Rising incidence of Merkel cell carcinoma

DEFF Research Database (Denmark)

Lyhne, Dorte; Lock-Andersen, Jørgen; Dahlstrøm, Karin

2011-01-01

Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investi......Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark......, and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We...... reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1-122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had...

Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma.

Science.gov (United States)

Dumble, Melissa L; Croager, Emma J; Yeoh, George C T; Quail, Elizabeth A

2002-03-01

Oval cells are bipotential liver stem cells able to differentiate into hepatocytes and bile duct epithelia. In normal adult liver oval cells are quiescent, existing in low numbers around the periportal region, and proliferate following severe, prolonged liver trauma. There is evidence implicating oval cells in the development of hepatocellular carcinoma, and hence the availability of an immortalized oval cell line would be invaluable for the study of liver cell lineage differentiation and carcinogenesis. A novel approach in the generation of cell lines is the use of the p53 knockout mouse. Absence of p53 allows a cell to cycle past the normal Hayflick limit, rendering it immortalized, although subsequent genetic alterations are thought necessary for transformation. p53 knockout mice were fed a choline-deficient, ethionine-supplemented diet, previously shown to increase oval cell numbers in wild-type mice. The oval cells were isolated by centrifugal elutriation and maintained in culture. Colonies of hepatic cells were isolated and characterized with respect to phenotype, growth characteristics and tumorigenicity. Analysis of gene expression by Northern blotting and immunocytochemistry suggests they are oval-like cells by virtue of albumin and transferrin expression, as well as the oval cell markers alpha fetoprotein, M(2)-pyruvate kinase and A6. Injection into athymic nude mice shows the cell lines are capable of forming tumors which phenotypically resemble hepatocellular carcinoma. Thus, the use of p53 null hepatic cells successfully generated immortalized and tumorigenic hepatic stem cell lines. The results presented support the idea that deleting p53 allows immortalization and contributes to the transformation of the oval-like cell lines. Further, the tumorigenic status of the cell lines is direct evidence for the participation of oval cells in the formation of hepatocellular carcinoma.

Very low temperature rise laser annealing of radiation-damaged solar cells in orbit

International Nuclear Information System (INIS)

Poulek, V.

1988-01-01

Solar cells of all space objects are damaged by radiation in orbit. This damage, however, can be removed by laser annealing. A new in-orbit laser regeneration system for both body- and spin-stabilized space objects is proposed. For successful annealing of solar cells damaged by 10 years' radiation dose in orbit it is necessary for the temperature rise in the incidence point of the laser beam to reach about 400 0 C. By continuous regeneration, however, between two annealing cycles the solar cells are hit by about two orders of magnitude lower radiation dose. This makes it possible to carry out the regeneration at a temperature rise well under 1 0 C! If an optimal laser regeneration system is used, such low temperature rise laser annealing of radiation-damaged solar cells is possible. A semiconductor GaAlAs diode laser with output power up to 10 mW CW was used for annealing. Some results of the very low temperature rise annealing experiment are given in this paper. (author)

On the merging rates of envelope-deprived components of binary systems which can give rise to supernova events

Science.gov (United States)

Tornambe, Amedeo

1989-08-01

Theoretical rates of mergings of envelope-deprived components of binary systems, which can give rise to supernova events are described. The effects of the various assumptions on the physical properties of the progenitor system and of its evolutionary behavior through common envelope phases are discussed. Four cases have been analyzed: CO-CO, He-CO, He-He double degenerate mergings and He star-CO dwarf merging. It is found that, above a critical efficiency of the common envelope action in system shrinkage, the rate of CO-CO mergings is not strongly sensitive to the efficiency. Below this critical value, no CO-CO systems will survive for times larger than a few Gyr. In contrast, He-CO dwarf systems will continue to merge at a reasonable rate up to 20 Gyr, and more, also under extreme conditions.

Identification and Targeting of Candidate Preexisting Lurker Cells That Give Rise to Castration-Resistant Prostate Cancer

Science.gov (United States)

2016-10-01

highly (4- to 5-fold) en- riched for organoid formation compared to CD38hi luminal cellsCell Reports 17, 2596–2606, December 6, 2016 2597 Figure 1... riched in CD38lo cells (Figure 3A) but has not been previously associated with PIA. In tissue sections, PSCA expression was observed more commonly in...without a mesenchymal niche . Nature 459, 262–265.2606 Cell Reports 17, 2596–2606, December 6, 2016Sboner, A., Demichelis, F., Calza, S., Pawitan, Y., Setlur

Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions

Science.gov (United States)

Sucker, Antje; Zhao, Fang; Pieper, Natalia; Heeke, Christina; Maltaner, Raffaela; Stadtler, Nadine; Real, Birgit; Bielefeld, Nicola; Howe, Sebastian; Weide, Benjamin; Gutzmer, Ralf; Utikal, Jochen; Loquai, Carmen; Gogas, Helen; Klein-Hitpass, Ludger; Zeschnigk, Michael; Westendorf, Astrid M.; Trilling, Mirko; Horn, Susanne; Schilling, Bastian; Schadendorf, Dirk; Griewank, Klaus G.; Paschen, Annette

2017-01-01

Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8+ T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-tumour IFNγ activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFNγ. Allelic JAK1/2 losses predisposing to IFNγ resistance development are frequent in melanoma. Subclones harbouring inactivating mutations emerge under various immunotherapies but are also detectable in pre-treatment biopsies. Our data demonstrate that JAK1/2 deficiency protects melanoma from anti-tumour IFNγ activity and results in T-cell-resistant HLA class I-negative lesions. Screening for mechanisms of IFNγ resistance should be considered in therapeutic decision-making. PMID:28561041

FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells.

Science.gov (United States)

Nguyen, Minh Binh; Cohen, Idan; Kumar, Vinod; Xu, Zijian; Bar, Carmit; Dauber-Decker, Katherine L; Tsai, Pai-Chi; Marangoni, Pauline; Klein, Ophir D; Hsu, Ya-Chieh; Chen, Ting; Mikkola, Marja L; Ezhkova, Elena

2018-06-13

Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.

From cell differentiation to cell collectives : Bacillus subtilis uses division of labor to migrate

NARCIS (Netherlands)

van Gestel, Jordi; Vlamakis, Hera; Kolter, Roberto

The organization of cells, emerging from cell-cell interactions, can give rise to collective properties. These properties are adaptive when together cells can face environmental challenges that they separately cannot. One particular challenge that is important for microorganisms is migration. In

Response of single bacterial cells to stress gives rise to complex history dependence at the population level

Science.gov (United States)

Mathis, Roland; Ackermann, Martin

2016-01-01

Most bacteria live in ever-changing environments where periods of stress are common. One fundamental question is whether individual bacterial cells have an increased tolerance to stress if they recently have been exposed to lower levels of the same stressor. To address this question, we worked with the bacterium Caulobacter crescentus and asked whether exposure to a moderate concentration of sodium chloride would affect survival during later exposure to a higher concentration. We found that the effects measured at the population level depended in a surprising and complex way on the time interval between the two exposure events: The effect of the first exposure on survival of the second exposure was positive for some time intervals but negative for others. We hypothesized that the complex pattern of history dependence at the population level was a consequence of the responses of individual cells to sodium chloride that we observed: (i) exposure to moderate concentrations of sodium chloride caused delays in cell division and led to cell-cycle synchronization, and (ii) whether a bacterium would survive subsequent exposure to higher concentrations was dependent on the cell-cycle state. Using computational modeling, we demonstrated that indeed the combination of these two effects could explain the complex patterns of history dependence observed at the population level. Our insight into how the behavior of single cells scales up to processes at the population level provides a perspective on how organisms operate in dynamic environments with fluctuating stress exposure. PMID:26960998

Accuracy of formulas used to predict post-transfusion packed cell volume rise in anemic dogs.

Science.gov (United States)

Short, Jacqueline L; Diehl, Shenandoah; Seshadri, Ravi; Serrano, Sergi

2012-08-01

To assess the accuracy of published formulas used to guide packed red blood cell (pRBC) transfusions in anemic dogs and to compare the predicted rise in packed cell volume (PCV) to the actual post-transfusion rise in PCV. Prospective observational study from April 2009 through July 2009. A small animal emergency and specialty hospital. Thirty-one anemic client-owned dogs that received pRBC transfusions for treatment of anemia. None Four formulas were evaluated to determine their predictive ability with respect to rise in PCV following transfusion with pRBC. Post-transfusion rise in PCV were compared to calculated rise in PCV using 4 different formulas. Bias and limits of agreement were investigated using Bland-Altman analyses. Accuracy of existing formulas to predict rise in PCV following transfusion varied significantly. Formula 1 (volume to be transfused [VT] [mL] = 1 mL × % PCV rise × kg body weight [BW]) overestimated the expected rise in PCV (mean difference, 6.30), while formula 2 (VT [mL] = 2 mL ×% PCV rise × kg BW) underestimated the rise in PCV (mean difference, -3.01). Formula 3 (VT [mL] = 90 mL × kg BW × [(desired PCV - Patient PCV)/PCV of donor blood]) and formula 4 (VT [mL] = 1.5 mL ×% PCV rise × kg BW) performed well (mean difference 0.23 and 0.09, respectively) in predicting rise in PCV following pRBC transfusion. Agreement between 2 formulas, "VT (mL) = kg BW × blood volume (90 mL) × [(desired PCV - recipient PCV)/Donor PCV]" and "VT (mL) = 1.5 ×desired rise in PCV × kg BW," was found when they were compared to the actual rise in PCV following pRBC transfusion in anemic dogs. Further research is warranted to determine whether these formulas perform similarly well for other species. © Veterinary Emergency and Critical Care Society 2012.

Role of bone marrow-derived stem cells, renal progenitor cells and ...

African Journals Online (AJOL)

It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Characterization of HSCs ...

Plume rise from multiple sources

International Nuclear Information System (INIS)

Briggs, G.A.

1975-01-01

A simple enhancement factor for plume rise from multiple sources is proposed and tested against plume-rise observations. For bent-over buoyant plumes, this results in the recommendation that multiple-source rise be calculated as [(N + S)/(1 + S)]/sup 1/3/ times the single-source rise, Δh 1 , where N is the number of sources and S = 6 (total width of source configuration/N/sup 1/3/ Δh 1 )/sup 3/2/. For calm conditions a crude but simple method is suggested for predicting the height of plume merger and subsequent behavior which is based on the geometry and velocity variations of a single buoyant plume. Finally, it is suggested that large clusters of buoyant sources might occasionally give rise to concentrated vortices either within the source configuration or just downwind of it

A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

Science.gov (United States)

Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

2015-11-01

Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation.

Directory of Open Access Journals (Sweden)

Diana Klein

Full Text Available Here, we identify CD44(+CD90(+CD73(+CD34(-CD45(- cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs. VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes.

Transitional paternalism: how shared normative powers give rise to the asymmetry of adolescent consent and refusal.

Science.gov (United States)

Manson, Neil C

2015-02-01

In many jurisdictions, adolescents acquire the right to consent to treatment; but in some cases their refusals - e.g. of life-saving treatment - may not be respected. This asymmetry of adolescent consent and refusal seems puzzling, even incoherent. The aim here is to offer an original explanation, and a justification, of this asymmetry. Rather than trying to explain the asymmetry in terms of a variable standard of competence - where the adolescent is competent to consent to, but not refuse, certain interventions - the account offered here focuses more closely on the normative power to render actions permissible. Where normative powers are shared they can readily give rise to an asymmetry between consent and refusal. We then turn to why it is justifiable that normative powers be shared in adolescence. Transitional paternalism holds that the acquisition of normative powers by competent adolescents should not be an instant one, achieved in a single step, but that there should be a transitional period where paternalistic protection is rolled back, but not entirely withdrawn until a later date. Transitional paternalism could be implemented without generating the asymmetry between consent and refusal but, it is argued, the asymmetric version of transitional paternalism is to be preferred insofar as it offers a greater respect for the adolescent's decisions than the symmetrical alternative. © 2014 John Wiley & Sons Ltd.

Gastric stem cells and gastric cancer stem cells

OpenAIRE

Han, Myoung-Eun; Oh, Sae-Ock

2013-01-01

The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal ev...

Rise of a cold plume

International Nuclear Information System (INIS)

Kakuta, Michio

1977-06-01

The rise of smoke from the stacks of two research reactors in normal operation was measured by photogrametric method. The temperature of effluent gas is less than 20 0 C higher than that of the ambient air (heat emission of the order 10 4 cal s -1 ), and the efflux velocity divided by the wind speed is between 0.5 and 2.8 in all 16 smoke runs. The field data obtained within downwind distance of 150m are compared with those by plume rise formulas presently available. Considering the shape of bending-over plume, the Briggs' formula for 'jet' gives a reasonable explanation of the observed plume rise. (auth.)

Red blood cell production

Science.gov (United States)

... bone marrow of bones. Stem cells in the red bone marrow called hemocytoblasts give rise to all of the formed elements in blood. If a hemocytoblast commits to becoming a cell called a proerythroblast, it will develop into a new red blood cell. The formation of a red blood ...

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

The Rise of CRISPR/Cas for Genome Editing in Stem Cells

Directory of Open Access Journals (Sweden)

Bing Shui

2016-01-01

Full Text Available Genetic manipulation is a powerful tool to establish the causal relationship between a genetic lesion and a particular pathological phenotype. The rise of CRISPR/Cas9 genome-engineering tools overcame the traditional technical bottleneck for routine site-specific genetic manipulation in cells. To create the perfect in vitro cell model, there is significant interest from the stem cell research community to adopt this fast evolving technology. This review addresses this need directly by providing both the up-to-date biochemical rationale of CRISPR-mediated genome engineering and detailed practical guidelines for the design and execution of CRISPR experiments in cell models. Ultimately, this review will serve as a timely and comprehensive guide for this fast developing technology.

Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis.

Science.gov (United States)

Dyment, Nathaniel A; Breidenbach, Andrew P; Schwartz, Andrea G; Russell, Ryan P; Aschbacher-Smith, Lindsey; Liu, Han; Hagiwara, Yusuke; Jiang, Rulang; Thomopoulos, Stavros; Butler, David L; Rowe, David W

2015-09-01

The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh-responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events - from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template - that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage. Copyright © 2015 Elsevier Inc. All rights reserved.

The investigation of minoxidil-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

Science.gov (United States)

Chen, I-Shu; Chou, Chiang-Ting; Liu, Yuan-Yuarn; Yu, Chia-Cheng; Liang, Wei-Zhe; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Chen, Fu-An; Jan, Chung-Ren

2017-02-01

Minoxidil is clinically used to prevent hair loss. However, its effect on Ca 2+ homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca 2+ levels ([Ca 2+ ] i ) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca 2+ ] i rises in a concentration-dependent manner. This Ca 2+ signal was inhibited by 60% by removal of extracellular Ca 2+ . Minoxidil-induced Ca 2+ influx was confirmed by Mn 2+ -induced quench of fura-2 fluorescence. Pre-treatment with the protein kinase C (PKC) inhibitor GF109203X, PKC activator phorbol 12-myristate 13 acetate (PMA), nifedipine and SKF96365 inhibited minoxidil-induced Ca 2+ signal in Ca 2+ containing medium by 60%. Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca 2+ -free medium abolished minoxidil-induced [Ca 2+ ] i rises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca 2+ ] i rises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca 2+ ] i rises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelation of cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent minoxidil's cytotoxicity. Together, in PC3 cells, minoxidil induced [Ca 2+ ] i rises that involved Ca 2+ entry through PKC-regulated store-operated Ca 2+ channels and PLC-dependent Ca 2+ release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca 2+ -independent manner.

Human natural killer cell committed thymocytes and their relation to the T cell lineage

NARCIS (Netherlands)

Sánchez, M. J.; Spits, H.; Lanier, L. L.; Phillips, J. H.

1993-01-01

Recent studies have demonstrated that mature natural killer (NK) cells can be grown from human triple negative (TN; CD3-, CD4-, CD8-) thymocytes, suggesting that a common NK/T cell precursor exists within the thymus that can give rise to both NK cells and T cells under appropriate conditions. In the

Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

NARCIS (Netherlands)

Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

2008-01-01

Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

Legal implications of translational promises of unproven stem cell ...

African Journals Online (AJOL)

2015-08-02

Aug 2, 2015 ... multipotent stem cells are haematopoietic stem cells (HSCs), which give rise ... include diseases such as arthritis, heart attacks, multiple sclerosis, diabetes ... regard to autologous stem cell therapy, where a patient's own stem.

Protein and peptide alkoxyl radicals can give rise to C-terminal decarboxylation and backbone cleavage

DEFF Research Database (Denmark)

Davies, Michael Jonathan

1996-01-01

Previous studies have demonstrated that gamma-irradiation of some free amino acids in the presence of oxygen gives high yields of side-chain hydroperoxides. It is shown in the present study that N-acetyl amino acids and peptides also give high levels of hydroperoxides on gamma-irradiation, even...

Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks.

Science.gov (United States)

Brandon, Mark P; Koenig, Julie; Leutgeb, Stefan

2014-03-01

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type-the place cell. We therefore suggest that parallel information processing in different classes of cells-as is typically observed at lower levels of sensory processing-continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

Stem Cells, Science, and Public Reasoning

Science.gov (United States)

Hurlbut, J. Benjamin; Robert, Jason Scott

2012-01-01

These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

Non-cultured adipose-derived CD45(-) side population cells are enriched for progenitors that give rise to myofibres in vivo

DEFF Research Database (Denmark)

Andersen, Ditte C; Schrøder, Henrik D; Jensen, Charlotte H

2008-01-01

Side population (SP) cells are highly able to exclude the Hoechst 33342 dye through membrane transporters, a feature associated with cell immaturity and therefore proposed as a marker of stem cells. Herein we demonstrate that the adipose tissue derived stromal vascular fraction (SVF) contains...... skeletal muscle repair mainly relies on the satellitecell, several reports have shown that vessel-associated cells may adopt a myogenic phenotype when exposed to a muscle environment. In accordance with these findings, we also observed invitro myogenic specification of SPCD45(-) cells when cocultured...... a novel population of non-haematopoietic "side population" (SPCD45(-)) cells. Simultaneous qRT-PCR of 64 genes revealed that the freshly isolated SPCD45(-) was highly enriched for cells expressing genes related to stem cells, the Notch pathway, and early vascular precursors. Notably, the expression...

Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

OpenAIRE

Hayam Abdel Meguid El Aggan; Mona Abdel Kader Salem; Nahla Mohamed Gamal Farahat; Ahmad Fathy El-Koraie; Ghaly Abd Al-Rahim Mohammed Kotb

2013-01-01

Introduction: Chronic allograft nephropathy (CAN) is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Char...

Modelling cell division and endoreduplication in tomato fruit pericarp

NARCIS (Netherlands)

Apri, M.; Kromdijk, J.; Visser, de P.H.B.; Gee, de M.; Molenaar, J.

2014-01-01

In many developing plant tissues and organs, differentiating cells switch from the classical cell cycle to an alternative partial cycle. This partial cycle bypasses mitosis and allows for multiple rounds of genome duplication without cell division, giving rise to cells with high ploidy numbers. This

Local infection of opium poppy leaves by Peronospora somniferi sporangia can give rise to systemic infections and seed infection in resistant cultivars

Energy Technology Data Exchange (ETDEWEB)

Montes-Borrego, M.; Muñoz-Ledesma, F.J.; Jiménez-Díaz, R.M.; Landa, B.B.

2017-07-01

Downy mildew (DM) of opium poppy (Papaver somniferum) caused by Peronospora somniferi is one of the most destructive diseases of this crop due to the systemic nature of infection as compared with local infections caused by Peronospora meconopsidis, the other downy mildew pathogen of this crop. We developed an inoculation method using Peronospora somniferi sporangia as inoculum and demonstrated for the first time that local infection of leaves by sporangia give rise to systemic infections in the plant as well as of seeds. Our results also showed that this inoculation protocol was very effective in reproducing disease symptoms and assessing the resistance response to DM in opium poppy genotypes under field conditions. More interestingly, results indicate that up to 100% of seed samples from some genotypes showing a complete (symptomless) resistant phenotype were infected by the pathogen when seeds were analyzed by a P. somniferi-specific nested-PCR protocol. This latter aspect deserves further attention while breeding opium poppy for resistance to P. somniferi.

Local infection of opium poppy leaves by Peronospora somniferi sporangia can give rise to systemic infections and seed infection in resistant cultivars

International Nuclear Information System (INIS)

Montes-Borrego, M.; Muñoz-Ledesma, F.J.; Jiménez-Díaz, R.M.; Landa, B.B.

2017-01-01

Downy mildew (DM) of opium poppy (Papaver somniferum) caused by Peronospora somniferi is one of the most destructive diseases of this crop due to the systemic nature of infection as compared with local infections caused by Peronospora meconopsidis, the other downy mildew pathogen of this crop. We developed an inoculation method using Peronospora somniferi sporangia as inoculum and demonstrated for the first time that local infection of leaves by sporangia give rise to systemic infections in the plant as well as of seeds. Our results also showed that this inoculation protocol was very effective in reproducing disease symptoms and assessing the resistance response to DM in opium poppy genotypes under field conditions. More interestingly, results indicate that up to 100% of seed samples from some genotypes showing a complete (symptomless) resistant phenotype were infected by the pathogen when seeds were analyzed by a P. somniferi-specific nested-PCR protocol. This latter aspect deserves further attention while breeding opium poppy for resistance to P. somniferi.

Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

Science.gov (United States)

Slepchenko, Kira G; Li, Yang V

2012-01-01

Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

Identification and Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to Castration-Resistant Prostate Cancer

Science.gov (United States)

2015-10-01

castration-resistance of each subset in humans. We also measured castration-resistance of isolated subsets in vitro in the presence or absence of DHT in...microns). In vitro growth in the absence of DHT also demonstrates castration-resistant properties of the intermediate/luminal progenitor cells...subsets without DHT compared to DHT -containing media, demonstrating castration-resistance). 4 4) other achievements: We found that tumors

Identification and Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to Castration-Resistant Prostate Cancer

Science.gov (United States)

2014-10-01

carcinoma with different signaling pathways characteristic of each histo- logical pattern. eIF4E-driven protein translation pathway is el - evated in...and 4EBP1 ( Epitomics ); Histone H3, AKT, and p4EBP1 (Thr37/46); pErk1/ 2 (T202/Y204), pSTAT3 (Y705), Sox2, MTA1, Src, and pSrc (Y416) (Cell Signaling

Correlation between membrane fluidity cellular development and stem cell differentiation

KAUST Repository

Noutsi, Bakiza Kamal

2016-01-01

Cell membranes are made up of a complex structure of lipids and proteins that diffuse laterally giving rise to what we call membrane fluidity. During cellular development, such as neuronal differentiation, cell membranes undergo dramatic structural

Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells

Directory of Open Access Journals (Sweden)

Kira G. Slepchenko

2012-01-01

Full Text Available Zinc (Zn2+ appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

Pathological modifications of plant stem cell destiny

Science.gov (United States)

In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

Stem Cell, Regenerative Medicine and Cancer | Center for Cancer Research

Science.gov (United States)

Of the estimated trillion cells that build up our bodies, only a little number can self-renew and give rise to many different cell types. These unspecialized cells are called stem cells. Stem cell division and differentiation is fundamental to the development of the mature organism. Stem cells have recently attracted significant attention largely due to their potential medical

The many ways to make a luminal cell and a prostate cancer cell

OpenAIRE

Strand, Douglas W; Goldstein, Andrew S

2015-01-01

Research in the area of stem/progenitor cells has led to the identification of multiple stem-like cell populations implicated in prostate homeostasis and cancer initiation. Given that there are multiple cells that can regenerate prostatic tissue and give rise to prostate cancer, our focus should shift to defining the signaling mechanisms that drive differentiation and progenitor self-renewal. In this article, we will review the literature, present the evidence and raise important unanswered q...

Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells

International Nuclear Information System (INIS)

Sansoni, P.; Silverman, E.D.; Khan, M.M.; Melmon, K.L.; Engleman, E.G.

1985-01-01

One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models

Directory of Open Access Journals (Sweden)

Alexander eHanuschkin

2013-06-01

Full Text Available Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: Random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, they allow for imitating arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions.Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird’s own song

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models.

Science.gov (United States)

Hanuschkin, A; Ganguli, S; Hahnloser, R H R

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli.

Lgr5 Identifies Progenitor Cells Capable of Taste Bud Regeneration after Injury.

Science.gov (United States)

Takeda, Norifumi; Jain, Rajan; Li, Deqiang; Li, Li; Lu, Min Min; Epstein, Jonathan A

2013-01-01

Taste buds are composed of a variety of taste receptor cell types that develop from tongue epithelium and are regularly replenished under normal homeostatic conditions as well as after injury. The characteristics of cells that give rise to regenerating taste buds are poorly understood. Recent studies have suggested that Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) identifies taste bud stem cells that contribute to homeostatic regeneration in adult circumvallate and foliate taste papillae, which are located in the posterior region of the tongue. Taste papillae in the adult anterior region of the tongue do not express Lgr5. Here, we confirm and extend these studies by demonstrating that Lgr5 cells give rise to both anterior and posterior taste buds during development, and are capable of regenerating posterior taste buds after injury induced by glossopharyngeal nerve transection.

Chemoresistance and chemotherapy targeting stem-like cells in malignant glioma

DEFF Research Database (Denmark)

Sørensen, Mia Dahl; Fosmark, Sigurd; Hellwege, Sofie

2015-01-01

Glioblastoma remains a tumor with a dismal prognosis because of failure of current treatment. Glioblastoma cells with stem cell (GSC) properties survive chemotherapy and give rise to tumor recurrences that invariably result in the death of the patients. Here we summarize the current knowledge on ...

Progenitor potential of nkx6.1-expressing cells throughout zebrafish life and during beta cell regeneration.

Science.gov (United States)

Ghaye, Aurélie P; Bergemann, David; Tarifeño-Saldivia, Estefania; Flasse, Lydie C; Von Berg, Virginie; Peers, Bernard; Voz, Marianne L; Manfroid, Isabelle

2015-09-02

In contrast to mammals, the zebrafish has the remarkable capacity to regenerate its pancreatic beta cells very efficiently. Understanding the mechanisms of regeneration in the zebrafish and the differences with mammals will be fundamental to discovering molecules able to stimulate the regeneration process in mammals. To identify the pancreatic cells able to give rise to new beta cells in the zebrafish, we generated new transgenic lines allowing the tracing of multipotent pancreatic progenitors and endocrine precursors. Using novel bacterial artificial chromosome transgenic nkx6.1 and ascl1b reporter lines, we established that nkx6.1-positive cells give rise to all the pancreatic cell types and ascl1b-positive cells give rise to all the endocrine cell types in the zebrafish embryo. These two genes are initially co-expressed in the pancreatic primordium and their domains segregate, not as a result of mutual repression, but through the opposite effects of Notch signaling, maintaining nkx6.1 expression while repressing ascl1b in progenitors. In the adult zebrafish, nkx6.1 expression persists exclusively in the ductal tree at the tip of which its expression coincides with Notch active signaling in centroacinar/terminal end duct cells. Tracing these cells reveals that they are able to differentiate into other ductal cells and into insulin-expressing cells in normal (non-diabetic) animals. This capacity of ductal cells to generate endocrine cells is supported by the detection of ascl1b in the nkx6.1:GFP ductal cell transcriptome. This transcriptome also reveals, besides actors of the Notch and Wnt pathways, several novel markers such as id2a. Finally, we show that beta cell ablation in the adult zebrafish triggers proliferation of ductal cells and their differentiation into insulin-expressing cells. We have shown that, in the zebrafish embryo, nkx6.1+ cells are bona fide multipotent pancreatic progenitors, while ascl1b+ cells represent committed endocrine precursors. In

Plasticity of spermatogonial stem cells

Directory of Open Access Journals (Sweden)

Paul S Cooke

2015-06-01

Full Text Available There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs, and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine.

X-ray-induced in vitro neoplastic transformation of human diploid cells

International Nuclear Information System (INIS)

Borek, C.

1980-01-01

The neoplastic transformation, in vitro, of human diploid cells by x-ray irradiation into cells which can progress, in vitro, into advanced stages of neoplastic development is described. The cells are shown to form colonies in agar and to give rise to tumours when injected into nude mice. (U.K.)

Regeneration of alveolar type I and II cells from Scgb1a1-expressing cells following severe pulmonary damage induced by bleomycin and influenza.

