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Directory of Open Access Journals (Sweden)

    Ángel Monteagudo

    Full Text Available Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  16. Fitting and Calibrating a Multilevel Mixed-Effects Stem Taper Model for Maritime Pine in NW Spain

    Science.gov (United States)

    Arias-Rodil, Manuel; Castedo-Dorado, Fernando; Cámara-Obregón, Asunción; Diéguez-Aranda, Ulises

    2015-01-01

    Stem taper data are usually hierarchical (several measurements per tree, and several trees per plot), making application of a multilevel mixed-effects modelling approach essential. However, correlation between trees in the same plot/stand has often been ignored in previous studies. Fitting and calibration of a variable-exponent stem taper function were conducted using data from 420 trees felled in even-aged maritime pine (Pinus pinaster Ait.) stands in NW Spain. In the fitting step, the tree level explained much more variability than the plot level, and therefore calibration at plot level was omitted. Several stem heights were evaluated for measurement of the additional diameter needed for calibration at tree level. Calibration with an additional diameter measured at between 40 and 60% of total tree height showed the greatest improvement in volume and diameter predictions. If additional diameter measurement is not available, the fixed-effects model fitted by the ordinary least squares technique should be used. Finally, we also evaluated how the expansion of parameters with random effects affects the stem taper prediction, as we consider this a key question when applying the mixed-effects modelling approach to taper equations. The results showed that correlation between random effects should be taken into account when assessing the influence of random effects in stem taper prediction. PMID:26630156

  17. Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.

    Science.gov (United States)

    Blacking, T M; Waterfall, M; Samuel, K; Argyle, D J

    2012-12-01

    The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria. © 2011 Blackwell Publishing Ltd.

  18. The developing cancer stem-cell model: clinical challenges and opportunities.

    Science.gov (United States)

    Vermeulen, Louis; de Sousa e Melo, Felipe; Richel, Dick J; Medema, Jan Paul

    2012-02-01

    During the past decade, a stem-cell-like subset of cancer cells has been identified in many malignancies. These cells, referred to as cancer stem cells (CSCs), are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population that drives growth and progression. Many efforts have been made to design therapies that specifically target the CSC population, since this was predicted to be the crucial population to eliminate. However, recent insights have complicated the initial elegant model, by showing a dominant role for the tumour microenvironment in determining CSC characteristics within a malignancy. This is particularly important since dedifferentiation of non-tumorigenic tumour cells towards CSCs can occur, and therefore the CSC population in a neoplasm is expected to vary over time. Moreover, evidence suggests that not all tumours are driven by rare CSCs, but might instead contain a large population of tumorigenic cells. Even though these results suggest that specific targeting of the CSC population might not be a useful therapeutic strategy, research into the hierarchical cellular organisation of malignancies has provided many important new insights in the biology of tumours. In this Personal View, we highlight how the CSC concept is developing and influences our thinking on future treatment for solid tumours, and recommend ways to design clinical trials to assess drugs that target malignant disease in a rational fashion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Neural stem cells for disease modeling of Wolman disease and evaluation of therapeutics.

    Science.gov (United States)

    Aguisanda, Francis; Yeh, Charles D; Chen, Catherine Z; Li, Rong; Beers, Jeanette; Zou, Jizhong; Thorne, Natasha; Zheng, Wei

    2017-06-28

    Wolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). Deficiency in LAL function causes accumulation of cholesteryl esters and triglycerides in lysosomes. Fatality usually occurs within the first year of life. While an enzyme replacement therapy has recently become available, there is currently no small-molecule drug treatment for WD. We have generated induced pluripotent stem cells (iPSCs) from two WD patient dermal fibroblast lines and subsequently differentiated them into neural stem cells (NSCs). The WD NSCs exhibited the hallmark disease phenotypes of neutral lipid accumulation, severely deficient LAL activity, and increased LysoTracker dye staining. Enzyme replacement treatment dramatically reduced the WD phenotype in these cells. In addition, δ-tocopherol (DT) and hydroxypropyl-beta-cyclodextrin (HPBCD) significantly reduced lysosomal size in WD NSCs, and an enhanced effect was observed in DT/HPBCD combination therapy. The results demonstrate that these WD NSCs are valid cell-based disease models with characteristic disease phenotypes that can be used to evaluate drug efficacy and screen compounds. DT and HPBCD both reduce LysoTracker dye staining in WD cells. The cells may be used to further dissect the pathology of WD, evaluate compound efficacy, and serve as a platform for high-throughput drug screening to identify new compounds for therapeutic development.

  20. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

    Science.gov (United States)

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-12-24

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

  1. Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model

    OpenAIRE

    Yousefifard, Mahmoud; Nasirinezhad, Farinaz; Shardi Manaheji, Homa; Janzadeh, Atousa; Hosseini, Mostafa; Keshavarz, Mansoor

    2016-01-01

    Background Stem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief. Methods A compression model was used to induce SCI in a rat model. A w...

  2. Model of the regulation of the rate of multiplication of the stem cells of the bone marrow. [X radiation, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, G P; Monichev, A Ya

    1975-01-01

    A mathematical model of regulation of the rate of multiplication of the stem cells of the bone marrow has been constructed and investigated. Two possible variants of regulation of the proliferative activity of the irradiated stem cells are compared: at the level of tissue and subtissue units. Comparison of the results of modeling with the results of experimental investigations supports the latter mechanism of regulation of the proliferation of the stem cells.

  3. Self-organized quantum rings : Physical characterization and theoretical modeling

    NARCIS (Netherlands)

    Fomin, V.M.; Gladilin, V.N.; Devreese, J.T.; Koenraad, P.M.; Fomin, V.M.

    2014-01-01

    An adequate modeling of the self-organized quantum rings is possible only on the basis of the modern characterization of those nanostructures.We discuss an atomic-scale analysis of the indium distribution of self-organized InGaAs quantum rings (QRs). The analysis of the shape, size and composition

  4. Resilient organizations: matrix model and service line management.

    Science.gov (United States)

    Westphal, Judith A

    2005-09-01

    Resilient organizations modify structures to meet the demands of the marketplace. The author describes a structure that enables multihospital organizations to innovate and rapidly adapt to changes. Service line management within a matrix model is an evolving organizational structure for complex systems in which nurses are pivotal members.

  5. (Tropical) soil organic matter modelling: problems and prospects

    NARCIS (Netherlands)

    Keulen, van H.

    2001-01-01

    Soil organic matter plays an important role in many physical, chemical and biological processes. However, the quantitative relations between the mineral and organic components of the soil and the relations with the vegetation are poorly understood. In such situations, the use of models is an

  6. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z

    2013-07-01

    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  7. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  8. Investigating ecological speciation in non-model organisms

    DEFF Research Database (Denmark)

    Foote, Andrew David

    2012-01-01

    Background: Studies of ecological speciation tend to focus on a few model biological systems. In contrast, few studies on non-model organisms have been able to infer ecological speciation as the underlying mechanism of evolutionary divergence. Questions: What are the pitfalls in studying ecological...... speciation in non-model organisms that lead to this bias? What alternative approaches might redress the balance? Organism: Genetically differentiated types of the killer whale (Orcinus orca) exhibiting differences in prey preference, habitat use, morphology, and behaviour. Methods: Review of the literature...... on killer whale evolutionary ecology in search of any difficulty in demonstrating causal links between variation in phenotype, ecology, and reproductive isolation in this non-model organism. Results: At present, we do not have enough evidence to conclude that adaptive phenotype traits linked to ecological...

  9. Modelling the self-organization and collapse of complex networks

    Indian Academy of Sciences (India)

    Modelling the self-organization and collapse of complex networks. Sanjay Jain Department of Physics and Astrophysics, University of Delhi Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore Santa Fe Institute, Santa Fe, New Mexico.

  10. Competency Maps: an Effective Model to Integrate Professional Competencies Across a STEM Curriculum

    Science.gov (United States)

    Sánchez Carracedo, Fermín; Soler, Antonia; Martín, Carme; López, David; Ageno, Alicia; Cabré, Jose; Garcia, Jordi; Aranda, Joan; Gibert, Karina

    2018-05-01

    Curricula designed in the context of the European Higher Education Area need to be based on both domain-specific and professional competencies. Whereas universities have had extensive experience in developing students' domain-specific competencies, fostering professional competencies poses a new challenge we need to face. This paper presents a model to globally develop professional competencies in a STEM (science, technology, engineering, and mathematics) degree program, and assesses the results of its implementation after 4 years. The model is based on the use of competency maps, in which each competency is defined in terms of competency units. Each competency unit is described by a set of expected learning outcomes at three domain levels. This model allows careful analysis, revision, and iteration for an effective integration of professional competencies in domain-specific subjects. A global competency map is also designed, including all the professional competency learning outcomes to be achieved throughout the degree. This map becomes a useful tool for curriculum designers and coordinators. The results were obtained from four sources: (1) students' grades (classes graduated from 2013 to 2016, the first 4 years of the new Bachelor's Degree in Informatics Engineering at the Barcelona School of Informatics); (2) students' surveys (answered by students when they finished the degree); (3) the government employment survey, where former students evaluate their satisfaction of the received training in the light of their work experience; and (4) the Everis Foundation University-Enterprise Ranking, answered by over 2000 employers evaluating their satisfaction regarding their employees' university training, where the Barcelona School of Informatics scores first in the national ranking. The results show that competency maps are a good tool for developing professional competencies in a STEM degree.

  11. Self-organizing map models of language acquisition

    Science.gov (United States)

    Li, Ping; Zhao, Xiaowei

    2013-01-01

    Connectionist models have had a profound impact on theories of language. While most early models were inspired by the classic parallel distributed processing architecture, recent models of language have explored various other types of models, including self-organizing models for language acquisition. In this paper, we aim at providing a review of the latter type of models, and highlight a number of simulation experiments that we have conducted based on these models. We show that self-organizing connectionist models can provide significant insights into long-standing debates in both monolingual and bilingual language development. We suggest future directions in which these models can be extended, to better connect with behavioral and neural data, and to make clear predictions in testing relevant psycholinguistic theories. PMID:24312061

  12. Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

    Science.gov (United States)

    Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

    2018-05-01

    The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

  13. Labour Quality Model for Organic Farming Food Chains

    OpenAIRE

    Gassner, B.; Freyer, B.; Leitner, H.

    2008-01-01

    The debate on labour quality in science is controversial as well as in the organic agriculture community. Therefore, we reviewed literature on different labour quality models and definitions, and had key informant interviews on labour quality issues with stakeholders in a regional oriented organic agriculture bread food chain. We developed a labour quality model with nine quality categories and discussed linkages to labour satisfaction, ethical values and IFOAM principles.

  14. Xanthusbase: adapting wikipedia principles to a model organism database

    OpenAIRE

    Arshinoff, Bradley I.; Suen, Garret; Just, Eric M.; Merchant, Sohel M.; Kibbe, Warren A.; Chisholm, Rex L.; Welch, Roy D.

    2006-01-01

    xanthusBase () is the official model organism database (MOD) for the social bacterium Myxococcus xanthus. In many respects, M.xanthus represents the pioneer model organism (MO) for studying the genetic, biochemical, and mechanistic basis of prokaryotic multicellularity, a topic that has garnered considerable attention due to the significance of biofilms in both basic and applied microbiology research. To facilitate its utility, the design of xanthusBase incorporates open-source software, leve...

  15. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Erin C. Hedges

    2016-01-01

    Full Text Available In recent years several genes have linked amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

  16. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine.

    Science.gov (United States)

    Hedges, Erin C; Mehler, Vera J; Nishimura, Agnes L

    2016-01-01

    In recent years several genes have linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs) have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

  17. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model

    DEFF Research Database (Denmark)

    Tønnesen, Jan; Parish, Clare L; Sørensen, Andreas T

    2011-01-01

    Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral...... of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation...... using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying...

  18. Engineering stem cell niches in bioreactors

    OpenAIRE

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “ni...

  19. Knowledge Loss: A Defensive Model In Nuclear Research Organization Memory

    International Nuclear Information System (INIS)

    Mohamad Safuan Bin Sulaiman; Muhd Noor Muhd Yunus

    2013-01-01

    Knowledge is an essential part of research based organization. It should be properly managed to ensure that any pitfalls of knowledge retention due to knowledge loss of both tacit and explicit is mitigated. Audit of the knowledge entities exist in the organization is important to identify the size of critical knowledge. It is very much related to how much know-what, know-how and know-why experts exist in the organization. This study conceptually proposed a defensive model for Nuclear Malaysia's organization memory and application of Knowledge Loss Risk Assessment (KLRA) as an important tool for critical knowledge identification. (author)

  20. NEW MODEL FOR QUANTIFICATION OF ICT DEPENDABLE ORGANIZATIONS RESILIENCE

    Directory of Open Access Journals (Sweden)

    Zora Arsovski

    2011-03-01

    Full Text Available Business environment today demands high reliable organizations in every segment to be competitive on the global market. Beside that, ICT sector is becoming irreplaceable in many fields of business, from the communication to the complex systems for process control and production. To fulfill those requirements and to develop further, many organizations worldwide are implementing business paradigm called - organizations resilience. Although resilience is well known term in many science fields, it is not well studied due to its complex nature. This paper is dealing with developing the new model for assessment and quantification of ICT dependable organizations resilience.

  1. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

    Directory of Open Access Journals (Sweden)

    Timothy M. Pierpont

    2017-11-01

    Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

  2. A model to accumulate fractionated dose in a deforming organ

    International Nuclear Information System (INIS)

    Yan Di; Jaffray, D.A.; Wong, J.W.

    1999-01-01

    Purpose: Measurements of internal organ motion have demonstrated that daily organ deformation exists throughout the course of radiation treatment. However, a method of constructing the resultant dose delivered to the organ volume remains a difficult challenge. In this study, a model to quantify internal organ motion and a method to construct a cumulative dose in a deforming organ are introduced. Methods and Materials: A biomechanical model of an elastic body is used to quantify patient organ motion in the process of radiation therapy. Intertreatment displacements of volume elements in an organ of interest is calculated by applying an finite element method with boundary conditions, obtained from multiple daily computed tomography (CT) measurements. Therefore, by incorporating also the measurements of daily setup error, daily dose delivered to a deforming organ can be accumulated by tracking the position of volume elements in the organ. Furthermore, distribution of patient-specific organ motion is also predicted during the early phase of treatment delivery using the daily measurements, and the cumulative dose distribution in the organ can then be estimated. This dose distribution will be updated whenever a new measurement becomes available, and used to reoptimize the ongoing treatment. Results: An integrated process to accumulate dosage in a daily deforming organ was implemented. In this process, intertreatment organ motion and setup error were systematically quantified, and incorporated in the calculation of the cumulative dose. An example of the rectal wall motion in a prostate treatment was applied to test the model. The displacements of volume elements in the rectal wall, as well as the resultant doses, were calculated. Conclusion: This study is intended to provide a systematic framework to incorporate daily patient-specific organ motion and setup error in the reconstruction of the cumulative dose distribution in an organ of interest. The realistic dose

  3. Ecophysiological modeling of photosynthesis and carbon allocation to the tree stem in the boreal forest

    Directory of Open Access Journals (Sweden)

    F. Gennaretti

    2017-11-01

    Full Text Available A better understanding of the coupling between photosynthesis and carbon allocation in the boreal forest, together with its associated environmental factors and mechanistic rules, is crucial to accurately predict boreal forest carbon stocks and fluxes, which are significant components of the global carbon budget. Here, we adapted the MAIDEN ecophysiological forest model to consider important processes for boreal tree species, such as nonlinear acclimation of photosynthesis to temperature changes, canopy development as a function of previous-year climate variables influencing bud formation and the temperature dependence of carbon partition in summer. We tested these modifications in the eastern Canadian taiga using black spruce (Picea mariana (Mill. B.S.P. gross primary production and ring width data. MAIDEN explains 90 % of the observed daily gross primary production variability, 73 % of the annual ring width variability and 20–30 % of its high-frequency component (i.e., when decadal trends are removed. The positive effect on stem growth due to climate warming over the last several decades is well captured by the model. In addition, we illustrate how we improve the model with each introduced model adaptation and compare the model results with those of linear response functions. Our results demonstrate that MAIDEN simulates robust relationships with the most important climate variables (those detected by classical response-function analysis and is a powerful tool for understanding how environmental factors interact with black spruce ecophysiology to influence present-day and future boreal forest carbon fluxes.

  4. Ecophysiological modeling of photosynthesis and carbon allocation to the tree stem in the boreal forest

    Science.gov (United States)

    Gennaretti, Fabio; Gea-Izquierdo, Guillermo; Boucher, Etienne; Berninger, Frank; Arseneault, Dominique; Guiot, Joel

    2017-11-01

    A better understanding of the coupling between photosynthesis and carbon allocation in the boreal forest, together with its associated environmental factors and mechanistic rules, is crucial to accurately predict boreal forest carbon stocks and fluxes, which are significant components of the global carbon budget. Here, we adapted the MAIDEN ecophysiological forest model to consider important processes for boreal tree species, such as nonlinear acclimation of photosynthesis to temperature changes, canopy development as a function of previous-year climate variables influencing bud formation and the temperature dependence of carbon partition in summer. We tested these modifications in the eastern Canadian taiga using black spruce (Picea mariana (Mill.) B.S.P.) gross primary production and ring width data. MAIDEN explains 90 % of the observed daily gross primary production variability, 73 % of the annual ring width variability and 20-30 % of its high-frequency component (i.e., when decadal trends are removed). The positive effect on stem growth due to climate warming over the last several decades is well captured by the model. In addition, we illustrate how we improve the model with each introduced model adaptation and compare the model results with those of linear response functions. Our results demonstrate that MAIDEN simulates robust relationships with the most important climate variables (those detected by classical response-function analysis) and is a powerful tool for understanding how environmental factors interact with black spruce ecophysiology to influence present-day and future boreal forest carbon fluxes.