Directory of Open Access Journals (Sweden)

Dahai Zheng

Full Text Available The lung comprises an extensive surface of epithelia constantly exposed to environmental insults. Maintaining the integrity of the alveolar epithelia is critical for lung function and gaseous exchange. However, following severe pulmonary damage, what progenitor cells give rise to alveolar type I and II cells during the regeneration of alveolar epithelia has not been fully determined. In this study, we have investigated this issue by using transgenic mice in which Scgb1a1-expressing cells and their progeny can be genetically labeled with EGFP. We show that following severe alveolar damage induced either by bleomycin or by infection with influenza virus, the majority of the newly generated alveolar type II cells in the damaged parenchyma were labeled with EGFP. A large proportion of EGFP-expressing type I cells were also observed among the type II cells. These findings strongly suggest that Scgb1a1-expressing cells, most likely Clara cells, are a major cell type that gives rise to alveolar type I and II cells during the regeneration of alveolar epithelia in response to severe pulmonary damage in mice.

A Set of Regioselective O-Methyltransferases Gives Rise to the Complex Pattern of Methoxylated Flavones in Sweet Basil1[C][W][OA

Science.gov (United States)

Berim, Anna; Hyatt, David C.; Gang, David R.

2012-01-01

Polymethoxylated flavonoids occur in a number of plant families, including the Lamiaceae. To date, the metabolic pathways giving rise to the diversity of these compounds have not been studied. Analysis of our expressed sequence tag database for four sweet basil (Ocimum basilicum) lines afforded identification of candidate flavonoid O-methyltransferase genes. Recombinant proteins displayed distinct substrate preferences and product specificities that can account for all detected 7-/6-/4′-methylated, 8-unsubstituted flavones. Their biochemical specialization revealed only certain metabolic routes to be highly favorable and therefore likely in vivo. Flavonoid O-methyltransferases catalyzing 4′- and 6-O-methylations shared high identity (approximately 90%), indicating that subtle sequence changes led to functional differentiation. Structure homology modeling suggested the involvement of several amino acid residues in defining the proteins’ stringent regioselectivities. The roles of these individual residues were confirmed by site-directed mutagenesis, revealing two discrete mechanisms as a basis for the switch between 6- and 4′-O-methylation of two different substrates. These findings delineate major pathways in a large segment of the flavone metabolic network and provide a foundation for its further elucidation. PMID:22923679

IODP Expedition 324: Ocean Drilling at Shatsky Rise Gives Clues about Oceanic Plateau Formation

Directory of Open Access Journals (Sweden)

Jörg Geldmacher

2011-09-01

Full Text Available Integrated Ocean Drilling Program (IODP Expedition 324 cored Shatsky Rise at five sites (U1346–U1350 to study processes of oceanic plateau formation and evolution. Site penetrations ranged from 191.8 m to 324.1 m with coring of 52.6 m to 172.7 m into igneous basement at four of the sites. Average recovery in basement was 38.7%–67.4%. Cored igneous sections consist mainly of variably evolved tholeiiticbasalts emplaced as pillows or massive flows. Massive flows are thickest and make up the largest percentage of section on the largest and oldest volcano, late Jurassic age Tamu Massif; thus, it may have formed at high effusion rates. Such massive flows are characteristic of flood basalts, and similar flows were cored at Ontong Java Plateau. Indeed, the similarity of igneous sections at Site U1347 with that cored on Ontong Java Plateau implies similar volcanic styles for these two plateaus. On younger, smaller Shatsky Rise volcanoes, pillow flows are common and massive flows thinner andfewer, which might mean volcanism waned with time. Cored sediments from summit sites contain fossils and structures implying shallow water depths or emergence at the time of eruption and normal subsidence since. Summit sites also show pervasive alteration that could be due to high fluid fluxes. A thick section of volcaniclastics cored on Tamu Massif suggests that shallow, explosive submarine volcanism played a significant role in the geologic development of the plateau summit. Expedition 324 results imply that Shatsky Risebegan with massive eruptions forming a huge volcano and that subsequent eruptions waned in intensity, forming volcanoes that are large, but which did not erupt with unusually high effusionrates. Similarities of cored sections on Tamu Massif with those ofOntong Java Plateau indicate that these oceanic plateaus formed insimilar fashion.

Engineered photoproteins that give rise to photosynthetically-incompetent bacteria are effective as photovoltaic materials for biohybrid photoelectrochemical cells.

Science.gov (United States)

Liu, Juntai; Friebe, Vincent M; Swainsbury, David J K; Crouch, Lucy I; Szabo, David A; Frese, Raoul N; Jones, Michael R

2018-04-17

Reaction centre/light harvesting proteins such as the RCLH1X complex from Rhodobacter sphaeroides carry out highly quantum-efficient conversion of solar energy through ultrafast energy transfer and charge separation, and these pigment-proteins have been incorporated into biohybrid photoelectrochemical cells for a variety of applications. In this work we demonstrate that, despite not being able to support normal photosynthetic growth of Rhodobacter sphaeroides, an engineered variant of this RCLH1X complex lacking the PufX protein and with an enlarged light harvesting antenna is unimpaired in its capacity for photocurrent generation in two types of bio-photoelectrochemical cells. Removal of PufX also did not impair the ability of the RCLH1 complex to act as an acceptor of energy from synthetic light harvesting quantum dots. Unexpectedly, the removal of PufX led to a marked improvement in the overall stability of the RCLH1 complex under heat stress. We conclude that PufX-deficient RCLH1 complexes are fully functional in solar energy conversion in a device setting and that their enhanced structural stability could make them a preferred choice over their native PufX-containing counterpart. Our findings on the competence of RCLH1 complexes for light energy conversion in vitro are discussed with reference to the reason why these PufX-deficient proteins are not capable of light energy conversion in vivo.

Relativistic rise measurement by cluster counting method in time expansion chamber

International Nuclear Information System (INIS)

Rehak, P.; Walenta, A.H.

1979-10-01

A new approach to the measurement of the ionization energy loss for the charged particle identification in the region of the relativistic rise was tested experimentally. The method consists of determining in a special drift chamber (TEC) the number of clusters of the primary ionization. The method gives almost the full relativistic rise and narrower landau distribution. The consequences for a practical detector are discussed

Non-Random Chromosome Segregation in Stem Cells

OpenAIRE

Conboy, Michael J; Karasov, Ariela O; Rando, Thomas A

2007-01-01

Decades ago, the "immortal strand hypothesis" was proposed as a means by which stem cells might limit acquiring mutations that could give rise to cancer, while continuing to proliferate for the life of an organism. Originally based on observations in embryonic cells, and later studied in terms of stem cell self-renewal, this hypothesis has remained largely unaccepted because of few additional reports, the rarity of the cells displaying template strand segregation, and alternative interpretati...

Lgr5 Identifies Progenitor Cells Capable of Taste Bud Regeneration after Injury.

Directory of Open Access Journals (Sweden)

Norifumi Takeda

Full Text Available Taste buds are composed of a variety of taste receptor cell types that develop from tongue epithelium and are regularly replenished under normal homeostatic conditions as well as after injury. The characteristics of cells that give rise to regenerating taste buds are poorly understood. Recent studies have suggested that Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5 identifies taste bud stem cells that contribute to homeostatic regeneration in adult circumvallate and foliate taste papillae, which are located in the posterior region of the tongue. Taste papillae in the adult anterior region of the tongue do not express Lgr5. Here, we confirm and extend these studies by demonstrating that Lgr5 cells give rise to both anterior and posterior taste buds during development, and are capable of regenerating posterior taste buds after injury induced by glossopharyngeal nerve transection.

Photo-oxidation of cells generates long-lived intracellular protein peroxides

DEFF Research Database (Denmark)

Wright, Adam; Hawkins, Clare Louise; Davies, Michael Jonathan

2003-01-01

Singlet oxygen is generated by several cellular, enzymatic, and chemical reactions as well as by exposure to UV or visible light in the presence of a sensitizer. Consequently, this oxidant has been proposed to be a damaging agent many pathologies. Proteins are major targets for singlet oxygen...... as a result of their abundance and high rate constants for reaction. In this study, we show that illumination of viable rose bengal-loaded THP-1 (human monocyte-like) cells with visible light gives rise to intracellular protein-derived peroxides. The peroxide yield increases with illumination time, requires....../2) about 4 h at 37 degrees C. Decomposition of protein peroxides formed within cells, or on isolated cellular proteins, by metal ions gives rise to radicals as detected by EPR spin trapping. These studies demonstrate that exposure of intact cells to visible light in the presence of a sensitizer leads...

The Bony Side of Endothelial Cells in Prostate Cancer.

Science.gov (United States)

Peng, Jia; Kang, Yibin

2017-06-05

Prostate cancer bone metastases are primarily osteoblastic, but the source of bone-forming cells in these lesions remains poorly defined. In this issue of Developmental Cell, Lin et al. (2017) demonstrate that tumor-associated endothelial cells can give rise to osteoblasts in prostate cancer through endothelial-to-osteoblast (EC-to-OSB) conversion. Copyright © 2017 Elsevier Inc. All rights reserved.

Retinoic acid: an educational "vitamin elixir" for gut-seeking T cells.

Science.gov (United States)

Mora, J Rodrigo; von Andrian, Ulrich H

2004-10-01

T cell priming by dendritic cells (DC) from gut-associated lymphoid tissues gives rise to effector cells with pronounced gut tropism. The mechanism for DC-dependent imprinting of gut specificity has remained unknown. New findings point to retinoic acid, which is uniquely produced by intestinal DC, but not by DC from other lymphoid organs.

Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes

Science.gov (United States)

Zhang, Mingfeng; Lin, Qing; Qi, Tong; Wang, Tiankun; Chen, Ching-Cheng; Riggs, Arthur D.; Zeng, Defu

2016-01-01

We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9+ (Sox9+) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9+ ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9+ ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300–450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9+ ductal cell differentiation into β cells in adult mice. PMID:26733677

Control of the proportion of inner cells by asymmetric divisions and the ensuing resilience of cloned rabbit embryos

Science.gov (United States)

Duranthon, Véronique

2018-01-01

ABSTRACT Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps that segregate outer cells, which are fated to extra-embryonic tissues, from inner cells, which give rise to the embryo proper. Exploring the cell lineage of wild-type embryos and clones, imaged in toto until hatching, highlights the respective contributions of cell proliferation, death and asymmetric divisions to phenotypic variability. Preferential cell death of inner cells in clones, probably pertaining to the epigenetic plasticity of the transferred nucleus, is identified as a major difference with effects on the proportion of inner cell. In wild type and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust proportion of inner cells observed in wild type. Asymmetric inner cell division, which is not described in mice, is identified as a regulator of the proportion of inner cells and likely gives rise to resilient clones. PMID:29567671

Transcriptomic comparisons between cultured human adipose tissue-derived pericytes and mesenchymal stromal cells

Directory of Open Access Journals (Sweden)

Lindolfo da Silva Meirelles

2016-03-01

Full Text Available Mesenchymal stromal cells (MSCs, sometimes called mesenchymal stem cells, are cultured cells able to give rise to mature mesenchymal cells such as adipocytes, osteoblasts, and chondrocytes, and to secrete a wide range of trophic and immunomodulatory molecules. Evidence indicates that pericytes, cells that surround and maintain physical connections with endothelial cells in blood vessels, can give rise to MSCs (da Silva Meirelles et al., 2008 [1]; Caplan and Correa, 2011 [2]. We have compared the transcriptomes of highly purified, human adipose tissue pericytes subjected to culture-expansion in pericyte medium or MSC medium, with that of human adipose tissue MSCs isolated with traditional methods to test the hypothesis that their transcriptomes are similar (da Silva Meirelles et al., 2015 [3]. Here, we provide further information and analyses of microarray data from three pericyte populations cultured in pericyte medium, three pericyte populations cultured in MSC medium, and three adipose tissue MSC populations deposited in the Gene Expression Omnibus under accession number GSE67747. Keywords: Mesenchymal stromal cells, Mesenchymal stem cells, Pericytes, Microarrays

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

Science.gov (United States)

Greim, Helmut; Kaden, Debra A.; Larson, Richard A.; Palermo, Christine M.; Rice, Jerry M.; Ross, David; Snyder, Robert

2014-01-01

Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy–induced disease. PMID:24495159

Noticeable rise in incidence of Hurthle cell carcinoma - Are we paying the Chernobyl toll ?

International Nuclear Information System (INIS)

Vojicic, J.; Popadic, S.; Malesevic, M.; Kermeci, K.; Peter, A.

2004-01-01

Full text: The Institute of Oncology in Sremska Kamenica is a reference centre for radioiodine treatment of different thyroid cancer (DTC) in our country. The majority of patients operated for DTC throughout the country are sent to us for further diagnostics and/or therapy. In our practice, we noticed a rising incidence of Hurthle cell cancer (HCC) during the past several years. We wanted to determine if there is statistically significant difference in the incidence of Hurthle cell cancer between several previous years. Data from the patients referred to our institution for 131-I whole body scanning and/or therapy between January 1998 and August 2003 were used to determine the incidence of HCC, which was presented as the percentage of total number of patients who were diagnosed to have DTC in the specific year. χ 2 test was used to test for significance of differences between the years. In the aforementioned period, there was a total number of 394 DTC patients among whom 17 with follicular carcinoma of oxyphyllic type (so called Hurthle cell carcinoma). Presented in percentage, the distribution of HCC throughout the years is as follows: 1998-0%; 1999-0%; 2000-3.85%; 2001-4.55%; 2002-5.3%; 2003-7.6%. We found significant difference (p<0.05 or less) between the incidence of HCC in year 2003 and all the previous years; also between years 1998 and 1999 and year of 2002 (p<0.05). These results show a rising incidence of Hurthle cell carcinoma over the past several years, with a significant peak in the year of 2003. Since these tumors also tend to show more aggressive clinical behaviour than they used to, our belief is that we might now be paying the toll of the Chernobyl accident. (author)

The Bone Marrow-Derived Stromal Cells

DEFF Research Database (Denmark)

Tencerova, Michaela; Kassem, Moustapha

2016-01-01

Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone...... diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage...

Stem cells and the evolving notion of cellular identity

OpenAIRE

Daley, George Q.

2015-01-01

Stem cells are but one class of the myriad types of cells within an organism. With potential to self-renew and capacity to differentiate, stem cells play essential roles at multiple stages of development. In the early embryo, pluripotent stem cells represent progenitors for all tissues while later in development, tissue-restricted stem cells give rise to cells with highly specialized functions. As best understood in the blood, skin and gut, stem cells are the seeds that sustain tissue homeost...

Secret handshakes: cell-cell interactions and cellular mimics.

Science.gov (United States)

Cohen, Daniel J; Nelson, W James

2018-02-01

Cell-cell junctions, acting as 'secret handshakes', mediate cell-cell interactions and make multicellularity possible. Work over the previous century illuminated key players comprising these junctions including the cadherin superfamily, nectins, CAMs, connexins, notch/delta, lectins, and eph/Ephrins. Recent work has focused on elucidating how interactions between these complex and often contradictory cues can ultimately give rise to large-scale organization in tissues. This effort, in turn, has enabled bioengineering advances such as cell-mimetic interfaces that allow us to better probe junction biology and to develop new biomaterials. This review details exciting, recent developments in these areas as well as providing both historical context and a discussion of some topical challenges and opportunities for the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

The many ways to make a luminal cell and a prostate cancer cell.

Science.gov (United States)

Strand, Douglas W; Goldstein, Andrew S

2015-12-01

Research in the area of stem/progenitor cells has led to the identification of multiple stem-like cell populations implicated in prostate homeostasis and cancer initiation. Given that there are multiple cells that can regenerate prostatic tissue and give rise to prostate cancer, our focus should shift to defining the signaling mechanisms that drive differentiation and progenitor self-renewal. In this article, we will review the literature, present the evidence and raise important unanswered questions that will help guide the field forward in dissecting critical mechanisms regulating stem-cell differentiation and tumor initiation. © 2015 Society for Endocrinology.

Histone H1- and other protein- and amino acid-hydroperoxides can give rise to free radicals which oxidize DNA

DEFF Research Database (Denmark)

Luxford, C; Morin, B; Dean, R T

1999-01-01

analysis has demonstrated that radicals from histone H1-hydroperoxides, and other protein and amino acid hydroperoxides, can also oxidize both free 2'-deoxyguanosine and intact calf thymus DNA to give the mutagenic oxidized base 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine, 8-oxod......Exposure of amino acids, peptides and proteins to radicals, in the presence of oxygen, gives high yields of hydroperoxides. These materials are readily decomposed by transition metal ions to give further radicals. We hypothesized that hydroperoxide formation on nuclear proteins, and subsequent...... decomposition of these hydroperoxides to radicals, might result in oxidative damage to associated DNA. We demonstrate here that exposure of histone H1 and model compounds to gamma-radiation in the presence of oxygen gives hydroperoxides in a dose-dependent manner. These hydroperoxides decompose to oxygen...

Singlet oxygen-mediated formation of protein peroxides within cells

International Nuclear Information System (INIS)

Wright, A.; Policarpio, V.

2003-01-01

Full text: Singlet oxygen is generated by a number of cellular, enzymatic and chemical reactions as well as by exposure to UV, or visible light in the presence of a sensitizer; as a consequence this oxidant has been proposed as a damaging agent in a number of pathologies including photo-aging and skin cancer. Proteins are major targets for singlet oxygen as a result of their abundance and high rate constants for reaction. In this study it is shown that illumination of viable, sensitizer-loaded, THP-1 (human monocyte-like) cells with visible light gives rise to intra-cellular protein-derived peroxides. The peroxide yield increases with illumination time, requires the presence of the sensitizer, is enhanced in D 2 O, and decreased by azide; these data are consistent with the mediation of singlet oxygen. The concentration of peroxides detected, which is not affected by glucose or ascorbate loading of the cells, corresponds to ca. 1.5 nmoles peroxide per 10 6 cells using rose bengal as sensitizer, or 10 nmoles per mg cell protein and account for up to ca. 15% of the O 2 consumed by the cells. Similar peroxides have been detected on isolated cellular proteins exposed to light in the presence of rose bengal and oxygen. After cessation of illumination, the cellular protein peroxide levels decreases with t 1/2 ca. 4 hrs at 37 deg C, and this is associated with increased cell lysis. Decomposition of protein peroxides formed within cells, or on isolated cellular proteins, by metal ions, gives rise to radicals as detected by EPR spin trapping. These protein peroxides, and radicals derived from them, can inactivate key cellular enzymes (including caspases, GAPDH and glutathione reductase) and induce DNA base oxidation, strand breaks and DNA-protein cross-links. These studies demonstrate that exposure of intact cells to visible light in the presence of a sensitizer gives rise to novel long-lived, but reactive, intra-cellular protein peroxides via singlet oxygen

Repair and regeneration: opportunities for carcinogenesis from tissue stem cells

OpenAIRE

Perryman, Scott V; Sylvester, Karl G

2007-01-01

This review will discuss the mechanisms of repair and regeneration in various tissue types and how dysregulation of these mechaisms may lead to cancer. Normal homeostasis involves a careful balance between cell loss and cell renewal. Stem and progenitor cells perform these biologic processes as the functional units of regeneration during both tissue homeostasis and repair. The concept of tissue stem cells capable of giving rise to all differentiated cells within a given tissue led to the conc...

In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus

Science.gov (United States)

Suh, Hoonkyo; Consiglio, Antonella; Ray, Jasodhara; Sawai, Toru; D'Amour, Kevin A.; Gage, Fred H.

2007-01-01

Summary To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate tracing studies showed that Sox2+ cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as a single cell level. More interestingly, a subpopulation of Sox2+ cells gives rise to cells that retain Sox2, highlighting Sox2+ cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2+ cells is coupled with the generation of Sox2+ NSCs as well as neuronal precursors. An asymmetric contribution of Sox2+ NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis. PMID:18371391

Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors

Directory of Open Access Journals (Sweden)

Julie Helft

2017-07-01

Full Text Available Conventional dendritic cells (cDCs are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP. However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A and CD141 (BDCA-3. Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.

Epigenetic control of root and nodule development : the role of plant-specific histone deacetylases and LHP1 in root cell reprogramming

NARCIS (Netherlands)

Schilderink, S.

2012-01-01

In plants, unlike in animals, most organs develop post embryonically. These organs originate from clusters of undifferentiated dividing cells that form so-called meristems. Differentiated cells can be re-activated to enter the cell cycle and to ultimately give rise to new meristems. These

Teratoma Formation by Human Embryonic Stem Cells is site-dependent and enhanced by the presence of Matrigel

DEFF Research Database (Denmark)

Prokhorova, Tatyana A; Harkness, Linda M; Frandsen, Ulrik

2008-01-01

When implanted into immunodeficient mice, human embryonic stem cells (hESC) give rise to teratoma, tumour-like formations containing tissues belonging to all three germ layers. The ability to form teratoma is a sine qua non characteristic of pluripotent stem cells. However, limited data...

The long adventurous journey of rhombic lip cells in jawed vertebrates: a comparative developmental analysis

Directory of Open Access Journals (Sweden)

Mario F Wullimann

2011-04-01

Full Text Available This review summarizes vertebrate rhombic lip and early cerebellar development covering classic approaches up to modern developmental genetics which identifies the relevant differential gene expression domains and their progeny. Most of this information is derived from amniotes. However, progress in anamniotes, particularly in the zebrafish, has recently been made. The current picture suggests that rhombic lip and cerebellar development in jawed vertebrates (gnathostomes share many characteristics. Regarding cerebellar development, these include a ptf1a expressing ventral cerebellar proliferation (VCP giving rise to Purkinje cells and other inhibitory cerebellar cell types, and an atoh1 expressing upper rhombic lip giving rise to an external granular layer (EGL, i.e., excitatory granule cells and an early ventral migration into the anterior rhombencephalon (cholinergic nuclei. As for the lower rhombic lip (LRL, gnathostome commonalities likely include the formation of precerebellar nuclei (mossy fiber origins and partially primary auditory nuclei (likely convergently evolved from the atoh1 expressing dorsal zone. The fate of the ptf1a expressing ventral LRL zone which gives rise to (excitatory cells of the inferior olive (climbing fiber origin and (inhibitory cells of cochlear nuclei in amniotes, has not been determined in anamniotes. Special for the zebrafish in comparison to amniotes is the predominant origin of anamniote excitatory deep cerebellar nuclei homologues (i.e., eurydendroid cells from ptf1a expressing VCP cells, the sequential activity of various atoh1 paralogues and the incomplete coverage of the subpial cerebellar plate with proliferative EGL cells. Nevertheless, the conclusion that a rhombic lip and its major derivatives evolved with gnathostome vertebrates only and are thus not an ancestral craniate character complex is supported by the absence of a cerebellum (and likely absence of its afferent and efferent nuclei in jawless

Male and female stem cells and sex reversal in Hydra polyps

OpenAIRE

Bosch, Thomas C. G.; David, Charles N.

1986-01-01

Single interstitial stem cells of male polyps of Hydra magnipapillata give rise to clones that differentiate either male or female gametes. To test the sexual stability of these clones, stem cells were recloned. The results indicate that stem cells from female clones are stable in their sexual differentiation capacity; male stem cells, by comparison, switch sexual phenotype at the rate of 10-2 per cell per generation. As a result, female polyps contain only female stem cells; male polyps cont...

A versatile class of cell surface directional motors gives rise to gliding motility and sporulation in Myxococcus xanthus.

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Morgane Wartel

2013-12-01

Full Text Available Eukaryotic cells utilize an arsenal of processive transport systems to deliver macromolecules to specific subcellular sites. In prokaryotes, such transport mechanisms have only been shown to mediate gliding motility, a form of microbial surface translocation. Here, we show that the motility function of the Myxococcus xanthus Agl-Glt machinery results from the recent specialization of a versatile class of bacterial transporters. Specifically, we demonstrate that the Agl motility motor is modular and dissociates from the rest of the gliding machinery (the Glt complex to bind the newly expressed Nfs complex, a close Glt paralogue, during sporulation. Following this association, the Agl system transports Nfs proteins directionally around the spore surface. Since the main spore coat polymer is secreted at discrete sites around the spore surface, its transport by Agl-Nfs ensures its distribution around the spore. Thus, the Agl-Glt/Nfs machineries may constitute a novel class of directional bacterial surface transporters that can be diversified to specific tasks depending on the cognate cargo and machinery-specific accessories.

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization.

Science.gov (United States)

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-04-30

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization

Science.gov (United States)

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-05-01

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting

Skeletal Muscle-derived Hematopoietic Stem Cells: Muscular Dystrophy Therapy by Bone Marrow Transplantation

OpenAIRE

Asakura, Atsushi

2012-01-01

For postnatal growth and regeneration of skeletal muscle, satellite cells, a self-renewing pool of muscle stem cells, give rise to daughter myogenic precursor cells that contribute to the formation of new muscle fibers. In addition to this key myogenic cell class, adult skeletal muscle also contains hematopoietic stem cell and progenitor cell populations which can be purified as a side population (SP) fraction or as a hematopoietic marker CD45-positive cell population. These muscle-derived he...

Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

Science.gov (United States)

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

Asymmetry and aging of mycobacterial cells leads to variable growth and antibiotic susceptibility

OpenAIRE

Aldridge, Bree B.; Fernandez-Suarez, Marta; Heller, Danielle; Ambravaneswaran, Vijay; Irimia, Daniel; Toner, Mehmet; Fortune, Sarah

2011-01-01

Cells use both deterministic and stochastic mechanisms to generate cell–to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is significant deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because ...

Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

OpenAIRE

Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua

2015-01-01

Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells ...

Modulating Leukemia-Initiating Cell Quiescence to Improve Leukemia Treatment

Science.gov (United States)

2015-09-01

T- cells and in innate immunity (Lacorazza et al., 2002). It controls the proliferation and homing of CD8+ T- cells via the Kruppel-like factors...Lin2Sca12IL7R2Kit1FccRII/ IIIhighCD34high), megakaryocyte-erythroid progenitor cell (MEP) (Lin2Sca12IL7R2Kit1FccRII/IIIlowCD34low), and common lymphoid ...to this model, the first wave gives rise exclusively to innate immune B cells in early embryonic life and may be derived from progenitor cells

Jagged gives endothelial tip cells an edge.

Science.gov (United States)

Suchting, Steven; Eichmann, Anne

2009-06-12

Sprouting blood vessels have tip cells that lead and stalk cells that follow. Benedito et al. (2009) now show that competition between endothelial cells for the tip position is regulated by glycosylation of Notch receptors and by the opposing actions of the Notch ligands Jagged1 and Delta-like 4.

Sox5 Functions as a Fate Switch in Medaka Pigment Cell Development

Science.gov (United States)

Nagao, Yusuke; Suzuki, Takao; Shimizu, Atsushi; Kimura, Tetsuaki; Seki, Ryoko; Adachi, Tomoko; Inoue, Chikako; Omae, Yoshihiro; Kamei, Yasuhiro; Hara, Ikuyo; Taniguchi, Yoshihito; Naruse, Kiyoshi; Wakamatsu, Yuko; Kelsh, Robert N.; Hibi, Masahiko; Hashimoto, Hisashi

2014-01-01

Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs) are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores), making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3) mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore) from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor). PMID:24699463

Sox5 functions as a fate switch in medaka pigment cell development.

Directory of Open Access Journals (Sweden)

Yusuke Nagao

2014-04-01

Full Text Available Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores, making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3 mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor.

Stem Cells from Dental Pulp: What Epigenetics Can Do with Your Tooth

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Beatriz A. Rodas-Junco

2017-12-01

Full Text Available Adult stem cells have attracted scientific attention because they are able to self-renew and differentiate into several specialized cell types. In this context, human dental tissue-derived mesenchymal stem cells (hDT-MSCs have emerged as a possible solution for repairing or regenerating damaged tissues. These cells can be isolated from primary teeth that are naturally replaced, third molars, or other dental tissues and exhibit self-renewal, a high proliferative rate and a great multilineage potential. However, the cellular and molecular mechanisms that determine lineage specification are still largely unknown. It is known that a change in cell fate requires the deletion of existing transcriptional programs, followed by the establishment of a new developmental program to give rise to a new cell lineage. Increasing evidence indicates that chromatin structure conformation can influence cell fate. In this way, reversible chemical modifications at the DNA or histone level, and combinations thereof can activate or inactivate cell-type-specific gene sequences, giving rise to an alternative cell fates. On the other hand, miRNAs are starting to emerge as a possible player in establishing particular somatic lineages. In this review, we discuss two new and promising research fields in medicine and biology, epigenetics and stem cells, by summarizing the properties of hDT-MSCs and highlighting the recent findings on epigenetic contributions to the regulation of cellular differentiation.

X-ray-induced in vitro neoplastic transformation of human diploid cells

International Nuclear Information System (INIS)

Borek, C.