  5. A bioengineered murine model using CD24+CD44+ pancreatic cancer stem cells for chemotherapy study

    International Nuclear Information System (INIS)

    Qin, Shengqi; Li, Jianshe; Zhang, Zhongtao; Deng, Yiming

    2015-01-01

    In this work we first developed a murine pancreatic tumor model using CD24 + CD44 + pancreatic cancer stem cells (CSC) supported by an electrospun scaffold. Unlike conventional models, the use of CSC and the scaffold, which were biologically and chemically defined, afforded scientists a reliable platform to evaluate novel chemotherapy regimens. CD24 + CD44 + CSC successfully initiated tumorigenesis in vitro on the scaffold without suffering apoptosis, evidencing the lack of cytotoxicity of scaffolding materials. Also, the scaffold contributed to the acceleration of in vivo tumorigenesis and increased the likelihood of tumor formation. Using this model, we set out to explore the effectiveness of irinotecan/gemcitabine (IRIN-GEM), a chemotherapy regimen, for pancreatic cancer. Our study showed that IRIN-GEM induced a tumor regression whereas gemcitabine alone could only arrest the tumor growth. Further study suggested that the superior performance of IRIN-GEM could be attributed to its capacity to demolish the CD24 + CD44 + CSC sub-population by inducing a large-scale apoptosis. The use of highly proliferative yet homogenous CD24 + CD44 + CSC along with a chemically defined scaffold accelerated the tumor formation and significantly reduced the variability associated with conventional murine models. Armed with this new model, we discovered that IRIN-GEM would be a promising chemotherapy candidate for patients with advanced pancreatic cancer. (paper)

  6. Genomic resources for the flatworm model organism Macrostomum lignano

    NARCIS (Netherlands)

    Simanov, D.

    2014-01-01

    The last two decades were marked by discoveries and breakthroughs in different biological disciplines, and stem cell biology is an example of the quickly developing field. Discovery of stem cell niches and successful reprogramming of somatic cells into pluripotent stem state are only a few step

  7. Charge carrier relaxation model in disordered organic semiconductors

    International Nuclear Information System (INIS)

    Lu, Nianduan; Li, Ling; Sun, Pengxiao; Liu, Ming

    2013-01-01

    The relaxation phenomena of charge carrier in disordered organic semiconductors have been demonstrated and investigated theoretically. An analytical model describing the charge carrier relaxation is proposed based on the pure hopping transport theory. The relation between the material disorder, electric field and temperature and the relaxation phenomena has been discussed in detail, respectively. The calculated results reveal that the increase of electric field and temperature can promote the relaxation effect in disordered organic semiconductors, while the increase of material disorder will weaken the relaxation. The proposed model can explain well the stretched-exponential law by adopting the appropriate parameters. The calculation shows a good agreement with the experimental data for organic semiconductors

  8. Modelling the fate of organic micropollutants in stormwater ponds

    DEFF Research Database (Denmark)

    Vezzaro, Luca; Eriksson, Eva; Ledin, Anna

    2011-01-01

    ). The four simulated organic stormwater MP (iodopropynyl butylcarbamate — IPBC, benzene, glyphosate and pyrene) were selected according to their different urban sources and environmental fate. This ensures that the results can be extended to other relevant stormwater pollutants. All three models use......Urban water managers need to estimate the potential removal of organic micropollutants (MP) in stormwater treatment systems to support MP pollution control strategies. This study documents how the potential removal of organic MP in stormwater treatment systems can be quantified by using multimedia...... models. The fate of four different MP in a stormwater retention pond was simulated by applying two steady-state multimedia fate models (EPI Suite and SimpleBox) commonly applied in chemical risk assessment and a dynamic multimedia fate model (Stormwater Treatment Unit Model for Micro Pollutants — STUMP...

  9. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model.

    Science.gov (United States)

    Huleihel, Luai; Sellares, Jacobo; Cardenes, Nayra; Álvarez, Diana; Faner, Rosa; Sakamoto, Koji; Yu, Guoying; Kapetanaki, Maria G; Kaminski, Naftali; Rojas, Mauricio

    2017-07-01

    Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation, and the mice were euthanized at day 14 Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis. Copyright © 2017 the American Physiological Society.

  10. Modelling the fate of oxidisable organic contaminants in groundwater

    DEFF Research Database (Denmark)

    Barry, D.A.; Prommer, H.; Miller, C.T.

    2002-01-01

    modelling framework is illustrated by pertinent examples, showing the degradation of dissolved organics by microbial activity limited by the availability of nutrients or electron acceptors (i.e., changing redox states), as well as concomitant secondary reactions. Two field-scale modelling examples......Subsurface contamination by organic chemicals is a pervasive environmental problem, susceptible to remediation by natural or enhanced attenuation approaches or more highly engineered methods such as pump-and-treat, amongst others. Such remediation approaches, along with risk assessment...... are discussed, the Vejen landfill (Denmark) and an example where metal contamination is remediated by redox changes wrought by injection of a dissolved organic compound. A summary is provided of current and likely future challenges to modelling of oxidisable organics in the subsurface. (C) 2002 Elsevier Science...

  11. Drosophila melanogaster as a model organism to study nanotoxicity.

    Science.gov (United States)

    Ong, Cynthia; Yung, Lin-Yue Lanry; Cai, Yu; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2015-05-01

    Drosophila melanogaster has been used as an in vivo model organism for the study of genetics and development since 100 years ago. Recently, the fruit fly Drosophila was also developed as an in vivo model organism for toxicology studies, in particular, the field of nanotoxicity. The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited due to high operational cost and ethical objections. Hence, Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity. This review discusses the basic biology of Drosophila, the toxicity of nanomaterials, as well as how the Drosophila model can be used to study the toxicity of various types of nanomaterials.

  12. Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.

    Science.gov (United States)

    Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Beers, Jeanette; Chen, Guokai; Soheilian, Ferri; Baxa, Ulrich; Wang, Mengqiao; Marugan, Juan J; Muro, Silvia; Li, Zhiyuan; Brady, Roscoe; Zheng, Wei

    2016-12-01

    : Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, δ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development. Currently, there is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were generated from patient dermal fibroblasts and differentiated into neural stem cells. By using the differentiated NPA neuronal cells as a cell-based disease model system, α-tocopherol, δ-tocopherol, and hydroxypropyl-β-cyclodextrin significantly reduced sphingomyelin accumulation in these NPA neuronal cells. Therefore, this cell-based NPA model can be used for further study of

  13. Stem cells: a model for screening, discovery and development of drugs.

    Science.gov (United States)

    Kitambi, Satish Srinivas; Chandrasekar, Gayathri

    2011-01-01

    The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.

  14. Development of a 3D co-culture model using human stem ...

    Science.gov (United States)

    Morphogenetic tissue fusion is a critical and complex event in embryonic development and failure of this event leads to birth defects, such as cleft palate. Palatal fusion requires adhesion and subsequent dissolution of the medial epithelial layer of the mesenchymal palatal shelves, and is regulated by the growth factors EGF and TGFβ, and others, although the complete regulatory mechanism is not understood. Three dimensional (3D) organotypic models allow us to mimic the native architecture of human tissue to facilitate the study of tissue dynamics and their responses to developmental toxicants. Our goal was to develop and characterize a spheroidal model of palatal fusion to investigate the mechanisms regulating fusion with exposure to growth factors and chemicals in the ToxCast program known to disrupt this event. We present a spheroidal model using human umbilical-derived mesenchymal stem cells (hMSC) spheroid cores cultured for 13 days and then coated with MaxGel™ basement membrane and a layer of human progenitor epithelial keratinocytes (hPEK) (hMSC+hPEK spheroids). We characterized the growth, differentiation, proliferation and fusion activity of the model. Spheroid diameter was dependent on hMSC seeding density, size of the seeding wells, time in culture, and type of medium. hMSC spheroid growth was enhanced with osteogenic differentiation medium. Alkaline phosphatase activity in the hMSC spheroid, indicating osteogenic differentiation, increased in inte

  15. Model-Based Analysis for Qualitative Data: An Application in Drosophila Germline Stem Cell Regulation

    Science.gov (United States)

    Pargett, Michael; Rundell, Ann E.; Buzzard, Gregery T.; Umulis, David M.

    2014-01-01

    Discovery in developmental biology is often driven by intuition that relies on the integration of multiple types of data such as fluorescent images, phenotypes, and the outcomes of biochemical assays. Mathematical modeling helps elucidate the biological mechanisms at play as the networks become increasingly large and complex. However, the available data is frequently under-utilized due to incompatibility with quantitative model tuning techniques. This is the case for stem cell regulation mechanisms explored in the Drosophila germarium through fluorescent immunohistochemistry. To enable better integration of biological data with modeling in this and similar situations, we have developed a general parameter estimation process to quantitatively optimize models with qualitative data. The process employs a modified version of the Optimal Scaling method from social and behavioral sciences, and multi-objective optimization to evaluate the trade-off between fitting different datasets (e.g. wild type vs. mutant). Using only published imaging data in the germarium, we first evaluated support for a published intracellular regulatory network by considering alternative connections of the same regulatory players. Simply screening networks against wild type data identified hundreds of feasible alternatives. Of these, five parsimonious variants were found and compared by multi-objective analysis including mutant data and dynamic constraints. With these data, the current model is supported over the alternatives, but support for a biochemically observed feedback element is weak (i.e. these data do not measure the feedback effect well). When also comparing new hypothetical models, the available data do not discriminate. To begin addressing the limitations in data, we performed a model-based experiment design and provide recommendations for experiments to refine model parameters and discriminate increasingly complex hypotheses. PMID:24626201

  16. StatSTEM: An efficient approach for accurate and precise model-based quantification of atomic resolution electron microscopy images

    Energy Technology Data Exchange (ETDEWEB)

    De Backer, A.; Bos, K.H.W. van den [Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Van den Broek, W. [AG Strukturforschung/Elektronenmikroskopie, Institut für Physik, Humboldt-Universität zu Berlin, Newtonstraße 15, 12489 Berlin (Germany); Sijbers, J. [iMinds-Vision Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (Belgium); Van Aert, S., E-mail: sandra.vanaert@uantwerpen.be [Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)

    2016-12-15

    An efficient model-based estimation algorithm is introduced to quantify the atomic column positions and intensities from atomic resolution (scanning) transmission electron microscopy ((S)TEM) images. This algorithm uses the least squares estimator on image segments containing individual columns fully accounting for overlap between neighbouring columns, enabling the analysis of a large field of view. For this algorithm, the accuracy and precision with which measurements for the atomic column positions and scattering cross-sections from annular dark field (ADF) STEM images can be estimated, has been investigated. The highest attainable precision is reached even for low dose images. Furthermore, the advantages of the model-based approach taking into account overlap between neighbouring columns are highlighted. This is done for the estimation of the distance between two neighbouring columns as a function of their distance and for the estimation of the scattering cross-section which is compared to the integrated intensity from a Voronoi cell. To provide end-users this well-established quantification method, a user friendly program, StatSTEM, is developed which is freely available under a GNU public license. - Highlights: • An efficient model-based method for quantitative electron microscopy is introduced. • Images are modelled as a superposition of 2D Gaussian peaks. • Overlap between neighbouring columns is taken into account. • Structure parameters can be obtained with the highest precision and accuracy. • StatSTEM, auser friendly program (GNU public license) is developed.

  17. Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

    Science.gov (United States)

    Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

  18. Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Philip W. Brownjohn

    2017-04-01

    Full Text Available Summary: Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP processing and the accumulation of APP-derived amyloid β (Aβ peptides are key processes in Alzheimer's disease (AD. We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation. : In this article, Livesey and colleagues perform a phenotypic drug screen in a human stem cell model of Alzheimer's disease. The anthelminthic avermectins are identified as a family of compounds that increase the production of short Aβ peptides over longer more toxic Aβ forms. The effect is analogous to existing γ-secretase modulators, but is independent of the core γ-secretase complex. Keywords: neural stem cells, Alzheimer's disease, phenotypic screening, iPSCs, human neurons, dementia, Down syndrome, amyloid beta, ivermectin, selamectin

  19. Mutant mice: experimental organisms as materialised models in biomedicine.

    Science.gov (United States)

    Huber, Lara; Keuck, Lara K

    2013-09-01

    Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Spatial arrangement of organic compounds on a model mineral surface: implications for soil organic matter stabilization.

    Science.gov (United States)

    Petridis, Loukas; Ambaye, Haile; Jagadamma, Sindhu; Kilbey, S Michael; Lokitz, Bradley S; Lauter, Valeria; Mayes, Melanie A

    2014-01-01

    The complexity of the mineral-organic carbon interface may influence the extent of stabilization of organic carbon compounds in soils, which is important for global climate futures. The nanoscale structure of a model interface was examined here by depositing films of organic carbon compounds of contrasting chemical character, hydrophilic glucose and amphiphilic stearic acid, onto a soil mineral analogue (Al2O3). Neutron reflectometry, a technique which provides depth-sensitive insight into the organization of the thin films, indicates that glucose molecules reside in a layer between Al2O3 and stearic acid, a result that was verified by water contact angle measurements. Molecular dynamics simulations reveal the thermodynamic driving force behind glucose partitioning on the mineral interface: The entropic penalty of confining the less mobile glucose on the mineral surface is lower than for stearic acid. The fundamental information obtained here helps rationalize how complex arrangements of organic carbon on soil mineral surfaces may arise.

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

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

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

  2. A Framework for Formal Modeling and Analysis of Organizations

    NARCIS (Netherlands)

    Jonker, C.M.; Sharpanskykh, O.; Treur, J.; P., Yolum

    2007-01-01

    A new, formal, role-based, framework for modeling and analyzing both real world and artificial organizations is introduced. It exploits static and dynamic properties of the organizational model and includes the (frequently ignored) environment. The transition is described from a generic framework of

  3. Healing models for organizations: description, measurement, and outcomes.

    Science.gov (United States)

    Malloch, K

    2000-01-01

    Healthcare leaders are continually searching for ways to improve their ability to provide optimal healthcare services, be financially viable, and retain quality caregivers, often feeling like such goals are impossible to achieve in today's intensely competitive environment. Many healthcare leaders intuitively recognize the need for more humanistic models and the probable connection with positive patient outcomes and financial success but are hesitant to make significant changes in their organizations because of the lack of model descriptions or documented recognition of the clinical and financial advantages of humanistic models. This article describes a study that was developed in response to the increasing work in humanistic or healing environment models and the need for validation of the advantages of such models. The healthy organization model, a framework for healthcare organizations that incorporates humanistic healing values within the traditional structure, is presented as a result of the study. This model addresses the importance of optimal clinical services, financial performance, and staff satisfaction. The five research-based organizational components that form the framework are described, and key indicators of organizational effectiveness over a five-year period are presented. The resulting empirical data are strongly supportive of the healing model and reflect positive outcomes for the organization.

  4. Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement.

    Science.gov (United States)

    Di Foggia, Valentina; Makwana, Priyanka; Ali, Robin R; Sowden, Jane C

    2016-06-01

    Stem cell therapies are being explored as potential treatments for retinal disease. How to replace neurons in a degenerated retina presents a continued challenge for the regenerative medicine field that, if achieved, could restore sight. The major issues are: (i) the source and availability of donor cells for transplantation; (ii) the differentiation of stem cells into the required retinal cells; and (iii) the delivery, integration, functionality, and survival of new cells in the host neural network. This review considers the use of induced pluripotent stem cells (iPSC), currently under intense investigation, as a platform for cell transplantation therapy. Moreover, patient-specific iPSC are being developed for autologous cell transplantation and as a tool for modeling specific retinal diseases, testing gene therapies, and drug screening.

  5. Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction

    Science.gov (United States)

    Tulpule, Asmin; Kelley, James M.; Lensch, M. William; McPherson, Jade; Park, In Hyun; Hartung, Odelya; Nakamura, Tomoka; Schlaeger, Thorsten M.; Shimamura, Akiko; Daley, George Q.

    2013-01-01

    Summary Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction, is caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. We created human pluripotent stem cell models of SDS by knock-down of SBDS in human embryonic stem cells (hESCs) and generation of induced pluripotent stem cell (iPSC) lines from two SDS patients. SBDS-deficient hESCs and iPSCs manifest deficits in exocrine pancreatic and hematopoietic differentiation in vitro, enhanced apoptosis and elevated protease levels in culture supernatants, which could be reversed by restoring SBDS protein expression through transgene rescue or by supplementing culture media with protease inhibitors. Protease-mediated auto-digestion provides a mechanistic link between the pancreatic and hematopoietic phenotypes in SDS, highlighting the utility of hESCs and iPSCs in obtaining novel insights into human disease. PMID:23602541

  6. The development of learning material using learning cycle 5E model based stem to improve students’ learning outcomes in Thermochemistry

    Science.gov (United States)

    sugiarti, A. C.; suyatno, S.; Sanjaya, I. G. M.

    2018-04-01

    The objective of this study is describing the feasibility of Learning Cycle 5E STEM (Science, Technology, Engineering, and Mathematics) based learning material which is appropriate to improve students’ learning achievement in Thermochemistry. The study design used 4-D models and one group pretest-posttest design to obtain the information about the improvement of sudents’ learning outcomes. The subject was learning cycle 5E based STEM learning materials which the data were collected from 30 students of Science class at 11th Grade. The techniques used in this study were validation, observation, test, and questionnaire. Some result attain: (1) all the learning materials contents were valid, (2) the practicality and the effectiveness of all the learning materials contents were classified as good. The conclution of this study based on those three condition, the Learnig Cycle 5E based STEM learning materials is appropriate to improve students’ learning outcomes in studying Thermochemistry.

  7. Generation of induced Pluripotent Stem Cells as disease modelling of NLSDM.

    Science.gov (United States)

    Tavian, D; Missaglia, S; Castagnetta, M; Degiorgio, D; Pennisi, E M; Coleman, R A; Dell'Era, P; Mora, C; Angelini, C; Coviello, D A

    2017-05-01

    Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare defect of triacylglycerol metabolism, characterized by the abnormal storage of neutral lipid in organelles known as lipid droplets (LDs). The main clinical features are progressive myopathy and cardiomyopathy. The onset of NLSDM is caused by autosomal recessive mutations in the PNPLA2 gene, which encodes adipose triglyceride lipase (ATGL). Despite its name, this enzyme is present in a wide variety of cell types and catalyzes the first step in triacylglycerol lipolysis and the release of fatty acids. Here, we report the derivation of NLSDM-induced pluripotent stem cells (NLSDM-iPSCs) from fibroblasts of two patients carrying different PNPLA2 mutations. The first patient was homozygous for the c.541delAC, while the second was homozygous for the c.662G>C mutation in the PNPLA2 gene. We verified that the two types of NLSDM-iPSCs possessed properties of embryonic-like stem cells and could differentiate into the three germ layers in vitro. Immunofluorescence analysis revealed that iPSCs had an abnormal accumulation of triglycerides in LDs, the hallmark of NLSDM. Furthermore, NLSDM-iPSCs were deficient in long chain fatty acid lipolysis, when subjected to a pulse chase experiment with oleic acid. Collectively, these results demonstrate that NLSDM-iPSCs are a promising in vitro model to investigate disease mechanisms and screen drug compounds for NLSDM, a rare disease with few therapeutic options. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model.

    Science.gov (United States)

    Sygnecka, Katja; Heider, Andreas; Scherf, Nico; Alt, Rüdiger; Franke, Heike; Heine, Claudia

    2015-04-01

    Mesenchymal stem cells (MSCs) have been identified as promising candidates for neuroregenerative cell therapies. However, the impact of different isolation procedures on the functional and regenerative characteristics of MSC populations has not been studied thoroughly. To quantify these differences, we directly compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by fluorescence-activated cell sorting from bulk BM-cell suspensions. Both populations were analyzed with respect to functional readouts, that are, frequency of fibroblast colony forming units (CFU-f), general morphology, and expression of stem cell markers. The SL45-MSC population is characterized by greater morphological homogeneity, higher CFU-f frequency, and significantly increased nestin expression compared with bulk BM-MSCs. We further quantified the potential of both cell populations to enhance neuronal fiber growth, using an ex vivo model of organotypic brain slice co-cultures of the mesocortical dopaminergic projection system. The MSC populations were cultivated underneath the slice co-cultures without direct contact using a transwell system. After cultivation, the fiber density in the border region between the two brain slices was quantified. While both populations significantly enhanced fiber outgrowth as compared with controls, purified SL45-MSCs stimulated fiber growth to a larger degree. Subsequently, we analyzed the expression of different growth factors in both cell populations. The results show a significantly higher expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched for primary MSCs promote neuronal regeneration and axonal regrowth, more effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF secretion.

  9. Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology.

    Directory of Open Access Journals (Sweden)

    Shaomei Wang

    Full Text Available BACKGROUND: Retinitis pigmentosa (RP is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS rat, a well-established animal model for RP. METHODOLOGY/PRINCIPAL FINDINGS: Animals received syngeneic MSCs (1x10(6 cells by tail vein at an age before major photoreceptor loss. PRINCIPAL RESULTS: both rod and cone photoreceptors were preserved (5-6 cells thick at the time when control animal has a single layer of photoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs. CONCLUSIONS/SIGNIFICANCE: These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with minor discomfort

  10. Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

  11. Modeling stem increment in individual Pinus occidentalis Sw. trees in La Sierra, Dominican Republic

    Energy Technology Data Exchange (ETDEWEB)

    Bueno, S.; Bevilacqua, E.

    2010-07-01

    One of the most common and important tree characteristics used in forest management decision-making is tree diameter-at-breast height (DBH). This paper presents results on an evaluation of two growth functions developed to model stem diameter increases in individual Pinus occidentalis Sw. trees in La Sierra, Dominican Republic. The first model was developed in order to predict future DBH (FDM) at different intervals of time and the other for predicting growth, that is, periodic annual diameter increment (PADIM). Each model employed two statistical techniques for fitting model parameters: stepwise ordinary least squares (OLS) regression, and mixed models. The two statistical approaches varied in how they accounted for the repeated measurements on individual trees over time, affecting standard error estimates and statistical inference of model parameters. Each approach was evaluated based on six goodness of- fit statistics, using both calibration and validation data sets. The objectives were 1) to determine the best model for predicting future tree DBH; 2) to determine the best model for predicting periodic annual diameter increment, both models using tree size, age, site index and different indices of competitive status; and 3) compare which of these two modeling approaches predicts better the future DBH. OLS provided a better fit for both of the growth functions, especially in regards to bias. Both models showed advantages and disadvantages when they were used to predict growth and future diameter. For the prediction of future diameter with FDM, accuracy of predictions were within one centimeter for a five-year projection interval. The PADIM presented negligible bias in estimating future diameter, although there was a small increase in bias as time of prediction increased. As expected, each model was the best in estimating the response variable it was developed for.. However, a closer examination of the distribution of errors showed a slight advantage of the FDM

  12. "It's worth our time": a model of culturally and linguistically supportive professional development for K-12 STEM educators

    Science.gov (United States)

    Charity Hudley, Anne H.; Mallinson, Christine

    2017-09-01

    Professional development on issues of language and culture is often separate from professional development on issues related to STEM education, resulting in linguistic and cultural gaps in K-12 STEM pedagogy and practice. To address this issue, we have designed a model of professional development in which we work with educators to build cultural and linguistic competence and to disseminate information about how educators view the relevance of language, communication, and culture to STEM teaching and learning. We describe the design and facilitation of our model of culturally and linguistically responsive professional development, grounded in theories of multicultural education and culturally supportive teaching, through professional development workshops to 60 K-12 STEM educators from schools in Maryland and Virginia that serve African American students. Participants noted that culturally and linguistically responsive approaches had yet to permeate their K-12 STEM settings, which they identified as a critical challenge to effectively teaching and engaging African-American students. Based on pre-surveys, workshops were tailored to participants' stated needs for information on literacy (e.g., disciplinary literacies and discipline-specific jargon), cultural conflict and mismatch (e.g., student-teacher miscommunication), and linguistic bias in student assessment (e.g., test design). Educators shared feedback via post-workshop surveys, and a subset of 28 participants completed in-depth interviews and a focus group. Results indicate the need for further implementation of professional development such as ours that address linguistic and cultural issues, tailored for K-12 STEM educators. Although participants in this study enumerated several challenges to meeting this need, they also identified opportunities for collaborative solutions that draw upon teacher expertise and are integrated with curricula across content areas.

  13. Development of a model system to analyze chondrogenic differentiation of mesenchymal stem cells

    Science.gov (United States)

    Ruedel, Anke; Hofmeister, Simone; Bosserhoff, Anja-Katrin

    2013-01-01

    High-density cell culture is widely used for the analysis of cartilage development of human mesenchymal stem cells (HMSCs) in vitro. Several cell culture systems, as micromass, pellet culture and alginate culture, are applied by groups in the field to induce chondrogenic differentiation of HMSCs. A draw back of all model systems is the high amount of cells necessary for the experiments. Further, handling of large experimental approaches is difficult due to culturing e.g. in 15 ml tubes. Therefore, we aimed to develop a new model system based on “hanging drop” cultures using 10 to 100 fold less cells. Here, we demonstrate that differentiation of chondrogenic cells was induced as previously shown in other model systems. Real time RT-PCR analysis demonstrated that Collagen type II and MIA/CD-RAP were upregulated during culturing whereas for induction of hypertrophic markers like Collagen type X and AP-2 epsilon treatment with TGF beta was needed. To further test the system, siRNA against Sox9 was used and effects on chondrogenic gene expression were evaluated. In summary, the hanging drop culture system was determined to be a promising tool for in vitro chondrogenic studies. PMID:24294400

  14. Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model.

    Science.gov (United States)

    Dilli, Dilek; Kılıç, Emine; Yumuşak, Nihat; Beken, Serdar; Uçkan Çetinkaya, Duygu; Karabulut, Ramazan; Zenciroğlu, Ayşegu L

    2017-06-01

    In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd injection. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.

  15. A self-organized criticality model for plasma transport

    International Nuclear Information System (INIS)

    Carreras, B.A.; Newman, D.; Lynch, V.E.

    1996-01-01

    Many models of natural phenomena manifest the basic hypothesis of self-organized criticality (SOC). The SOC concept brings together the self-similarity on space and time scales that is common to many of these phenomena. The application of the SOC modelling concept to the plasma dynamics near marginal stability opens new possibilities of understanding issues such as Bohm scaling, profile consistency, broad band fluctuation spectra with universal characteristics and fast time scales. A model realization of self-organized criticality for plasma transport in a magnetic confinement device is presented. The model is based on subcritical resistive pressure-gradient-driven turbulence. Three-dimensional nonlinear calculations based on this model show the existence of transport under subcritical conditions. This model that includes fluctuation dynamics leads to results very similar to the running sandpile paradigm

  16. An Ising model for metal-organic frameworks

    Science.gov (United States)

    Höft, Nicolas; Horbach, Jürgen; Martín-Mayor, Victor; Seoane, Beatriz

    2017-08-01

    We present a three-dimensional Ising model where lines of equal spins are frozen such that they form an ordered framework structure. The frame spins impose an external field on the rest of the spins (active spins). We demonstrate that this "porous Ising model" can be seen as a minimal model for condensation transitions of gas molecules in metal-organic frameworks. Using Monte Carlo simulation techniques, we compare the phase behavior of a porous Ising model with that of a particle-based model for the condensation of methane (CH4) in the isoreticular metal-organic framework IRMOF-16. For both models, we find a line of first-order phase transitions that end in a critical point. We show that the critical behavior in both cases belongs to the 3D Ising universality class, in contrast to other phase transitions in confinement such as capillary condensation.

  17. Isolation of chicken embryonic stem cell and preparation of chicken chimeric model.

    Science.gov (United States)

    Zhang, Yani; Yang, Haiyan; Zhang, Zhentao; Shi, Qingqing; Wang, Dan; Zheng, Mengmeng; Li, Bichun; Song, Jiuzhou

    2013-03-01

    Chicken embryonic stem cells (ESCs) were separated from blastoderms at stage-X and cultured in vitro. Alkaline phosphatase activity and stage-specific embryonic antigen-1 staining was conducted to detect ESCs. Then, chicken ESCs were transfected with linearized plasmid pEGFP-N1 in order to produce chimeric chicken. Firstly, the optimal electrotransfection condition was compared; the results showed the highest transfection efficiency was obtained when the field strength and pulse duration was 280 V and 75 μs, respectively. Secondly, the hatchability of shedding methods, drilling a window at the blunt end of egg and drilling a window at the lateral shell of egg was compared, the results showed that the hatchability was the highest for drilling a window at the lateral shell of egg. Thirdly, the hatchability of microinjection (ESCs was microinjected into chick embryo cavity) was compared too, the results showed there were significant difference between the injection group transfected with ESCs and that of other two groups. In addition, five chimeric chickens were obtained in this study and EGFP gene was expressed in some organs, but only two chimeric chicken expressed EGFP gene in the gonad, indicating that the chimeric chicken could be obtained through chick embryo cavity injection by drilling a window at the lateral shell of egg.

  18. Regional Persistent Organic Pollutants' Environmental Impact Assessment and Control Model

    Directory of Open Access Journals (Sweden)

    Jurgis Staniskis

    2008-10-01

    Full Text Available The sources of formation, environmental distribution and fate of persistent organic pollutants (POPs are increasingly seen as topics to be addressed and solved at the global scale. Therefore, there are already two international agreements concerning persistent organic pollutants: the Protocol of 1998 to the 1979 Convention on the Long-Range Transboundary Air Pollution on Persistent Organic Pollutants (Aarhus Protocol; and the Stockholm Convention on Persistent Organic Pollutants. For the assessment of environmental pollution of POPs, for the risk assessment, for the evaluation of new pollutants as potential candidates to be included in the POPs list of the Stokholmo or/and Aarhus Protocol, a set of different models are developed or under development. Multimedia models help describe and understand environmental processes leading to global contamination through POPs and actual risk to the environment and human health. However, there is a lack of the tools based on a systematic and integrated approach to POPs management difficulties in the region.

  19. Faults self-organized by repeated earthquakes in a quasi-static antiplane crack model

    Directory of Open Access Journals (Sweden)

    D. Sornette

    1996-01-01

    Full Text Available We study a 2D quasi-static discrete crack anti-plane model of a tectonic plate with long range elastic forces and quenched disorder. The plate is driven at its border and the load is transferred to all elements through elastic forces. This model can be considered as belonging to the class of self-organized models which may exhibit spontaneous criticality, with four additional ingredients compared to sandpile models, namely quenched disorder, boundary driving, long range forces and fast time crack rules. In this 'crack' model, as in the 'dislocation' version previously studied, we find that the occurrence of repeated earthquakes organizes the activity on well-defined fault-like structures. In contrast with the 'dislocation' model, after a transient, the time evolution becomes periodic with run-aways ending each cycle. This stems from the 'crack' stress transfer rule preventing criticality to organize in favour of cyclic behaviour. For sufficiently large disorder and weak stress drop, these large events are preceded by a complex spacetime history of foreshock activity, characterized by a Gutenberg-Richter power law distribution with universal exponent B = 1±0.05. This is similar to a power law distribution of small nucleating droplets before the nucleation of the macroscopic phase in a first-order phase transition. For large disorder and large stress drop, and for certain specific initial disorder configurations, the stress field becomes frustrated in fast time: out-of-plane deformations (thrust and normal faulting and/or a genuine dynamics must be introduced to resolve this frustration.

  20. Modelization of tritium transfer into the organic compartments of algae

    International Nuclear Information System (INIS)

    Bonotto, S.; Gerber, G.B.; Arapis, G.; Kirchmann, R.

    1982-01-01

    Uptake of tritium oxide and its conversion into organic tritium was studied in four different types of algae with widely varying size and growth characteristics (Acetabularia acetabulum, Boergesenia forbesii, two strains of Chlamydomonas and Dunaliella bioculata). Water in the cell and the vacuales equilibrates rapidly with external tritium water. Tritium is actively incorporated into organically bound form as the organisms grow. During the stationary phase, incorporation of tritium is slow. There exists a discrimination against the incorporation of tritium into organically bound form. A model has been elaborated taking in account these different factors. It appears that transfer of organic tritium by algae growing near the sites of release would be significant only for actively growing algae. Algae growing slowly may, however, be useful as cumulative indicators of discontinuous tritium release. (author)

  1. MODELLING CONSUMERS' DEMAND FOR ORGANIC FOOD PRODUCTS: THE SWEDISH EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Manuchehr Irandoust

    2016-07-01

    Full Text Available This paper attempts to examine a few factors characterizing consumer preferences and behavior towards organic food products in the south of Sweden using a proportional odds model which captures the natural ordering of dependent variables and any inherent nonlinearities. The findings show that consumer's choice for organic food depends on perceived benefits of organic food (environment, health, and quality and consumer's perception and attitudes towards labelling system, message framing, and local origin. In addition, high willingness to pay and income level will increase the probability to buy organic food, while the cultural differences and socio-demographic characteristics have no effect on consumer behaviour and attitudes towards organic food products. Policy implications are offered.

  2. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2017-01-01

    Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

  3. Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering.

    Science.gov (United States)

    Lowenthal, Justin; Gerecht, Sharon

    2016-05-06

    Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine - including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering - have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Modeling cadmium in the feed chain and cattle organs

    OpenAIRE

    Fels-Klerx, van der, H.J.; Romkens, P.F.A.M.; Franz, E.; Raamsdonk, van, L.W.D.

    2011-01-01

    The objectives of this study were to estimate cadmium contamination levels in different scenarios related to soil characteristics and assumptions regarding cadmium accumulation in the animal tissues, using quantitative supply chain modeling. The model takes into account soil cadmium levels, soil pH, soil-to-plant transfer, animal consumption patterns, and transfer into animal organs (liver and kidneys). The model was applied to cattle up to the age of six years which were fed roughage (maize ...