1980-01-01

Techniques have recently been developed to identify and score quantitatively neoplastic transformation caused by x-rays in cultured cells derived from rodents. The present report describes for the first time the neoplastic transformation in vitro of human diploid cells by x-ray irradiation into cells which can progress in vitro into advanced stages of neoplastic development, namely, to form colonies in agar and give rise to tumors when injected into nude mice

Reconciling projections of the Antarctic contribution to sea level rise

Science.gov (United States)

Edwards, Tamsin; Holden, Philip; Edwards, Neil; Wernecke, Andreas

2017-04-01

Two recent studies of the Antarctic contribution to sea level rise this century had best estimates that differed by an order of magnitude (around 10 cm and 1 m by 2100). The first, Ritz et al. (2015), used a model calibrated with satellite data, giving a 5% probability of exceeding 30cm by 2100 for sea level rise due to Antarctic instability. The second, DeConto and Pollard (2016), used a model evaluated with reconstructions of palaeo-sea level. They did not estimate probabilities, but using a simple assumption here about the distribution shape gives up to a 5% chance of Antarctic contribution exceeding 2.3 m this century with total sea level rise approaching 3 m. If robust, this would have very substantial implications for global adaptation to climate change. How are we to make sense of this apparent inconsistency? How much is down to the data - does the past tell us we will face widespread and rapid Antarctic ice losses in the future? How much is due to the mechanism of rapid ice loss ('cliff failure') proposed in the latter paper, or other parameterisation choices in these low resolution models (GRISLI and PISM, respectively)? How much is due to choices made in the ensemble design and calibration? How do these projections compare with high resolution, grounding line resolving models such as BISICLES? Could we reduce the huge uncertainties in the palaeo-study? Emulation provides a powerful tool for understanding these questions and reconciling the projections. By describing the three numerical ice sheet models with statistical models, we can re-analyse the ensembles and re-do the calibrations under a common statistical framework. This reduces uncertainty in the PISM study because it allows massive sampling of the parameter space, which reduces the sensitivity to reconstructed palaeo-sea level values and also narrows the probability intervals because the simple assumption about distribution shape above is no longer needed. We present reconciled probabilistic

Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

DEFF Research Database (Denmark)

Kim, Yung Hae; Larsen, Hjalte List; Rué, Paul

2015-01-01

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine...

Posttranscriptional (Re)programming of Cell Fate: Examples in Stem Cells, Progenitor, and Differentiated Cells.

Science.gov (United States)

Kanellopoulou, Chrysi; Muljo, Stefan A

2018-01-01

How a single genome can give rise to many different transcriptomes and thus all the different cell lineages in the human body is a fundamental question in biology. While signaling pathways, transcription factors, and chromatin architecture, to name a few determinants, have been established to play critical roles, recently, there is a growing appreciation of the roles of non-coding RNAs and RNA-binding proteins in controlling cell fates posttranscriptionally. Thus, it is vital that these emerging players are also integrated into models of gene regulatory networks that underlie programs of cellular differentiation. Sometimes, we can leverage knowledge about such posttranscriptional circuits to reprogram patterns of gene expression in meaningful ways. Here, we review three examples from our work.

Completely ES cell-derived mice produced by tetraploid complementation using inner cell mass (ICM deficient blastocysts.

Directory of Open Access Journals (Sweden)

Duancheng Wen

Full Text Available Tetraploid complementation is often used to produce mice from embryonic stem cells (ESCs by injection of diploid (2n ESCs into tetraploid (4n blastocysts (ESC-derived mice. This method has also been adapted to mouse cloning and the derivation of mice from induced pluripotent stem (iPS cells. However, the underlying mechanism(s of the tetraploid complementation remains largely unclear. Whether this approach can give rise to completely ES cell-derived mice is an open question, and has not yet been unambiguously proven. Here, we show that mouse tetraploid blastocysts can be classified into two groups, according to the presence or absence of an inner cell mass (ICM. We designate these as type a (presence of ICM at blastocyst stage or type b (absence of ICM. ESC lines were readily derived from type a blastocysts, suggesting that these embryos retain a pluripotent epiblast compartment; whereas the type b blastocysts possessed very low potential to give rise to ESC lines, suggesting that they had lost the pluripotent epiblast. When the type a blastocysts were used for tetraploid complementation, some of the resulting mice were found to be 2n/4n chimeric; whereas when type b blastocysts were used as hosts, the resulting mice are all completely ES cell-derived, with the newborn pups displaying a high frequency of abdominal hernias. Our results demonstrate that completely ES cell-derived mice can be produced using ICM-deficient 4n blastocysts, and provide evidence that the exclusion of tetraploid cells from the fetus in 2n/4n chimeras can largely be attributed to the formation of ICM-deficient blastocysts.

To give or not to give, that's the question: How methodology is destiny in Dutch giving data

NARCIS (Netherlands)

Bekkers, R.H.F.P.; Wiepking, P.

2006-01-01

In research on giving, methodology is destiny. The volume of donations estimated from sample surveys strongly depends on the length of the questionnaire used to measure giving. By comparing two giving surveys from the Netherlands, the authors show that a short questionnaire on giving not only

Single-cell protein secretomic signatures as potential correlates to tumor cell lineage evolution and cell-cell interaction

Directory of Open Access Journals (Sweden)

Minsuk eKwak

2013-02-01

Full Text Available Secreted proteins including cytokines, chemokines and growth factors represent important functional regulators mediating a range of cellular behavior and cell-cell paracrine/autocrine signaling, e.g. in the immunological system, tumor microenvironment or stem cell niche. Detection of these proteins is of great value not only in basic cell biology but also for diagnosis and therapeutic monitoring of human diseases such as cancer. However, due to co-production of multiple effector proteins from a single cell, referred to as polyfunctionality, it is biologically informative to measure a panel of secreted proteins, or secretomic signature, at the level of single cells. Recent evidence further indicates that a genetically-identical cell population can give rise to diverse phenotypic differences. It is known that cytokines, for example, in the immune system define the effector functions and lineage differentiation of immune cells. In this Perspective Article, we hypothesize that protein secretion profile may represent a universal measure to identify the definitive correlate in the larger context of cellular functions to dissect cellular heterogeneity and evolutionary lineage relationship in human cancer.

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

Tbx1 coordinates addition of posterior second heart field progenitor cells to the arterial and venous poles of the heart

NARCIS (Netherlands)

Rana, M. Sameer; Théveniau-Ruissy, Magali; de Bono, Christopher; Mesbah, Karim; Francou, Alexandre; Rammah, Mayyasa; Domínguez, Jorge N.; Roux, Marine; Laforest, Brigitte; Anderson, Robert H.; Mohun, Timothy; Zaffran, Stephane; Christoffels, Vincent M.; Kelly, Robert G.

2014-01-01

Cardiac progenitor cells from the second heart field (SHF) contribute to rapid growth of the embryonic heart, giving rise to right ventricular and outflow tract (OFT) myocardium at the arterial pole of the heart, and atrial myocardium at the venous pole. Recent clonal analysis and cell-tracing

Hypochlorite- and hypobromite-mediated radical formation and its role in cell lysis

DEFF Research Database (Denmark)

Hawkins, C L; Brown, B E; Davies, Michael Jonathan

2001-01-01

. In this study it is shown that HOBr induces red blood cell lysis at approximately 10-fold lower concentrations than HOCl, whereas with monocyte (THP1) and macrophage (J774) cells HOCl and HOBr induce lysis at similar concentrations. The role of radical formation during lysis has been investigated by EPR spin...... trapping, and it is shown that reaction of both oxidants with each cell type generates cell-derived radicals. Red blood cells exposed to nonlytic doses of HOCl generate novel nitrogen-centered radicals whose formation is GSH dependent. In contrast, HOBr gives rise to nitrogen-centered, membrane......-derived protein radicals. With lytic doses of either oxidant, protein (probably hemoglobin)-derived, nitrogen-centered radicals are observed. Unlike the red blood cells, treatment of monocytes and macrophages with HOCl gives significant radical formation only under conditions where cell lysis occurs concurrently...

Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

Directory of Open Access Journals (Sweden)

Brand Andrea H

2007-01-01

Full Text Available Abstract Background The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. Results Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. Conclusion We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

Stem cell plasticity.

Science.gov (United States)

Lakshmipathy, Uma; Verfaillie, Catherine

2005-01-01

The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

Shapes and rising velocities of single bubbles rising through an inner subchannel

International Nuclear Information System (INIS)

Tomiyama, Akio; Nakahara, Yusuke; Adachi, Yoshihiro; Hosokawa, Shigeo

2003-01-01

Shapes and velocities of single air bubbles rising through stagnant and flowing waters in an inner subchannel are measured by making use of fluorocarbon tubes. It is confirmed that (1) bubble shapes and motions in the subchannel are by far different from those in simple geometry, and they depend on the ratio λ of the bubble diameter to the subchannel hydraulic diameter, (2) when λ > 0.9, a part of a bubble intrudes into neighboring subchannels, and thereby a kind of void drift takes place even with a single bubble, (3) the terminal velocity V T of a small bubble (λ T for cell-Taylor bubbles (λ > 0.9) is presented, and (5) the rising velocity V B in laminar an turbulent flow conditions are well evaluated by substituting the proposed V T models and the ratio of the maximum liquid velocity to the mean liquid velocity into the Nicklin correlation. (author)

Cancer stem cells, cancer cell plasticity and radiation therapy.

Science.gov (United States)

Vlashi, Erina; Pajonk, Frank

2015-04-01

Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stepwise development of hematopoietic stem cells from embryonic stem cells.

Directory of Open Access Journals (Sweden)

Kenji Matsumoto

Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

Engineering bone tissue from human embryonic stem cells

OpenAIRE

Marolt, Darja; Campos, Iván Marcos; Bhumiratana, Sarindr; Koren, Ana; Petridis, Petros; Zhang, Geping; Spitalnik, Patrice F.; Grayson, Warren L.; Vunjak-Novakovic, Gordana

2012-01-01

In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the i...

Bangladesh’s dynamic coastal regions and sea-level rise

Directory of Open Access Journals (Sweden)

Hugh Brammer

2014-01-01

Full Text Available The physical geography of Bangladesh’s coastal area is more diverse and dynamic than is generally recognised. Failure to recognise this has led to serious misconceptions about the potential impacts of a rising sea-level on Bangladesh with global warming. This situation has been aggravated by accounts giving incorrect information on current rates of coastal erosion and land subsidence. This paper describes physical conditions within individual physiographic regions in Bangladesh’s coastal area based on ground-surveyed information, and it reviews possible area-specific mitigation measures to counter predicted rates of sea-level rise in the 21st century. Two important conclusions are drawn: the adoption of appropriate measures based on knowledge of the physical geography of potentially-affected areas could significantly reduce the currently-predicted displacement of many millions of people; and the impacts of a slowly-rising sea-level are currently much less than those generated by rapidly increasing population pressure on Bangladesh’s available land and water resources and by exposure to existing environmental hazards, and the latter problems need priority attention.

Wnt Signalling in Gastrointestinal Epithelial Stem Cells

Directory of Open Access Journals (Sweden)

Dustin J. Flanagan

2018-03-01

Full Text Available Wnt signalling regulates several cellular functions including proliferation, differentiation, apoptosis and migration, and is critical for embryonic development. Stem cells are defined by their ability for self-renewal and the ability to be able to give rise to differentiated progeny. Consequently, they are essential for the homeostasis of many organs including the gastrointestinal tract. This review will describe the huge advances in our understanding of how stem cell functions in the gastrointestinal tract are regulated by Wnt signalling, including how deregulated Wnt signalling can hijack these functions to transform cells and lead to cancer.

Luminal Cells Are Favored as the Cell of Origin for Prostate Cancer

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Zhu A. Wang

2014-09-01

Full Text Available The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we use a novel lineage-tracing strategy to assess the cell of origin in a diverse range of mouse models, including Nkx3.1+/−; Pten+/−, Pten+/−, Hi-Myc, and TRAMP mice, as well as a hormonal carcinogenesis model. Our results show that luminal cells are consistently the observed cell of origin for each model in situ; however, explanted basal cells from these mice can generate tumors in grafts. Consequently, we propose that luminal cells are favored as cells of origin in many contexts, whereas basal cells only give rise to tumors after differentiation into luminal cells.

To Give or Not to Give, That Is the Question : How Methodology Is Destiny in Dutch Giving Data

NARCIS (Netherlands)

Bekkers, René; Wiepking, Pamala

2006-01-01

In research on giving, methodology is destiny. The volume of donations estimated from sample surveys strongly depends on the length of the questionnaire used to measure giving. By comparing two giving surveys from the Netherlands, the authors show that a short questionnaire on giving not only

Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

Science.gov (United States)

Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

2016-01-28

Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function. © 2016 by The American Society of Hematology.

Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events.

Science.gov (United States)

Araujo, Ana Rita; Gelens, Lendert; Sheriff, Rahuman S M; Santos, Silvia D M

2016-10-20

Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Blood on the tracks: hematopoietic stem cell-endothelial cell interactions in homing and engraftment.

Science.gov (United States)

Perlin, Julie R; Sporrij, Audrey; Zon, Leonard I

2017-08-01

Cells of the hematopoietic system undergo rapid turnover. Each day, humans require the production of about one hundred billion new blood cells for proper function. Hematopoietic stem cells (HSCs) are rare cells that reside in specialized niches and are required throughout life to produce specific progenitor cells that will replenish all blood lineages. There is, however, an incomplete understanding of the molecular and physical properties that regulate HSC migration, homing, engraftment, and maintenance in the niche. Endothelial cells (ECs) are intimately associated with HSCs throughout the life of the stem cell, from the specialized endothelial cells that give rise to HSCs, to the perivascular niche endothelial cells that regulate HSC homeostasis. Recent studies have dissected the unique molecular and physical properties of the endothelial cells in the HSC vascular niche and their role in HSC biology, which may be manipulated to enhance hematopoietic stem cell transplantation therapies.

Colony, hanging drop, and methylcellulose three dimensional hypoxic growth optimization of renal cell carcinoma cell lines.

Science.gov (United States)

Matak, Damian; Brodaczewska, Klaudia K; Lipiec, Monika; Szymanski, Łukasz; Szczylik, Cezary; Czarnecka, Anna M

2017-08-01

Renal cell carcinoma (RCC) is the most lethal of the common urologic malignancies, comprising 3% of all human neoplasms, and the incidence of kidney cancer is rising annually. We need new approaches to target tumor cells that are resistant to current therapies and that give rise to recurrence and treatment failure. In this study, we focused on low oxygen tension and three-dimensional (3D) cell culture incorporation to develop a new RCC growth model. We used the hanging drop and colony formation methods, which are common in 3D culture, as well as a unique methylcellulose (MC) method. For the experiments, we used human primary RCC cell lines, metastatic RCC cell lines, human kidney cancer stem cells, and human healthy epithelial cells. In the hanging drop assay, we verified the potential of various cell lines to create solid aggregates in hypoxic and normoxic conditions. With the semi-soft agar method, we also determined the ability of various cell lines to create colonies under different oxygen conditions. Different cell behavior observed in the MC method versus the hanging drop and colony formation assays suggests that these three assays may be useful to test various cell properties. However, MC seems to be a particularly valuable alternative for 3D cell culture, as its higher efficiency of aggregate formation and serum independency are of interest in different areas of cancer biology.

Neural crest stem cell population in craniomaxillofacial development and tissue repair

Directory of Open Access Journals (Sweden)

M La Noce

2014-10-01

Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

MicroRNAs as Regulators of Adipogenic Differentiation of Mesenchymal Stem Cells

DEFF Research Database (Denmark)

Hamam, Dana; Ali, Dalia; Kassem, Moustapha

2015-01-01

MicroRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma......, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel...

Cytosolic calcium rises and related events in ergosterol-treated Nicotiana cells.

Science.gov (United States)

Vatsa, Parul; Chiltz, Annick; Luini, Estelle; Vandelle, Elodie; Pugin, Alain; Roblin, Gabriel

2011-07-01

The typical fungal membrane component ergosterol was previously shown to trigger defence responses and protect plants against pathogens. Most of the elicitors mobilize the second messenger calcium, to trigger plant defences. We checked the involvement of calcium in response to ergosterol using Nicotiana plumbaginifolia and Nicotiana tabacum cv Xanthi cells expressing apoaequorin in the cytosol. First, it was verified if ergosterol was efficient in these cells inducing modifications of proton fluxes and increased expression of defence-related genes. Then, it was shown that ergosterol induced a rapid and transient biphasic increase of free [Ca²⁺](cyt) which intensity depends on ergosterol concentration in the range 0.002-10 μM. Among sterols, this calcium mobilization was specific for ergosterol and, ergosterol-induced pH and [Ca²⁺](cyt) changes were specifically desensitized after two subsequent applications of ergosterol. Specific modulators allowed elucidating some events in the signalling pathway triggered by ergosterol. The action of BAPTA, LaCl₃, nifedipine, verapamil, neomycin, U73122 and ruthenium red suggested that the first phase was linked to calcium influx from external medium which subsequently triggered the second phase linked to calcium release from internal stores. The calcium influx and the [Ca²⁺](cyt) increase depended on upstream protein phosphorylation. The extracellular alkalinization and ROS production depended on calcium influx but, the ergosterol-induced MAPK activation was calcium-independent. ROS were not involved in cytosolic calcium rise as described in other models, indicating that ROS do not systematically participate in the amplification of calcium signalling. Interestingly, ergosterol-induced ROS production is not linked to cell death and ergosterol does not induce any calcium elevation in the nucleus. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Mini-Review: Limbal Stem Cells Deficiency in Companion Animals: Time to Give Something Back?

Science.gov (United States)

Sanchez, Rick F; Daniels, Julie T

2016-04-01

Experimental animals have been used extensively in the goal of developing sight-saving therapies for humans. One example is the development of transplantation of cultured limbal epithelial stem cells (LESC) to restore vision following ocular surface injury or disease. With clinical trials of cultured LESC therapy underway in humans and a potential companion animal population suffering from similar diseases, it is perhaps time to give something back. Comparatively to humans, what is known about the healthy limbus and corneal surface physiology of companion animals is still very little. Blinding corneal diseases in animals such as symblepharon in cats with Feline Herpes Virus-1 infections require a basic understanding of the functional companion animal limbus and corneal stem cells. Our understanding of many other vision threatening conditions such as scarring of the cornea post-inflammation with lymphocytic-plasmacytic infiltrate in dogs (aka chronic superficial keratitis) or pigment proliferation with Pigmentary Keratitis of Pugs would benefit from a better understanding of the animal cornea in health and disease. This is also vital when new therapeutic approaches are considered. This review will explore the current challenges and future research directions that will be required to increase our understanding of corneal diseases in animals and consider the potential development and delivery of cultured stem cell therapy to veterinary ocular surface patients.

Stomach Organ and Cell Lineage Differentiation: From?Embryogenesis to Adult Homeostasis

OpenAIRE

Willet, Spencer G.; Mills, Jason C.

2016-01-01

Gastric diseases cause considerable worldwide burden. However, the stomach is still poorly understood in terms of the molecularâcellular processes that govern its development and homeostasis. In particular, the complex relationship between the differentiated cell types located within the stomach and the stem and progenitor cells that give rise to them is significantly understudied relative to other organs. In this review, we highlight the current state of the literature relating to specificat...

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

DEFF Research Database (Denmark)

Fornara, O; Bartek, J; Rahbar, A

2016-01-01

Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

Investigation of Rising-Sun Magnetrons Operated at Relativistic Voltages Using Three Dimensional Particle-in-Cell Simulation

International Nuclear Information System (INIS)

Lemke, R.W.; Genoni, T.C.; Spencer, T.A.

1999-01-01

This work is an attempt to elucidate effects that may limit efficiency in magnetrons operated at relativistic voltages (V ∼ 500 kV). Three-dimensional particle-in-cell simulation is used to investigate the behavior of 14 and 22 cavity, cylindrical, rising-sun magnetrons. Power is extracted radially through a single iris located at the end of every other cavity. Numerical results show that in general output power and efficiency increase approximately linearly with increasing iris width (decreasing vacuum Q) until the total Q becomes too low for stable oscillation in the n-mode to be maintained. Beyond this point mode competition and/or switching occur and efficiency decreases. Results reveal that the minimum value of Q (maximum efficiency) that can be achieved prior to the onset of mode competition is significantly affected by the magnitude of the 0-space-harmonic of the π-mode, a unique characteristic of rising-suns, and by the magnitude of the electron current density (space-charge effects). By minimizing these effects, up to 3.7 GW output power has been produced at an efficiency of 40%

System for the chemical professing and evaluation gives the residual thickness the gives detecting for gives appearances LR115 type 2

International Nuclear Information System (INIS)

Carrazana Gonzalez, J.A.; Tomas Zerquera, J.; Prendes Alonso, M.

1998-01-01

In this work the system is described built in the CPHR for the homogeneous chemical processing gives detecting gives nuclear appearances. A new developed method is exposed, based on the application gives the technique optical densitometry, for the precise estimate gives the residual thickness, gives detecting, gives nuclear appearances LR115 type 2 after the process gives chemical engraving

Inequality and redistribution behavior in a give-or-take game

Science.gov (United States)

Bechtel, Michael M.; Scheve, Kenneth F.

2018-01-01

Political polarization and extremism are widely thought to be driven by the surge in economic inequality in many countries around the world. Understanding why inequality persists depends on knowing the causal effect of inequality on individual behavior. We study how inequality affects redistribution behavior in a randomized “give-or-take” experiment that created equality, advantageous inequality, or disadvantageous inequality between two individuals before offering one of them the opportunity to either take from or give to the other. We estimate the causal effect of inequality in representative samples of German and American citizens (n = 4,966) and establish two main findings. First, individuals imperfectly equalize payoffs: On average, respondents transfer 12% of the available endowments to realize more equal wealth distributions. This means that respondents tolerate a considerable degree of inequality even in a setting in which there are no costs to redistribution. Second, redistribution behavior in response to disadvantageous and advantageous inequality is largely asymmetric: Individuals who take from those who are richer do not also tend to give to those who are poorer, and individuals who give to those who are poorer do not tend to take from those who are richer. These behavioral redistribution types correlate in meaningful ways with support for heavy taxes on the rich and the provision of welfare benefits for the poor. Consequently, it seems difficult to construct a majority coalition willing to back the type of government interventions needed to counter rising inequality. PMID:29555734

Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas

DEFF Research Database (Denmark)

Møller, C J; Christgau, S; Williamson, M R

1992-01-01

The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin...... primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N...

Projections of tsunami inundation area coupled with impacts of sea level rise in Banda Aceh, Indonesia

Science.gov (United States)

Tursina, Syamsidik, Kato, Shigeru

2017-10-01

In a long term, sea level rise is anticipated to give devastating effects on Banda Aceh, as one of the coastal cities in the northern tip of Sumatra. The growth of the population and buildings in the city has come to the stage where the coastal area is vulnerable to any coastal hazard. Some public facilities and settlements have been constructed and keep expanding in the future. According to TOPEX/POSEIDON satellite images, 7 mm/year the sea level has been risen between 1992 and 2015 in this area. It is estimated that in the next 100 years, there will be 700 mm additional sea level rise which will give a setback more over to a rather flat area around the coast. This research is aim at investigating the influence of sea level rise toward the tsunami inundation on the land area particularly the impacts on Banda Aceh city. Cornell Multigrid Coupled Tsunami Model (COMCOT) simulation numerically generated tsunami propagation. Topography and bathymetry data were collected from GEBCO and updated with the available nautical chart (DISHIDROS, JICA, and field measurements). Geological movement of the underwater fault was generated using Piatanesi and Lorito of 9.15 Mw 2004 multi-fault scenario. The inundation area produced by COMCOT revealed that the inundation area was expanded to several hundred meters from the shoreline. To investigate the impacts of tsunami wave on Banda Aceh, the inundation area were digitized and analyzed with Quantum GIS spatial tools. The Quantum GIS analyzed inundations area affected by the projected tsunami. It will give a new tsunami-prone coastal area map induced by sea level rise in 100 years.

Reproduction, symbiosis, and the eukaryotic cell

Science.gov (United States)

Godfrey-Smith, Peter

2015-01-01

This paper develops a conceptual framework for addressing questions about reproduction, individuality, and the units of selection in symbiotic associations, with special attention to the origin of the eukaryotic cell. Three kinds of reproduction are distinguished, and a possible evolutionary sequence giving rise to a mitochondrion-containing eukaryotic cell from an endosymbiotic partnership is analyzed as a series of transitions between each of the three forms of reproduction. The sequence of changes seen in this “egalitarian” evolutionary transition is compared with those that apply in “fraternal” transitions, such as the evolution of multicellularity in animals. PMID:26286983

Nanog Fluctuations in Embryonic Stem Cells Highlight the Problem of Measurement in Cell Biology.

Science.gov (United States)

Smith, Rosanna C G; Stumpf, Patrick S; Ridden, Sonya J; Sim, Aaron; Filippi, Sarah; Harrington, Heather A; MacArthur, Ben D

2017-06-20

A number of important pluripotency regulators, including the transcription factor Nanog, are observed to fluctuate stochastically in individual embryonic stem cells. By transiently priming cells for commitment to different lineages, these fluctuations are thought to be important to the maintenance of, and exit from, pluripotency. However, because temporal changes in intracellular protein abundances cannot be measured directly in live cells, fluctuations are typically assessed using genetically engineered reporter cell lines that produce a fluorescent signal as a proxy for protein expression. Here, using a combination of mathematical modeling and experiment, we show that there are unforeseen ways in which widely used reporter strategies can systematically disturb the dynamics they are intended to monitor, sometimes giving profoundly misleading results. In the case of Nanog, we show how genetic reporters can compromise the behavior of important pluripotency-sustaining positive feedback loops, and induce a bifurcation in the underlying dynamics that gives rise to heterogeneous Nanog expression patterns in reporter cell lines that are not representative of the wild-type. These findings help explain the range of published observations of Nanog variability and highlight the problem of measurement in live cells. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The Emerging Cell Biology of Thyroid Stem Cells

Science.gov (United States)

Latif, Rauf; Minsky, Noga C.; Ma, Risheng

2011-01-01

Context: Stem cells are undifferentiated cells with the property of self-renewal and give rise to highly specialized cells under appropriate local conditions. The use of stem cells in regenerative medicine holds great promise for the treatment of many diseases, including those of the thyroid gland. Evidence Acquisition: This review focuses on the progress that has been made in thyroid stem cell research including an overview of cellular and molecular events (most of which were drawn from the period 1990–2011) and discusses the remaining problems encountered in their differentiation. Evidence Synthesis: Protocols for the in vitro differentiation of embryonic stem cells, based on normal developmental processes, have generated thyroid-like cells but without full thyrocyte function. However, agents have been identified, including activin A, insulin, and IGF-I, which are able to stimulate the generation of thyroid-like cells in vitro. In addition, thyroid stem/progenitor cells have been identified within the normal thyroid gland and within thyroid cancers. Conclusions: Advances in thyroid stem cell biology are providing not only insight into thyroid development but may offer therapeutic potential in thyroid cancer and future thyroid cell replacement therapy. PMID:21778219

Cancer cell imaging by stable wet near-field scanning optical microscope with resonance tracking method

International Nuclear Information System (INIS)

Park, Kyoung-Duck; Park, Doo-Jae; Jeong, Mun-Seok; Choi, Geun-Chang; Lee, Seung-Gol; Byeon, Clare-Chisu; Choi, Soo-Bong

2014-01-01

We report on a successful topographical and optical imaging of various cancer cells in liquid and in air by using a stable wet near-field scanning optical microscope that utilizes a resonance tracking method. We observed a clear dehydration which gives rise to a decrease in the cell volume down to 51%. In addition, a micro-ball lens effect due to the round-shaped young cancer cells was observed from near-field imaging, where the refractive index of young cancer cells was deduced.

Cancer cell imaging by stable wet near-field scanning optical microscope with resonance tracking method

Energy Technology Data Exchange (ETDEWEB)

Park, Kyoung-Duck [Sungkyunkwan University, Suwon (Korea, Republic of); Inha University, Incheon (Korea, Republic of); Park, Doo-Jae; Jeong, Mun-Seok [Sungkyunkwan University, Suwon (Korea, Republic of); Choi, Geun-Chang [Seoul National University, Seoul (Korea, Republic of); Lee, Seung-Gol [Inha University, Incheon (Korea, Republic of); Byeon, Clare-Chisu [Kyungpook National University, Daegu (Korea, Republic of); Choi, Soo-Bong [Incheon National University, Incheon (Korea, Republic of)

2014-05-15

We report on a successful topographical and optical imaging of various cancer cells in liquid and in air by using a stable wet near-field scanning optical microscope that utilizes a resonance tracking method. We observed a clear dehydration which gives rise to a decrease in the cell volume down to 51%. In addition, a micro-ball lens effect due to the round-shaped young cancer cells was observed from near-field imaging, where the refractive index of young cancer cells was deduced.

Studying apoptotic cell death by flow cytometry

International Nuclear Information System (INIS)

Ormerod, Michael G.

1998-01-01

Full text: Programmed cell death (PCD) is of fundamental importance in the normal development of an animal and also in tumour biology and radiation biology. During PCD a sequence of changes occurs in cells giving rise to an apoptotic cascade of events. The main elements of this cascade are rapidly being elucidated. Flow cytometry has been used to follow many of these changes. It also has been used to quantify the number of apoptotic cells in a culture and, more recently, in clinical samples. In this review, the properties of apoptotic cells and the main feature of apoptotic cascade will be described. How flow cytometry can be used to follow changes during the apoptotic cascade will be discussed

Lamotrigine increases the number of BrdU-labeled cells in the rat hippocampus

DEFF Research Database (Denmark)

Kondziella, Daniel; Strandberg, Joakim; Lindquist, Catarina

2011-01-01

Antidepressant medication and electroconvulsive therapy stabilize mood symptoms and increase hippocampal neurogenesis. We examined whether lamotrigine, suggested to give rise to mood-stabilizing and antidepressant effects in addition to its antiepileptic properties, also increases the number of n...... in the granule cell layer of the dentate gyrus showed an increased number of newborn cells in rats receiving lamotrigine (42.6 ± 3.5 cells/slice) compared with valproate (31.6 ± 2.8) and controls (32.2 ± 3.1; P...

Progressive rise in red blood cell distribution width predicts mortality and cardiovascular events in end-stage renal disease patients.

Science.gov (United States)

Yoon, Hye Eun; Kim, Sung Jun; Hwang, Hyeon Seok; Chung, Sungjin; Yang, Chul Woo; Shin, Seok Joon

2015-01-01

Red blood cell distribution width (RDW) is a robust marker of adverse clinical outcomes in various populations. However, the clinical significance of a progressive rise in RDW is undetermined in end-stage renal disease (ESRD) patients. The purpose of this study was to determine the prognostic importance of a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis patients were retrospectively analyzed. Temporal changes in RDW during 12 months after dialysis initiation were assessed by calculating the coefficients by linear regression. Patients were divided into two groups: an RDW-decreased group who had negative coefficient values (n = 177) and an RDW-increased group who had positive values (n = 149). The associations between rising RDW and mortality and cardiovascular (CV) events were investigated. During a median follow-up of 2.7 years (range, 1.0-7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events (18.4%) occurred. The event-free survival rate for the composite of end-points was lower in the RDW-increased group (P = 0.004). After categorizing patients according to baseline RDW, the event-free survival rate was lowest in patients with a baseline RDW >14.9% and increased RDW, and highest in patients with a baseline RDW ≤14.9% and decreased RDW (P = 0.02). In multivariate analysis, rising RDW was independently associated with the composite of end-points (hazard ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that a progressive rise in RDW independently predicted mortality and CV events in ESRD patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD patients.

The continuum of stem cell transdifferentiation: possibility of hematopoietic stem cell plasticity with concurrent CD45 expression.

Science.gov (United States)

Udani, V M

2006-02-01

Recent years have seen a surge of scientific research examining adult stem cell plasticity. For example, the hematopoietic stem cell has been shown to give rise to skin, respiratory epithelium, intestinal epithelium, renal epithelium, liver parenchyma, pancreas, skeletal muscle, vascular endothelium, myocardium, and central nervous system (CNS) neurons. The potential for such stem cell plasticity seems to be enhanced by stressors such as injury and neoplasia. Interestingly, recent studies have demonstrated that hematopoietic stem cells may be able to adopt certain nonhematopoietic phenotypes, such as endothelial, neural, or skeletal muscle phenotypes, without entirely losing their initial hematopoietic identity. We propose that transdifferentiation can, in certain conditions, be a partial rather than a complete event, and we encourage further investigation into the phenomenon of a stem cell simultaneously expressing phenotypic features of two distinct cell fates.

My Dog's Cheeks: A PBL Project on Collagen for Cell Biology and Genetics Courses

Science.gov (United States)

Casla, Alberto Vicario; Zubiaga, Isabel Smith

2010-01-01

Students often have an oversimplified view of biological facts, which may hinder subsequent understanding when conceptual complexity gives rise to cognitive conflicts. To avoid this situation here, we present a PBL approach for the analysis of Ehlers-Danlos syndrome (EDS), which integrates a variety of topics in cell biology, genetics, and…

Effect of atomic noise on optical squeezing via polarization self-rotation in a thermal vapor cell

DEFF Research Database (Denmark)

Hsu, M.T.L.; Hetet, G.; Peng, A.

2006-01-01

The traversal of an elliptically polarized optical field through a thermal vapor cell can give rise to a rotation of its polarization axis. This process, known as polarization self-rotation (PSR), has been suggested as a mechanism for producing squeezed light at atomic transition wavelengths. We ...

Rising cyclin-CDK levels order cell cycle events.

Directory of Open Access Journals (Sweden)

Catherine Oikonomou

Full Text Available Diverse mitotic events can be triggered in the correct order and time by a single cyclin-CDK. A single regulator could confer order and timing on multiple events if later events require higher cyclin-CDK than earlier events, so that gradually rising cyclin-CDK levels can sequentially trigger responsive events: the "quantitative model" of ordering.This 'quantitative model' makes predictions for the effect of locking cyclin at fixed levels for a protracted period: at low cyclin levels, early events should occur rapidly, while late events should be slow, defective, or highly variable (depending on threshold mechanism. We titrated the budding yeast mitotic cyclin Clb2 within its endogenous expression range to a stable, fixed level and measured time to occurrence of three mitotic events: growth depolarization, spindle formation, and spindle elongation, as a function of fixed Clb2 level. These events require increasingly more Clb2 according to their normal order of occurrence. Events occur efficiently and with low variability at fixed Clb2 levels similar to those observed when the events normally occur. A second prediction of the model is that increasing the rate of cyclin accumulation should globally advance timing of all events. Moderate (<2-fold overexpression of Clb2 accelerates all events of mitosis, resulting in consistently rapid sequential cell cycles. However, this moderate overexpression also causes a significant frequency of premature mitoses leading to inviability, suggesting that Clb2 expression level is optimized to balance the fitness costs of variability and catastrophe.We conclude that mitotic events are regulated by discrete cyclin-CDK thresholds. These thresholds are sequentially triggered as cyclin increases, yielding reliable order and timing. In many biological processes a graded input must be translated into discrete outputs. In such systems, expression of the central regulator is likely to be tuned to an optimum level, as we

Dynamic Interactions between Pit-1 and C/EBPα in the Pituitary Cell Nucleus▿

OpenAIRE

Demarco, Ignacio A.; Voss, Ty C.; Booker, Cynthia F.; Day, Richard N.

2006-01-01

The homeodomain (HD) transcription factors are a structurally conserved family of proteins that, through networks of interactions with other nuclear proteins, control patterns of gene expression during development. For example, the network interactions of the pituitary-specific HD protein Pit-1 control the development of anterior pituitary cells and regulate the expression of the hormone products in the adult cells. Inactivating mutations in Pit-1 disrupt these processes, giving rise to the s...

Open questions: The disrupted circuitry of the cancer cell

Energy Technology Data Exchange (ETDEWEB)

Wiley, H. S.

2014-10-24

Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise to a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it.

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.

Science.gov (United States)

White, Patricia M; Doetzlhofer, Angelika; Lee, Yun Shain; Groves, Andrew K; Segil, Neil

2006-06-22

Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

Glucocorticoids promote a glioma stem cell-like phenotype and resistance to chemotherapy in human glioblastoma primary cells

DEFF Research Database (Denmark)

Kostopoulou, Ourania N; Mohammad, Abdul-Aleem; Bartek, Jiri

2018-01-01

Glioma stem cells (GSCs) are glioblastoma (GBM) cells that are resistant to therapy and can give rise to recurrent tumors. The identification of patient-related factors that support GSCs is thus necessary to design effective therapies for GBM patients. Glucocorticoids (GCs) are used to treat GBM......-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, which has been linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and GSCs. Here, we treated primary human GBM cells with dexamethasone and evaluated GC......-driven changes in cell morphology, proliferation, migration, gene expression, secretory activity and growth as neurospheres. Dexamethasone treatment of GBM cells appeared to promote the development of a GSC-like phenotype and conferred resistance to physiological stress and chemotherapy. We also analyzed...

The giving standard: conditional cooperation in the case of charitable giving

NARCIS (Netherlands)

P. Wiepking (Pamala); M. Heijnen (Merijn)

2011-01-01

textabstractIn this study, we make a first attempt to investigate the mechanisms of conditional cooperation in giving outside experiments, using retrospective survey data on charitable giving (the Giving the Netherlands Panel Study 2005 (GINPS05, 2005 ; N  = 1474)). Our results show that in the case

Placenta - organ important for fetus and interesting for the rise of the Attention Deficit Hyperactivity Disorder Syndrome - interdisciplinary study.

Science.gov (United States)

Foltin, Viktor; Foltinova, Janka; Neu, Eva; Morvova, Marcela; Lettrichova, Ivana

2011-01-01

This work is aiming at broadening knowledge about placenta and giving evidence that lead penetrates through transplacental barrier. We have intended to find further possible reasons of the rise of Attention Deficit Hyperactivity Disorder (ADHD) and to suggest ways of preventing development of this syndrome. For revealing presence of lead in placenta and umbilical cord blood we used histochemical methods, scanning and transmission electron microscopy, Energy dispersive spectroscopy (EDS) analysis of element composition and infrared spectroscopy. We are presenting new findings that emphasize importance of Hofbauer cells. These cells have high phagocyting activity and form filter regulating entering lead into umbilical cord blood and thus influence possibility of the ADHD rise. We found positivity on lipids in placenta. Importance of this finding consists in the fact that lead is lipophilic metal and tissue containing lipid is available path for the transport of lead. We explained why just striatum is affected with toxic action of lead in case of ADHD syndrome. We have also shown that more blood elements circulate in umbilical cord blood than in a common circulation. High number of patients with the ADHD syndrome inspired us to suggest establishment of centers where these children would be registered. Staff of specialists consisting of psychologist, physician and physicist (responsible for application of methods of early diagnosis) will take care of the development of their health conditions and further treatment.

Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification.

Science.gov (United States)

Moretti, Alessandra; Caron, Leslie; Nakano, Atsushi; Lam, Jason T; Bernshausen, Alexandra; Chen, Yinhong; Qyang, Yibing; Bu, Lei; Sasaki, Mika; Martin-Puig, Silvia; Sun, Yunfu; Evans, Sylvia M; Laugwitz, Karl-Ludwig; Chien, Kenneth R

2006-12-15

Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, thought to arise from distinct embryonic precursors. We use genetic fate-mapping studies to document that isl1(+) precursors from the second heart field can generate each of these diverse cardiovascular cell types in vivo. Utilizing embryonic stem (ES) cells, we clonally amplified a cellular hierarchy of isl1(+) cardiovascular progenitors, which resemble the developmental precursors in the embryonic heart. The transcriptional signature of isl1(+)/Nkx2.5(+)/flk1(+) defines a multipotent cardiovascular progenitor, which can give rise to cells of all three lineages. These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1(+) cardiovascular progenitor cell (MICP). The discovery of ES cell-derived MICPs suggests a strategy for cardiovascular tissue regeneration via their isolation, renewal, and directed differentiation into specific mature cardiac, pacemaker, smooth muscle, and endothelial cell types.

Should a carbon tax rise or fall over time?

International Nuclear Information System (INIS)

Ulph, Alistair; Ulph, David; Pezzey, John

1991-01-01

A carbon tax has been proposed as one possible way of reducing the emissions of ''greenhouse gases''. Much of the recent work on carbon taxation has concentrated on analysing the effects of introducing such a tax at a level which would meet certain emission targets at some fixed date. Less attention has been devoted to the time profile of this tax. Yet in securing international agreement on the introduction of a carbon tax it could matter greatly whether what is being proposed is a tax which is initially low but rising, or initially high but falling. We show that in a wide class of cases the optimal time path of the tax will be that it initially rises and then falls as the exhaustion constraint starts to bite. However there are few general conclusions, and much depends on more detailed modelling assumptions on which the scientific evidence gives no firm guidance. (author)

AGL61 interacts with AGL80 and is required for central cell development in Arabidopsis.

Science.gov (United States)

Steffen, Joshua G; Kang, Il-Ho; Portereiko, Michael F; Lloyd, Alan; Drews, Gary N

2008-09-01

The central cell of the female gametophyte plays a role in pollen tube guidance and in regulating the initiation of endosperm development. Following fertilization, the central cell gives rise to the seed's endosperm, which nourishes the developing embryo within the seed. The molecular mechanisms controlling specification and differentiation of the central cell are poorly understood. We identified AGL61 in a screen for transcription factor genes expressed in the female gametophyte. AGL61 encodes a Type I MADS domain protein, which likely functions as a transcription factor. Consistent with this, an AGL61-green fluorescent protein fusion protein is localized to the nucleus. In the context of the ovule and seed, AGL61 is expressed exclusively in the central cell and early endosperm. agl61 female gametophytes are affected in the central cell specifically. The morphological defects include an overall reduction in size of the central cell and a reduced or absent central cell vacuole. When fertilized with wild-type pollen, agl61 central cells fail to give rise to endosperm. In addition, synergid- and antipodal-expressed genes are ectopically expressed in agl61 central cells. The expression pattern and mutant phenotype of AGL61 are similar to those of AGL80, suggesting that AGL61 may function as a heterodimer with AGL80 within the central cell; consistent with this, AGL61 and AGL80 interact in yeast two-hybrid assays. Together, these data suggest that AGL61 functions as a transcription factor and controls the expression of downstream genes during central cell development.

Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 undergo the stochastic cardiomyogenic fate and behave like transient amplifying cells

International Nuclear Information System (INIS)

Yamada, Yoji; Sakurada, Kazuhiro; Takeda, Yukiji; Gojo, Satoshi; Umezawa, Akihiro

2007-01-01

Bone marrow-derived stromal cells can give rise to cardiomyocytes as well as adipocytes, osteocytes, and chondrocytes in vitro. The existence of mesenchymal stem cells has been proposed, but it remains unclear if a single-cell-derived stem cell stochastically commits toward a cardiac lineage. By single-cell marking, we performed a follow-up study of individual cells during the differentiation of 9-15c mesenchymal stromal cells derived from bone marrow cells. Three types of cells, i.e., cardiac myoblasts, cardiac progenitors and multipotent stem cells were differentiated from a single cell, implying that cardiomyocytes are generated stochastically from a single-cell-derived stem cell. We also demonstrated that overexpression of Csx/Nkx2.5 and GATA4, precardiac mesodermal transcription factors, enhanced cardiomyogenic differentiation of 9-15c cells, and the frequency of cardiomyogenic differentiation was increased by co-culturing with fetal cardiomyocytes. Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 behaved like cardiac transient amplifying cells, and still retained their plasticity in vivo

Differential receptive field organizations give rise to nearly identical neural correlations across three parallel sensory maps in weakly electric fish.

Science.gov (United States)

Hofmann, Volker; Chacron, Maurice J

2017-09-01

Understanding how neural populations encode sensory information thereby leading to perception and behavior (i.e., the neural code) remains an important problem in neuroscience. When investigating the neural code, one must take into account the fact that neural activities are not independent but are actually correlated with one another. Such correlations are seen ubiquitously and have a strong impact on neural coding. Here we investigated how differences in the antagonistic center-surround receptive field (RF) organization across three parallel sensory maps influence correlations between the activities of electrosensory pyramidal neurons. Using a model based on known anatomical differences in receptive field center size and overlap, we initially predicted large differences in correlated activity across the maps. However, in vivo electrophysiological recordings showed that, contrary to modeling predictions, electrosensory pyramidal neurons across all three segments displayed nearly identical correlations. To explain this surprising result, we incorporated the effects of RF surround in our model. By systematically varying both the RF surround gain and size relative to that of the RF center, we found that multiple RF structures gave rise to similar levels of correlation. In particular, incorporating known physiological differences in RF structure between the three maps in our model gave rise to similar levels of correlation. Our results show that RF center overlap alone does not determine correlations which has important implications for understanding how RF structure influences correlated neural activity.

MLL-ENL cooperates with SCF to transform primary avian multipotent cells.

Science.gov (United States)

Schulte, Cathleen E; von Lindern, Marieke; Steinlein, Peter; Beug, Hartmut; Wiedemann, Leanne M

2002-08-15

The MLL gene is targeted by chromosomal translocations, which give rise to heterologous MLL fusion proteins and are associated with distinct types of acute lymphoid and myeloid leukaemia. To determine how MLL fusion proteins alter the proliferation and/or differentiation of primary haematopoietic progenitors, we introduced the MLL-AF9 and MLL-ENL fusion proteins into primary chicken bone marrow cells. Both fusion proteins caused the sustained outgrowth of immature haematopoietic cells, which was strictly dependent on stem cell factor (SCF). The renewing cells have a long in vitro lifespan exceeding the Hayflick limit of avian cells. Analysis of clonal cultures identified the renewing cells as immature, multipotent progenitors, expressing erythroid, myeloid, lymphoid and stem cell surface markers. Employing a two-step commitment/differentiation protocol involving the controlled withdrawal of SCF, the MLL-ENL-transformed progenitors could be induced to terminal erythroid or myeloid differentiation. Finally, in cooperation with the weakly leukaemogenic receptor tyrosine kinase v-Sea, the MLL-ENL fusion protein gave rise to multilineage leukaemia in chicks, suggesting that other activated, receptor tyrosine kinases can substitute for ligand-activated c-Kit in vivo.

Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

International Nuclear Information System (INIS)

Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara

2011-01-01

Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs

Nuclear Reprogramming in Mouse Primordial Germ Cells: Epigenetic Contribution

Directory of Open Access Journals (Sweden)

Massimo De Felici

2011-01-01

Full Text Available The unique capability of germ cells to give rise to a new organism, allowing the transmission of primary genetic information from generation to generation, depends on their epigenetic reprogramming ability and underlying genomic totipotency. Recent studies have shown that genome-wide epigenetic modifications, referred to as “epigenetic reprogramming”, occur during the development of the gamete precursors termed primordial germ cells (PGCs in the embryo. This reprogramming is likely to be critical for the germ line development itself and necessary to erase the parental imprinting and setting the base for totipotency intrinsic to this cell lineage. The status of genome acquired during reprogramming and the associated expression of key pluripotency genes render PGCs susceptible to transform into pluripotent stem cells. This may occur in vivo under still undefined condition, and it is likely at the origin of the formation of germ cell tumors. The phenomenon appears to be reproduced under partly defined in vitro culture conditions, when PGCs are transformed into embryonic germ (EG cells. In the present paper, I will try to summarize the contribution that epigenetic modifications give to nuclear reprogramming in mouse PGCs.

Appendiceal goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid are genetically distinct from primary colorectal-type adenocarcinoma of the appendix

DEFF Research Database (Denmark)

Jesinghaus, Moritz; Konukiewitz, Björn; Foersch, Sebastian

2018-01-01

The appendix gives rise to goblet cell carcinoids, which represent special carcinomas with distinct biological and histological features. Their genetic background and molecular relationship to colorectal adenocarcinoma is largely unknown. We therefore performed a next-generation sequencing analysis...... a morphomolecular entity, histologically and genetically distinct from appendiceal colorectal-type adenocarcinomas and its colorectal counterparts. Altered Wnt-signaling associated genes, apart from APC, may act as potential drivers of these neoplasms. The absence of KRAS/NRAS mutations might render some....../adenocarcinoma ex-goblet cell carcinoid (n=2, respectively). Mutations in colorectal cancer-related genes (eg, TP53, KRAS, APC) were rare to absent in both, goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid, but frequent in primary colorectal-type adenocarcinomas of the appendix. Additional large...

A Panel of Embryonic Stem Cell Lines Reveals the Variety and Dynamic of Pluripotent States in Rabbits

Directory of Open Access Journals (Sweden)

Pierre Osteil

2016-09-01

Full Text Available Conventional rabbit embryonic stem cell (ESC lines are derived from the inner cell mass (ICM of pre-implantation embryos using methods and culture conditions that are established for primate ESCs. In this study, we explored the capacity of the rabbit ICM to give rise to ESC lines using conditions similar to those utilized to generate naive ESCs in mice. On single-cell dissociation and culture in fibroblast growth factor 2 (FGF2-free, serum-supplemented medium, rabbit ICMs gave rise to ESC lines lacking the DNA-damage checkpoint in the G1 phase like mouse ESCs, and with a pluripotency gene expression profile closer to the rabbit ICM/epiblast profiles. These cell lines can be converted to FGF2-dependent ESCs after culture in conventional conditions. They can also colonize the rabbit pre-implantation embryo. These results indicate that rabbit epiblast cells can be coaxed toward different types of pluripotent stem cells and reveal the dynamics of pluripotent states in rabbit ESCs.

Molecular dosimetry of DNA damage caused by alkylation. I. Single-strand breaks induced by ethylating agents in cultured mammalian cells in relation to survival

NARCIS (Netherlands)

Abbondandolo, A.; Dogliotti, E.; Lohman, P.H.M.; Berends, F.

1982-01-01

Cultured Chinese hamster ovary cells were treated with ethylating agents. DNA lesions giving rise to single-strand breaks (ssb) or alkali-labile sites were measured by centrifugation in alkaline sucrose gradients after lysis in alkali. 4 agents with different tendencies to ethylate preferentially

Satellite Cell Self-Renewal.

Science.gov (United States)

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

2018-01-01

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

High-rise Buildings versus Outdoor Thermal Environment in Chongqing

Directory of Open Access Journals (Sweden)

Jin-sha Wang

2007-10-01

Full Text Available This paper gives a brief description of the over quick urbanization sinceChongqing, one of the biggest cities in China, has been a municipality directly under theCentral Government in 1997, excessive development and exceeding increase of high-risebuildings because of its special geographical position which finally leads to the worseningof the urban outdoor thermal environment. Then, this paper makes a bright balance to thefield measurement and simulated results of the wind speed field, temperature field of onemultifunctional high-rise building in Chongqing university located in the city center, andthe contrasted results validate the correctness of CFD in the outdoor thermal environmentalsimulation, expose the disadvantages of high-rise buildings on the aspects of blocking thewind field, decreasing wind speed which results in accumulation of the air-conditioningheat revolving around and periscian region where sunshine can not rip into. Finally, inorder to improve the urban outdoor thermal environment near the high-rise buildingsespecially for the angle of natural ventilation, this paper simulates the wind environment indifferent architectural compositions and architectural layouts by CFD, and the simulatedresults show that freestyle and tower buildings which can guarantee the wind speed andtake the air-conditioning heat away are much suitable and reasonable for the specialChongqing geography. These conclusions can also be used as a reference in othermountain cities, especially for the one with a great number of populations.

Scanning the cell surface proteome of cancer cells and identification of metastasis-associated proteins using a subtractive immunization strategy

DEFF Research Database (Denmark)

Rasmussen, Nicolaj; Ditzel, Henrik J

2009-01-01

and technologically challenging, and no ideal method is currently available. Here, we describe a strategy that allows scanning of the entire cell surface and identification of molecules that exhibit altered expression between two cell types. Concurrently, this method gives rise to valuable reagents for further...... characterization of the identified proteins. The strategy is based on subtractive immunization of mice, and we used the two isogenic cell lines, NM-2C5 and M-4A4, derived from the MDA-MB-435 cancer cell line, as a model system. Although the two cell lines are equally tumorigenic, only M-4A4 has metastatic...... capabilities. Our results yielded a large panel of monoclonal antibodies (mAbs) that recognized cell surface markers preferentially or exclusively expressed on metastatic vs nonmetastatic cancer cells. Four mAbs and their corresponding antigens were further characterized. Importantly, analysis on an extended...

Enzymatic Modification of Plant Cell Wall Polysaccharides

DEFF Research Database (Denmark)

Øbro, Jens; Hayashi, Takahisa; Mikkelsen, Jørn Dalgaard

2011-01-01

Plant cell walls are intricate structures with remarkable properties, widely used in almost every aspect of our life. Cell walls consist largely of complex polysaccharides and there is often a need for chemical and biochemical processing before industrial use. There is an increasing demand...... for sustainable processes that replace chemical treatments with white biotechnology. Plants can contribute significantly to this sustainable process by producing plant or microbialenzymes in planta that are necessary for plant cell wall modification or total degradation. This will give rise to superior food...... fibres, hydrocolloids, paper,textile, animal feeds or biofuels. Classical microbial-based fermentation systems could in the future face serious competition from plant-based expression systems for enzyme production. Plant expressed enzymes can either be targeted to specific cellular compartments...

IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage.

Science.gov (United States)

Barik, Subhasis; Miller, Mindy M; Cattin-Roy, Alexis N; Ukah, Tobechukwu K; Chen, Weirong; Zaghouani, Habib

2017-10-15

Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR + ETPs, but not HR - ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR + ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR - ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development. Copyright © 2017 by The American Association of Immunologists, Inc.

Electrical safety of commercial Li-ion cells based on NMC and NCA technology compared to LFP technology

OpenAIRE

Brand, Martin; Gläser, Simon; Geder, Jan; Menacher, Stefan; Obpacher, Sebastian; Jossen, Andreas; Quinger, Daniel

2013-01-01

Since a laptop caught fire in 2006 at the latest, Li-ion cells were considered as more dangerous than other accumulators [1]. Recent incidents, such as the one involving a BYD e6 electric taxi [2] or the Boeing Dreamliner [3], give rise to questions concerning the safety of L#i-ion cells. This is a crucial point, since Li-ion cells are increasingly integrated in all kinds of (electric) vehicles. Therefore the economic success of hybrid electric vehicles (HEV) and battery electric vehicles (BE...

Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice.

Science.gov (United States)

Farace, Francoise; Prestoz, Laetitita; Badaoui, Sabrina; Guillier, Martine; Haond, Celine; Opolon, Paule; Thomas, Jean-Leon; Zalc, Bernard; Vainchenker, William; Turhan, Ali G

2004-02-01

Muscle tissue of adult mice has been shown to contain stem cells with hematopoietic repopulation ability in vivo. To determine the functional characteristics of stem cells giving rise to this hematopoietic activity, we have performed hematopoietic reconstitution experiments by the use of muscle versus marrow transplantation in lethally irradiated mice and followed the fate of transplanted cells by Y-chimerism using PCR and fluorescence in situ hybridization (FISH) analysis. We report here that transplantation of murine muscle generate a major hematopoietic chimerism at the level of CFU-C, CFU-S, and terminally-differentiated cells in three generations of lethally irradiated mice followed up to 1 year after transplantation. This potential is totally abolished when muscle grafts were performed by the use of muscle from previously irradiated mice. As compared to marrow transplantation, muscle transplants were able to generate similar potencies to give rise to myeloid, T, B, and natural killer (NK) cells. Interestingly, marrow stem cells that have been generated in primary and then in secondary recipients were able to contribute efficiently to myofibers in the muscle tissue of tertiary recipients. Altogether, our data demonstrate that muscle-derived stem cells present a major hematopoietic repopulating ability with evidence of self-replication in vivo. They are radiation-sensitive and similar to marrow-derived stem cells in terms of their ability to generate multilineage hematopoiesis. Finally, our data demonstrate that muscle-derived hematopoietic stem cells do not lose their ability to contribute to myofiber generation after at least two rounds of serial transplantation, suggesting a potential that is probably equivalent to that generated by marrow transplantation.

Quantitative high-resolution genomic analysis of single cancer cells.

Science.gov (United States)

Hannemann, Juliane; Meyer-Staeckling, Sönke; Kemming, Dirk; Alpers, Iris; Joosse, Simon A; Pospisil, Heike; Kurtz, Stefan; Görndt, Jennifer; Püschel, Klaus; Riethdorf, Sabine; Pantel, Klaus; Brandt, Burkhard

2011-01-01

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics.

Short-lived, transitory cell-cell interactions foster migration-dependent aggregation.

Directory of Open Access Journals (Sweden)

Melissa D Pope

Full Text Available During embryonic development, motile cells aggregate into cohesive groups, which give rise to tissues and organs. The role of cell migration in regulating aggregation is unclear. The current paradigm for aggregation is based on an equilibrium model of differential cell adhesivity to neighboring cells versus the underlying substratum. In many biological contexts, however, dynamics is critical. Here, we provide evidence that multicellular aggregation dynamics involves both local adhesive interactions and transport by cell migration. Using time-lapse video microscopy, we quantified the duration of cell-cell contacts among migrating cells that collided and adhered to another cell. This lifetime of cell-cell interactions exhibited a monotonic decreasing dependence on substratum adhesivity. Parallel quantitative measurements of cell migration speed revealed that across the tested range of adhesive substrata, the mean time needed for cells to migrate and encounter another cell was greater than the mean adhesion lifetime, suggesting that aggregation dynamics may depend on cell motility instead of the local differential adhesivity of cells. Consistent with this hypothesis, aggregate size exhibited a biphasic dependence on substratum adhesivity, matching the trend we observed for cell migration speed. Our findings suggest a new role for cell motility, alongside differential adhesion, in regulating developmental aggregation events and motivate new design principles for tuning aggregation dynamics in tissue engineering applications.

From cell differentiation to cell collectives: Bacillus subtilis uses division of labor to migrate.