  5. Lotka-Volterra competition models for sessile organisms.

    Science.gov (United States)

    Spencer, Matthew; Tanner, Jason E

    2008-04-01

    Markov models are widely used to describe the dynamics of communities of sessile organisms, because they are easily fitted to field data and provide a rich set of analytical tools. In typical ecological applications, at any point in time, each point in space is in one of a finite set of states (e.g., species, empty space). The models aim to describe the probabilities of transitions between states. In most Markov models for communities, these transition probabilities are assumed to be independent of state abundances. This assumption is often suspected to be false and is rarely justified explicitly. Here, we start with simple assumptions about the interactions among sessile organisms and derive a model in which transition probabilities depend on the abundance of destination states. This model is formulated in continuous time and is equivalent to a Lotka-Volterra competition model. We fit this model and a variety of alternatives in which transition probabilities do not depend on state abundances to a long-term coral reef data set. The Lotka-Volterra model describes the data much better than all models we consider other than a saturated model (a model with a separate parameter for each transition at each time interval, which by definition fits the data perfectly). Our approach provides a basis for further development of stochastic models of sessile communities, and many of the methods we use are relevant to other types of community. We discuss possible extensions to spatially explicit models.

  6. Bidirectional interconversion of stem and non-stem cancer cell populations: A reassessment of theoretical models for tumor heterogeneity

    NARCIS (Netherlands)

    van Neerven, Sanne M.; Tieken, Mathijs; Vermeulen, Louis; Bijlsma, Maarten F.

    2016-01-01

    Resolving the origin of intratumor heterogeneity has proven to be one of the central challenges in cancer research during recent years. Two theoretical models explaining the emergence of intratumor heterogeneity have come to dominate cancer biology literature: the clonal evolution model and the

  7. A Bridge to the Stars: A Model High School-to-College Pipeline for Encouraging Positive STEM Identities

    Science.gov (United States)

    McIntosh, Daniel H.; Jennings, Derrick H.

    2018-01-01

    The need to grow and diversify the STEM workforce remains a critical national challenge. Research shows that STEM identity (how one views herself/himself with respect to STEM) is an important factor for success or failure. A Bridge to the Stars (ABttS) offers URM and low-income high-school students a high impact exposure to science through innovative experiential learning with a professional scientist in freshmen astronomy at UMKC, an urban research university. Showing students who traditionally do not self-identify with high-tech careers that they can succeed in a university science course is a promising way to help build positive STEM identities and aspirations during the critical bridge between high school and college. In five years, we have awarded 45 ABttS scholarships; 93% of these 15-17 year-old students have passed the course satisfactorily with an average grade of 80%. Remarkably, the ABttS scholar performance is on par with that of 600 UMKC students enrolled in the same courses over 8 semesters. Long-term tracking of former scholars shows positive attitudes regarding ABttS and persistence in STEM aspirations at promising rates based on small-number statistics. I will describe the implementation of this unique STEM immersion program offering extended and inclusive engagement in astronomy, arguably the most accessible window to science. I will share classroom and near-peer mentoring innovations, and a new third ABttS tier in which previous scholars can enroll in a freshmen science laboratory experience for UMKC credit. This novel course introduces novices to scientific research and Big Data science through authentic hands-on experiences centered on their own exploration of data from McIntosh's actual research. The long-term mission of ABttS is to see urban educational institutions across the U.S. adopt similar pipelines in all STEM disciplines built on the ABttS model. Adopting programs like ABttS for freshmen STEM majors, especially in urban colleges and

  8. Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cell–collagen constructs: A three-dimensional in vitro model to study hematopoietic stem cell niche

    Directory of Open Access Journals (Sweden)

    WY Lai

    2013-10-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and osteoblasts are important niche cells for hematopoietic stem cells (HSCs in bone marrow osteoblastic niche. Here, we aim to partially reconstitute the bone marrow HSC niche in vitro using collagen microencapsulation for investigation of the interactions between HSCs and MSCs. Mouse MSCs (mMSCs microencapsulated in collagen were osteogenically differentiated to derive a bone-like matrix consisting of osteocalcin, osteopontin, and calcium deposits and secreted bone morphogenic protein 2 (BMP2. Decellularized bone-like matrix was seeded with fluorescence-labeled human MSCs and HSCs. Comparing with pure collagen scaffold, significantly more HSCs and HSC–MSC pairs per unit area were found in the decellularized bone-like matrix. Moreover, incubation with excess neutralizing antibody of BMP2 resulted in a significantly higher number of HSC per unit area than that without in the decellularized matrix. This work suggests that the osteogenic differentiated MSC–collagen microsphere is a valuable three-dimensional in vitro model to elucidate cell–cell and cell–matrix interactions in HSC niche.

  9. Modeling Temperature Dependent Singlet Exciton Dynamics in Multilayered Organic Nanofibers

    DEFF Research Database (Denmark)

    de Sousa, Leonardo Evaristo; de Oliveira Neto, Pedro Henrique; Kjelstrup-Hansen, Jakob

    2018-01-01

    Organic nanofibers have shown potential for application in optoelectronic devices because of the tunability of their optical properties. These properties are influenced by the electronic structure of the molecules that compose the nanofibers, but also by the behavior of the excitons generated...... dynamics in multilayered organic nanofibers. By simulating absorption and emission spectra, the possible Förster transitions are identified. Then, a Kinetic Monte Carlo (KMC) model is employed in combination with a genetic algorithm to theoretically reproduce time resolved photoluminescence measurements...

  10. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells

  11. Green Action through Education: A Model for Fostering Positive Attitudes about STEM

    Science.gov (United States)

    Wheland, Ethel R.; Donovan, William J.; Dukes, J. Thomas; Qammar, Helen K.; Smith, Gregory A.; Williams, Bonnie L.

    2013-01-01

    This paper describes an innovative collaboration between instructors of non-STEM (science, technology, engineering, and mathematics) courses and scientists who teach STEM courses in the GATE (Green Action Through Education) learning community. The scientists in this project presented engaging science--in such diverse locations as a sewage…

  12. The developing cancer stem-cell model: clinical challenges and opportunities

    NARCIS (Netherlands)

    Vermeulen, Louis; de Sousa E Melo, Felipe; Richel, Dick J.; Medema, Jan Paul

    2012-01-01

    During the past decade, a stem-cell-like subset of cancer cells has been identified in many malignancies. These cells, referred to as cancer stem cells (CSCs), are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population

  13. Single-cell and coupled GRN models of cell patterning in the Arabidopsis thaliana root stem cell niche

    Directory of Open Access Journals (Sweden)

    Alvarez-Buylla Elena R

    2010-10-01

    Full Text Available Abstract Background Recent experimental work has uncovered some of the genetic components required to maintain the Arabidopsis thaliana root stem cell niche (SCN and its structure. Two main pathways are involved. One pathway depends on the genes SHORTROOT and SCARECROW and the other depends on the PLETHORA genes, which have been proposed to constitute the auxin readouts. Recent evidence suggests that a regulatory circuit, composed of WOX5 and CLE40, also contributes to the SCN maintenance. Yet, we still do not understand how the niche is dynamically maintained and patterned or if the uncovered molecular components are sufficient to recover the observed gene expression configurations that characterize the cell types within the root SCN. Mathematical and computational tools have proven useful in understanding the dynamics of cell differentiation. Hence, to further explore root SCN patterning, we integrated available experimental data into dynamic Gene Regulatory Network (GRN models and addressed if these are sufficient to attain observed gene expression configurations in the root SCN in a robust and autonomous manner. Results We found that an SCN GRN model based only on experimental data did not reproduce the configurations observed within the root SCN. We developed several alternative GRN models that recover these expected stable gene configurations. Such models incorporate a few additional components and interactions in addition to those that have been uncovered. The recovered configurations are stable to perturbations, and the models are able to recover the observed gene expression profiles of almost all the mutants described so far. However, the robustness of the postulated GRNs is not as high as that of other previously studied networks. Conclusions These models are the first published approximations for a dynamic mechanism of the A. thaliana root SCN cellular pattering. Our model is useful to formally show that the data now available are not

  14. Electrochemical model of the polyaniline based organic memristive device

    International Nuclear Information System (INIS)

    Demin, V. A.; Erokhin, V. V.; Kashkarov, P. K.; Kovalchuk, M. V.

    2014-01-01

    The electrochemical organic memristive device with polyaniline active layer is a stand-alone device designed and realized for reproduction of some synapse properties in the innovative electronic circuits, including the neuromorphic networks capable for learning. In this work, a new theoretical model of the polyaniline memristive is presented. The developed model of organic memristive functioning was based on the detailed consideration of possible electrochemical processes occuring in the active zone of this device. Results of the calculation have demonstrated not only the qualitative explanation of the characteristics observed in the experiment but also the quantitative similarities of the resultant current values. It is shown how the memristive could behave at zero potential difference relative to the reference electrode. This improved model can establish a basis for the design and prediction of properties of more complicated circuits and systems (including stochastic ones) based on the organic memristive devices

  15. A model-independent view of the mature organization

    Energy Technology Data Exchange (ETDEWEB)

    Hanna, M.; Langston, D.

    1996-12-31

    Over the last 10 years, industry has been dealing with the issues of process and organizational maturity. This focus on process is driven by the success that manufacturing organizations have had implementing the management principles of W. Edwards Deming and Joseph M. Juran. The organizational-maturity focus is driven by organizations striving to be ISO 9000 compliant or to achieve a specific level on one of the maturity models. Unfortunately, each of the models takes a specific view into what is a very broad arena. That is to say, each model addresses only a specific subset of the characteristics of maturity. This paper attempts to extend beyond these specific views to answer the general question, What is a mature organization and its relationship to Quantitative management and statistical process control?

  16. The effect of cutting origin and organic plant growth regulator on the growth of Daun Ungu (Graptophyllum pictum) through stem cutting method

    Science.gov (United States)

    Pratama, S. P.; Yunus, A.; Purwanto, E.; Widyastuti, Y.

    2018-03-01

    Graptophyllum pictum is one of medical plants which has important chemical content to treat diseases. Leaf, bark and flower can be used to facilitate menstruation, treat hemorrhoid, constipation, ulcers, ulcers, swelling, and earache. G. pictum is difficult to propagated by seedling due to the long duration of seed formation, thusvegetative propagation is done by stem cutting. The aims of this study are to obtain optimum combination of cutting origin and organic plant growth regulator in various consentration for the growth of Daun Ungu through stem cutting method. This research was conducted at Research center for Medicinal Plant and Traditional DrugTanjungsari, Tegal Gede, Karanganyar in June to August 2016. Origin of cuttings and organic plant growth regulator were used as treatments factor. A completely randomized design (RAL) is used and data were analyzed by F test (ANOVA) with a confidence level of 95%. Any significant differences among treatment followed with Duncan test at a = 5%. The research indicates that longest root was resulted from the treatment of 0,5 ml/l of organic plant growth regulator. The treatment of 1 ml/l is able to increase the fresh and dry weight of root, treatment of 1,5 ml/l of organic plant growth regulator was able to increase the percentage of growing shoots. Treatment of base part as origin of cuttings increases the length, fresh weight and and dry weight of shoot, increase the number of leaves. Interaction treatment between 1 ml/l consentration of organic plant growth regulator and central part origin of cuttings is capable of increasing the leaf area, whereas treatment without organic plant growth regulator and base part as planting material affects the smallest leaf area.

  17. Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model.

    Science.gov (United States)

    Irons, Robin F; Cahill, Kevin W; Rattigan, Deviney A; Marcotte, Joseph H; Fromer, Marc W; Chang, Shaohua; Zhang, Ping; Behling, Eric M; Behling, Kathryn C; Caputo, Francis J

    2018-05-09

    The purpose of our study was to investigate the effect of adipose-derived stem cells (ASCs), endothelial-differentiated ASCs (EC/ASCs), and various conditioned media (CM) on wound healing in a diabetic swine model. We hypothesized that ASC-based therapies would accelerate wound healing. Diabetes was induced in four Yorkshire swine through intravenous injection of streptozotocin. ASCs were harvested from flank fat and cultured in either M199 or EGM-2 medium. A duplicate series of seven full-thickness dorsal wounds were surgically created on each swine. The wounds in the cellular treatment group underwent injection of low-dose or high-dose ASCs or EC/ASCs on day 0, with a repeat injection of one half of the initial dose on day 15. Wounds assigned to the topical CM therapy were covered with 2 mL of either serum-free M199 primed by ASCs or human umbilical vein endothelial cells every 3 days. Wounds were assessed at day 0, 10, 15, 20, and 28. The swine were sacrificed on day 28. ImageJ software was used to evaluate the percentage of wound healing. The wounded skin underwent histologic, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay examinations to evaluate markers of angiogenesis and inflammation. We found an increase in the percentage of wound closure rates in cell-based treatments and topical therapies at various points compared with the untreated control wounds (P swine model. Enhanced angiogenesis and immunomodulation might be key contributors to this process. The purpose of the present study was to translate the known beneficial effects of adipose-derived stem cells and associated conditioned medium therapy on diabetic wound healing to a large animal model. We demonstrated that stem cell and conditioned medium therapy significantly accelerate gross wound healing in diabetic swine, with data suggesting this might result from a decreased inflammatory response and increased angiogenesis. Copyright © 2018 Society for

  18. Stability and bifurcation in a model for the dynamics of stem-like cells in leukemia under treatment

    Science.gov (United States)

    Rǎdulescu, I. R.; Cândea, D.; Halanay, A.

    2012-11-01

    A mathematical model for the dynamics of leukemic cells during treatment is introduced. Delay differential equations are used to model cells' evolution and are based on the Mackey-Glass approach, incorporating Goldie-Coldman law. Since resistance is propagated by cells that have the capacity of self-renewal, a population of stem-like cells is studied. Equilibrium points are calculated and their stability properties are investigated.

  19. Directed midbrain and spinal cord neurogenesis from pluripotent stem cells to model development and disease in a dish.

    Science.gov (United States)

    Allodi, Ilary; Hedlund, Eva

    2014-01-01

    Induction of specific neuronal fates is restricted in time and space in the developing CNS through integration of extrinsic morphogen signals and intrinsic determinants. Morphogens impose regional characteristics on neural progenitors and establish distinct progenitor domains. Such domains are defined by unique expression patterns of fate determining transcription factors. These processes of neuronal fate specification can be recapitulated in vitro using pluripotent stem cells. In this review, we focus on the generation of dopamine neurons and motor neurons, which are induced at ventral positions of the neural tube through Sonic hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of these morphogenic signals typically results in the generation of multiple neuronal cell types, which are defined at the intersection of these signals. If the purpose of in vitro neurogenesis is to generate one cell type only, further lineage restriction can be accomplished by forced expression of specific transcription factors in a permissive environment. Alternatively, cell-sorting strategies allow for selection of neuronal progenitors or mature neurons. However, modeling development, disease and prospective therapies in a dish could benefit from structured heterogeneity, where desired neurons are appropriately synaptically connected and thus better reflect the three-dimensional structure of that region. By modulating the extrinsic environment to direct sequential generation of neural progenitors within a domain, followed by self-organization and synaptic establishment, a reductionist model of that brain region could be created. Here we review recent advances in neuronal fate induction in vitro, with a focus on the interplay between cell intrinsic and extrinsic factors, and discuss the implications for studying development and disease in a dish.

  20. Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

    Directory of Open Access Journals (Sweden)

    Gayathri Subramanian

    2017-01-01

    Full Text Available Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

  1. Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds.

    Science.gov (United States)

    Subramanian, Gayathri; Stasuk, Alexander; Elsaadany, Mostafa; Yildirim-Ayan, Eda

    2017-01-01

    Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

  2. Ancestral trees for modeling stem cell lineages genetically rather than functionally: understanding mutation accumulation and distinguishing the restrictive cancer stem cell propagation theory and the unrestricted cell propagation theory of human tumorigenesis.