Directory of Open Access Journals (Sweden)

Jordi van Gestel

2015-04-01

Full Text Available The organization of cells, emerging from cell-cell interactions, can give rise to collective properties. These properties are adaptive when together cells can face environmental challenges that they separately cannot. One particular challenge that is important for microorganisms is migration. In this study, we show how flagellum-independent migration is driven by the division of labor of two cell types that appear during Bacillus subtilis sliding motility. Cell collectives organize themselves into bundles (called "van Gogh bundles" of tightly aligned cell chains that form filamentous loops at the colony edge. We show, by time-course microscopy, that these loops migrate by pushing themselves away from the colony. The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing cells. We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles. The folding properties of these bundles determine the rate of colony expansion. Our study illustrates how the simple organization of cells within a community can yield a strong ecological advantage. This is a key factor underlying the diverse origins of multicellularity.

From cell differentiation to cell collectives: Bacillus subtilis uses division of labor to migrate.

Science.gov (United States)

van Gestel, Jordi; Vlamakis, Hera; Kolter, Roberto

2015-04-01

The organization of cells, emerging from cell-cell interactions, can give rise to collective properties. These properties are adaptive when together cells can face environmental challenges that they separately cannot. One particular challenge that is important for microorganisms is migration. In this study, we show how flagellum-independent migration is driven by the division of labor of two cell types that appear during Bacillus subtilis sliding motility. Cell collectives organize themselves into bundles (called "van Gogh bundles") of tightly aligned cell chains that form filamentous loops at the colony edge. We show, by time-course microscopy, that these loops migrate by pushing themselves away from the colony. The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing cells. We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles. The folding properties of these bundles determine the rate of colony expansion. Our study illustrates how the simple organization of cells within a community can yield a strong ecological advantage. This is a key factor underlying the diverse origins of multicellularity.

Origin and evolution of binucleated cells and binucleated cells with micronuclei in cisplatin-treated CHO cultures.

Science.gov (United States)

Rodilla, V

1993-08-01

It has recently been described that cisplatin is an agent able to induce binucleated cells (BC) in cultured CHO cells. Both the origin and the significance of those cells within a population are unknown although several hypothesis have been suggested such as blocking of cytokinesis or cell fusion. Using interval photography we have found that at least two mechanisms are involved in the production of BC. These cells can arise in a culture as a result of an incomplete process of cell division, i.e. karyokinesis with incomplete cytokinesis or as a result of the mitotic division of a pre-existent BC. The mitotic division of a BC can give rise to different types of daughter cells. These BC sometimes enter mitosis but fail to divide and as a consequence they remain BC. When the process of division is successful (in the vast majority of cases), the results that have been found are either two mononucleated cells or one mononucleated and one binucleated cell. The possible implications and significance of BC and BC with micronuclei in a given population are discussed.

Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice.

Directory of Open Access Journals (Sweden)

Daphne Pinheiro

Full Text Available Bone marrow cells (BMC migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation. Regarding total cell populations, there was a significant reduction in CD68+ cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver, related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-γ and HGF and reduction of pro-inflammatory cytokines (IL-17A and IL-6. Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration.

The Global Experience of Deployment of Energy-Efficient Technologies in High-Rise Construction

Science.gov (United States)

Potienko, Natalia D.; Kuznetsova, Anna A.; Solyakova, Darya N.; Klyueva, Yulia E.

2018-03-01

The objective of this research is to examine issues related to the increasing importance of energy-efficient technologies in high-rise construction. The aim of the paper is to investigate modern approaches to building design that involve implementation of various energy-saving technologies in diverse climates and at different structural levels, including the levels of urban development, functionality, planning, construction and engineering. The research methodology is based on the comprehensive analysis of the advanced global expertise in the design and construction of energy-efficient high-rise buildings, with the examination of their positive and negative features. The research also defines the basic principles of energy-efficient architecture. Besides, it draws parallels between the climate characteristics of countries that lead in the field of energy-efficient high-rise construction, on the one hand, and the climate in Russia, on the other, which makes it possible to use the vast experience of many countries, wholly or partially. The paper also gives an analytical review of the results arrived at by implementing energy efficiency principles into high-rise architecture. The study findings determine the impact of energy-efficient technologies on high-rise architecture and planning solutions. In conclusion, the research states that, apart from aesthetic and compositional interpretation of architectural forms, an architect nowadays has to address the task of finding a synthesis between technological and architectural solutions, which requires knowledge of advanced technologies. The study findings reveal that the implementation of modern energy-efficient technologies into high-rise construction is of immediate interest and is sure to bring long-term benefits.

Multiplicity of Buc copies in Atlantic salmon contrasts with loss of the germ cell determinant in primates, rodents and axolotl

OpenAIRE

Skugor, Adrijana; Tveiten, Helge; Johnsen, Hanne; Andersen, Øivind

2016-01-01

Background The primordial germ cells (PGCs) giving rise to gametes are determined by two different mechanisms in vertebrates. While the germ cell fate in mammals and salamanders is induced by zygotic signals, maternally delivered germ cell determinants specify the PGCs in birds, frogs and teleost fish. Assembly of the germ plasm in the oocyte is organized by the single Buc in zebrafish, named Velo1 in Xenopus, and by Oskar in Drosophila. Secondary loss of oskar in several insect lineages coin...

Brain mesenchymal stem cells: physiology and pathological implications.

Science.gov (United States)

Pombero, Ana; Garcia-Lopez, Raquel; Martinez, Salvador

2016-06-01

Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively evolved towards an all-encompassing concept including multipotent perivascular cells of almost any tissue. In central nervous system, pericytes are involved in blood-brain barrier, and angiogenesis and vascular tone regulation. They form the neurovascular unit (NVU) together with endothelial cells, astrocytes and neurons. This functional structure provides an optimal microenvironment for neural proliferation in the adult brain. Neurovascular niche include both diffusible signals and direct contact with endothelial and pericytes, which are a source of diffusible neurotrophic signals that affect neural precursors. Therefore, MSCs/pericyte properties such as differentiation capability, as well as immunoregulatory and paracrine effects make them a potential resource in regenerative medicine. © 2016 Japanese Society of Developmental Biologists.

Cell fusion and nuclear fusion in plants.

Science.gov (United States)

Maruyama, Daisuke; Ohtsu, Mina; Higashiyama, Tetsuya

2016-12-01

Eukaryotic cells are surrounded by a plasma membrane and have a large nucleus containing the genomic DNA, which is enclosed by a nuclear envelope consisting of the outer and inner nuclear membranes. Although these membranes maintain the identity of cells, they sometimes fuse to each other, such as to produce a zygote during sexual reproduction or to give rise to other characteristically polyploid tissues. Recent studies have demonstrated that the mechanisms of plasma membrane or nuclear membrane fusion in plants are shared to some extent with those of yeasts and animals, despite the unique features of plant cells including thick cell walls and intercellular connections. Here, we summarize the key factors in the fusion of these membranes during plant reproduction, and also focus on "non-gametic cell fusion," which was thought to be rare in plant tissue, in which each cell is separated by a cell wall. Copyright © 2016 Elsevier Ltd. All rights reserved.

Different Chondrogenic Potential among Human Induced Pluripotent Stem Cells from Diverse Origin Primary Cells

Directory of Open Access Journals (Sweden)

Yeri Alice Rim

2018-01-01

Full Text Available Scientists have tried to reprogram various origins of primary cells into human induced pluripotent stem cells (hiPSCs. Every somatic cell can theoretically become a hiPSC and give rise to targeted cells of the human body. However, there have been debates on the controversy about the differentiation propensity according to the origin of primary cells. We reprogrammed hiPSCs from four different types of primary cells such as dermal fibroblasts (DF, n=3, peripheral blood mononuclear cells (PBMC, n=3, cord blood mononuclear cells (CBMC, n=3, and osteoarthritis fibroblast-like synoviocytes (OAFLS, n=3. Established hiPSCs were differentiated into chondrogenic pellets. All told, cartilage-specific markers tended to express more by the order of CBMC > DF > PBMC > FLS. Origin of primary cells may influence the reprogramming and differentiation thereafter. In the context of chondrogenic propensity, CBMC-derived hiPSCs can be a fairly good candidate cell source for cartilage regeneration. The differentiation of hiPSCs into chondrocytes may help develop “cartilage in a dish” in the future. Also, the ideal cell source of hiPSC for chondrogenesis may contribute to future application as well.

Force acting on a spherical bubble rising through a quiescent liquid

International Nuclear Information System (INIS)

Takagi, Shu; Matsumoto, Yoichiro

1996-01-01

The direct numerical simulation is performed on the spherical bubble unsteadily rising through a quiescent liquid. The method is based on a finite-volume solution of the equations on an orthogonal curvilinear coordinate system. The calculations are performed for a bubble rising through a clean liquid and contaminated one. Following the former experimental results, the tangential stress free condition is given for a clean bubble, and no-slip condition for contaminated one. The numerical results are compared with those of the model equation of the translational motion of the bubble, which is often used in numerical models of a bubbly flow. The steady drag, added mass and history terms are checked up by the comparison. It is revealed that the history force effect is negligible for a bubble rising through the clean liquid beyond Re=O(50). From the numerical point of view, the fact that the history force is negligible is quite important, because it reduces the calculation time and memory for a bubbly flow model. For a contaminated bubble, history force effect is not negligible even though the Reynolds number is high enough. It is found that the expression of the history force by Basset kernel gives an over-estimation of the history force for the bubble rising at moderate Reynolds number. This error becomes larger with increasing Reynolds number and it reduces the accuracy to calculate the bubble motion by the model equation. (author)

Predictions of the spontaneous symmetry-breaking theory for visual code completeness and spatial scaling in single-cell learning rules.

Science.gov (United States)

Webber, C J

2001-05-01

This article shows analytically that single-cell learning rules that give rise to oriented and localized receptive fields, when their synaptic weights are randomly and independently initialized according to a plausible assumption of zero prior information, will generate visual codes that are invariant under two-dimensional translations, rotations, and scale magnifications, provided that the statistics of their training images are sufficiently invariant under these transformations. Such codes span different image locations, orientations, and size scales with equal economy. Thus, single-cell rules could account for the spatial scaling property of the cortical simple-cell code. This prediction is tested computationally by training with natural scenes; it is demonstrated that a single-cell learning rule can give rise to simple-cell receptive fields spanning the full range of orientations, image locations, and spatial frequencies (except at the extreme high and low frequencies at which the scale invariance of the statistics of digitally sampled images must ultimately break down, because of the image boundary and the finite pixel resolution). Thus, no constraint on completeness, or any other coupling between cells, is necessary to induce the visual code to span wide ranges of locations, orientations, and size scales. This prediction is made using the theory of spontaneous symmetry breaking, which we have previously shown can also explain the data-driven self-organization of a wide variety of transformation invariances in neurons' responses, such as the translation invariance of complex cell response.

Suppression of transformed foci, induced by alpha radiation of C3H 10T1/2 cells, by untransformed cells

International Nuclear Information System (INIS)

Lloyd, E.L.; Gemmell, M.A.; Henning, C.B.

1978-01-01

The C3H 10T1/2 CL8 cell line obtained from a mouse embryo has been widely used for screening chemical carcinogens. Transformed foci are easily distinguishable in this system as crisscrossed, piled-up cells which stain more deeply than the surrounding untransformed cells. When these foci are ringcloned and subcultured, they have been shown to give rise to malignant tumors in C3H immunodepressed mice. Previous work showed that such malignant transformations, which occurred with a dose dependent frequency, could be induced by alpha particle irradiation. The present study, in turn, demonstrates that the expression of these transformations can be completely suppressed by co-cultivating the transformed cells with a large number of untransformed cells. The precise ratio of the number of untransformed cells to transformed cells to give complete suppression was found to vary in different experiments. Maximum effects were seen when a small number of transformed cells in low passage were used. These experiments may provide at least a partial explanation for the greatly increased frequency of transformations per cell irradiated in vitro, compared with the number of tumors observed after irradiation of the same number of cells in vivo. In addition, if conditions could be optimized whereby transformed foci could reproducibly be eliminated by the use of a known number of untransformed cells, this might have important applications in the prevention and treatment of certain human cancers

In vitro regeneration of kidney from pluripotent stem cells

Energy Technology Data Exchange (ETDEWEB)

Osafune, Kenji, E-mail: osafu@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); JST Yamanaka iPS Cell Special Project, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

2010-10-01

Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

In vitro regeneration of kidney from pluripotent stem cells

International Nuclear Information System (INIS)

Osafune, Kenji

2010-01-01

Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

The economic impact of giving up nuclear power in France

International Nuclear Information System (INIS)

Carnot, N.; Gallon, St.

2001-01-01

French nuclear plants will have to be shut down in the 2020's. Electricite de France (EDF) could replace them by either nuclear or gas-fired plants. Choosing the latter would lead to an increase in Green House Gases (GHG) emissions and to a rise of EDF's generation costs. In 2020, the price of electricity in Europe will be determined by a competitive market. Therefore, a rise of EDF's generation costs will mainly depress its operating profit (and slightly increase the market's price). Giving up nuclear power in 2020 would consequently lead to a fall of EDF's value and would penalize its shareholders, the State. On a macro-economic scale, the shock on the production cost of electricity would lead to a 0,5 to 1,0 percentage point drop of GDP (depending on the hypotheses). Structural unemployment would rise by 0,3 to 0,6 percentage point. The model used to find these results does not take into account the risk of nuclear accidents nor the uncertainty on the costs of nuclear waste disposal. On the other hand, gas-price is assumed to be low, and the costs of gas-fired generation do not integrate the risk premium due to gas-price volatility. In conclusion, the best choice on both micro and macro scales, consists in extending the life of current nuclear plants (if such an extension is authorised by safety regulators). These plants would be financially-amortized, produce electricity at a very competitive cost and emit no GHG. Furthermore, extending the life of current nuclear plants will defer any irreversible commitment on their replacement. The necessary decision could therefore be taken later on, with more information on the cost of alternative generation technologies and their efficiency. (author)

Give Me Strength.

Institute of Scientific and Technical Information of China (English)

维拉

1996-01-01

Mort had an absolutely terrible day at the office.Everythingthat could go wrong did go wrong.As he walked home he could beheard muttering strange words to himself:“Oh,give me strength,give me strength.”Mort isn’t asking for the kind of strength thatbuilds strong muscles:he’s asking for the courage or ability to

Rising tides, rising gates: The complex ecogeomorphic response of coastal wetlands to sea-level rise and human interventions

Science.gov (United States)

Sandi, Steven G.; Rodríguez, José F.; Saintilan, Neil; Riccardi, Gerardo; Saco, Patricia M.

2018-04-01

Coastal wetlands are vulnerable to submergence due to sea-level rise, as shown by predictions of up to 80% of global wetland loss by the end of the century. Coastal wetlands with mixed mangrove-saltmarsh vegetation are particularly vulnerable because sea-level rise can promote mangrove encroachment on saltmarsh, reducing overall wetland biodiversity. Here we use an ecogeomorphic framework that incorporates hydrodynamic effects, mangrove-saltmarsh dynamics, and soil accretion processes to assess the effects of control structures on wetland evolution. Migration and accretion patterns of mangrove and saltmarsh are heavily dependent on topography and control structures. We find that current management practices that incorporate a fixed gate for the control of mangrove encroachment are useful initially, but soon become ineffective due to sea-level rise. Raising the gate, to counteract the effects of sea level rise and promote suitable hydrodynamic conditions, excludes mangrove and maintains saltmarsh over the entire simulation period of 100 years

The effects of the Boussinesq model to the rising of the explosion clouds

International Nuclear Information System (INIS)

Li Xiaoli; Zheng Yi

2010-01-01

It is to study the rising of the explosion clouds in the normal atmosphere using Boussinesq model and the Incompressible model, the numerical model is based on the assumption that effects the clouds are gravity and buoyancy. By comparing the evolvement of different density cloud, and gives the conclusion-the Boussinesq model and the Incompressible model is accord when the cloud's density is larger compared to the density of the environment. (authors)

Evaluation of Indoor Radio Deployment Options in High-Rise Building

DEFF Research Database (Denmark)

Nguyen, Huan Cong; Wigard, Jeroen; Kovacs, Istvan

2017-01-01

to the increase of inter-cell interference (ICI). Increasing transmit power brings largest gain when the density of indoor cell is low, and the noise and/or outdoor interference is the dominant source of performance degradation. When analyzing performance gain of an ideal receiver-side Interference Cancellation......In this paper we set out to analyze the indoor capacity under a realistic high-rise building scenario. The study takes into consideration the number of indoor cells deployed per floor, different inter-site distances (ISDs), transmit power settings and outdoor macro interference levels. The outcome...

Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors

Directory of Open Access Journals (Sweden)

Xihe Tang

2016-03-01

Full Text Available Human neural stem cells (NSCs hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine.

Relation between number of hemopoietic stem cells in newborn mice and their radiosensitivity

International Nuclear Information System (INIS)

Sutter, T.; Maes, J.; Gerber, G.B.; Leonard, A.

1985-01-01

Fractionation of a radiation exposure causes greater damage in newborn mice than a single application since it induces radioresistant foetal hemopoietic stem cells to differentiate prematurely to more radiosensitive adult ones. In the present investigation, it was studied whether other agents that give rise to extensive stem cell destruction also lead to such a change in radiosensitivity. Indeed, treatment with cytostatic drugs which reduces the number of spleen colony forming units (CFU-s) and total cells also diminished the D 0 value of the surviving cells 3 days later. Adriamycin was most effective in causing damage to hemopoietic stem cells and in inducing micronuclei in bone marrow; it also had the most marked action on the D 0 of the surviving stem cells. (orig.)

Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture.

Science.gov (United States)

Kim, Euiseok J; Battiste, James; Nakagawa, Yasushi; Johnson, Jane E

2008-08-01

Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate-mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones. Ascl1 lineage cells contribute to distinct cell types in each major brain division: the forebrain including the cerebral cortex, olfactory bulb, hippocampus, striatum, hypothalamus, and thalamic nuclei, the midbrain including superior and inferior colliculi, and the hindbrain including Purkinje and deep cerebellar nuclei cells and cells in the trigeminal sensory system. Ascl1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes. In conclusion, Ascl1-expressing progenitor cells in the brain give rise to multiple, but not all, neuronal subtypes and oligodendrocytes depending on the temporal and spatial context, consistent with a broad role in neural differentiation with some subtype specification.

Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

Science.gov (United States)

Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

2009-04-01

The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

Quantitative high-resolution genomic analysis of single cancer cells.

Directory of Open Access Journals (Sweden)

Juliane Hannemann

Full Text Available During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics.

[The rise and fall of an physician entrepreneur].

Science.gov (United States)

Dörnyei, Sándor

2002-01-01

In 1927 one of the most up-to-date and most beautiful sanatoriums of Central Europe was built on the hills of Buda by László Jakab MD (1875-1940), who at that time had already run - since 1909 - a successful health-resort, the rather popular and successful "Liget-Sanatorium": following a period of expansion and flourishing, his enterprise bankrupted. (The building itself was renewed after World War II - it served first as a hospital for tuberculosis patients and later as a university clinic for internal medicine.) This article tells the story of an entrepreneur physician, including his former and more successful attempts to run a health-care business, and gives detailed account of the rise and fall of private health-resort in prewar Hungary.

Epigenetic regulation of neural stem cell property from embryo to adult

Directory of Open Access Journals (Sweden)

Naoya Murao

2016-03-01

Full Text Available Neural stem cells (NSCs have the ability to self-renew and give rise to neurons and glial cells (astrocytes and oligodendrocytes in the mammalian central nervous system. This multipotency is acquired by NSCs during development and is maintained throughout life. Proliferation, fate specification, and maturation of NSCs are regulated by both cell intrinsic and extrinsic factors. Epigenetic modification is a representative intrinsic factor, being involved in many biological aspects of central nervous system development and adult neurogenesis through the regulation of NSC dynamics. In this review, we summarize recent progress in the epigenetic regulation of NSC behavior in the embryonic and adult brain, with particular reference to DNA methylation, histone modification, and noncoding RNAs.

Genome-driven evolutionary game theory helps understand the rise of metabolic interdependencies in microbial communities.

Science.gov (United States)

Zomorrodi, Ali R; Segrè, Daniel

2017-11-16

Metabolite exchanges in microbial communities give rise to ecological interactions that govern ecosystem diversity and stability. It is unclear, however, how the rise of these interactions varies across metabolites and organisms. Here we address this question by integrating genome-scale models of metabolism with evolutionary game theory. Specifically, we use microbial fitness values estimated by metabolic models to infer evolutionarily stable interactions in multi-species microbial "games". We first validate our approach using a well-characterized yeast cheater-cooperator system. We next perform over 80,000 in silico experiments to infer how metabolic interdependencies mediated by amino acid leakage in Escherichia coli vary across 189 amino acid pairs. While most pairs display shared patterns of inter-species interactions, multiple deviations are caused by pleiotropy and epistasis in metabolism. Furthermore, simulated invasion experiments reveal possible paths to obligate cross-feeding. Our study provides genomically driven insight into the rise of ecological interactions, with implications for microbiome research and synthetic ecology.

Salt Damage and Rising Damp Treatment in Building Structures

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J. M. P. Q. Delgado

2016-01-01

Full Text Available Salt damage can affect the service life of numerous building structures, both historical and contemporary, in a significant way. In this review, various damage mechanisms to porous building materials induced by salt action are analyzed. The importance of pretreatment investigations is discussed as well; in combination with the knowledge of salt and moisture transport mechanisms they can give useful indications regarding treatment options. The methods of salt damage treatment are assessed then, including both passive techniques based on environmental control, reduction of water transport, or conversion to less soluble salts and active procedures resulting in the removal of salts from deterioration zones. It is concluded that cellulose can still be considered as the favorite material presently used in desalination poultices but hydrophilic mineral wool can serve as its prospective alternative in future applications. Another important cause of building pathologies is the rising damp and, in this phenomenon, it is particularly severe considering the presence of salts in water. The treatment of rising damp in historic building walls is a very complex procedure and at Laboratory of Building Physics (LFC-FEUP a wall base hygroregulated ventilation system was developed and patented.

Role-modeling and conversations about giving in the socialization of adolescent charitable giving and volunteering.

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Ottoni-Wilhelm, Mark; Estell, David B; Perdue, Neil H

2014-01-01

This study investigated the relationship between the monetary giving and volunteering behavior of adolescents and the role-modeling and conversations about giving provided by their parents. The participants are a large nationally-representative sample of 12-18 year-olds from the Panel Study of Income Dynamics' Child Development Supplement (n = 1244). Adolescents reported whether they gave money and whether they volunteered. In a separate interview parents reported whether they talked to their adolescent about giving. In a third interview, parents reported whether they gave money and volunteered. The results show that both role-modeling and conversations about giving are strongly related to adolescents' giving and volunteering. Knowing that both role-modeling and conversation are strongly related to adolescents' giving and volunteering suggests an often over-looked way for practitioners and policy-makers to nurture giving and volunteering among adults: start earlier, during adolescence, by guiding parents in their role-modeling of, and conversations about, charitable giving and volunteering. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

No impact on P-gp level in radio-resistant Mcf-7 cells

International Nuclear Information System (INIS)

Madhu, L.N.; Rao, Shama; Sarojini, B.K.

2016-01-01

Cancer has become the leading cause of human death worldwide. One possible cause for therapeutic failure is that residual tumor cells are reminiscent of stem cells, which ultimately give rise to secondary tumors or distant metastasis. The property of resistance to radiation therapy or chemotherapy might be the major clinical criterion to characterize 'cancer stem cells (CSCs)'. In the process of radiotherapy, the radiosensitive cancer will become a radioresistant one. Such radio-resistance cells might also show the characters of multi drug resistance (MRD) properties which may affect the chemotherapy process. The present study was carried out to know the expression level of P-gp, a MRD protein in radioresistance breast cancer cells. The study conducted by exposing the MCF-7 cells to 4Gy of gamma radiation

Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

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Matilde Cacciatore

2012-01-01

Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

Super-resolution microscopy in studying neuroendocrine cell function

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Anneka eBost

2013-11-01

Full Text Available The last two decades have seen a tremendous development in high resolution microscopy techniques giving rise to acronyms such as TIRFM, SIM, PALM, STORM, and STED. The goal of all these techniques is to overcome the physical resolution barrier of light microscopy in order to resolve precise protein localization and possibly their interaction in cells. Neuroendocrine cell function is to secrete hormones and peptides on demand. This fine-tuned multi-step process is mediated by a large array of proteins. Here, we review the new microscopy techniques used to obtain high resolution and how they have been applied to increase our knowledge of the molecular mechanisms involved in neuroendocrine cell secretion. Further the limitations of these methods are discussed and insights in possible new applications are provided.

Characterization of perovskite solar cells: Towards a reliable measurement protocol

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Eugen Zimmermann

2016-09-01

Full Text Available Lead halide perovskite solar cells have shown a tremendous rise in power conversion efficiency with reported record efficiencies of over 20% making this material very promising as a low cost alternative to conventional inorganic solar cells. However, due to a differently severe “hysteretic” behaviour during current density-voltage measurements, which strongly depends on scan rate, device and measurement history, preparation method, device architecture, etc., commonly used solar cell measurements do not give reliable or even reproducible results. For the aspect of commercialization and the possibility to compare results of different devices among different laboratories, it is necessary to establish a measurement protocol which gives reproducible results. Therefore, we compare device characteristics derived from standard current density-voltage measurements with stabilized values obtained from an adaptive tracking of the maximum power point and the open circuit voltage as well as characteristics extracted from time resolved current density-voltage measurements. Our results provide insight into the challenges of a correct determination of device performance and propose a measurement protocol for a reliable characterisation which is easy to implement and has been tested on varying perovskite solar cells fabricated in different laboratories.

Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue.

Science.gov (United States)

Yee, Karen K; Li, Yan; Redding, Kevin M; Iwatsuki, Ken; Margolskee, Robert F; Jiang, Peihua

2013-05-01

Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate (CV) and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knockin allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of CV and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue. Copyright © 2013 AlphaMed Press.

Integrative systems and synthetic biology of cell-matrix adhesion sites.

Science.gov (United States)

Zamir, Eli

2016-09-02

The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

Generation of germ cells in vitro in the era of induced pluripotent stem cells.

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Imamura, Masanori; Hikabe, Orie; Lin, Zachary Yu-Ching; Okano, Hideyuki

2014-01-01

Induced pluripotent stem cells (iPSCs) are stem cells that can be artificially generated via "cellular reprogramming" using gene transduction in somatic cells. iPSCs have enormous potential in stem-cell biology as they can give rise to numerous cell lineages, including the three germ layers. An evaluation of germ-line competency by blastocyst injection or tetraploid complementation, however, is critical for determining the developmental potential of mouse iPSCs towards germ cells. Recent studies have demonstrated that primordial germ cells obtained by the in vitro differentiation of iPSCs produce functional gametes as well as healthy offspring. These findings illustrate not only that iPSCs are developmentally similar to embryonic stem cells (ESCs), but also that somatic cells from adult tissues can produce gametes in vitro, that is, if they are reprogrammed into iPSCs. In this review, we discuss past and recent advances in the in vitro differentiation of germ cells using pluripotent stem cells, with an emphasis on ESCs and iPSCs. While this field of research is still at a stage of infancy, it holds great promises for investigating the mechanisms of germ-cell development, especially in humans, and for advancing reproductive and developmental engineering technologies in the future. © 2013 Wiley Periodicals, Inc.

How effects of chemicals might differ from those of radiations in giving rise to genetic ill-health in man

International Nuclear Information System (INIS)

Evans, H.J.

1980-01-01

Possible differences between the effects of the two groups of agents are considered. Two types of genetic damage are discussed. The first type involves mutational changes induced in germ cells or germ cell precursors which are then transmitted to the products of conception and to any resultant offspring and their descendants. The second kind is that damage sustained by the genome in somatic cells which is transmitted to daughter cells. Such somatic mutations are not heritable in the familiar sense, but they are transmitted to descendant cells within the body. It is concluded that a greater heterogeneity is expected in mutagenic response to chemical mutagens than to radiations in human populations, that the spectrum of mutations following chemical exposure may be quite different from that following radiation exposure, and that for many chemical agents, and in contrast to ionising radiations, one might expect a greater burden of genetic ill-health due to increased frequencies of mildly deleterious recessive and polygenic mutations. (Auth.)

All-Weather Solar Cells: A Rising Photovoltaic Revolution.

Science.gov (United States)

Tang, Qunwei

2017-06-16

Solar cells have been considered as one of the foremost solutions to energy and environmental problems because of clean, high efficiency, cost-effective, and inexhaustible features. The historical development and state-of-the-art solar cells mainly focus on elevating photoelectric conversion efficiency upon direct sunlight illumination. It is still a challenging problem to realize persistent high-efficiency power generation in rainy, foggy, haze, and dark-light conditions (night). The physical proof-of-concept for all-weather solar cells opens a door for an upcoming photovoltaic revolution. Our group has been exploring constructive routes to build all-weather solar cells so that these advanced photovoltaic technologies can be an indication for global solar industry in bringing down the cost of energy harvesting. How the all-weather solar cells are built without reducing photo performances and why such architectures can realize electricity outputs with no visible-light are discussed. Potential pathways and opportunities to enrich all-weather solar cell families are envisaged. The aspects discussed here may enable researchers to develop undiscovered abilities and to explore wide applications of advanced photovoltaics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fully solution-processed organic solar cells on metal foil substrates

KAUST Repository

Gaynor, Whitney

2009-08-19

We demonstrate fully solution-processed organic photovoltaic cells on metal foil substrates with power conversion efficiencies similar to those obtained in devices on transparent substrates. The cells are based on the regioregular poly- (3-hexylthiophene) and C61 butyric acid methyl ester bulk heterojunction system. The bottom electrode is a silver film whose workfunction is lowered by Cs2CO3 using spin-coating to serve as a cathode. The transparent top anode consists of a conductive polymer in combination with a solution-processed silver nanowire mesh that is laminated onto the devices. Each layer of the device, including the transparent electrode, is fabricated from solution, giving rise to the possibility of completely printed solar cells on low-cost substrates.

Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria -transformed leukocytes

KAUST Repository

Haidar, Malak

2017-09-08

One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets. Theileria-transformed leukocytes display high PKA activity, but PKAis an enzyme that plays key roles in multiple cellular processes; consequently genetic ablation of kinase activity gives rise to a myriad of confounding phenotypes. By contrast, ablation of a specific kinase-substrate interaction has the potential to give more refined information and we illustrate this here by describing how surgically ablating PKA interactions with BAD gives precise information on the type of glycolysis performed by Theileria-transformed leukocytes. In addition, we provide two other examples of how ablating specific protein-protein interactions in Theileria-infected leukocytes leads to precise phenotypes and argue that constrained penetrating peptides have great therapeutic potential to combat infectious diseases in general.

LOCAL IMMUNITY BY TISSUE-RESIDENT CD8+ MEMORY T CELLS

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Thomas eGebhardt

2012-11-01

Full Text Available Microbial infection primes a CD8+ cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8+ T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103+ memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Here, we review evolving concepts regarding the generation and long-term persistence of these tissue-resident memory T cells (TRM in epithelial and neuronal tissues. We further discuss the role of TRM cells in local infection control and their contribution to localized immune phenomena, in both mice and humans.

TET2 mutations in B cells of patients affected by angioimmunoblastic T-cell lymphoma.

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Schwartz, Friederike H; Cai, Qian; Fellmann, Eva; Hartmann, Sylvia; Mäyränpää, Mikko I; Karjalainen-Lindsberg, Marja-Liisa; Sundström, Christer; Scholtysik, René; Hansmann, Martin-Leo; Küppers, Ralf

2017-06-01

Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1 + cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.

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Reyes, M; Lund, T; Lenvik, T; Aguiar, D; Koodie, L; Verfaillie, C M

2001-11-01

It is here reported that mesenchymal stem cells known to give rise to limb-bud mesoderm can, at the single-cell level, also differentiate into cells of visceral mesoderm and can be expanded extensively by means of clinically applicable methods. These cells were named mesodermal progenitor cells (MPCs). MPCs were selected by depleting bone marrow mononuclear cells from more than 30 healthy human donors of CD45(+)/glycophorin-A (GlyA)(+) cells. Cells were cultured on fibronectin with epidermal growth factor and platelet-derived growth factor BB and 2% or less fetal calf serum. It was found that 1/5 x 10(3) CD45(-)GlyA(-) cells, or 1/10(6) bone marrow mononuclear cells, gave rise to clusters of small adherent cells. Cell-doubling time was 48 to 72 hours, and cells have been expanded in culture for more than 60 cell doublings. MPCs are CD34(-), CD44(low), CD45(-), CD117 (cKit)(-), class I-HLA(-), and HLA-DR(-). MPCs differentiated into cells of limb-bud mesoderm (osteoblasts, chondrocytes, adipocytes, stroma cells, and skeletal myoblasts) as well as visceral mesoderm (endothelial cells). Retroviral marking was used to definitively prove that single MPCs can differentiate into cells of limb bud and visceral mesoderm. Thus, MPCs that proliferate without obvious senescence under clinically applicable conditions and differentiate at the single-cell level not only into mesenchymal cells but also cells of visceral mesoderm may be an ideal source of stem cells for treatment of genetic or degenerative disorders affecting cells of mesodermal origin.

On the coherent behavior of pancreatic beta cell clusters

Energy Technology Data Exchange (ETDEWEB)

Loppini, Alessandro, E-mail: a.loppini@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Capolupo, Antonio, E-mail: capolupo@sa.infn.it [Physics Department, University of Salerno, Fisciano, 84084 (Italy); Cherubini, Christian, E-mail: c.cherubini@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); International Center for Relativistic Astrophysics, University Campus Bio-Medico, Via A. del Portillo 21, I-00128, Rome (Italy); Gizzi, Alessio, E-mail: a.gizzi@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Bertolaso, Marta, E-mail: m.bertolaso@unicampus.it [Faculty of Engineering and Institute of Philosophy of Scientific and Technological Practice, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Filippi, Simonetta, E-mail: s.filippi@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); International Center for Relativistic Astrophysics, University Campus Bio-Medico, Via A. del Portillo 21, I-00128, Rome (Italy); Vitiello, Giuseppe, E-mail: vitiello@sa.infn.it [Physics Department, University of Salerno, Fisciano, 84084 (Italy)

2014-09-12

Beta cells in pancreas represent an example of coupled biological oscillators which via communication pathways, are able to synchronize their electrical activity, giving rise to pulsatile insulin release. In this work we numerically analyze scale free self-similarity features of membrane voltage signal power density spectrum, through a stochastic dynamical model for beta cells in the islets of Langerhans fine tuned on mouse experimental data. Adopting the algebraic approach of coherent state formalism, we show how coherent molecular domains can arise from proper functional conditions leading to a parallelism with “phase transition” phenomena of field theory. - Highlights: • Beta cells in pancreas are coupled oscillators able to synchronize their activity. • We analyze scale free self-similarity features for beta cells. • We adopt the algebraic approach of coherent state formalism. • We show that coherent molecular domains arise from functional conditions.

Acute Cocaine Exposure elicits rises in calcium in Arousal Related Laterodorsal Tegmental Neurons

DEFF Research Database (Denmark)

Lambert, Mads; Ipsen, Theis; Kohlmeier, Kristi Anne

2017-01-01

Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus...... (LDT). Chronic, systemic cocaine exposure has been shown to have cellular effects on LDT cells, but acute actions of local application have never been demonstrated. Using calcium imaging, we show that acute application of cocaine to mouse brain slices induces calcium spiking in cells of the LDT....... Spiking was attenuated by tetrodotoxin (TTX) and low calcium solutions, and abolished by prior exhaustion of intracellular calcium stores. Further, DA receptor antagonists reduced these transients, whereas DA induced rises with similar spiking kinetics. Amphetamine, which also results in elevated levels...

Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum.

Science.gov (United States)

Seifert, Ashley W; Harfe, Brian D; Cohn, Martin J

2008-06-01

Congenital malformations of anorectal and genitourinary (collectively, anogenital) organs occur at a high frequency in humans, however the lineage of cells that gives rise to anogenital organs remains poorly understood. The penile urethra has been reported to develop from two cell populations, with the proximal urethra developing from endoderm and the distal urethra forming from an apical ectodermal invagination, however this has never been tested by direct analysis of cell lineage. During gut development, endodermal cells express Sonic hedgehog (Shh), which is required for normal patterning of digestive and genitourinary organs. We have taken advantage of the properties of Shh expression to genetically label and follow the fate of posterior gut endoderm during anogenital development. We report that the entire urethra, including the distal (glandar) region, is derived from endoderm. Cloacal endoderm also gives rise to the epithelial linings of the bladder, rectum and anterior region of the anus. Surprisingly, the lineage map also revealed an endodermal origin of the perineum, which is the first demonstration that endoderm differentiates into skin. In addition, we fate mapped genital tubercle ectoderm and show that it makes no detectable contribution to the urethra. In males, formation of the urethral tube involves septation of the urethral plate by continued growth of the urorectal septum. Analysis of cell lineage following disruption of androgen signaling revealed that the urethral plate of flutamide-treated males does not undergo this septation event. Instead, urethral plate cells persist to the ventral margin of the tubercle, mimicking the pattern seen in females. Based on these spatial and temporal fate maps, we present a new model for anogenital development and suggest that disruptions at specific developmental time points can account for the association between anorectal and genitourinary defects.

Giving presentations

CERN Document Server

Ellis, Mark

1997-01-01

This is part of a series of books, which gives training in key business communication skills. Emphasis is placed on building awareness of language appropriateness and fluency in typical business interactions. This new edition is in full colour.

Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.

Science.gov (United States)

Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal

2015-01-01

During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.

Hematopoietic and mesenchymal stem cells for the treatment of chronic respiratory diseases: role of plasticity and heterogeneity.

Science.gov (United States)

Conese, Massimo; Piro, Donatella; Carbone, Annalucia; Castellani, Stefano; Di Gioia, Sante

2014-01-01

Chronic lung diseases, such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) are incurable and represent a very high social burden. Stem cell-based treatment may represent a hope for the cure of these diseases. In this paper, we revise the overall knowledge about the plasticity and engraftment of exogenous marrow-derived stem cells into the lung, as well as their usefulness in lung repair and therapy of chronic lung diseases. The lung is easily accessible and the pathophysiology of these diseases is characterized by injury, inflammation, and eventually by remodeling of the airways. Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal (stem) cells (MSCs), encompass a wide array of cell subsets with different capacities of engraftment and injured tissue regenerating potential. Proof-of-principle that marrow cells administered locally may engraft and give rise to specialized epithelial cells has been given, but the efficiency of this conversion is too limited to give a therapeutic effect. Besides the identification of plasticity mechanisms, the characterization/isolation of the stem cell subpopulations represents a major challenge to improving the efficacy of transplantation protocols used in regenerative medicine for lung diseases.

The Effect of Media on Charitable Giving and Volunteering: Evidence from the "Give Five" Campaign

Science.gov (United States)

Yoruk, Baris K.

2012-01-01

Fundraising campaigns advertised via mass media are common. To what extent such campaigns affect charitable behavior is mostly unknown, however. Using giving and volunteering surveys conducted biennially from 1988 to 1996, I investigate the effect of a national fundraising campaign, "Give Five," on charitable giving and volunteering patterns. The…

Hematopoietic Stem Cell Transplantation: Need for Research & Potential Applications. It’s status in India

Directory of Open Access Journals (Sweden)

Shripad D. Banavali

2009-01-01

Full Text Available Stem cells are undifferentiated cells that through replications have the capabilities of both self-renewal and differentiation into mature specialized cells. Broadly, there are two types of stem cells, embryonic stem cells and adult stem cells. Embryonic stem cell biology has been associated with ethical controversy and also their growth is difficult to control. Adult stem cells are located in tissues throughout the body and function as a reservoir to replace damaged or aging cells. Embryonic stem cells are by definitions, the master cells capable of differentiating into every type of cells either in-vitro or in-vivo. Several lines of evidence suggests, however, that adult stem cells and even terminally differentiated somatic cells under appropriate micro-environmental cues are able to be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. Hematopoietic Stem Cells (HSCs, for example, from different sources have been shown to cross the tissue boundaries and give rise to the cells of the other germ layers.In the past few years, the plasticity of adult cells in several post-natal tissues has attracted special attention in regenerative medicine. Stem cell therapies represent a new field of biomedical science which could provide in the future the cure for diseases until now considered incurable. The reconstitution of adult stem cells may be promising source for the regeneration of damaged tissues and for the resolution of organ dysfunction. However, there are two major limitations to the use of such cells:- (i They are rare and (ii Only a few types exist that can be isolated without harming the patient.Due to the inability to efficiently and safely harvest or expand stem cells from most adult organs (e.g. liver, gastrointestinal tract, heart, brain, the majority of human stem cell trials have focused on clinical applications for HSCs, mesenchymal stem cells (MSCs, or both, which can be easily

Adult neural stem cells: The promise of the future

Directory of Open Access Journals (Sweden)

Philippe Taupin

2007-01-01

Full Text Available Philippe TaupinNational Neuroscience Institute, National University of SingaporeAbstract: Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS, the adult brain has the potential to regenerate and may be amenable to repair. The function(s of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries.Keywords: neurogenesis, transdifferentiation, plasticity, cellular therapy

Stem/progenitor cells in pituitary organ homeostasis and tumourigenesis

Science.gov (United States)

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

Photoelectrochemical water splitting in separate oxygen and hydrogen cells

Science.gov (United States)

Landman, Avigail; Dotan, Hen; Shter, Gennady E.; Wullenkord, Michael; Houaijia, Anis; Maljusch, Artjom; Grader, Gideon S.; Rothschild, Avner

2017-06-01

Solar water splitting provides a promising path for sustainable hydrogen production and solar energy storage. One of the greatest challenges towards large-scale utilization of this technology is reducing the hydrogen production cost. The conventional electrolyser architecture, where hydrogen and oxygen are co-produced in the same cell, gives rise to critical challenges in photoelectrochemical water splitting cells that directly convert solar energy and water to hydrogen. Here we overcome these challenges by separating the hydrogen and oxygen cells. The ion exchange in our cells is mediated by auxiliary electrodes, and the cells are connected to each other only by metal wires, enabling centralized hydrogen production. We demonstrate hydrogen generation in separate cells with solar-to-hydrogen conversion efficiency of 7.5%, which can readily surpass 10% using standard commercial components. A basic cost comparison shows that our approach is competitive with conventional photoelectrochemical systems, enabling safe and potentially affordable solar hydrogen production.

HPV-Induced Field Cancerisation: Transformation of Adult Tissue Stem Cell Into Cancer Stem Cell.

Science.gov (United States)

Olivero, Carlotta; Lanfredini, Simone; Borgogna, Cinzia; Gariglio, Marisa; Patel, Girish K

2018-01-01

Field cancerisation was originally described as a basis for multiple head and neck squamous cell carcinoma (HNSCC) and is a pre-malignant phenomenon that is frequently attributable to oncogenic human papillomavirus (HPV) infection. Our work on β-HPV-induced cutaneous squamous cell carcinomas identified a novel Lrig1+ hair follicle junctional zone keratinocyte stem cell population as the basis for field cancerisation. Herein, we describe the ability for HPV to infect adult tissue stem cells in order to establish persistent infection and induce their proliferation and displacement resulting in field cancerisation. By review of the HPV literature, we reveal how this mechanism is conserved as the basis of field cancerisation across many tissues. New insights have identified the capacity for HPV early region genes to dysregulate adult tissue stem cell self-renewal pathways ensuring that the expanded population preserve its stem cell characteristics beyond the stem cell niche. HPV-infected cells acquire additional transforming mutations that can give rise to intraepithelial neoplasia (IEN), from environmental factors such as sunlight or tobacco induced mutations in skin and oral cavity, respectively. With establishment of IEN, HPV viral replication is sacrificed with loss of the episome, and the tissue is predisposed to multiple cancer stem cell-driven carcinomas.

Different Selection Pressures Give Rise to Distinct Ethnic Phenomena

Science.gov (United States)

Moya, Cristina; Boyd, Robert

2015-01-01

Many accounts of ethnic phenomena imply that processes such as stereotyping, essentialism, ethnocentrism, and intergroup hostility stem from a unitary adaptation for reasoning about groups. This is partly justified by the phenomena’s co-occurrence in correlational studies. Here we argue that these behaviors are better modeled as functionally independent adaptations that arose in response to different selection pressures throughout human evolution. As such, different mechanisms may be triggered by different group boundaries within a single society. We illustrate this functionalist framework using ethnographic work from the Quechua-Aymara language boundary in the Peruvian Altiplano. We show that different group boundaries motivate different ethnic phenomena. For example, people have strong stereotypes about socioeconomic categories, which are not cooperative units, whereas they hold fewer stereotypes about communities, which are the primary focus of cooperative activity. We also show that, despite the cross-cultural importance of ethnolinguistic boundaries, the Quechua-Aymara linguistic distinction does not strongly motivate any of these intergroup processes. PMID:25731969

Skeletal Stem Cells: Origins, Functions and Uncertainties.

Science.gov (United States)

Mohamed, Fatma F; Franceschi, Renny T

2017-12-01

The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

Mapping the imaginary of charitable giving

DEFF Research Database (Denmark)

Bajde, Domen

2012-01-01

The meaningfulness of charitable giving is largely owed to the imaginary conceptions that underpin this form of giving. Building on Taylor's notion of “social imaginary” and Godelier's work on “gift imaginary,” we theorize the imaginary of charitable giving. Through a combination of qualitative m...... across relatively stable assemblages of conceptions of poverty, donors, end-recipients and charitable giving. These assemblages are suggested to form a multifaceted imaginary that is both cultural (shared) and personal (individually performed).......The meaningfulness of charitable giving is largely owed to the imaginary conceptions that underpin this form of giving. Building on Taylor's notion of “social imaginary” and Godelier's work on “gift imaginary,” we theorize the imaginary of charitable giving. Through a combination of qualitative...

Magnetophoretic separation of blood cells at the microscale

International Nuclear Information System (INIS)

Furlani, E P

2007-01-01

We present a method and model for the direct and continuous separation of red and white blood cells in plasma. The method is implemented at the microscale using a microfluidic system that consists of an array of integrated soft-magnetic elements embedded adjacent to a microfluidic channel. The microsystem is passive and is activated via application of a bias field that magnetizes the elements. Once magnetized, the elements produce a nonuniform magnetic field distribution in the microchannel, which gives rise to a force on blood cells as they pass through the microsystem. In whole blood, white blood cells behave as diamagnetic microparticles while red blood cells exhibit diamagnetic or paramagnetic behaviour depending on the oxygenation of their haemoglobin. We develop a mathematical model for predicting the motion of blood cells in the microsystem that takes into account the dominant magnetic, fluidic and buoyant forces on the cells. We use the model to study red/white blood cell transport, and our analysis indicates that the microsystem is capable of rapid and efficient red/white blood cell separation

Hydro-galvanic and rising - temperature bath therapy for chronic elbow epicondylitis: a comparative study

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C. Mucha

2004-02-01

Full Text Available The efficacy of two different regimens of physiotherapy for epicondylitis was compared. A combination treatment with hydrogalvanic four-cell bath and arm bath with rising temperature, which had showed good effects in treatment of tennis elbow in an earlier observational study (Mucha 1987, was compared with the analgesic interference current treatment often recommended in the literature (Sadil and Sadil 1994, Noteboom et al 1994, Becker and Reuter 1982. For this study, 60 patients with epicondylitis that was resistant to conservative treatment were randomized into two groups for comparison. In group 1, interference currents were administered twice a day for six weeks and group 2 received combination treatment with the hydrogalvanic four-cell bath and rising- temperature arm bath once a day for six weeks. Criteria for inclusion, control and appraisal were laid down prospectively. Several parameters were used, recorded and statistically evaluated as outcome measures.  These were active joint range of movement of the elbow, grip strength, pain provocation with muscle contraction, palpation pain and pain with functional activities.  The results showed a significant superiority of combination treatment over therapy with interference current. It is therefore recommended that hydrogalvanic four-cell bath and arm bath with rising temperature should be carried out before considering surgical treatment for chronic epicondylitis.

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

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Giachino, Claudio; Taylor, Verdon

2009-07-01

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

Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Dae-Hee, E-mail: leedneo@gmail.com [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Dong-Wook [Department of Microbiology, Immunology, and Cancer Biology, University of VA (United States); Jung, Chang-Hwa [Division of Metabolism and Functionality Research, Korea Food Research Institute (Korea, Republic of); Lee, Yong J. [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Park, Daeho, E-mail: daehopark@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

2014-09-15

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.

Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

International Nuclear Information System (INIS)

Lee, Dae-Hee; Kim, Dong-Wook; Jung, Chang-Hwa; Lee, Yong J.; Park, Daeho

2014-01-01

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway

Concise review: preleukemic stem cells: molecular biology and clinical implications of the precursors to leukemia stem cells.

Science.gov (United States)

Pandolfi, Ashley; Barreyro, Laura; Steidl, Ulrich

2013-02-01

Recent experimental evidence has shown that acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) arise from transformed immature hematopoietic cells following the accumulation of multiple stepwise genetic and epigenetic changes in hematopoietic stem cells and committed progenitors. The series of transforming events initially gives rise to preleukemic stem cells (pre-LSC), preceding the formation of fully transformed leukemia stem cells (LSC). Despite the established use of poly-chemotherapy, relapse continues to be the most common cause of death in AML and MDS. The therapeutic elimination of all LSC, as well as pre-LSC, which provide a silent reservoir for the re-formation of LSC, will be essential for achieving lasting cures. Conventional sequencing and next-generation genome sequencing have allowed us to describe many of the recurrent mutations in the bulk cell populations in AML and MDS, and recent work has also focused on identifying the initial molecular changes contributing to leukemogenesis. Here we review recent and ongoing advances in understanding the roles of pre-LSC, and the aberrations that lead to pre-LSC formation and subsequent LSC transformation.

MRO's HiRISE Education and Public Outreach during the Primary Science Phase

Science.gov (United States)

Gulick, V. C.; Davatzes, A. K.; Deardorff, G.; Kanefsky, B.; Conrad, L. B.; HiRISE Team

2008-12-01

Looking back over one Mars year, we report on the accomplishments of the HiRISE EPO program during the primary science phase of MRO. A highlight has been our student image suggestion program, conducted in association with NASA Quest as HiRISE Image Challenges (http://quest.arc.nasa.gov/challenges/hirise/). During challenges, students, either individually or as part of a collaborative classroom or group, learn about Mars through our webcasts, web chats and our educational material. They use HiWeb, HiRISE's image suggestion facility, to submit image suggestions and include a short rationale for why their target is scientifically interesting. The HiRISE team gives priority to obtaining a sampling of these suggestions as quickly as possible so that the acquired images can be examined by the students. During the challenge, a special password-protected web site allows participants to view their returned images before they are released to the public (http://marsoweb.nas.nasa.gov/hirise/quest/). Students are encouraged to write captions for the returned images. Finished captions are then posted and highlighted on the HiRISE web site (http://hirise.lpl.arizona.edu) along with their class, teacher's name and the name of their school. Through these HiRISE challenges, students and teachers become virtual science team members, participating in the same process (selecting and justifying targets, analyzing and writing captions for acquired images), and using the same software tools as the HiRISE team. Such an experience is unique among planetary exploration EPO programs. To date, we have completed three HiRISE challenges and a fourth is currently ongoing. More than 200 image suggestions were submitted during the previous challenges and over 85 of these image requests have been acquired so far. Over 675 participants from 45 states and 42 countries have registered for the previous challenges. These participants represent over 8000 students in grades 2 through 14 and consist

Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein

DEFF Research Database (Denmark)

Järås, Marcus; Johnels, Petra; Hansen, Nils Gunder

2010-01-01

Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9 and 22 and giving rise to the constitutively active tyrosine kinase P210 BCR/ABL1. Therapeutic strategies aiming for a cure of CML...... will require full eradication of Ph chromosome-positive (Ph(+)) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34(+) cells and also in cord blood CD34(+) cells as a consequence of retroviral BCR/ABL1 expression. To test...

GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

Directory of Open Access Journals (Sweden)

Meeri Eeva-Liisa Mäkinen

2018-03-01

Full Text Available The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging and temporal resolution microelectrode array (MEA. We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling.

GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

Science.gov (United States)

Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

2018-01-01

The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance

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Alessandra Zingoni

2017-09-01

Full Text Available Natural killer (NK cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i.e., mitotic catastrophe, senescence, and autophagy. However, it is becoming increasingly clear that they can trigger additional stress responses. Indeed, relevant immunostimulating effects of different therapeutic programs include also the activation of pathways able to promote their recognition by immune effector cells. Among stress-inducible immunostimulating proteins, changes in the expression levels of NK cell-activating and inhibitory ligands, as well as of death receptors on tumor cells, play a critical role in their detection and elimination by innate immune effectors, including NK cells. Here, we will review recent advances in chemotherapy-mediated cellular stress pathways able to stimulate NK cell effector functions. In particular, we will address how these cytotoxic lymphocytes sense and respond to different types of drug-induced stresses contributing to anticancer activity.

Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation

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Xihang Chen

2018-01-01

Full Text Available Autophagy is a highly conserved cellular process that degrades modified, surplus, or harmful cytoplasmic components by sequestering them in autophagosomes which then fuses with the lysosome for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis, as well as for remodeling during normal development. Impairment of this process has been implicated in various diseases, in the pathogenic response to bacterial and viral infections, and in aging. Pluripotent stem cells, with their ability to self-replicate and to give rise to any specialized cell type, are very valuable resources for cell-based medical therapies and open a number of promising avenues for studying human development and disease. It has been suggested that autophagy is vital for the maintenance of cellular homeostasis in stem cells, and subsequently more in-depth knowledge about the regulation of autophagy in stem cell biology has been acquired recently. In this review, we describe the most significant advances in the understanding of autophagy regulation in hematopoietic and mesenchymal stem cells, as well as in induced pluripotent stem cells. In particular, we highlight the roles of various autophagy activities in the regulation of self-renewal and differentiation of these stem cells.

Stem cell-derived kidney cells and organoids: Recent breakthroughs and emerging applications.

Science.gov (United States)

Chuah, Jacqueline Kai Chin; Zink, Daniele

The global rise in the numbers of kidney patients and the shortage in transplantable organs have led to an increasing interest in kidney-specific regenerative therapies, renal disease modelling and bioartificial kidneys. Sources for large quantities of high-quality renal cells and tissues would be required, also for applications in in vitro platforms for compound safety and efficacy screening. Stem cell-based approaches for the generation of renal-like cells and tissues would be most attractive, but such methods were not available until recently. This situation has drastically changed since 2013, and various protocols for the generation of renal-like cells and precursors from pluripotent stem cells (PSC) have been established. The most recent breakthroughs were related to the establishment of various protocols for the generation of PSC-derived kidney organoids. In combination with recent advances in genome editing, bioprinting and the establishment of predictive renal screening platforms this results in exciting new possibilities. This review will give a comprehensive overview over current PSC-based protocols for the generation of renal-like cells, precursors and organoids, and their current and potential applications in regenerative medicine, compound screening, disease modelling and bioartificial organs. Copyright © 2016 Elsevier Inc. All rights reserved.

The Practical Realities of Giving Back

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Ashton Bree Wesner

2014-07-01

Full Text Available In this thematic section, authors consider practical ways of giving back to the communities in which they conduct research. Each author discusses their evolving thoughts on how to give back in these practical ways. Some of these authors discuss giving back by giving money, food, rides, parties, and water bottles. In other cases, authors discuss giving back by creating jobs in the short or long term, grant writing, advocacy, and education. Story-telling is also a theme that many of the authors in this section discuss. For some authors, non-material forms of giving back are critical—simply maintaining social ties to the communities in which they worked, or sharing humor. The authors consider the utility of their attempts at giving back, and in some cases present their personal philosophy or guidelines on the subject.

An Unusual Ligand Coordination Gives Rise to a New Family of Rhodium Metalloinsertors with Improved Selectivity and Potency

Science.gov (United States)

2015-01-01

Rhodium metalloinsertors are octahedral complexes that bind DNA mismatches with high affinity and specificity and exhibit unique cell-selective cytotoxicity, targeting mismatch repair (MMR)-deficient cells over MMR-proficient cells. Here we describe a new generation of metalloinsertors with enhanced biological potency and selectivity, in which the complexes show Rh–O coordination. In particular, it has been found that both Δ- and Λ-[Rh(chrysi)(phen)(DPE)]2+ (where chrysi =5,6 chrysenequinone diimmine, phen =1,10-phenanthroline, and DPE = 1,1-di(pyridine-2-yl)ethan-1-ol) bind to DNA containing a single CC mismatch with similar affinities and without racemization. This is in direct contrast with previous metalloinsertors and suggests a possible different binding disposition for these complexes in the mismatch site. We ascribe this difference to the higher pKa of the coordinated immine of the chrysi ligand in these complexes, so that the complexes must insert into the DNA helix with the inserting ligand in a buckled orientation; spectroscopic studies in the presence and absence of DNA along with the crystal structure of the complex without DNA support this assignment. Remarkably, all members of this new family of compounds have significantly increased potency in a range of cellular assays; indeed, all are more potent than cisplatin and N-methyl-N′-nitro-nitrosoguanidine (MNNG, a common DNA-alkylating chemotherapeutic agent). Moreover, the activities of the new metalloinsertors are coupled with high levels of selective cytotoxicity for MMR-deficient versus proficient colorectal cancer cells. PMID:25254630

Cytological diagnosis of a rare case of cutaneous metastasis from transitional cell carcinoma, renal pelvis

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Pragya Singh

2017-12-01

Full Text Available Transitional cell carcinoma (TCC arising from renal pelvis rarely gives rise to cutaneous metastasis. Due to the insufficient literature, the exact incidence is not known till date. Moreover, the diagnosis is confirmed on histopathological examination with the aid of immunohistochemistry wherever needed. We are presenting a case of a 70-year-old female with metastatic TCC from the renal pelvis to the abdominal skin, which was diagnosed on cytology alone along with the cell block preparation. We also highlight the important cytomorphological and immunohistochemical features noted, which need to be known to avoid any diagnostic delay.