    Science.gov (United States)

    Shibata, Darryl K; Kern, Scott E

    2008-01-01

    Cancer stem cells either could be rare or common in tumors, constituting the major distinction between the two fundamentally opposed theoretical models of tumor progression: A newer and restrictive stem cell propagation model, in which the stem cells are a small and special minority of the tumor cells, and a standard older model, an unrestricted cell proliferation theory, in which many or most tumor cells are capable of indefinite generations of cell division. Stem cells of tumors are difficult to quantitate using functional assays, and the validity of the most common assays is seriously questioned. Nonetheless, stem cells are an essential component of any tumorigenesis model. Alternative approaches to studying tumor stem cells should be explored. Cell populations can be conceived of as having a genealogy, a relationship of cells to their ancestral lineage, from the zygote to the adult cells or neoplasms. Models using ancestral trees thus offer an anatomic and genetic means to "observe" stem cells independent of artificial conditions. Ancestral trees broaden our attention backward along a lineage, to the zygote stage, and thereby add insight into how the mutations of tumors accumulate. It is possible that a large fraction of mutations in a tumor originate from normal, endogenous, replication errors (nearly all being passenger mutations) occurring prior to the emergence of the first transformed cell. Trees can be constructed from experimental measurements - molecular clocks - of real human tissues and tumors. Detailed analysis of single-cell methylation patterns, heritable yet slightly plastic, now can provide this information in the necessary depth. Trees based on observations of molecular clocks may help us to distinguish between competing theories regarding the proliferative properties among cells of actual human tumors, to observe subtle and difficult phenomena such as the extinction of stem lineages, and to address the origins and rates of mutations in various

  3. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

    Science.gov (United States)

    Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

    2011-08-01

    Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

    Science.gov (United States)

    Almeida, Sandra; Zhang, Zhijun; Coppola, Giovanni; Mao, Wenjie; Futai, Kensuke; Karydas, Anna; Geschwind, Michael D.; Tartaglia, M. Carmela; Gao, Fuying; Gianni, Davide; Sena-Esteves, Miguel; Geschwind, Daniel H.; Miller, Bruce L.; Farese, Robert V.; Gao, Fen-Biao

    2012-01-01

    SUMMARY The pathogenic mechanisms of frontotemporal dementia (FTD) remain poorly understood. Here we generated multiple induced pluripotent stem cell (iPSC) lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel GRN mutation (PGRN S116X). In neurons and microglia differentiated from PGRN S116X iPSCs, the levels of intracellular and secreted progranulin were reduced, establishing patient-specific cellular models of progranulin haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the PI3K and MAPK pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by progranulin expression. Our findings identify cell-autonomous, reversible defects in patient neurons with progranulin deficiency and provide a new model for studying progranulin-dependent pathogenic mechanisms and testing potential therapies. PMID:23063362

  5. Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

    Directory of Open Access Journals (Sweden)

    Malihe Nakhaeifard

    2016-02-01

    Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

  6. Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

    Science.gov (United States)

    Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

    2017-05-01

    Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Comparison of ultramicrotomy and focused-ion-beam for the preparation of TEM and STEM cross section of organic solar cells

    DEFF Research Database (Denmark)

    Corazza, Michael; Simonsen, Søren Bredmose; Gnaegi, Helmut

    2016-01-01

    The challenge of preparing cross sections of organic photovoltaics (OPV) suitable for transmission electron microscopy (TEM) and scanning TEM (STEM) is addressed. The samples were polymer solar cells fabricated using roll-to-roll (R2R) processing methods on a flexible polyethylene terephthalate...... resolution, enabling further studies of phase separation of P3HT:PCBM by means of energy filtered TEM (EFTEM). The sample prepared by FIB shows good structure preservation, but reduced resolution due to non-optimal thicknesses achieved after treatment. Degradation studies of samples prepared...

  8. Molecular analysis of the replication program in unicellular model organisms.

    Science.gov (United States)

    Raghuraman, M K; Brewer, Bonita J

    2010-01-01

    Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program of replication in particular. But what exactly is a temporal program of replication, and how might it arise? In this article, we explore this question, drawing again on the wealth of experimental information in unicellular model organisms.

  9. Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.

    Science.gov (United States)

    Gener, Petra; Gouveia, Luis Pleno; Sabat, Guillem Romero; de Sousa Rafael, Diana Fernandes; Fort, Núria Bergadà; Arranja, Alexandra; Fernández, Yolanda; Prieto, Rafael Miñana; Ortega, Joan Sayos; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2015-11-01

    To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[(d,l-lactide-co-glycolide)-co-PEG] (PLGA-co-PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

    Science.gov (United States)

    Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

    2018-03-01

    Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

  11. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.

    Directory of Open Access Journals (Sweden)

    Jan Tønnesen

    Full Text Available Intrastriatal grafts of stem cell-derived dopamine (DA neurons induce behavioral recovery in animal models of Parkinson's disease (PD, but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2 and halorhodopsin (NpHR, respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.

  12. Collaborative Testing as a Model for Addressing Equity in Student Success in STEM Classes

    Science.gov (United States)

    Dileonardo, C.; James, B. R.

    2016-12-01

    Introductory Earth science classes at two-year colleges play a critical role as "gateway courses" for underrepresented student populations into undergraduate STEM programs. Students entering college underprepared in math and science typically receive their only exposure to science at the undergraduate level in introductory courses in the Earth and space sciences. In many colleges a huge disparity exists in these classes between success rates amongst students from groups traditionally represented in the STEM fields and those from underrepresented populations. Closing the equity gap in success in these courses is a major focus of many pilot projects nationally. This concern has also led to the adoption of new teaching and learning practices, based on research in learning, in introductory Earth science pedagogy. Models of teaching practices including greater engagement, active learning approaches, and collaborative learning structures seem to help with student achievement in introductory courses. But, whereas these practices might increase overall student success they have not proven to close the equity gap in achievement. De Anza a two-year college in the San Francisco bay area has a long history in the geology department of incorporating and testing teaching practices developed out of research in learning. Collaborative learning has infused every aspect of our learning approaches in the Earth sciences, including laboratory, fieldwork, and test preparation. Though these approaches seemed to have educational benefit the huge equity gap department-wide persisted between targeted and non-targeted populations. Three years ago collaborative testing models were introduced into our geology and meteorology classes. The mechanism included methods for directly comparing collaborative to individual testing. The net result was that targeted populations including African Americans, Latinos, and Filipinos increased steadily at around 3.5% per year from 66% to 73%. The overall

  13. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Maaike eHoekstra

    2012-08-01

    Full Text Available Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially characterized.Human iPSC (hiPSC models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these

  14. Modeling insertional mutagenesis using gene length and expression in murine embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Alex S Nord

    2007-07-01

    Full Text Available High-throughput mutagenesis of the mammalian genome is a powerful means to facilitate analysis of gene function. Gene trapping in embryonic stem cells (ESCs is the most widely used form of insertional mutagenesis in mammals. However, the rules governing its efficiency are not fully understood, and the effects of vector design on the likelihood of gene-trapping events have not been tested on a genome-wide scale.In this study, we used public gene-trap data to model gene-trap likelihood. Using the association of gene length and gene expression with gene-trap likelihood, we constructed spline-based regression models that characterize which genes are susceptible and which genes are resistant to gene-trapping techniques. We report results for three classes of gene-trap vectors, showing that both length and expression are significant determinants of trap likelihood for all vectors. Using our models, we also quantitatively identified hotspots of gene-trap activity, which represent loci where the high likelihood of vector insertion is controlled by factors other than length and expression. These formalized statistical models describe a high proportion of the variance in the likelihood of a gene being trapped by expression-dependent vectors and a lower, but still significant, proportion of the variance for vectors that are predicted to be independent of endogenous gene expression.The findings of significant expression and length effects reported here further the understanding of the determinants of vector insertion. Results from this analysis can be applied to help identify other important determinants of this important biological phenomenon and could assist planning of large-scale mutagenesis efforts.

  15. "It's Worth Our Time": A Model of Culturally and Linguistically Supportive Professional Development for K-12 STEM Educators

    Science.gov (United States)

    Hudley, Anne H. Charity; Mallinson, Christine

    2017-01-01

    Professional development on issues of language and culture is often separate from professional development on issues related to STEM education, resulting in linguistic and cultural gaps in K-12 STEM pedagogy and practice. To address this issue, we have designed a model of professional development in which we work with educators to build cultural…

  16. Evaluation of expansile nanoparticle tumor localization and efficacy in a cancer stem cell-derived model of pancreatic peritoneal carcinomatosis

    Science.gov (United States)

    Herrera, Victoria LM; Colby, Aaron H; Tan, Glaiza AL; Moran, Ann M; O’Brien, Michael J; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W

    2016-01-01

    Aim: To evaluate the tumor localization and efficacy pH-responsive expansile nanoparticles (eNPs) as a drug delivery system for pancreatic peritoneal carcinomatosis (PPC) modeled in nude rats. Methods & materials: A Panc-1-cancer stem cell xeno1graft model of PPC was validated in vitro and in vivo. Tumor localization was tracked via in situ imaging of fluorescent eNPs. Survival of animals treated with paclitaxel-loaded eNPs (PTX-eNPs) was evaluated in vivo. Results: The Panc-1-cancer stem cell xenograft model recapitulates significant features of PPC. Rhodamine-labeled eNPs demonstrate tumor-specific, dose- and time-dependent localization to macro- and microscopic tumors following intraperitoneal injection. PTX-eNPs are as effective as free PTX in treating established PPC; but, PTX-eNPs result in fewer side effects. Conclusion: eNPs are a promising tool for the detection and treatment of PPC. PMID:27078118

  17. Development of model for analysing respective collections of intended hematopoietic stem cells and harvests of unintended mature cells in apheresis for autologous hematopoietic stem cell collection.

    Science.gov (United States)

    Hequet, O; Le, Q H; Rodriguez, J; Dubost, P; Revesz, D; Clerc, A; Rigal, D; Salles, G; Coiffier, B

    2014-04-01

    Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (pcollections and harvests, which showed that only pre-leukapheresis blood levels (CD34+cells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (pcollections and mature unintended cells harvests (pcollections or unintended mature cell harvests were pre-leukapheresis blood cell levels. Our model was meant to assist apheresis teams in analysing shares of HSC collected and mature cells harvested with new devices or with new types of HSC mobilization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Self-organized Criticality Model for Ocean Internal Waves

    International Nuclear Information System (INIS)

    Wang Gang; Hou Yijun; Lin Min; Qiao Fangli

    2009-01-01

    In this paper, we present a simple spring-block model for ocean internal waves based on the self-organized criticality (SOC). The oscillations of the water blocks in the model display power-law behavior with an exponent of -2 in the frequency domain, which is similar to the current and sea water temperature spectra in the actual ocean and the universal Garrett and Munk deep ocean internal wave model [Geophysical Fluid Dynamics 2 (1972) 225; J. Geophys. Res. 80 (1975) 291]. The influence of the ratio of the driving force to the spring coefficient to SOC behaviors in the model is also discussed. (general)

  19. Device model investigation of bilayer organic light emitting diodes

    International Nuclear Information System (INIS)

    Crone, B. K.; Davids, P. S.; Campbell, I. H.; Smith, D. L.

    2000-01-01

    Organic materials that have desirable luminescence properties, such as a favorable emission spectrum and high luminescence efficiency, are not necessarily suitable for single layer organic light-emitting diodes (LEDs) because the material may have unequal carrier mobilities or contact limited injection properties. As a result, single layer LEDs made from such organic materials are inefficient. In this article, we present device model calculations of single layer and bilayer organic LED characteristics that demonstrate the improvements in device performance that can occur in bilayer devices. We first consider an organic material where the mobilities of the electrons and holes are significantly different. The role of the bilayer structure in this case is to move the recombination away from the electrode that injects the low mobility carrier. We then consider an organic material with equal electron and hole mobilities but where it is not possible to make a good contact for one carrier type, say electrons. The role of a bilayer structure in this case is to prevent the holes from traversing the device without recombining. In both cases, single layer device limitations can be overcome by employing a two organic layer structure. The results are discussed using the calculated spatial variation of the carrier densities, electric field, and recombination rate density in the structures. (c) 2000 American Institute of Physics

  20. Green Algae as Model Organisms for Biological Fluid Dynamics

    Science.gov (United States)

    Goldstein, Raymond E.

    2015-01-01

    In the past decade, the volvocine green algae, spanning from the unicellular Chlamydomonas to multicellular Volvox, have emerged as model organisms for a number of problems in biological fluid dynamics. These include flagellar propulsion, nutrient uptake by swimming organisms, hydrodynamic interactions mediated by walls, collective dynamics and transport within suspensions of microswimmers, the mechanism of phototaxis, and the stochastic dynamics of flagellar synchronization. Green algae are well suited to the study of such problems because of their range of sizes (from 10 μm to several millimeters), their geometric regularity, the ease with which they can be cultured, and the availability of many mutants that allow for connections between molecular details and organism-level behavior. This review summarizes these recent developments and highlights promising future directions in the study of biological fluid dynamics, especially in the context of evolutionary biology, that can take advantage of these remarkable organisms.

  1. There Is No Simple Model of the Plasma Membrane Organization

    Science.gov (United States)

    Bernardino de la Serna, Jorge; Schütz, Gerhard J.; Eggeling, Christian; Cebecauer, Marek

    2016-01-01

    Ever since technologies enabled the characterization of eukaryotic plasma membranes, heterogeneities in the distributions of its constituents were observed. Over the years this led to the proposal of various models describing the plasma membrane organization such as lipid shells, picket-and-fences, lipid rafts, or protein islands, as addressed in numerous publications and reviews. Instead of emphasizing on one model we in this review give a brief overview over current models and highlight how current experimental work in one or the other way do not support the existence of a single overarching model. Instead, we highlight the vast variety of membrane properties and components, their influences and impacts. We believe that highlighting such controversial discoveries will stimulate unbiased research on plasma membrane organization and functionality, leading to a better understanding of this essential cellular structure. PMID:27747212

  2. Study of bone remodeling of two models of femoral cementless stems by means of DEXA and finite elements

    Directory of Open Access Journals (Sweden)

    López-Prats Fernando

    2010-05-01

    Full Text Available Abstract Background A hip replacement with a cemented or cementless femoral stem produces an effect on the bone called adaptive remodelling, attributable to mechanical and biological factors. All of the cementless prostheses designs try to achieve an optimal load transfer in order to avoid stress-shielding, which produces an osteopenia. Long-term densitometric studies taken after implanting ABG-I and ABG-II stems confirm that the changes made to the design and alloy of the ABG-II stem help produce less proximal atrophy of the femur. The simulation with FE allowed us to study the biomechanical behaviour of two stems. The aim of this study was, if possible, to correlate the biological and mechanical findings. Methods Both models with prostheses ABG-I and II have been simulated in five different moments of time which coincide with the DEXA measurements: postoperative, 6 months, 1, 3 and 5 years, in addition to the healthy femur as the initial reference. For the complete comparative analysis of both stems, all of the possible combinations of bone mass (group I and group II of pacients in two controlled studies for ABG-I and II stems, respectively, prosthetic geometry (ABG-I and ABG-II and stem material (Wrought Titanium or TMZF were simulated. Results and Discussion In both groups of bone mass an increase of stress in the area of the cancellous bone is produced, which coincides with the end of the HA coating, as a consequence of the bottleneck effect which is produced in the transmission of loads, and corresponds to Gruen zones 2 and 6, where no osteopenia can be seen in contrast to zones 1 and 7. Conclusions In this study it is shown that the ABG-II stem is more effective than the ABG-I given that it generates higher tensional values on the bone, due to which proximal bone atrophy diminishes. This biomechanical behaviour with an improved transmission of loads confirmed by means of FE simulation corresponds to the biological findings obtained with

  3. Gene Transfer Properties and Structural Modeling of Human Stem Cell-derived AAV

    OpenAIRE

    Smith, Laura J; Ul-Hasan, Taihra; Carvaines, Sarah K; Van Vliet, Kim; Yang, Ethel; Wong, Kamehameha K; Agbandje-McKenna, Mavis; Chatterjee, Saswati

    2014-01-01

    Adeno-associated virus (AAV) vectors are proving to be remarkably successful for in vivo gene delivery. Based upon reports of abundant AAV in the human marrow, we tested CD34+ hematopoietic stem cells for the presence of natural AAV. Here, we report for the first time, the presence of novel AAV variants in healthy CD34+ human peripheral blood stem cells. The majority of healthy peripheral blood stem cell donors were found to harbor AAV in their CD34+ cells. Every AAV isolated from CD34+ cells...

  4. An Ontology for Modeling Complex Inter-relational Organizations

    Science.gov (United States)

    Wautelet, Yves; Neysen, Nicolas; Kolp, Manuel

    This paper presents an ontology for organizational modeling through multiple complementary aspects. The primary goal of the ontology is to dispose of an adequate set of related concepts for studying complex organizations involved in a lot of relationships at the same time. In this paper, we define complex organizations as networked organizations involved in a market eco-system that are playing several roles simultaneously. In such a context, traditional approaches focus on the macro analytic level of transactions; this is supplemented here with a micro analytic study of the actors' rationale. At first, the paper overviews enterprise ontologies literature to position our proposal and exposes its contributions and limitations. The ontology is then brought to an advanced level of formalization: a meta-model in the form of a UML class diagram allows to overview the ontology concepts and their relationships which are formally defined. Finally, the paper presents the case study on which the ontology has been validated.

  5. Zebrabase: An intuitive tracking solution for aquatic model organisms

    OpenAIRE

    Oltova, Jana; Bartunek, Petr; Machonova, Olga; Svoboda, Ondrej; Skuta, Ctibor; Jindrich, Jindrich

    2018-01-01

    Small fish species, like zebrafish or medaka, are constantly gaining popularity in basic research and disease modeling as a useful alternative to rodent model organisms. However, the tracking options for fish within a facility are rather limited. Here, we present an aquatic species tracking database, Zebrabase, developed in our zebrafish research and breeding facility that represents a practical and scalable solution and an intuitive platform for scientists, fish managers and caretakers, in b...

  6. A model of virtual organization for corporate visibility and ...

    African Journals Online (AJOL)

    This paper considers the existing numerous research in business, Information and Communication Technology (ICT), examines a theoretical framework for value creation in a virtual world. Following a proposed model, a new strategic paradigm is created for corporate value; and virtual organization (VO) apply the use of ...

  7. Modeling of the transient mobility in disordered organic semiconductors

    NARCIS (Netherlands)

    Germs, W.C.; Van der Holst, J.M.M.; Van Mensfoort, S.L.M.; Bobbert, P.A.; Coehoorn, R.