Controlling laser-induced jet formation for bioprinting mesenchymal stem cells with high viability and high resolution

International Nuclear Information System (INIS)

Ali, Muhammad; Pages, Emeline; Ducom, Alexandre; Fontaine, Aurelien; Guillemot, Fabien

2014-01-01

Laser-assisted bioprinting is a versatile, non-contact, nozzle-free printing technique which has demonstrated high potential for cell printing with high resolution. Improving cell viability requires determining printing conditions which minimize shear stress for cells within the jet and cell impact at droplet landing. In this context, this study deals with laser-induced jet dynamics to determine conditions from which jets arise with minimum kinetic energies. The transition from a sub-threshold regime to jetting regime has been associated with a geometrical parameter (vertex angle) which can be harnessed to print mesenchymal stem cells with high viability using slow jet conditions. Finally, hydrodynamic jet stability is also studied for higher laser pulse energies which give rise to supersonic but turbulent jets. (paper)

Extraembryonic origin of circulating endothelial cells.

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Luc Pardanaud

Full Text Available Circulating endothelial cells (CEC are contained in the bone marrow and peripheral blood of adult humans and participate to the revascularization of ischemic tissues. These cells represent attractive targets for cell or gene therapy aimed at improving ischemic revascularization or inhibition of tumor angiogenesis. The embryonic origin of CEC has not been addressed previously. Here we use quail-chick chimeras to study CEC origin and participation to the developing vasculature. CEC are traced with different markers, in particular the QH1 antibody recognizing only quail endothelial cells. Using yolk-sac chimeras, where quail embryos are grafted onto chick yolk sacs and vice-versa, we show that CEC are generated in the yolk sac. These cells are mobilized during wound healing, demonstrating their participation to angiogenic repair processes. Furthermore, we found that the allantois is also able to give rise to CEC in situ. In contrast to the yolk sac and allantois, the embryo proper does not produce CEC. Our results show that CEC exclusively originate from extra-embryonic territories made with splanchnopleural mesoderm and endoderm, while definitive hematopoietic stem cells and endothelial cells are of intra-embryonic origin.

Extraembryonic origin of circulating endothelial cells.

Science.gov (United States)

Pardanaud, Luc; Eichmann, Anne

2011-01-01

Circulating endothelial cells (CEC) are contained in the bone marrow and peripheral blood of adult humans and participate to the revascularization of ischemic tissues. These cells represent attractive targets for cell or gene therapy aimed at improving ischemic revascularization or inhibition of tumor angiogenesis. The embryonic origin of CEC has not been addressed previously. Here we use quail-chick chimeras to study CEC origin and participation to the developing vasculature. CEC are traced with different markers, in particular the QH1 antibody recognizing only quail endothelial cells. Using yolk-sac chimeras, where quail embryos are grafted onto chick yolk sacs and vice-versa, we show that CEC are generated in the yolk sac. These cells are mobilized during wound healing, demonstrating their participation to angiogenic repair processes. Furthermore, we found that the allantois is also able to give rise to CEC in situ. In contrast to the yolk sac and allantois, the embryo proper does not produce CEC. Our results show that CEC exclusively originate from extra-embryonic territories made with splanchnopleural mesoderm and endoderm, while definitive hematopoietic stem cells and endothelial cells are of intra-embryonic origin.

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

Science.gov (United States)

Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

2011-09-01

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

Methods to Manipulate and Monitor Wnt Signaling in Human Pluripotent Stem Cells.

Science.gov (United States)

Huggins, Ian J; Brafman, David; Willert, Karl

2016-01-01

Human pluripotent stem cells (hPSCs) may revolutionize medical practice by providing: (a) a renewable source of cells for tissue replacement therapies, (b) a powerful system to model human diseases in a dish, and (c) a platform for examining efficacy and safety of novel drugs. Furthermore, these cells offer a unique opportunity to study early human development in vitro, in particular, the process by which a seemingly uniform cell population interacts to give rise to the three main embryonic lineages: ectoderm, endoderm. and mesoderm. This process of lineage allocation is regulated by a number of inductive signals that are mediated by growth factors, including FGF, TGFβ, and Wnt. In this book chapter, we introduce a set of tools, methods, and protocols to specifically manipulate the Wnt signaling pathway with the intention of altering the cell fate outcome of hPSCs.

Opto-electronic analysis of silicon solar cells by LBIC investigations and current-voltage characterization

International Nuclear Information System (INIS)

Thantsha, N.M.; Macabebe, E.Q.B.; Vorster, F.J.; Dyk, E.E. van

2009-01-01

A different laser beam induced current (LBIC) mapping technique has been used for the measurements of spatial variation of light generated current of a solar cell. These variations are caused by parasitic resistances and defects at grain boundaries (GBs) in multicrystalline silicon solar cells (mc-Si). This study investigates and identifies the regions within mc-Si solar cells where dominating recombination and lifetime limiting processes occur. A description of the LBIC technique is presented and the results show how multicrystalline GBs and other defects affect the light generated current of a spot illuminated mc-Si solar cell. The results of the internal quantum efficiency (IQE) at wavelength of 660 nm revealed that some regions in mc-Si solar cell give rise to paths that lead current away from the intended load.

Opto-electronic analysis of silicon solar cells by LBIC investigations and current-voltage characterization

Energy Technology Data Exchange (ETDEWEB)

Thantsha, N.M.; Macabebe, E.Q.B.; Vorster, F.J. [Department of Physics, PO Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Dyk, E.E. van, E-mail: ernest.vandyk@nmmu.ac.z [Department of Physics, PO Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa)

2009-12-01

A different laser beam induced current (LBIC) mapping technique has been used for the measurements of spatial variation of light generated current of a solar cell. These variations are caused by parasitic resistances and defects at grain boundaries (GBs) in multicrystalline silicon solar cells (mc-Si). This study investigates and identifies the regions within mc-Si solar cells where dominating recombination and lifetime limiting processes occur. A description of the LBIC technique is presented and the results show how multicrystalline GBs and other defects affect the light generated current of a spot illuminated mc-Si solar cell. The results of the internal quantum efficiency (IQE) at wavelength of 660 nm revealed that some regions in mc-Si solar cell give rise to paths that lead current away from the intended load.

Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells.

Directory of Open Access Journals (Sweden)

Satoru Yoshida

Full Text Available BACKGROUND: Application of induced pluripotent stem (iPS cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required. METHODOLOGY/PRINCIPAL FINDINGS: We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo. CONCLUSIONS/SIGNIFICANCE: These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets.

Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

Energy Technology Data Exchange (ETDEWEB)

Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

1999-02-01

The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells

DEFF Research Database (Denmark)

Chandrasekaran, Abinaya; Avci, Hasan; Ochalek, Anna

2017-01-01

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency......), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells...... the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6+/NESTIN+ cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural...

An update clinical application of amniotic fluid-derived stem cells (AFSCs) in cancer cell therapy and tissue engineering.

Science.gov (United States)

Gholizadeh-Ghaleh Aziz, Shiva; Fathi, Ezzatollah; Rahmati-Yamchi, Mohammad; Akbarzadeh, Abolfazl; Fardyazar, Zahra; Pashaiasl, Maryam

2017-06-01

Recent studies have elucidated that cell-based therapies are promising for cancer treatments. The human amniotic fluid stem (AFS) cells are advantageous cells for such therapeutic schemes that can be innately changed to express therapeutic proteins. HAFSCs display a natural tropism to cancer cells in vivo. They can be useful in cancer cells targeting. Moreover, they are easily available from surplus diagnostic samples during pregnancy and less ethical and legal concern are associated with the collection and application than other putative cells are subjected. This review will designate representatives of amniotic fluid and stem cell derived from amniotic fluid. For this propose, we collect state of human AFS cells data applicable in cancer therapy by dividing this approach into two main classes (nonengineered and engineered based approaches). Our study shows the advantage of AFS cells over other putative cells types in terms differentiation ability to a wide range of cells by potential and effective use in preclinical studies for a variety of diseases. This study has shown the elasticity of human AFS cells and their favorable potential as a multipotent cell source for regenerative stem cell therapy and capable of giving rise to multiple lineages including such as osteoblasts and adipocyte.

Authorization gives the personnel he/she gives the center he/she gives Isotopes for the acting he/she gives tied functions with the security and the radiological protection

International Nuclear Information System (INIS)

Perez Pijuan, S.; Hernandez Alvarez, R.; Peres Reyes, Y.; Venegas Bernal, M.C.

1998-01-01

The conception is described used in a center production labelled compound and radiopharmaceuticals for the authorization to the support, operation and supervision personnel The approaches are exposed used to define the excellent positions for the security the installation. The are described the training programs, designed starting from the indentification the specific competitions for each duty station and with particular emphasis in the development gives abilities you practice. It is used for the administration and evaluation gives the programs training the Automated System Administration Programs Training (GESAT)

Scrape-off layer profile modifications by convective cells

International Nuclear Information System (INIS)

Myra, J.R.; DIppolito, D.A.

1996-01-01

Convective cells (CC close-quote s) are important in understanding density profile modifications induced by ion cyclotron range of frequencies (ICRF) antennas. This has motivated the present work in which the effect of CC close-quote s on transport in the scrape-off layer is studied, in the regime where the density gradient scale length L n and the cell size L are comparable. Monte Carlo simulations show that closed cell convection acts to flatten the density profile, and that open cells enhance the particle flow to the wall, depleting the density and yielding profiles similar to those measured near ICRF antennas. A new one-dimensional, two-branch model of CC transport is shown to agree well with the simulations. The model gives rise to two characteristic scale lengths, only one of which is retained in the enhanced diffusion models that are applicable for L n >L. The two-branch model is expected to be useful in analyzing ICRF experiments. copyright 1996 American Institute of Physics

Buoyancy-Driven Ventilation Generated by the Double-Skin Façade of a High-Rise Building in Tropical Climate: Case Study Bandung, Indonesia

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Aziiz Akhlish Diinal

2017-01-01

Full Text Available High-rise buildings in tropical region is identical to the use of mechanical Air Conditioning in massive scale. Nevertheless, there is an encouragement to high-rise buildings to reduce its energy consumptions, since they consume quite large amount of energy. This challenge can be overcome with various of strategies, one of them, by means of reducing the cooling load of mechanical Air Conditioning in high-rise building. Prospects come from the modern tall building design strategies, for example the use of double-skin façade to give addition of building skin which could provide indoor temperature protection from outside. Double-skin façade system has continued to increase in buildings in a tropical region such as in Indonesia. However, there is another potential of double skin façade, which is the possibility to increase the buoyancy effect in the air gap between the skin and building envelope. The possibility needs to be studied in order to give a proper way in designing double-skin façade of a high-rise building, especially on Bandung-Indonesia tropical climate. This paper explores the potential of double-skin façade in driving the air inside the façade to generate natural ventilation for a high-rise building in Bandung climate condition. Two parameters are used in exploring the buoyancy force, the width of double-skin façade and the temperature of the skin façade. In general, double-skin façade of a high-rise building in tropical climate can generate buoyancy driven ventilation for the building, it relates strongly to the distance between of the double-skin façade and the building envelope.

Sox1 marks an activated neural stem/progenitor cell in the hippocampus

OpenAIRE

Venere, Monica; Han, Young-Goo; Bell, Robert; Song, Jun S.; Alvarez-Buylla, Arturo; Blelloch, Robert

2012-01-01

The dentate gyrus of the hippocampus continues generating new neurons throughout life. These neurons originate from radial astrocytes within the subgranular zone (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population that gives rise to most if not all newly born ...

Implementation of Microfluidic Chip Electrophoresis for the Detection of B-cell Clonality

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Vazan M

2016-04-01

Full Text Available Introduction: A clonal population of B-cells is defined as those cells arising from the mitotic division of a single somatic cell with the same rearrangement of immunoglobulin genes. This gives rise to DNA markers for each individual lymphoid cell and its progenies and enables us to study clonality in different B-cell malignancies using multiplex polymerase chain reaction - PCR. The BIOMED-2 protocol has been implemented for clonality detection in lymphoproliferative diseases and exploits multiplex PCR reaction, subsequently analyzed by heteroduplex analysis (HDA using polyacrylamide gel electrophoresis (PAGE. With the advent of miniaturization and automation of molecular biology methods, lab-on-chip technologies were developed and replace partially the conventional approaches. We tested device for microfluidic chip, which is used for B-cells clonality analysis, using a PCR reaction for three subregions called frameworks (FR of the immunoglobulin heavy locus (IGH gene.

Giving what one should: explanations for the knowledge-behavior gap for altruistic giving.

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Blake, Peter R

2018-04-01

Several studies have shown that children struggle to give what they believe that they should: the so-called knowledge-behavior gap. Over a dozen recent Dictator Game studies find that, although young children believe that they should give half of a set of resources to a peer, they typically give less and often keep all of the resources for themselves. This article reviews recent evidence for five potential explanations for the gap and how children close it with age: self-regulation, social distance, theory of mind, moral knowledge and social learning. I conclude that self-regulation, social distance, and social learning show the most promising evidence for understanding the mechanisms that can close the gap. Copyright © 2017 Elsevier Ltd. All rights reserved.

The suture provides a niche for mesenchymal stem cells of craniofacial bones

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Zhao, Hu; Feng, Jifan; Ho, Thach-Vu; Grimes, Weston; Urata, Mark; Chai, Yang

2015-01-01

Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the major MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating these cells are an indispensible stem cell population. Twist1+/− mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair. PMID:25799059

Regional approaches in high-rise construction

Science.gov (United States)

Iconopisceva, O. G.; Proskurin, G. A.

2018-03-01

The evolutionary process of high-rise construction is in the article focus. The aim of the study was to create a retrospective matrix reflecting the tasks of the study such as: structuring the most iconic high-rise objects within historic boundaries. The study is based on contemporary experience of high-rise construction in different countries. The main directions and regional specifics in the field of high-rise construction as well as factors influencing the further evolution process are analyzed. The main changes in architectural stylistics, form-building, constructive solutions that focus on the principles of energy efficiency and bio positivity of "sustainable buildings", as well as the search for a new typology are noted. The most universal constructive methods and solutions that turned out to be particularly popular are generalized. The new typology of high-rises and individual approach to urban context are noted. The results of the study as a graphical scheme made it possible to represent the whole high-rise evolution. The new spatial forms of high-rises lead them to new role within the urban environments. Futuristic hyperscalable concepts take the autonomous urban space functions itself and demonstrate us how high-rises can replace multifunctional urban fabric, developing it inside their shells.

The risks associated with consumer magazines giving advice on complementary therapies.

Science.gov (United States)

Mantle, Fiona

The increased popularity of complementary and alternative medicine (CAM) has led to increased demand for information on it, giving rise to the concept of "new experts". However, there is concern about the quality and accuracy of this information, much of which is published in popular magazines and written by contributors with no medical qualifications. To examine the extent of CAM product advice in women's and health magazines, and the potential for adverse drug/herbal interaction. Fifteen women's magazines were examined over one month. A total of 150 articles were identified, of which 131 were written by non-medically qualified contributors, mainly journalists. Out of the 150, 95 discussed ingested herbs which had the potential for adverse interactions and are contraindicated for certain groups. The findings have legal and ethical implications. The re-evaluation of the journalists' code of conduct to reflect this development in journalism should be considered.

On the dynamics of neutral mutations in a mathematical model for a homogeneous stem cell population.

Science.gov (United States)

Traulsen, Arne; Lenaerts, Tom; Pacheco, Jorge M; Dingli, David

2013-02-01

The theory of the clonal origin of cancer states that a tumour arises from one cell that acquires mutation(s) leading to the malignant phenotype. It is the current belief that many of these mutations give a fitness advantage to the mutant population allowing it to expand, eventually leading to disease. However, mutations that lead to such a clonal expansion need not give a fitness advantage and may in fact be neutral--or almost neutral--with respect to fitness. Such mutant clones can be eliminated or expand stochastically, leading to a malignant phenotype (disease). Mutations in haematopoietic stem cells give rise to diseases such as chronic myeloid leukaemia (CML) and paroxysmal nocturnal haemoglobinuria (PNH). Although neutral drift often leads to clonal extinction, disease is still possible, and in this case, it has important implications both for the incidence of disease and for therapy, as it may be more difficult to eliminate neutral mutations with therapy. We illustrate the consequences of such dynamics, using CML and PNH as examples. These considerations have implications for many other tumours as well.

Cell therapy for pediatric disorders of glia

DEFF Research Database (Denmark)

Albuquerque Osório, Maria Joana; Goldman, Steven A.

2016-01-01

The childhood disorders of glia comprise a group of diseases that include the pediatric leukodystrophies and lysosomal storage disorders, cerebral palsies and perinatal hypoxic ischemic encephalopathies, and selected neurodevelopmental disorders of glial origin. Essentially, all of these disorders...... (GPCs) and their derivatives, the glial disorders may be uniquely attractive targets for cell-based therapeutic strategies, and the pediatric disorders especially so. As a result, GPCs, which can distribute throughout the neuraxis and give rise to new astrocytes and myelinogenic oligodendrocytes, have...... become of great interest as candidates for the therapeutic restoration of normal glial architecture and function, as well as new myelin, to the pediatric brain....

Soil Structure Interaction Effect on High Rise and Low Rise Buildings

OpenAIRE

Divya Pathak; PAresh H. SHAH

2000-01-01

Effect of supporting soil on the response of structure has been analyzed in the present study. A low rise (G+ 5 storey) and a high rise (G+12 storey) building has been taken for the analysis. For both type of buildings, the response of building with and without consideration of soil structure interaction effect has been compared.Without interaction case is the case in which ends of the structure are assumed to be fixed while in interaction case, structure is assumed to be...

The role of satellite cells in muscle hypertrophy.

Science.gov (United States)

Blaauw, Bert; Reggiani, Carlo

2014-02-01

The role of satellite cells in muscle hypertrophy has long been a debated issue. In the late 1980s it was shown that proteins remain close to the myonucleus responsible for its synthesis, giving rise to the idea of a nuclear domain. This, together with the observation that during various models of muscle hypertrophy there is an activation of the muscle stem cells, i.e. satellite cells, lead to the idea that satellite cell activation is required for muscle hypertrophy. Thus, satellite cells are not only responsible for muscle repair and regeneration, but also for hypertrophic growth. Further support for this line of thinking was obtained after studies showing that irradiation of skeletal muscle, and therefore elimination of all satellite cells, completely prevented overload-induced hypertrophy. Recently however, using different transgenic approaches, it has become clear that muscle hypertrophy can occur without a contribution of satellite cells, even though in most situations of muscle hypertrophy satellite cells are activated. In this review we will discuss the contribution of satellite cells, and other muscle-resident stem cells, to muscle hypertrophy both in mice as well as in humans.

Enhanced performance on high current discharges in JET produced by ICRF heating during the current rise

International Nuclear Information System (INIS)

Bures, M.; Bhatnagar, V.; Cotrell, G.; Corti, S.; Christiansen, J.P.; Hellsten, T.; Jacquinot, J.; Lallia, P.; Lomas, P.; O'Rourke, J.; Taroni, A.; Tibone, F.; Start, D.F.H.

1989-01-01

The performance of high current discharges can be increased by applying central ICRF heating before or shortly after the onset of sawtooth activity in the plasma current rise phase. Sawtooth-free periods have been obtained resulting in the enhanced discharge performance. High T e (0) 9 - 10.5 keV with peaked profiles T e (0)/ e > = 3 - 4 were obtained giving values of n e (0)T e (0) up to 6x10 20 (keV m -3 ). Improvements in T i (0) and neutron production are observed. A 60 % enhancement in D-D reaction rate from 2nd harmonic deuterium (2ω CD ) heating appears to be present. In all current rise (CR) discharges radiation amounts to 25-50 % of total power. (author) 4 refs., 6 figs

JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFNα.

Science.gov (United States)

Hasan, Salma; Lacout, Catherine; Marty, Caroline; Cuingnet, Marie; Solary, Eric; Vainchenker, William; Villeval, Jean-Luc

2013-08-22

The acquired gain-of-function V617F mutation in the Janus Kinase 2 (JAK2(V617F)) is the main mutation involved in BCR/ABL-negative myeloproliferative neoplasms (MPNs), but its effect on hematopoietic stem cells as a driver of disease emergence has been questioned. Therefore, we reinvestigated the role of endogenous expression of JAK2(V617F) on early steps of hematopoiesis as well as the effect of interferon-α (IFNα), which may target the JAK2(V617F) clone in humans by using knock-in mice with conditional expression of JAK2(V617F) in hematopoietic cells. These mice develop a MPN mimicking polycythemia vera with large amplification of myeloid mature and precursor cells, displaying erythroid endogenous growth and progressing to myelofibrosis. Interestingly, early hematopoietic compartments [Lin-, LSK, and SLAM (LSK/CD48-/CD150+)] increased with the age. Competitive repopulation assays demonstrated disease appearance and progressive overgrowth of myeloid, Lin-, LSK, and SLAM cells, but not lymphocytes, from a low number of engrafted JAK2(V617F) SLAM cells. Finally, IFNα treatment prevented disease development by specifically inhibiting JAK2(V617F) cells at an early stage of differentiation and eradicating disease-initiating cells. This study shows that JAK2(V617F) in mice amplifies not only late but also early hematopoietic cells, giving them a proliferative advantage through high cell cycling and low apoptosis that may sustain MPN emergence but is lost upon IFNα treatment.

Can molluscan assemblages give insights into Holocene environmental changes other than sea level rise? A case study from a macrotidal bay (Marennes-Oleron, France)

OpenAIRE

Poirier, Clement; Sauriau, Pierre-guy; Chaumillon, Eric; Allard, Jonathan

2009-01-01

During the Late Holocene, the rate of sea level rise decreased and climate changes, hydrodynamic processes or anthropogenic impacts became predominant parameters governing the sedimentary infill of estuarine environments. The aim of this study is to describe the response of past benthic mollusc communities to these forcing factors. Mollusc skeletal remains were sampled from three 8000, 5500 and 2600 year-long sedimentary records in the Marennes-Oleron Bay (Atlantic Coast, France), where envir...

Tumorigenicity studies for human pluripotent stem cell-derived products.

Science.gov (United States)

Kuroda, Takuya; Yasuda, Satoshi; Sato, Yoji

2013-01-01

Human pluripotent stem cells (hPSCs), i.e. human embryonic stem cells and human induced pluripotent stem cells, are able to self-renew and differentiate into multiple cell types. Because of these abilities, numerous attempts have been made to utilize hPSCs in regenerative medicine/cell therapy. hPSCs are, however, also tumorigenic, that is, they can give rise to the progressive growth of tumor nodules in immunologically unresponsive animals. Therefore, assessing and managing the tumorigenicity of all final products is essential in order to prevent ectopic tissue formation, tumor development, and/or malignant transformation elicited by residual pluripotent stem cells after implantation. No detailed guideline for the tumorigenicity testing of hPSC-derived products has yet been issued for regenerative medicine/cell therapy, despite the urgent necessity. Here, we describe the current situations and issues related to the tumorigenicity testing of hPSC-derived products and we review the advantages and disadvantages of several types of tumorigenicity-associated tests. We also refer to important considerations in the execution and design of specific studies to monitor the tumorigenicity of hPSC-derived products.

Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid.

Science.gov (United States)

Aihara, Eitaro; Mahe, Maxime M; Schumacher, Michael A; Matthis, Andrea L; Feng, Rui; Ren, Wenwen; Noah, Taeko K; Matsu-ura, Toru; Moore, Sean R; Hong, Christian I; Zavros, Yana; Herness, Scott; Shroyer, Noah F; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A; Montrose, Marshall H

2015-11-24

Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy.

Science.gov (United States)

Fry, Christopher S; Kirby, Tyler J; Kosmac, Kate; McCarthy, John J; Peterson, Charlotte A

2017-01-05

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

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Jamie Trott

2017-06-01

Full Text Available Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.

Hematopoietic and Mesenchymal Stem Cells for the Treatment of Chronic Respiratory Diseases: Role of Plasticity and Heterogeneity

Directory of Open Access Journals (Sweden)

Massimo Conese

2014-01-01

Full Text Available Chronic lung diseases, such as cystic fibrosis (CF, asthma, and chronic obstructive pulmonary disease (COPD are incurable and represent a very high social burden. Stem cell-based treatment may represent a hope for the cure of these diseases. In this paper, we revise the overall knowledge about the plasticity and engraftment of exogenous marrow-derived stem cells into the lung, as well as their usefulness in lung repair and therapy of chronic lung diseases. The lung is easily accessible and the pathophysiology of these diseases is characterized by injury, inflammation, and eventually by remodeling of the airways. Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells (HSPCs and mesenchymal stromal (stem cells (MSCs, encompass a wide array of cell subsets with different capacities of engraftment and injured tissue regenerating potential. Proof-of-principle that marrow cells administered locally may engraft and give rise to specialized epithelial cells has been given, but the efficiency of this conversion is too limited to give a therapeutic effect. Besides the identification of plasticity mechanisms, the characterization/isolation of the stem cell subpopulations represents a major challenge to improving the efficacy of transplantation protocols used in regenerative medicine for lung diseases.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

Science.gov (United States)

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

2013-10-14

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

How to Safely Give Ibuprofen

Science.gov (United States)

... of ibuprofen are available in similar forms. How to Give When giving ibuprofen, refer to the following dosage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

Thiophene dendrimer-based low donor content solar cells

Science.gov (United States)

Stoltzfus, Dani M.; Ma, Chang-Qi; Nagiri, Ravi C. R.; Clulow, Andrew J.; Bäuerle, Peter; Burn, Paul L.; Gentle, Ian R.; Meredith, Paul

2016-09-01

Low donor content solar cells containing polymeric and non-polymeric donors blended with fullerenes have been reported to give rise to efficient devices. In this letter, we report that a dendrimeric donor can also be used in solution-processed low donor content devices when blended with a fullerene. A third generation dendrimer containing 42 thiophene units (42T) was found to give power conversion efficiencies of up to 3.5% when blended with PC70BM in optimized devices. The best efficiency was measured with 10 mole percent (mol. %) of 42T in PC70BM and X-ray reflectometry showed that the blends were uniform. Importantly, while 42T comprised 10 mol. % of the film, it made up 31% of the film by volume. Finally, it was found that solvent annealing was required to achieve the largest open circuit voltage and highest device efficiencies.

The Limits to Giving Back

Directory of Open Access Journals (Sweden)

Jade S. Sasser

2014-07-01

Full Text Available In this thematic section, authors consider the limitations on giving back that they faced in field research, or saw others face. For some authors, their attempts at giving back were severely limited by the scope of their projects, or their understandings of local cultures or histories. For others, very specific circumstances and historical interventions of foreigners in certain places can limit how and to what extent a researcher is able to have a reciprocal relationship with the participating community. Some authors, by virtue of their lesser positions of power relative to those that they were studying, simply decided not to give back to those communities. In each article it becomes apparent that how and in what ways people give back is unique (and limited both to their personal values and the contexts in which they do research.

Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in human embryonic stem cell-derived oligodendrocyte precursor cells

Directory of Open Access Journals (Sweden)

Sebastian Werneburg

2015-05-01

Full Text Available Oligodendrocyte precursor cells (OPCs are the progenitors of myelinating oligodendrocytes in brain development and repair. Successful myelination depends on the control of adhesiveness during OPC migration and axon contact formation. The decoration of cell surface proteins with the glycan polysialic acid (polySia is a key regulatory element of OPC interactions during development and under pathological conditions. By far the major protein carrier of polySia is the neural cell adhesion molecule NCAM, but recently, polysialylation of the synaptic cell adhesion molecule SynCAM 1 has been detected in the developing mouse brain. In mice, polySia-SynCAM 1 is associated with cells expressing NG2, a marker of a heterogeneous precursor cell population, which is the primary source for oligodendrocytes in development and myelin repair but can also give rise to astrocytes and possibly neurons. It is not yet clear if polySia-SynCAM 1 is expressed by OPCs and its occurrence in humans is elusive. By generating uniform human embryonic stem cell-derived OPC cultures, we demonstrate that polySia is present on human OPCs but down-regulated during differentiation into myelin basic protein-positive oligodendrocytes. PolySia on NCAM resides on the isoforms NCAM-180 and NCAM-140, and SynCAM 1 is identified as a novel polySia acceptor in human OPCs.