    2011-01-01

    In non-steady-state experiments, the electrical response of devicesbased on disordered organic semiconductors often shows a large transient contribution due to relaxation of the out-of-equilibrium charge-carrier distribution. We have developed a model describing this process, based only on the

  8. An Integrated Model for Effective Knowledge Management in Chinese Organizations

    Science.gov (United States)

    An, Xiaomi; Deng, Hepu; Wang, Yiwen; Chao, Lemen

    2013-01-01

    Purpose: The purpose of this paper is to provide organizations in the Chinese cultural context with a conceptual model for an integrated adoption of existing knowledge management (KM) methods and to improve the effectiveness of their KM activities. Design/methodology/approaches: A comparative analysis is conducted between China and the western…

  9. Waste Reduction Model (WARM) Resources for Small Businesses and Organizations

    Science.gov (United States)

    This page provides a brief overview of how EPA’s Waste Reduction Model (WARM) can be used by small businesses and organizations. The page includes a brief summary of uses of WARM for the audience and links to other resources.

  10. SOMPROF: A vertically explicit soil organic matter model

    NARCIS (Netherlands)

    Braakhekke, M.C.; Beer, M.; Hoosbeek, M.R.; Kruijt, B.; Kabat, P.

    2011-01-01

    Most current soil organic matter (SOM) models represent the soil as a bulk without specification of the vertical distribution of SOM in the soil profile. However, the vertical SOM profile may be of great importance for soil carbon cycling, both on short (hours to years) time scale, due to

  11. Modeling growth of specific spoilage organisms in tilapia ...

    African Journals Online (AJOL)

    Tilapia is an important aquatic fish, but severe spoilage of tilapia is most likely related to the global aquaculture. The spoilage is mostly caused by specific spoilage organisms (SSO). Therefore, it is very important to use microbial models to predict the growth of SSO in tilapia. This study firstly verified Pseudomonas and Vibrio ...

  12. There Is No Simple Model of the Plasma Membrane Organization

    Czech Academy of Sciences Publication Activity Database

    de la serna, J. B.; Schütz, G.; Eggeling, Ch.; Cebecauer, Marek

    2016-01-01

    Roč. 4, SEP 2016 (2016), 106 ISSN 2296-634X R&D Projects: GA ČR GA15-06989S Institutional support: RVO:61388955 Keywords : plasma membrane * membrane organization models * heterogeneous distribution Subject RIV: CF - Physical ; Theoretical Chemistry

  13. The Biological Diversity and Production of Volatile Organic Compounds by Stem-Inhabiting Endophytic Fungi of Ecuador

    OpenAIRE

    Rundell, Susan; Spakowicz, Daniel; Narváez-Trujillo, Alexandra; Strobel, Scott

    2015-01-01

    Fungal endophytes colonize every major lineage of land plants without causing apparent harm to their hosts. Despite their production of interesting and potentially novel compounds, endophytes—particularly those inhabiting stem tissues—are still a vastly underexplored component of microbial diversity. In this study, we explored the diversity of over 1500 fungal endophyte isolates collected from three Ecuadorian ecosystems: lowland tropical forest, cloud forest, and coastal dry forest. We sough...

  14. Scaffold composition affects cytoskeleton organization, cell-matrix interaction and the cellular fate of human mesenchymal stem cells upon chondrogenic differentiation.

    Science.gov (United States)

    Li, Yuk Yin; Choy, Tze Hang; Ho, Fu Chak; Chan, Pui Barbara

    2015-06-01

    The stem cell niche, or microenvironment, consists of soluble, matrix, cell and mechanical factors that together determine the cellular fates and/or differentiation patterns of stem cells. Collagen and glycosaminoglycans (GAGs) are important scaffolding materials that can mimic the natural matrix niche. Here, we hypothesize that imposing changes in the scaffold composition or, more specifically, incorporating GAGs into the collagen meshwork, will affect the morphology, cytoskeletal organization and integrin expression profiles, and hence the fate of human mesenchymal stem cells (MSCs) upon the induction of differentiation. Using chondrogenesis as an example, we microencapsulated MSCs in three scaffold systems that had varying matrix compositions: collagen alone (C), aminated collagen (AC) and aminated collagen with GAGs (ACG). We then induced the MSCs to differentiate toward a chondrogenic lineage, after which, we characterized the cell viability and morphology, as well as the level of cytoskeletal organization and the integrin expression profile. We also studied the fate of the MSCs by evaluating the major chondrogenic markers at both the gene and protein level. In C, MSC chondrogenesis was successfully induced and MSCs that spread in the scaffolds had a clear actin cytoskeleton; they expressed integrin α2β1, α5 and αv; promoted sox9 nuclear localization transcription activation; and upregulated the expression of chondrogenic matrix markers. In AC, MSC chondrogenesis was completely inhibited but the scaffold still supported cell survival. The MSCs did not spread and they had no actin cytoskeleton; did not express integrin α2 or αv; they failed to differentiate into chondrogenic lineage cells even on chemical induction; and there was little colocalization or functional interaction between integrin α5 and fibronectin. In ACG, although the MSCs did not express integrin α2, they did express integrin αv and there was strong co-localization and hence functional

  15. The Metadistrict as the Territorial Strategy: From Set Theory and a Matrix Organization Model Hypothesis

    Directory of Open Access Journals (Sweden)

    Francesco Contò

    2012-06-01

    Full Text Available The purpose of this proposal is to explore a new concept of 'Metadistrict' to be applied in a region of Southern Italy – Apulia ‐ in order to analyze the impact that the activation of a special network between different sector chains and several integrated projects may have for revitalizing the local economy; an important role is assigned to the network of relationships and so to the social capital. The Metadistrict model stems from the Local Action Groups and the Integrated Projects of Food Chain frameworks. It may represent a crucial driver of the rural economy through the realization of sector circuits connected to the concept of multi‐functionality in agriculture, that is Network of the Territorial Multi‐functionality. It was formalized by making use of a set of theories and of a Matrix Organization Model. The adoption of the Metadistrict perspective as the territorial strategy may play a key role to revitalize the primary sector, through the increase of economic and productive opportunities due to the implementation of a common and shared strategy and organization.

  16. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models

    Science.gov (United States)

    Shin, Jin Young; Park, Hyun Jung; Kim, Ha Na; Oh, Se Hee; Bae, Jae-Sung; Ha, Hee-Jin; Lee, Phil Hyu

    2014-01-01

    Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment. PMID:24149893

  17. Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells.

    Directory of Open Access Journals (Sweden)

    Heather E Wheeler

    Full Text Available There are no effective agents to prevent or treat chemotherapy-induced peripheral neuropathy (CIPN, the most common non-hematologic toxicity of chemotherapy. Therefore, we sought to evaluate the utility of human neuron-like cells derived from induced pluripotent stem cells (iPSCs as a means to study CIPN. We used high content imaging measurements of neurite outgrowth phenotypes to compare the changes that occur to iPSC-derived neuronal cells among drugs and among individuals in response to several classes of chemotherapeutics. Upon treatment of these neuronal cells with the neurotoxic drug paclitaxel, vincristine or cisplatin, we identified significant differences in five morphological phenotypes among drugs, including total outgrowth, mean/median/maximum process length, and mean outgrowth intensity (P < 0.05. The differences in damage among drugs reflect differences in their mechanisms of action and clinical CIPN manifestations. We show the potential of the model for gene perturbation studies by demonstrating decreased expression of TUBB2A results in significantly increased sensitivity of neurons to paclitaxel (0.23 ± 0.06 decrease in total neurite outgrowth, P = 0.011. The variance in several neurite outgrowth and apoptotic phenotypes upon treatment with one of the neurotoxic drugs is significantly greater between than within neurons derived from four different individuals (P < 0.05, demonstrating the potential of iPSC-derived neurons as a genetically diverse model for CIPN. The human neuron model will allow both for mechanistic studies of specific genes and genetic variants discovered in clinical studies and for screening of new drugs to prevent or treat CIPN.

  18. High Resolution Modelling of the Congo River's Multi-Threaded Main Stem Hydraulics

    Science.gov (United States)

    Carr, A. B.; Trigg, M.; Tshimanga, R.; Neal, J. C.; Borman, D.; Smith, M. W.; Bola, G.; Kabuya, P.; Mushie, C. A.; Tschumbu, C. L.

    2017-12-01

    We present the results of a summer 2017 field campaign by members of the Congo River users Hydraulics and Morphology (CRuHM) project, and a subsequent reach-scale hydraulic modelling study on the Congo's main stem. Sonar bathymetry, ADCP transects, and water surface elevation data have been collected along the Congo's heavily multi-threaded middle reach, which exhibits complex in-channel hydraulic processes that are not well understood. To model the entire basin's hydrodynamics, these in-channel hydraulic processes must be parameterised since it is not computationally feasible to represent them explicitly. Furthermore, recent research suggests that relative to other large global rivers, in-channel flows on the Congo represent a relatively large proportion of total flow through the river-floodplain system. We therefore regard sufficient representation of in-channel hydraulic processes as a Congo River hydrodynamic research priority. To enable explicit representation of in-channel hydraulics, we develop a reach-scale (70 km), high resolution hydraulic model. Simulation of flow through individual channel threads provides new information on flow depths and velocities, and will be used to inform the parameterisation of a broader basin-scale hydrodynamic model. The basin-scale model will ultimately be used to investigate floodplain fluxes, flood wave attenuation, and the impact of future hydrological change scenarios on basin hydrodynamics. This presentation will focus on the methodology we use to develop a reach-scale bathymetric DEM. The bathymetry of only a small proportion of channel threads can realistically be captured, necessitating some estimation of the bathymetry of channels not surveyed. We explore different approaches to this bathymetry estimation, and the extent to which it influences hydraulic model predictions. The CRuHM project is a consortium comprising the Universities of Kinshasa, Rhodes, Dar es Salaam, Bristol, and Leeds, and is funded by Royal

  19. Lamination of organic solar cells and organic light emitting devices: Models and experiments

    International Nuclear Information System (INIS)

    Oyewole, O. K.; Yu, D.; Du, J.; Asare, J.; Fashina, A.; Anye, V. C.; Zebaze Kana, M. G.; Soboyejo, W. O.

    2015-01-01

    In this paper, a combined experimental, computational, and analytical approach is used to provide new insights into the lamination of organic solar cells and light emitting devices at macro- and micro-scales. First, the effects of applied lamination force (on contact between the laminated layers) are studied. The crack driving forces associated with the interfacial cracks (at the bi-material interfaces) are estimated along with the critical interfacial crack driving forces associated with the separation of thin films, after layer transfer. The conditions for successful lamination are predicted using a combination of experiments and computational models. Guidelines are developed for the lamination of low-cost organic electronic structures

  20. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors

    NARCIS (Netherlands)

    Sottoriva, Andrea; Vermeulen, Louis; Tavaré, Simon

    2011-01-01

    The cancer stem cell (CSC) concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data

  1. Application of human induced pluripotent stem cells to model fibrodysplasia ossificans progressiva.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2018-04-01

    Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients have mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Since it is often difficult or impossible to obtain large amounts of tissue from human donors due to the risks of inciting more heterotopic bone formation, human induced pluripotent stem cells (hiPSCs) provide an attractive source for establishing in vitro disease models and for applications in drug screening. hiPSCs have the ability to self-renew, allowing researchers to obtain large amounts of starting material. hiPSCs also have the potential to differentiate into any cell type in the body. In this review, we discuss how the application of hiPSC technology to studying FOP has changed our perspectives on FOP disease pathogenesis. We also consider ongoing challenges and emerging opportunities for the use of human iPSCs in drug discovery and regenerative medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Instructional designing the STEM education model for fostering creative thinking abilities in physics laboratory environment classes

    Science.gov (United States)

    Chanthala, Chumpon; Santiboon, Toansakul; Ponkham, Kamon

    2018-01-01

    To investigate the effects of students' activity-based on learning approaching management through the STEM Education Instructional Model for fostering their creative thinking abilities of their learning achievements in physics laboratory classroom environments with the sample size consisted of 48 students at the 10th grade level in two classes in Mahasarakham University Demonstration School(Secondary Division) in Thailand. Students' creative thinking abilities were assessed with the with the 24-item GuilfordCreative Thinking Questionnaire (GCTQ). Students' perceptions of their physics classroom learning environments were obtained using the 35-item Physics Laboratory Environment Inventory (PLEI). Associations between students' learning achievements of their post-test assessment indicated that 26% of the coefficient predictive value (R2) of the variance in students' creative thinking abilities was attributable to their perceptions for the GCTQ. Students' learning outcomes of their post-test assessment, the R2value indicated that 35% of the variances for the PLEI, the R2value indicated that 63% of the variances for their creative thinking abilities were attributable to theiraffecting the activity-based on learning for fostering their creative thinking are provided.

  3. Modeling conduction in host-graft interactions between stem cell grafts and cardiomyocytes.

    Science.gov (United States)

    Chen, Michael Q; Yu, Jin; Whittington, R Hollis; Wu, Joseph C; Kovacs, Gregory T A; Giovangrandi, Laurent

    2009-01-01

    Cell therapy has recently made great strides towards aiding heart failure. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. A model using microelectrode array technology that maps the electrical interactions between host and graft tissues in co-culture is presented and sheds light on the effects of having a mismatch of conduction properties at the boundary. Skeletal myoblasts co-cultured with cardiomyocytes demonstrated that conduction velocity significantly decreases at the boundary despite electromechanical coupling. In an attempt to improve the uniformity of conduction with host cells, differentiating human embryonic stem cells (hESC) were used in co-culture. Over the course of four to seven days, synchronous electrical activity was observed at the hESC boundary, implying differentiation and integration. Activity did not extend far past the boundary, and conduction velocity was significantly greater than that of the host tissue, implying the need for other external measures to properly match the conduction properties between host and graft tissue.

  4. Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

    Science.gov (United States)

    Yoshinaga, Toshihiro; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Shirasaka, Tomohiro; Kigawa, Yoshiyasu; Tateno, Masaru; Kaneta, Hiroo; Watanabe, Kimihiko; Igarashi, Takeshi; Kobayashi, Seiju; Sohma, Hitoshi; Kato, Tadafumi; Saito, Toshikazu

    2013-10-01

    Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

  5. [Multiple organ failure presumably due to alkylating agents used as preconditioning drugs for autologous peripheral blood stem cell transplantation in an acute promyelocytic leukemia].

    Science.gov (United States)

    Ida, Tori; Hashimoto, Shigeo; Suzuki, Nobuaki; Ebe, Yusuke; Yano, Toshio; Sato, Naoko; Koike, Tadashi

    2016-01-01

    A 52-year-old male was diagnosed as having acute promyelocytic leukemia (APL) in 2006. He received induction chemotherapy including all-trans retinoic acid and initially achieved a complete remission (CR). After several courses of consolidation therapy combining anthracyclines and cytarabine, he maintained CR. In 2009, an APL relapse was diagnosed, and he was treated with arsenic trioxide. Since he achieved a second CR, he underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) with a conditioning regimen consisting of busulfan and melphalan. At four months after auto-PBSCT, he developed a pneumothorax and acute respiratory failure. He died despite intensive therapy. Autopsy findings included various atypical and apoptotic cells in his pulmonary tissue. These changes were confirmed in multiple organs throughout the body, suggesting them to be drug-induced. The findings in this case suggested multiple organ failure due to alkylating agents.

  6. Stem cells: a model for screening, discovery and development of drugs

    OpenAIRE

    Kitambi, Satish Srinivas; Chandrasekar, Gayathri

    2011-01-01

    Satish Srinivas Kitambi1, Gayathri Chandrasekar21Department of Medical Biochemistry and Biophysics; 2Department of Biosciences, Karolinska Institutet, Stockholm, SwedenAbstract: The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficac...

  7. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening

    OpenAIRE

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-01-01

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scienti...

  8. Sustainable Organic Farming For Environmental Health A Social Development Model

    Directory of Open Access Journals (Sweden)

    Ijun Rijwan Susanto

    2015-05-01

    Full Text Available ABSTRACT In this study the researcher attempted 1 to understand the basic features of organic farming in The Paguyuban Pasundans Cianjur 2 to describe and understand how the stakeholders were are able to internalize the challenges of organic farming on their lived experiences in the community 3 to describe and understand how the stakeholders were are able to internalize and applied the values of benefits of organic farming in support of environmental health on their lived experiences in the community 4 The purpose was to describe and understand how the stakeholders who are able to articulate their ideas regarding the model of sustainable organic farming 5 The Policy Recommendation for Organic Farming. The researcher employed triangulation thorough finding that provides breadth and depth to an investigation offering researchers a more accurate picture of the phenomenon. In the implementation of triangulation researchers conducted several interviews to get saturation. After completion of the interview results are written compiled and shown to the participants to check every statement by every participant. In addition researchers also checked the relevant documents and direct observation in the field The participants of this study were the stakeholders namely 1 The leader of Paguyuban Pasundans Organic Farmer Cianjur PPOFC 2 Members of Paguyuban Pasundans Organic FarmersCianjur 3 Leader of NGO 4 Government officials of agriculture 5 Business of organic food 6 and Consumer of organic food. Generally the findings of the study revealed the following 1 PPOFC began to see the reality as the impact of modern agriculture showed in fertility problems due to contaminated soil by residues of agricultural chemicals such as chemical fertilizers and chemical pesticides. So he wants to restore the soil fertility through environmentally friendly of farming practices 2 the challenges of organic farming on their lived experiences in the community farmers did not

  9. On the influence of the exposure model on organ doses

    International Nuclear Information System (INIS)

    Drexler, G.; Eckerl, H.

    1988-01-01

    Based on the design characteristics of the MIRD-V phantom, two sex-specific adult phantoms, ADAM and EVA were introduced especially for the calculation of organ doses resulting from external irradiation. Although the body characteristics of all the phantoms are in good agreement with those of the reference man and woman, they have some disadvantages related to the location and shape of organs and the form of the whole body. To overcome these disadvantages related to the location and shape of organs and form of the whole body. To overcome these disadvantages related to the location and shape of organs and the form of the whole body. To overcome these disadvantages and to obtain more realistic phantoms, a technique based on computer tomographic data (voxel-phantom) was developed. This technique allows any physical phantom or real body to be converted into computer files. The improvements are of special importance with regard to the skeleton, because a better modeling of the bone surfaces and separation of hard bone and bone marrow can be achieved. For photon irradiation, the sensitivity of the model on organ doses or the effective dose equivalent is important for operational radiation protection

  10. Modeling of secondary organic aerosol yields from laboratory chamber data

    Directory of Open Access Journals (Sweden)

    M. N. Chan

    2009-08-01

    Full Text Available Laboratory chamber data serve as the basis for constraining models of secondary organic aerosol (SOA formation. Current models fall into three categories: empirical two-product (Odum, product-specific, and volatility basis set. The product-specific and volatility basis set models are applied here to represent laboratory data on the ozonolysis of α-pinene under dry, dark, and low-NOx conditions in the presence of ammonium sulfate seed aerosol. Using five major identified products, the model is fit to the chamber data. From the optimal fitting, SOA oxygen-to-carbon (O/C and hydrogen-to-carbon (H/C ratios are modeled. The discrepancy between measured H/C ratios and those based on the oxidation products used in the model fitting suggests the potential importance of particle-phase reactions. Data fitting is also carried out using the volatility basis set, wherein oxidation products are parsed into volatility bins. The product-specific model is most likely hindered by lack of explicit inclusion of particle-phase accretion compounds. While prospects for identification of the majority of SOA products for major volatile organic compounds (VOCs classes remain promising, for the near future empirical product or volatility basis set models remain the approaches of choice.

  11. Accounting for microbial habitats in modeling soil organic matter dynamics

    Science.gov (United States)

    Chenu, Claire; Garnier, Patricia; Nunan, Naoise; Pot, Valérie; Raynaud, Xavier; Vieublé, Laure; Otten, Wilfred; Falconer, Ruth; Monga, Olivier

    2017-04-01

    The extreme heterogeneity of soils constituents, architecture and inhabitants at the microscopic scale is increasingly recognized. Microbial communities exist and are active in a complex 3-D physical framework of mineral and organic particles defining pores of various sizes, more or less inter-connected. This results in a frequent spatial disconnection between soil carbon, energy sources and the decomposer organisms and a variety of microhabitats that are more or less suitable for microbial growth and activity. However, current biogeochemical models account for C dynamics at the macroscale (cm, m) and consider time- and spatially averaged relationships between microbial activity and soil characteristics. Different modelling approaches have intended to account for this microscale heterogeneity, based either on considering aggregates as surrogates for microbial habitats, or pores. Innovative modelling approaches are based on an explicit representation of soil structure at the fine scale, i.e. at µm to mm scales: pore architecture and their saturation with water, localization of organic resources and of microorganisms. Three recent models are presented here, that describe the heterotrophic activity of either bacteria or fungi and are based upon different strategies to represent the complex soil pore system (Mosaic, LBios and µFun). These models allow to hierarchize factors of microbial activity in soil's heterogeneous architecture. Present limits of these approaches and challenges are presented, regarding the extensive information required on soils at the microscale and to up-scale microbial functioning from the pore to the core scale.

  12. [Biomechanical modeling of pelvic organ mobility: towards personalized medicine].

    Science.gov (United States)

    Cosson, Michel; Rubod, Chrystèle; Vallet, Alexandra; Witz, Jean-François; Brieu, Mathias

    2011-11-01

    Female pelvic mobility is crucial for urinary, bowel and sexual function and for vaginal delivery. This mobility is ensured by a complex organ suspension system composed of ligaments, fascia and muscles. Impaired pelvic mobility affects one in three women of all ages and can be incapacitating. Surgical management has a high failure rate, largely owing to poor knowledge of the organ support system, including the barely discernible ligamentous system. We propose a 3D digital model of the pelvic cavity based on MRI images and quantitative tools, designed to locate the pelvic ligaments. We thus obtain a coherent anatomical and functional model which can be used to analyze pelvic pathophysiology. This work represents a first step towards creating a tool for localizing and characterizing the source of pelvic imbalance. We examine possible future applications of this model, in terms of personalized therapy and prevention.

  13. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    Science.gov (United States)

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though

  14. Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

    Science.gov (United States)

    Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

    2012-03-31

    The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

  15. Modeling Secondary Organic Aerosol Formation From Emissions of Combustion Sources

    Science.gov (United States)

    Jathar, Shantanu Hemant

    Atmospheric aerosols exert a large influence on the Earth's climate and cause adverse public health effects, reduced visibility and material degradation. Secondary organic aerosol (SOA), defined as the aerosol mass arising from the oxidation products of gas-phase organic species, accounts for a significant fraction of the submicron atmospheric aerosol mass. Yet, there are large uncertainties surrounding the sources, atmospheric evolution and properties of SOA. This thesis combines laboratory experiments, extensive data analysis and global modeling to investigate the contribution of semi-volatile and intermediate volatility organic compounds (SVOC and IVOC) from combustion sources to SOA formation. The goals are to quantify the contribution of these emissions to ambient PM and to evaluate and improve models to simulate its formation. To create a database for model development and evaluation, a series of smog chamber experiments were conducted on evaporated fuel, which served as surrogates for real-world combustion emissions. Diesel formed the most SOA followed by conventional jet fuel / jet fuel derived from natural gas, gasoline and jet fuel derived from coal. The variability in SOA formation from actual combustion emissions can be partially explained by the composition of the fuel. Several models were developed and tested along with existing models using SOA data from smog chamber experiments conducted using evaporated fuel (this work, gasoline, fischertropschs, jet fuel, diesels) and published data on dilute combustion emissions (aircraft, on- and off-road gasoline, on- and off-road diesel, wood burning, biomass burning). For all of the SOA data, existing models under-predicted SOA formation if SVOC/IVOC were not included. For the evaporated fuel experiments, when SVOC/IVOC were included predictions using the existing SOA model were brought to within a factor of two of measurements with minor adjustments to model parameterizations. Further, a volatility

  16. Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.

    Science.gov (United States)

    Yan, Huaming; Konstorum, Anna; Lowengrub, John S

    2018-05-01

    We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.

  17. Prediction model for cabbage stem weevil ceutorhynchus pallidactylus Mrsh. occurrence on winther rape based on an artificial neural network

    Czech Academy of Sciences Publication Activity Database

    Klem, Karel; Spitzer, T.

    2017-01-01

    Roč. 19, č. 3 (2017), s. 302-308 ISSN 1461-9555 R&D Projects: GA MZe QJ1530373 Institutional support: RVO:67179843 Keywords : Brassica napus L * cabbage stem weevil * Ceutorhynchus pallidactylus * model * neural network * oilseed rape * weather conditions Subject RIV: EG - Zoology OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 1.726, year: 2016

  18. Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model.

    Directory of Open Access Journals (Sweden)

    Darren Paul Burke

    Full Text Available Extrinsic mechanical signals have been implicated as key regulators of mesenchymal stem cell (MSC differentiation. It has been possible to test different hypotheses for mechano-regulated MSC differentiation by attempting to simulate regenerative events such as bone fracture repair, where repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues such as substrate stiffness and oxygen tension as key regulators of MSC differentiation; however it remains unclear if and how such cues determine stem cell fate in vivo. As part of this study, a computational model was developed to test the hypothesis that substrate stiffness and oxygen tension regulate stem cell differentiation during fracture healing. Rather than assuming mechanical signals act directly on stem cells to determine their differentiation pathway, it is postulated that they act indirectly to regulate angiogenesis and hence partially determine the local oxygen environment within a regenerating tissue. Chondrogenesis of MSCs was hypothesized to occur in low oxygen regions, while in well vascularised regions of the regenerating tissue a soft local substrate was hypothesised to facilitate adipogenesis while a stiff substrate facilitated osteogenesis. Predictions from the model were compared to both experimental data and to predictions of a well established computational mechanobiological model where tissue differentiation is assumed to be regulated directly by the local mechanical environment. The model predicted all the major events of fracture repair, including cartilaginous bridging, endosteal and periosteal bony bridging and bone remodelling. It therefore provides support for the hypothesis that substrate stiffness and oxygen play a key role in regulating MSC fate during regenerative events such as fracture healing.

  19. Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

    Science.gov (United States)

    2013-06-01

    38, 40, 41]. Because these “ mela - noma stem cells” (MSC) are sometimes so numerous, some have argued that the CSC model may not apply to melanoma...40]. There are data from two groups indicating that mela - noma lesions contain a CSC subset character- ized by CD271 expression [25, 26]. In a...neuronal proteins and neuron- like differentiation has been long recognized in neoplastic melanocytes [46, 47]. Certain mela - noma cell lines that

  20. Predicting long-term organic carbon dynamics in organically amended soils using the CQESTR model

    Energy Technology Data Exchange (ETDEWEB)

    Plaza, Cesar; Polo, Alfredo [Consejo Superior de Investigaciones Cientificas, Madrid (Spain). Inst. de Ciencias Agrarias; Gollany, Hero T. [Columbia Plateau Conservation Research Center, Pendleton, OR (United States). USDA-ARS; Baldoni, Guido; Ciavatta, Claudio [Bologna Univ. (Italy). Dept. of Agroenvironmental Sciences and Technologies

    2012-04-15

    Purpose: The CQESTR model is a process-based C model recently developed to simulate soil organic matter (SOM) dynamics and uses readily available or easily measurable input parameters. The current version of CQESTR (v. 2.0) has been validated successfully with a number of datasets from agricultural sites in North America but still needs to be tested in other geographic areas and soil types under diverse organic management systems. Materials and methods: We evaluated the predictive performance of CQESTR to simulate long-term (34 years) soil organic C (SOC) changes in a SOM-depleted European soil either unamended or amended with solid manure, liquid manure, or crop residue. Results and discussion: Measured SOC levels declined over the study period in the unamended soil, remained constant in the soil amended with crop residues, and tended to increase in the soils amended with manure, especially with solid manure. Linear regression analysis of measured SOC contents and CQESTR predictions resulted in a correlation coefficient of 0.626 (P < 0.001) and a slope and an intercept not significantly different from 1 and 0, respectively (95% confidence level). The mean squared deviation and root mean square error were relatively small. Simulated values fell within the 95% confidence interval of the measured SOC, and predicted errors were mainly associated with data scattering. Conclusions: The CQESTR model was shown to predict, with a reasonable degree of accuracy, the organic C dynamics in the soils examined. The CQESTR performance, however, could be improved by adding an additional parameter to differentiate between pre-decomposed organic amendments with varying degrees of stability. (orig.)

  1. Organized versus self-organized criticality in the abelian sandpile model

    OpenAIRE

    Fey-den Boer, AC Anne; Redig, FHJ Frank

    2005-01-01

    We define stabilizability of an infinite volume height configuration and of a probability measure on height configurations. We show that for high enough densities, a probability measure cannot be stabilized. We also show that in some sense the thermodynamic limit of the uniform measures on the recurrent configurations of the abelian sandpile model (ASM) is a maximal element of the set of stabilizable measures. In that sense the self-organized critical behavior of the ASM can be understood in ...

  2. IT Business Value Model for Information Intensive Organizations

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Gastaud Maçada

    2012-01-01

    Full Text Available Many studies have highlighted the capacity Information Technology (IT has for generating value for organizations. Investments in IT made by organizations have increased each year. Therefore, the purpose of the present study is to analyze the IT Business Value for Information Intensive Organizations (IIO - e.g. banks, insurance companies and securities brokers. The research method consisted of a survey that used and combined the models from Weill and Broadbent (1998 and Gregor, Martin, Fernandez, Stern and Vitale (2006. Data was gathered using an adapted instrument containing 5 dimensions (Strategic, Informational, Transactional, Transformational and Infra-structure with 27 items. The instrument was refined by employing statistical techniques such as Exploratory and Confirmatory Factorial Analysis through Structural Equations (first and second order Model Measurement. The final model is composed of four factors related to IT Business Value: Strategic, Informational, Transactional and Transformational, arranged in 15 items. The dimension Infra-structure was excluded during the model refinement process because it was discovered during interviews that managers were unable to perceive it as a distinct dimension of IT Business Value.

  3. Scalability of Sustainable Business Models in Hybrid Organizations

    Directory of Open Access Journals (Sweden)

    Adam Jabłoński

    2016-02-01

    Full Text Available The dynamics of change in modern business create new mechanisms for company management to determine their pursuit and the achievement of their high performance. This performance maintained over a long period of time becomes a source of ensuring business continuity by companies. An ontological being enabling the adoption of such assumptions is such a business model that has the ability to generate results in every possible market situation and, moreover, it has the features of permanent adaptability. A feature that describes the adaptability of the business model is its scalability. Being a factor ensuring more work and more efficient work with an increasing number of components, scalability can be applied to the concept of business models as the company’s ability to maintain similar or higher performance through it. Ensuring the company’s performance in the long term helps to build the so-called sustainable business model that often balances the objectives of stakeholders and shareholders, and that is created by the implemented principles of value-based management and corporate social responsibility. This perception of business paves the way for building hybrid organizations that integrate business activities with pro-social ones. The combination of an approach typical of hybrid organizations in designing and implementing sustainable business models pursuant to the scalability criterion seems interesting from the cognitive point of view. Today, hybrid organizations are great spaces for building effective and efficient mechanisms for dialogue between business and society. This requires the appropriate business model. The purpose of the paper is to present the conceptualization and operationalization of scalability of sustainable business models that determine the performance of a hybrid organization in the network environment. The paper presents the original concept of applying scalability in sustainable business models with detailed

  4. Stem cell engineering a WTEC global assessment

    CERN Document Server

    Loring, Jeanne; McDevitt, Todd; Palecek, Sean; Schaffer, David; Zandstra, Peter

    2014-01-01

    This book describes a global assessment of stem cell engineering research, achieved through site visits by a panel of experts to leading institutes, followed by dedicated workshops. The assessment made clear that engineers and the engineering approach with its quantitative, system-based thinking can contribute much to the progress of stem cell research and development. The increased need for complex computational models and new, innovative technologies, such as high-throughput screening techniques, organ-on-a-chip models and in vitro tumor models require an increasing involvement of engineers and physical scientists. Additionally, this book will show that although the US is still in a leadership position in stem cell engineering, Asian countries such as Japan, China and Korea, as well as European countries like the UK, Germany, Sweden and the Netherlands are rapidly expanding their investments in the field. Strategic partnerships between countries could lead to major advances of the field and scalable expansi...

  5. Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

    Full Text Available BACKGROUND: Familial dysautonomia (FD is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion:MU (exon 20 skipping ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation. CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better

  6. A taxonomy of nursing care organization models in hospitals.

    Science.gov (United States)

    Dubois, Carl-Ardy; D'Amour, Danielle; Tchouaket, Eric; Rivard, Michèle; Clarke, Sean; Blais, Régis

    2012-08-28

    Over the last decades, converging forces in hospital care, including cost-containment policies, rising healthcare demands and nursing shortages, have driven the search for new operational models of nursing care delivery that maximize the use of available nursing resources while ensuring safe, high-quality care. Little is known, however, about the distinctive features of these emergent nursing care models. This article contributes to filling this gap by presenting a theoretically and empirically grounded taxonomy of nursing care organization models in the context of acute care units in Quebec and comparing their distinctive features. This study was based on a survey of 22 medical units in 11 acute care facilities in Quebec. Data collection methods included questionnaire, interviews, focus groups and administrative data census. The analytical procedures consisted of first generating unit profiles based on qualitative and quantitative data collected at the unit level, then applying hierarchical cluster analysis to the units' profile data. The study identified four models of nursing care organization: two professional models that draw mainly on registered nurses as professionals to deliver nursing services and reflect stronger support to nurses' professional practice, and two functional models that draw more significantly on licensed practical nurses (LPNs) and assistive staff (orderlies) to deliver nursing services and are characterized by registered nurses' perceptions that the practice environment is less supportive of their professional work. This study showed that medical units in acute care hospitals exhibit diverse staff mixes, patterns of skill use, work environment design, and support for innovation. The four models reflect not only distinct approaches to dealing with the numerous constraints in the nursing care environment, but also different degrees of approximations to an "ideal" nursing professional practice model described by some leaders in the

  7. A taxonomy of nursing care organization models in hospitals

    Science.gov (United States)

    2012-01-01

    Background Over the last decades, converging forces in hospital care, including cost-containment policies, rising healthcare demands and nursing shortages, have driven the search for new operational models of nursing care delivery that maximize the use of available nursing resources while ensuring safe, high-quality care. Little is known, however, about the distinctive features of these emergent nursing care models. This article contributes to filling this gap by presenting a theoretically and empirically grounded taxonomy of nursing care organization models in the context of acute care units in Quebec and comparing their distinctive features. Methods This study was based on a survey of 22 medical units in 11 acute care facilities in Quebec. Data collection methods included questionnaire, interviews, focus groups and administrative data census. The analytical procedures consisted of first generating unit profiles based on qualitative and quantitative data collected at the unit level, then applying hierarchical cluster analysis to the units’ profile data. Results The study identified four models of nursing care organization: two professional models that draw mainly on registered nurses as professionals to deliver nursing services and reflect stronger support to nurses’ professional practice, and two functional models that draw more significantly on licensed practical nurses (LPNs) and assistive staff (orderlies) to deliver nursing services and are characterized by registered nurses’ perceptions that the practice environment is less supportive of their professional work. Conclusions This study showed that medical units in acute care hospitals exhibit diverse staff mixes, patterns of skill use, work environment design, and support for innovation. The four models reflect not only distinct approaches to dealing with the numerous constraints in the nursing care environment, but also different degrees of approximations to an “ideal” nursing professional practice

  8. Drosophila embryos as model to assess cellular and developmental toxicity of multi-walled carbon nanotubes (MWCNT in living organisms.

    Directory of Open Access Journals (Sweden)

    Boyin Liu

    Full Text Available Different toxicity tests for carbon nanotubes (CNT have been developed to assess their impact on human health and on aquatic and terrestrial animal and plant life. We present a new model, the fruit fly Drosophila embryo offering the opportunity for rapid, inexpensive and detailed analysis of CNTs toxicity during embryonic development. We show that injected DiI labelled multi-walled carbon nanotubes (MWCNTs become incorporated into cells in early Drosophila embryos, allowing the study of the consequences of cellular uptake of CNTs on cell communication, tissue and organ formation in living embryos. Fluorescently labelled subcellular structures showed that MWCNTs remained cytoplasmic and were excluded from the nucleus. Analysis of developing ectodermal and neural stem cells in MWCNTs injected embryos revealed normal division patterns and differentiation capacity. However, an increase in cell death of ectodermal but not of neural stem cells was observed, indicating stem cell-specific vulnerability to MWCNT exposure. The ease of CNT embryo injections, the possibility of detailed morphological and genomic analysis and the low costs make Drosophila embryos a system of choice to assess potential developmental and cellular effects of CNTs and test their use in future CNT based new therapies including drug delivery.

  9. A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue.

    Science.gov (United States)

    Zhu, Xiaofei; Liu, Jie; Yu, Zongdong; Chen, Chao-An; Aksel, Hacer; Azim, Adham A; Huang, George T-J

    2018-02-01

    The goal of this study was to establish mini-swine as a large animal model for stem cell-based pulp regeneration studies. Swine dental pulp stem cells (sDPSCs) were isolated from mini-swine and characterized in vitro. For in vivo studies, we first employed both ectopic and semi-orthotopic study models using severe combined immunodeficiency mice. One is hydroxyapatite-tricalcium phosphate (HA/TCP) model for pulp-dentin complex formation, and the other is tooth fragment model for complete pulp regeneration with new dentin depositing along the canal walls. We found that sDPSCs are similar to their human counterparts exhibiting mesenchymal stem cell characteristics with ability to form colony forming unit-fibroblastic and odontogenic differentiation potential. sDPSCs formed pulp-dentin complex in the HA/TCP model and showed pulp regeneration capacity in the tooth fragment model. We then tested orthotopic pulp regeneration on mini-swine including the use of multi-rooted teeth. Using autologous sDPSCs carried by hydrogel and transplanted into the mini-swine root canal space, we observed regeneration of vascularized pulp-like tissue with a layer of newly deposited dentin-like (rD) tissue or osteodentin along the canal walls. In some cases, dentin bridge-like structure was observed. Immunohistochemical analysis detected the expression of nestin, dentin sialophosphoprotein, dentin matrix protein 1, and bone sialoprotein in odontoblast-like cells lining against the produced rD. We also tested the use of allogeneic sDPSCs for the same procedures. Similar findings were observed in allogeneic transplantation. This study is the first to show an establishment of mini-swine as a suitable large animal model utilizing multi-rooted teeth for further cell-based pulp regeneration studies.

  10. Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian [Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J., E-mail: madlamba@oakland.edu [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States)

    2013-12-01

    Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133{sup +} HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b{sup +} counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors.

  11. Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

    International Nuclear Information System (INIS)

    Kane, Jonathan; Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian; Madlambayan, Gerard J.

    2013-01-01

    Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133 + HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b + counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors

  12. Mesenchymal stem cells expressing interleukin-18 inhibit breast cancer in a mouse model.

    Science.gov (United States)

    Liu, Xiaoyi; Hu, Jianxia; Li, Yueyun; Cao, Weihong; Wang, Yu; Ma, Zhongliang; Li, Funian

    2018-05-01

    Development of an improved breast cancer therapy has been an elusive goal of cancer gene therapy for a long period of time. Human mesenchymal stem cells derived from umbilical cord (hUMSCs) genetically modified with the interleukin (IL)-18 gene (hUMSCs/IL-18) were previously demonstrated to be able to suppress the proliferation, migration and invasion of breast cancer cells in vitro . In the present study, the effect of hUMSCs/IL-18 on breast cancer in a mouse model was investigated. A total of 128 mice were divided into 2 studies (the early-effect study and the late-effect study), with 4 groups in each, including the PBS-, hUMSC-, hUMSC/vector- and hUMSC/IL-18-treated groups. All treatments were injected along with 200 µl PBS. Following therapy, the tumor size, histological examination, and expression of lymphocytes, Ki-67, cluster of differentiation 31 and cytokines [interleukin (IL)-18, IL-12, interferon (IFN)-γ and TNF-α] in each group were analyzed. Proliferation of cells (assessed by measuring tumor size and Ki-67 expression) and metastasis, (by determining pulmonary and hepatic metastasis) of breast cancer cells in the hUMSC/IL-18 group were significantly decreased compared with all other groups. hUMSCs/IL-18 suppressed tumor cell proliferation by activating immunocytes and immune cytokines, decreasing the proliferation index of proliferation marker protein Ki-67 of tumor cells and inhibiting tumor angiogenesis. Furthermore, hUMSCs/IL-18 were able to induce a more marked and improved therapeutic effect in the tumor sites, particularly in early tumors. The results of the present study indicate that hUMSCs/IL-18 were able to inhibit the proliferation and metastasis of breast cancer cells in vivo , possibly leading to an approach for a novel antitumor therapy in breast cancer.

  13. Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

    Directory of Open Access Journals (Sweden)

    Xinyi Mu

    2017-01-01

    Full Text Available Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP, a major active ingredient in dong quai (Chinese Angelica Sinensis, on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1 ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS, 8-OHdG, and 4-HNE were declined, (2 ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3 ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

  14. Interactive Higher Education Instruction to Advance STEM Instruction in the Environmental Sciences - the Brownfield Action Model

    Science.gov (United States)

    Liddicoat, J. C.; Bower, P.

    2015-12-01

    The U.S. Environmental Protection Agency estimates that presently there are over half a million brownfields in the United States, but this number only includes sites for which an Environmental Site Assessment has been conducted. The actual number of brownfields is certainly in the millions and constitutes one of the major environmental issues confronting all communities today. Taught in part or entirely online for more than 15 years in environmental science, engineering, and hydrology courses at over a dozen colleges, universities, and high schools in the United States, Brownfield Action (BA) is an interactive, web-based simulation that combines scientific expertise, constructivist education philosophy, and multimedia to advance the teaching of environmental science (Bower et al., 2011, 2014; Liddicoat and Bower, 2015). In the online simulation and classroom, students form geotechnical consulting companies with a peer chosen at random to solve a problem in environmental forensics. The BA model contains interdisciplinary scientific and social information that are integrated within a digital learning environment that encourages students to construct their knowledge as they learn by doing. As such, the approach improves the depth and coherence of students understanding of the course material. Like real-world environmental consultants and professionals, students are required to develop and apply expertise from a wide range of fields, including environmental science and engineering as well as journalism, medicine, public health, law, civics, economics, and business management. The overall objective is for students to gain an unprecedented appreciation of the complexity, ambiguity, and risk involved in any environmental issue, and to acquire STEM knowledge that can be used constructively when confronted with such an issue.

  15. Molecular analysis of the replication program in unicellular model organisms

    OpenAIRE

    Raghuraman, M. K.; Brewer, Bonita J.

    2010-01-01

    Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program o...

  16. Understanding rare disease pathogenesis: a grand challenge for model organisms.

    Science.gov (United States)

    Hieter, Philip; Boycott, Kym M

    2014-10-01

    In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

  17. THE HISTOPATHOLOGICAL EFFECT OF LEAF, STEM AND ROOT BARK EXTRACTS OF MORINDA LUCIDA ON SOME VISCERAL ORGANS AND MUSCLES OF WISTAR MICE

    Directory of Open Access Journals (Sweden)

    2016-11-01

    Full Text Available The leaf, stem and root bark of Morinda lucida (Ezeogwu, are bitter and astringent used in Nigeria in the treatment of fever, malaria, yellow fever, jaundice and dysentery. They are also used as dyestuff. The aim of the study was to investigate and compare histological effects of the leaves, stem and root bark extracts of Morinda lucida on some visceral organs and muscles of albino Wistar mice. Acute intraperitoneal toxicity tests were performed for each of the extracts to determine their LD50s using modified Lorke\\'s method. Sub-chronic toxicity study was then carried out by intraperitoneal administration of different doses of the extracts on daily basis to the different groups of male mice for 21 days. The weights of the mice were taken before, during and after administration of the substance at weekly intervals. The animals were subsequently sacrificed and the liver, kidney, stomach, colon and muscle excised for histology processing and analysis. The acute intraperitoneal toxicity result (LD50 revealed Morinda lucida leaf, stem and root bark extracts to be lethal at 1,732.1; 1,058.3 and 970.8mg/kg body weight respectively. Microscopic examinations of the kidney, liver, stomach, colon and cardiac muscles showed that the effects of sub-chronic administration of Morinda lucida on the liver varied with the type of extracts and was dose dependent. The root extract had higher toxic effect. It had no adverse effect on the kidney, muscles, stomach and colon. This result may form the basis for further trials. It shows that Morinda lucida extracts are nontoxic at the dosage and oral route used by local traditional healers for its administration. However, caution is necessary in case of over dose.

  18. Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2018-03-01

    Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Modeling Human Neurological and Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Neuronal Differentiation and Its Applications in Neurotrauma.

    Science.gov (United States)

    Bahmad, Hisham; Hadadeh, Ola; Chamaa, Farah; Cheaito, Katia; Darwish, Batoul; Makkawi, Ahmad-Kareem; Abou-Kheir, Wassim

    2017-01-01

    With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine. They further aid in the development of regenerative medicine, autologous cell therapy and drug or toxicity screening. Here, we provide a comprehensive overview of the recent development in the field of iPSCs research, specifically for modeling human neurological and neurodegenerative diseases, and its applications in neurotrauma. These are mainly characterized by progressive functional or structural neuronal loss rendering them extremely challenging to manage. Many of these diseases, including Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) have been explored in vitro . The main purpose is to generate patient-specific iPS cell lines from the somatic cells that carry mutations or genetic instabilities for the aim of studying their differentiation potential and behavior. This new technology will pave the way for future development in the field of stem cell research anticipating its use in clinical settings and in regenerative medicine in order to treat various human diseases, including neurological and neurodegenerative diseases.

  20. Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

    Directory of Open Access Journals (Sweden)

    Hong J Lee

    Full Text Available BACKGROUND: Intracerebral hemorrhage (ICH is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

  1. Overexpression of CYP3A4 in a COLO 205 Colon Cancer Stem Cell Model in vitro

    International Nuclear Information System (INIS)

    Olszewski, Ulrike; Liedauer, Richard; Ausch, Christoph; Thalhammer, Theresia; Hamilton, Gerhard

    2011-01-01

    Cancer stem cells (CSCs) seem to constitute a subpopulation of tumor cells that escape from chemotherapy and cause recurrent disease. Low proliferation rates, protection in a stem cell niche and overexpression of drug resistance proteins are considered to confer chemoresistance. We established an in vitro colon CSC-like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium. Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR. ALDH1A1 is a CSC marker for certain tumor entities and confers resistance to cyclophosphamide. CYP3A4 is expressed in liver and colon and its overexpression seems particularly relevant in colon cancer, since it inactivates irinotecan and other xenobiotics, such as taxols and vinca alkaloids. In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients

  2. Quasi-dynamic model for an organic Rankine cycle

    International Nuclear Information System (INIS)

    Bamgbopa, Musbaudeen O.; Uzgoren, Eray

    2013-01-01

    Highlights: • Study presents a simplified transient modeling approach for an ORC under variable heat input. • The ORC model is presented as a synthesis of its models of its sub-components. • The model is compared to benchmark numerical simulations and experimental data at different stages. - Abstract: When considering solar based thermal energy input to an organic Rankine cycle (ORC), intermittent nature of the heat input does not only adversely affect the power output but also it may prevent ORC to operate under steady state conditions. In order to identify reliability and efficiency of such systems, this paper presents a simplified transient modeling approach for an ORC operating under variable heat input. The approach considers that response of the system to heat input variations is mainly dictated by the evaporator. Consequently, overall system is assembled using dynamic models for the heat exchangers (evaporator and condenser) and static models of the pump and the expander. In addition, pressure drop within heat exchangers is neglected. The model is compared to benchmark numerical and experimental data showing that the underlying assumptions are reasonable for cases where thermal input varies in time. Furthermore, the model is studied on another configuration and mass flow rates of both the working fluid and hot water and hot water’s inlet temperature to the ORC unit are shown to have direct influence on the system’s response

  3. Sordaria macrospora, a model organism to study fungal cellular development.

    Science.gov (United States)

    Engh, Ines; Nowrousian, Minou; Kück, Ulrich

    2010-12-01

    During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

  4. Aging, neurogenesis, and caloric restriction in different model organisms.

    Science.gov (United States)

    Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

    2013-08-01

    Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

  5. Turbulence and Self-Organization Modeling Astrophysical Objects

    CERN Document Server

    Marov, Mikhail Ya

    2013-01-01

    This book focuses on the development of continuum models of natural turbulent media. It provides a theoretical approach to the solutions of different problems related to the formation, structure and evolution of astrophysical and geophysical objects. A stochastic modeling approach is used in the mathematical treatment of these problems, which reflects self-organization processes in open dissipative systems. The authors also consider examples of ordering for various objects in space throughout their evolutionary processes. This volume is aimed at graduate students and researchers in the fields of mechanics, astrophysics, geophysics, planetary and space science.

  6. Generation of an ICF syndrome model by efficient genome editing of human induced pluripotent stem cells using the CRISPR system.

    Science.gov (United States)

    Horii, Takuro; Tamura, Daiki; Morita, Sumiyo; Kimura, Mika; Hatada, Izuho

    2013-09-30

    Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR) system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF) syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B) in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells.

  7. Generation of an ICF Syndrome Model by Efficient Genome Editing of Human Induced Pluripotent Stem Cells Using the CRISPR System

    Directory of Open Access Journals (Sweden)

    Izuho Hatada

    2013-09-01

    Full Text Available Genome manipulation of human induced pluripotent stem (iPS cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells.

  8. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Dhruv Sareen

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC lines generated from two Type I SMA subjects-one produced with lentiviral constructs and the second using a virus-free plasmid-based approach-recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients.

  9. Conceptual hierarchical modeling to describe wetland plant community organization

    Science.gov (United States)

    Little, A.M.; Guntenspergen, G.R.; Allen, T.F.H.

    2010-01-01

    Using multivariate analysis, we created a hierarchical modeling process that describes how differently-scaled environmental factors interact to affect wetland-scale plant community organization in a system of small, isolated wetlands on Mount Desert Island, Maine. We followed the procedure: 1) delineate wetland groups using cluster analysis, 2) identify differently scaled environmental gradients using non-metric multidimensional scaling, 3) order gradient hierarchical levels according to spatiotem-poral scale of fluctuation, and 4) assemble hierarchical model using group relationships with ordination axes and post-hoc tests of environmental differences. Using this process, we determined 1) large wetland size and poor surface water chemistry led to the development of shrub fen wetland vegetation, 2) Sphagnum and water chemistry differences affected fen vs. marsh / sedge meadows status within small wetlands, and 3) small-scale hydrologic differences explained transitions between forested vs. non-forested and marsh vs. sedge meadow vegetation. This hierarchical modeling process can help explain how upper level contextual processes constrain biotic community response to lower-level environmental changes. It creates models with more nuanced spatiotemporal complexity than classification and regression tree procedures. Using this process, wetland scientists will be able to generate more generalizable theories of plant community organization, and useful management models. ?? Society of Wetland Scientists 2009.

  10. Silkworm: A Promising Model Organism in Life Science.

    Science.gov (United States)

    Meng, Xu; Zhu, Feifei; Chen, Keping

    2017-09-01

    As an important economic insect, silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) has numerous advantages in life science, such as low breeding cost, large progeny size, short generation time, and clear genetic background. Additionally, there are rich genetic resources associated with silkworms. The completion of the silkworm genome has further accelerated it to be a modern model organism in life science. Genomic studies showed that some silkworm genes are highly homologous to certain genes related to human hereditary disease and, therefore, are a candidate model for studying human disease. In this article, we provided a review of silkworm as an important model in various research areas, including human disease, screening of antimicrobial agents, environmental safety monitoring, and antitumor studies. In addition, the application potentiality of silkworm model in life sciences was discussed. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.