From Rising Bubble to RNA/DNA and Bacteria

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Marks, Roman; Cieszyńska, Agata; Wereszka, Marzena; Borkowski, Wojciech

2017-04-01

In this study we have focused on the movement of rising bubbles in a salty water body. Experiments reviled that free buoyancy movement of bubbles forces displacement of ions, located on the outer side of the bubble wall curvatures. During the short moment of bubble passage, all ions in the vicinity of rising bubble, are separated into anions that are gathered on the bubble upper half sphere and cations that slip along the bottom concave half-sphere of a bubble and develop a sub-bubble vortex. The principle of ions separation bases on the differences in displacement resistance. In this way, relatively heavier and larger, thus more resistant to displacement anions are gathered on the rising bubble upper half sphere, while smaller and lighter cations are assembled on the bottom half sphere and within the sub-bubble vortex. The acceleration of motion generates antiparallel rotary of bi-ionic domains, what implies that anions rotate in clockwise (CW) and cationic in counter-clockwise (CCW) direction. Then, both rotational systems may undergo splicing and extreme condensing by bi-pirouette narrowing of rotary. It is suggested that such double helix motion of bi-ionic domains creates RNA/DNA molecules. Finally, when the bubble reaches the water surface it burst and the preprocessed RNA/DNA matter is ejected into the droplets. Since that stage, droplet is suspended in positively charged troposphere, thus the cationic domain is located in the droplet center, whilst negative ions are attracted to configure the outer areola. According to above, the present study implies that the rising bubbles in salty waters may incept synergistic processing of matter resulting in its rotational/spherical organization that led to assembly of RNA/DNA molecules and bacteria cells.

Numerical Investigation of Microgravity Tank Pressure Rise Due to Boiling

Science.gov (United States)

Hylton, Sonya; Ibrahim, Mounir; Kartuzova, Olga; Kassemi, Mohammad

2015-01-01

The ability to control self-pressurization in cryogenic storage tanks is essential for NASAs long-term space exploration missions. Predictions of the tank pressure rise in Space are needed in order to inform the microgravity design and optimization process. Due to the fact that natural convection is very weak in microgravity, heat leaks into the tank can create superheated regions in the liquid. The superheated regions can instigate microgravity boiling, giving rise to pressure spikes during self-pressurization. In this work, a CFD model is developed to predict the magnitude and duration of the microgravity pressure spikes. The model uses the Schrage equation to calculate the mass transfer, with a different accommodation coefficient for evaporation at the interface, condensation at the interface, and boiling in the bulk liquid. The implicit VOF model was used to account for the moving interface, with bounded second order time discretization. Validation of the models predictions was carried out using microgravity data from the Tank Pressure Control Experiment, which flew aboard the Space Shuttle Mission STS-52. Although this experiment was meant to study pressurization and pressure control, it underwent boiling during several tests. The pressure rise predicted by the CFD model compared well with the experimental data. The ZBOT microgravity experiment is scheduled to fly on February 2016 aboard the ISS. The CFD model was also used to perform simulations for setting parametric limits for the Zero-Boil-Off Tank (ZBOT) Experiments Test Matrix in an attempt to avoid boiling in the majority of the test runs that are aimed to study pressure increase rates during self-pressurization. *Supported in part by NASA ISS Physical Sciences Research Program, NASA HQ, USA

Determinants of cell-to-cell variability in protein kinase signaling.

Science.gov (United States)

Jeschke, Matthias; Baumgärtner, Stephan; Legewie, Stefan

2013-01-01

Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity') and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s) or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

Umbilical Cord Blood Stem Cells. Who has the right word?

Directory of Open Access Journals (Sweden)

Gisela Laporta

2014-12-01

Full Text Available In this article we analyze bioethical and legal aspects related to the cryopreservation of cord blood stem cells in Argentina. To unify definitions, the concept and variety of stem cells, together with the understanding of the means to obtain and store umbilical cord blood stem cells, are provided.  Options that arise in our country, mainly analyzing the conceptual differences underlying legal body and parts by public and private biobanks, are described. Additionally, the current Argentinean legislation and circumstances arising from a resolution which INCUCAI sought to regulate private biobanks, is analyzed. This analysis leads to thoughts on the way conflicts are solved when the health and life of people are judicialized. In this particular case, the appearance of a complex new topic which gives rise to new social and healthcare scenarios, must be further understood.

HiRISE: The People's Camera

Science.gov (United States)

McEwen, A. S.; Eliason, E.; Gulick, V. C.; Spinoza, Y.; Beyer, R. A.; HiRISE Team

2010-12-01

The High Resolution Imaging Science Experiment (HiRISE) camera, orbiting Mars since 2006 on the Mars Reconnaissance Orbiter (MRO), has returned more than 17,000 large images with scales as small as 25 cm/pixel. From it’s beginning, the HiRISE team has followed “The People’s Camera” concept, with rapid release of useful images, explanations, and tools, and facilitating public image suggestions. The camera includes 14 CCDs, each read out into 2 data channels, so compressed images are returned from MRO as 28 long (up to 120,000 line) images that are 1024 pixels wide (or binned 2x2 to 512 pixels, etc.). This raw data is very difficult to use, especially for the public. At the HiRISE operations center the raw data are calibrated and processed into a series of B&W and color products, including browse images and JPEG2000-compressed images and tools to make it easy for everyone to explore these enormous images (see http://hirise.lpl.arizona.edu/). Automated pipelines do all of this processing, so we can keep up with the high data rate; images go directly to the format of the Planetary Data System (PDS). After students visually check each image product for errors, they are fully released just 1 month after receipt; captioned images (written by science team members) may be released sooner. These processed HiRISE images have been incorporated into tools such as Google Mars and World Wide Telescope for even greater accessibility. 51 Digital Terrain Models derived from HiRISE stereo pairs have been released, resulting in some spectacular flyover movies produced by members of the public and viewed up to 50,000 times according to YouTube. Public targeting began in 2007 via NASA Quest (http://marsoweb.nas.nasa.gov/HiRISE/quest/) and more than 200 images have been acquired, mostly by students and educators. At the beginning of 2010 we released HiWish (http://www.uahirise.org/hiwish/), opening HiRISE targeting to anyone in the world with Internet access, and already more

Human development VIII: a theory of "deep" quantum chemistry and cell consciousness: quantum chemistry controls genes and biochemistry to give cells and higher organisms consciousness and complex behavior.

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Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-11-14

Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it "sees", and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam's razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules' orbitals make one huge "cell-orbital", which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

Concise Review: Stem Cells in Osteoimmunology.

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Fierro, Fernando A; Nolta, Jan A; Adamopoulos, Iannis E

2017-06-01

Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent. Latest advances in the area of stem cell biology have enabled us to gain a better understanding of how these differentiation processes occur in physiological and pathological conditions. In this review we postulate that modulation of stem cells during inflammatory conditions is a necessary prerequisite of bone remodeling and therefore an essential new component to the field of osteoimmunology. In this context, we highlight the role of transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1), because it directly links inflammation with differentiation of osteoclasts and osteoblasts. Stem Cells 2017;35:1461-1467. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate in response to local signaling cues

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Row, Richard H.; Tsotras, Steve R.; Goto, Hana; Martin, Benjamin L.

2016-01-01

Vertebrate body axis formation depends on a population of bipotential neuromesodermal cells along the posterior wall of the tailbud that make a germ layer decision after gastrulation to form spinal cord and mesoderm. Despite exhibiting germ layer plasticity, these cells never give rise to midline tissues of the notochord, floor plate and dorsal endoderm, raising the question of whether midline tissues also arise from basal posterior progenitors after gastrulation. We show in zebrafish that local posterior signals specify germ layer fate in two basal tailbud midline progenitor populations. Wnt signaling induces notochord within a population of notochord/floor plate bipotential cells through negative transcriptional regulation of sox2. Notch signaling, required for hypochord induction during gastrulation, continues to act in the tailbud to specify hypochord from a notochord/hypochord bipotential cell population. Our results lend strong support to a continuous allocation model of midline tissue formation in zebrafish, and provide an embryological basis for zebrafish and mouse bifurcated notochord phenotypes as well as the rare human congenital split notochord syndrome. We demonstrate developmental equivalency between the tailbud progenitor cell populations. Midline progenitors can be transfated from notochord to somite fate after gastrulation by ectopic expression of msgn1, a master regulator of paraxial mesoderm fate, or if transplanted into the bipotential progenitors that normally give rise to somites. Our results indicate that the entire non-epidermal posterior body is derived from discrete, basal tailbud cell populations. These cells remain receptive to extracellular cues after gastrulation and continue to make basic germ layer decisions. PMID:26674311

Whether and How Much to Give

DEFF Research Database (Denmark)

Petrovski, Erik

This study evaluates whether factors known to foster charitable giving have a uniform influence on both (1) the decision to give and (2) the decision of how much to give. I establish that these two decisions are independent by dismissing the widely used Tobit model, which assumes a singe decision...

Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice.

Science.gov (United States)

Maridas, David E; Rendina-Ruedy, Elizabeth; Le, Phuong T; Rosen, Clifford J

2018-01-06

Bone marrow stromal cells (BMSCs) constitute a cell population routinely used as a representation of mesenchymal stem cells in vitro. They reside within the bone marrow cavity alongside hematopoietic stem cells (HSCs), which can give rise to red blood cells, immune progenitors, and osteoclasts. Thus, extractions of cell populations from the bone marrow results in a very heterogeneous mix of various cell populations, which can present challenges in experimental design and confound data interpretation. Several isolation and culture techniques have been developed in laboratories in order to obtain more or less homogeneous populations of BMSCs and HSCs invitro. Here, we present two methods for isolation of BMSCs and HSCs from mouse long bones: one method that yields a mixed population of BMSCs and HSCs and one method that attempts to separate the two cell populations based on adherence. Both methods provide cells suitable for osteogenic and adipogenic differentiation experiments as well as functional assays.

X-ray induced polyploidization in the male germline cells of Poekilocerus pictus (acrididoidea : orthopta)

International Nuclear Information System (INIS)

Gururaj, M.E.; Rajasekarasetty, M.R.

1977-01-01

After the irradiation of male germline cells of Poekilocerus pictus with 20r, 40r, 80r, 120r doses of X-rays, both first and second meiotic polyploid cells were recovered. While various degrees of polyploidy were encountered in first meiotic cells, second meiotic polyploid cells, second meitoic polyploid cells contained diploid number of half bivalents only. The former never progressed beyond leptotene and showed symptoms of degeneration. Among the latter, a few cells showed either emainingative tendencies like uncoiling and stickiness or failure of cellsted meiosis successfully. It has been shown that the dicentric bridges and/or laggards in anaphase-I interfere with the elongation and regression of the spindle, thereby giving rise to metaphase-II polyploid cells through restitution. The possible role of fragmentation of chromosomes in decreasing the incidence of metaphase-II polyploid cells at higher doses of irradiation and the causes for the differential fate of the first and second meiotic polyploid cells have been discussed. (author)

The Role of TOX in the Development of Innate Lymphoid Cells.

Science.gov (United States)

Seehus, Corey R; Kaye, Jonathan

2015-01-01

TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

The Role of TOX in the Development of Innate Lymphoid Cells

Directory of Open Access Journals (Sweden)

Corey R. Seehus

2015-01-01

Full Text Available TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

Biochemistry of epidermal stem cells.

Science.gov (United States)

Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

2013-02-01

The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

The Implications of Cancer Stem Cells for Cancer Therapy

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Wenjing Jiang

2012-12-01

Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

Classification of Hydrogels Based on Their Source: A Review and Application in Stem Cell Regulation

Science.gov (United States)

Khansari, Maziyar M.; Sorokina, Lioudmila V.; Mukherjee, Prithviraj; Mukhtar, Farrukh; Shirdar, Mostafa Rezazadeh; Shahidi, Mahnaz; Shokuhfar, Tolou

2017-08-01

Stem cells are recognized by their self-renewal ability and can give rise to specialized progeny. Hydrogels are an established class of biomaterials with the ability to control stem cell fate via mechanotransduction. They can mimic various physiological conditions to influence the fate of stem cells and are an ideal platform to support stem cell regulation. This review article provides a summary of recent advances in the application of different classes of hydrogels based on their source (e.g., natural, synthetic, or hybrid). This classification is important because the chemistry of substrate affects stem cell differentiation and proliferation. Natural and synthetic hydrogels have been widely used in stem cell regulation. Nevertheless, they have limitations that necessitate a new class of material. Hybrid hydrogels obtained by manipulation of the natural and synthetic ones can potentially overcome these limitations and shape the future of research in application of hydrogels in stem cell regulation.

Rise, stagnation, and rise of Danish women's life expectancy

DEFF Research Database (Denmark)

Lindahl-Jacobsen, Rune; Rau, Roland; Jeune, Bernard

2016-01-01

Health conditions change from year to year, with a general tendency in many countries for improvement. These conditions also change from one birth cohort to another: some generations suffer more adverse events in childhood, smoke more heavily, eat poorer diets, etc., than generations born earlier...... favor forecasts that hinge on cohort differences. We use a combination of age decomposition and exchange of survival probabilities between countries to study the remarkable recent history of female life expectancy in Denmark, a saga of rising, stagnating, and now again rising lifespans. The gap between...... female life expectancy in Denmark vs. Sweden grew to 3.5 y in the period 1975-2000. When we assumed that Danish women born 1915-1945 had the same survival probabilities as Swedish women, the gap remained small and roughly constant. Hence, the lower Danish life expectancy is caused by these cohorts...

Enhanced performance of high current discharges in JET produced by ICRF heating during the current rise

International Nuclear Information System (INIS)

Bures, M.; Bhatnagar, V.; Christiansen, J.P.

1989-01-01

The performance of high current discharges can be improved by applying central ICRF heating before or shortly after the onset of sawtooth activity in the plasma current rise phase. Long sawtooth-free periods have been obtained which result in a transiently-enhanced discharge performance. High T c (0) = 9-10.5 keV with peaked profile T e (0)/ e > = 3-4 were obtained giving values of N e (0)T e (0) up to 6 x 10 20 (keV m -3 ). Improvements in T i (0) and neutron production are observed. A best value of n Dd (0)T i (0)τ E = 1.65 x 10 20 (m -3 keV s) was achieved. Local transport simulation shows that the electron and ion thermal diffusivities do not differ substantially in the two cases of current-rise (CR) and flat-top (FT) heating, the performance of the central plasma region being enhanced, in the case of current-rise, entirely by the elimination of the sawtooth instability. The maximum D-D reaction rate is enhanced by a factor of 2 compared to the flat-top value. An appreciable part of the reaction rate is attributed to 2nd harmonic deuterium (2ω CD ) heating. In all current-rise discharges radiation amounts to 25-50% of total power and Ζ eff remains roughly constant. (author)

Clinical potentials of human pluripotent stem cells.

Science.gov (United States)

Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell'Era, Patrizia

2017-08-01

Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening.

Rise, fall and resurrection of chromosome territories: a historical perspective. Part I. The rise of chromosome territories

Directory of Open Access Journals (Sweden)

T Cremer

2009-06-01

Full Text Available It is now generally accepted that chromosomes in the cell nucleus are organized in distinct domains, first called chromosome territories in 1909 by the great cytologist Theodor Boveri. Yet, even today chromosomes have remained enigmatic individuals, whose structures, arrangements and functions in cycling and post-mitotic cells still need to be explored in full detail. Whereas numerous recent reviews describe present evidence for a dynamic architecture of chromosome territories and discuss the potential significance within the functional compartmentalization of the nucleus, a comprehensive historical account of this important concept of nuclear organization was lacking so far. Here, we describe the early rise of chromosome territories within the context of the discovery of chromosomes and their fundamental role in heredity, covering a period from the 1870th to the early 20th century (part I, this volume. In part II (next volume we review the abandonment of the chromosome territory concept during the 1950th to 1980th and the compelling evidence, which led to its resurrection during the 1970th to 1980th.

Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

Science.gov (United States)

Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

2017-09-01

Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

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Razmik Mirzayans

2016-05-01

Full Text Available It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E2, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional “repair and survive, or die” hypothesis.

Giving behavior of millionaires.

Science.gov (United States)

Smeets, Paul; Bauer, Rob; Gneezy, Uri

2015-08-25

This paper studies conditions influencing the generosity of wealthy people. We conduct incentivized experiments with individuals who have at least €1 million in their bank account. The results show that millionaires are more generous toward low-income individuals in a giving situation when the other participant has no power, than in a strategic setting, where the other participant can punish unfair behavior. Moreover, the level of giving by millionaires is higher than in any other previous study. Our findings have important implications for charities and financial institutions that deal with wealthy individuals.

Whether and How Much to Give

DEFF Research Database (Denmark)

Petrovski, Erik

2017-01-01

Charitable giving involves two seemingly distinct decisions: whether to give and how much to give. However, many researchers methodologically assume that these decisions are one and the same. The present study supports the argument that this is an incorrect assumption that is likely to generate...... misleading conclusions, in part, since the second decision is much more financial in nature than the first. The argument that charitable giving entails two distinct decisions is validated by empirically dismissing the prevailing Tobit model, which assumes a single decision, in favor of less restrictive two......-stage approaches: Cragg’s model and the Heckman model. Most importantly, it is shown that only by adopting a two-stage approach may it be uncovered that common determinants of charitable giving such as income and gender affect the two decisions at hand very differently. Data comes from a high-quality 2012 Danish...

The final cut: cell polarity meets cytokinesis at the bud neck in S. cerevisiae.

Science.gov (United States)

Juanes, Maria Angeles; Piatti, Simonetta

2016-08-01

Cell division is a fundamental but complex process that gives rise to two daughter cells. It includes an ordered set of events, altogether called "the cell cycle", that culminate with cytokinesis, the final stage of mitosis leading to the physical separation of the two daughter cells. Symmetric cell division equally partitions cellular components between the two daughter cells, which are therefore identical to one another and often share the same fate. In many cases, however, cell division is asymmetrical and generates two daughter cells that differ in specific protein inheritance, cell size, or developmental potential. The budding yeast Saccharomyces cerevisiae has proven to be an excellent system to investigate the molecular mechanisms governing asymmetric cell division and cytokinesis. Budding yeast is highly polarized during the cell cycle and divides asymmetrically, producing two cells with distinct sizes and fates. Many components of the machinery establishing cell polarization during budding are relocalized to the division site (i.e., the bud neck) for cytokinesis. In this review we recapitulate how budding yeast cells undergo polarized processes at the bud neck for cell division.

Androgen-Forming Stem Leydig cells: Identification, Function and Therapeutic Potential

Directory of Open Access Journals (Sweden)

Yunhui Zhang

2008-01-01

Full Text Available Leydig cells are the primary source of testosterone in the male, and differentiation of Leydig cells in the testes is one of the primary events in the development of the male body and fertility. Stem Leydig cells (SLCs exist in the testis throughout postnatal life, but a lack of cell surface markers previously hindered attempts to obtain purified SLC fractions. Once isolated, the properties of SLCs provide interesting clues for the ontogeny of these cells within the embryo. Moreover, the clinical potential of SLCs might be used to reverse age-related declines in testosterone levels in aging men, and stimulate reproductive function in hypogonadal males. This review focuses on the source, identification and outlook for therapeutic applications of SLCs. Separate pools of SLCs may give rise to fetal and adult generations of Leydig cell, which may account for their observed functional differences. These differences should in turn be taken into account when assessing the consequences of environmental pollutants such as the phthalate ester, diethylhexylphthalate (DEHP.

Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth

Directory of Open Access Journals (Sweden)

Jan Krivanek

2017-06-01

Full Text Available Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix–producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

Post-irradiation regeneration of early B-lymphocyte precursor cells in mouse bone marrow

International Nuclear Information System (INIS)

Park, Y.-H.; Osmond, D.G.

1989-01-01

To examine the sequential development of early B-cell precursors in mouse bone marrow, B-lineage cells have been examined during a wave of post-irradiation regeneration. Cell phenotypes have been defined for (i) terminal deoxynucleotidyl transferase (TdT); (ii) B220 glycoprotein, (iii) μ heavy chains in the cytoplasm (cμ) and at the cell surface (sμ). Three populations of μ - cells (TdT + 14.8 - ; TdT + 14.8 + ; TdT - 14.8 + ) have been proposed to be early B-cell precursors which would give rise to cμ + sμ - pre-B cells and to sμ + B lymphocytes. The timing, cell-size shifts and progressive amplification of the waves of regeneration accord with a dynamic model in which the TdT + 14.8 - , TdT + 14.8 + and TdT - 14.8 + cells form three successive stages in B-cell differentiation before the expression of μ chains, presumptively including the stage of μ chain gene rearrangement. In addition, the results provide an experimental system for the enrichment of early B-cell precursors in mouse bone marrow. (author)

Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

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Vladislav Volarevic

2014-01-01

Full Text Available Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

Differentiation in Stem Cell Lineages and in Life: Explorations in the Male Germ Line Stem Cell Lineage.

Science.gov (United States)

Fuller, Margaret T

2016-01-01

I have been privileged to work on cellular differentiation during a great surge of discovery that has revealed the molecular mechanisms and genetic regulatory circuitry that control embryonic development and adult tissue maintenance and repair. Studying the regulation of proliferation and differentiation in the male germ line stem cell lineage has allowed us investigate how the developmental program imposes layers of additional controls on fundamental cellular processes like cell cycle progression and gene expression to give rise to the huge variety of specialized cell types in our bodies. We are beginning to understand how local signals from somatic support cells specify self-renewal versus differentiation in the stem cell niche at the apical tip of the testis. We are discovering the molecular events that block cell proliferation and initiate terminal differentiation at the switch from mitosis to meiosis-a signature event of the germ cell program. Our work is beginning to reveal how the developmental program that sets up the dramatic new cell type-specific transcription program that prepares germ cells for meiotic division and spermatid differentiation is turned on when cells become spermatocytes. I have had the privilege of working with incredible students, postdocs, and colleagues who have discovered, brainstormed, challenged, and refined our science and our ideas of how developmental pathways and cellular mechanisms work together to drive differentiation. © 2016 Elsevier Inc. All rights reserved.

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

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

2017-09-01

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

Dynamical principles of cell-cycle arrest: Reversible, irreversible, and mixed strategies

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Pfeuty, Benjamin

2012-08-01

Living cells often alternate between proliferating and nonproliferating states as part of individual or collective strategies to adapt to complex and changing environments. To this aim, they have evolved a biochemical regulatory network enabling them to switch between cell-division cycles (i.e., oscillatory state) and cell-cycle arrests (i.e., steady state) in response to extracellular cues. This can be achieved by means of a variety of bifurcation mechanisms that potentially give rise to qualitatively distinct cell-cycle arrest properties. In this paper, we study the dynamics of a minimal biochemical network model in which a cell-division oscillator and a differentiation switch mutually antagonize. We identify the existence of three biologically plausible bifurcation scenarios organized around a codimension-four swallowtail-homoclinic singularity. As a result, the model exhibits a broad repertoire of cell-cycle arrest properties in terms of reversibility of these arrests, tunability of interdivision time, and ability to track time-varying signals. This dynamic versatility would explain the diversity of cell-cycle arrest strategies developed in different living species and functional contexts.

Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts

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Akhilesh Kumar

2017-05-01

Full Text Available Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs and smooth muscle cells (SMCs originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB. In clonogenic cultures, MBs differentiate into primitive PDGFRβ+CD271+CD73− mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells. MB-derived PCs can be further specified to CD274+ capillary and DLK1+ arteriolar PCs with a proinflammatory and contractile phenotype, respectively. SMC maturation was induced using a MEK inhibitor. Establishing the vasculogenic lineage tree, along with identification of stage- and lineage-specific markers, provides a platform for interrogating the molecular mechanisms that regulate vasculogenic cell specification and diversification and manufacturing well-defined mural cell populations for vascular engineering and cellular therapies from hPSCs.

T cell progenitors in the mouse fetal liver

International Nuclear Information System (INIS)

Rabinowich, H.; Umiel, T.; Globerson, A.

1983-01-01

Fourteen-day mouse fetal liver was found to contain cells capable of giving rise to T as well as B cell functions. The experimental system consisted of congenic C3H/DiSn and (C3H/DiSn X C3H.SW)F1 lethally irradiated (900 R) mice reconstituted with C3H/DiSn fetal liver or bone marrow cells. Assays included thyroid allograft rejection as well as in vitro measurement of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) and in a mixed lymphocyte culture (MLC) system in spleen, lymph node, and thymus cells. The fetal liver chimeras were found to become as capable as the bone marrow chimeras in responding in these various assays. The T cell responses lagged behind the responses to the B cell mitogens dextran sulfate (DXS) and lipopolysaccharide (LPS) (30 days after reconstitution, as compared with 14 days for DXS and 21 for LPS). The reacting cells were of the donor genotype, as revealed after treatment with C3H/DiSn (H-2k) anti-C3H.SW (H-2b) congenic sera. T cell responses were not manifest in thymectomized (TX) chimeras. Hence, the liver seems to contain cells capable of developing into T cell lineages in a thymus-dependent process

Giving Back, Moving Forward

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Louise Fortmann

2014-07-01

Full Text Available While reflecting on her own experience with giving back in Zimbabwe, Fortmann considers how the idea of “giving back” sits at the intersection of feminist theory, participatory research, and the democratization of science. From feminist theory arises the question of how to reciprocate to those who have contributed to our research. The participatory research and democratization of science literature push us to recognize and consider the collaborative nature of our research. Fortmann concludes by identifying three categories of reciprocity in research: material, intellectual, and personal. Sharing must occur, regardless of the kind of research taking place.

Sun Radio Interferometer Space Experiment (SunRISE)

Science.gov (United States)

Kasper, Justin C.; SunRISE Team

2018-06-01

The Sun Radio Interferometer Space Experiment (SunRISE) is a NASA Heliophysics Explorer Mission of Opportunity currently in Phase A. SunRISE is a constellation of spacecraft flying in a 10-km diameter formation and operating as the first imaging radio interferometer in space. The purpose of SunRISE is to reveal critical aspects of solar energetic particle (SEP) acceleration at coronal mass ejections (CMEs) and transport into space by making the first spatially resolved observations of coherent Type II and III radio bursts produced by electrons accelerated at CMEs or released from flares. SunRISE will focus on solar Decametric-Hectometric (DH, 0.1 space before major SEP events, but cannot be seen on Earth due to ionospheric absorption. This talk will describe SunRISE objectives and implementation. Presented on behalf of the entire SunRISE team.

Quark-gluon structure of the pomeron and the rise of inclusive spectra at high energies

International Nuclear Information System (INIS)

Kaidalov, A.V.

1982-01-01

The topological expansion and the nodel of a colour tube are used for the calculation of inclusive hadronic spectra in the central region. The higher-order terms of the 1/Nsub(f)-expansion, which correspond to the contribution of the poliperipheral diagrams are taken into account. It is shown that the intrinsic motion of quarks inside colliding hadrons leads to the rise of inclusive spectra with energy in the central region. The model gives a good quantitative description of the effects observed recently at the CERN SPS Collider

Transfection of bovine spermatogonial stem cells in vitro.

Science.gov (United States)

Tajik, P; Hoseini Pajooh, Kh; Fazle Elahi, Z; Javdani Shahedin, G; Ghasemzadeh-Nava, H

2017-01-01

Spermatogonial stem cells (SSCs) are the only stem cells in adults that can transfer genetic information to the future generations. Considering the fact that a single SSC gives rise to a vast number of spermatozoa, genetic manipulation of these cells is a potential novel technology with feasible application to various animal species. The aim of this study was to evaluate enhanced green fluorescent protein (EGFP) gene transfection into bovine SSCs via liposome carrier and assess the best incubation day in uptake exogenous gene by SSCs. Transfection efficiency of EGFP gene with lipofectamine 2000 was determined in days following each three day of transfection (day 4, 6 and 8 of the culture) by fluorescent microscope. Results showed that the transfected cells through lipofection increased significantly (Ptransfection in comparison with those of the control groups. The transfected SSCs were higher in comparison with those of the free exogenous gene carrier groups (Ptransfection proceeds at day four. It was concluded that lipofectamine can be used safely for direct loading exogenous DNA to SSCs particularly during the fourth day of culture.

Colony variation of Helicobacter pylori: pathogenic potential is correlated to cell wall lipid composition.

Science.gov (United States)

Bukholm, G; Tannaes, T; Nedenskov, P; Esbensen, Y; Grav, H J; Hovig, T; Ariansen, S; Guldvog, I

1997-05-01

Differences in expression of disease after infection with Helicobacter pylori have so far been connected with host factors and bacterial interstrain variation. In this study, spontaneous and ecology-mediated intrastrain variation was examined. Four clinical isolates of H. pylori were shown to give rise to two colony forms. Bacterial morphology was examined by electron microscopy. Bacterial fractions were examined for proteins using ion exchange chromatography and SDS-PAGE; for lipids using thin-layer chromatography, lipid anion-exchange chromatography, column chromatography on silica gel, 31P-NMR, gas chromatography and mass spectrometry. Bacterial in vitro invasiveness and adhesiveness were examined in two different systems, and urease and VacA toxin were assayed by Western blot analysis. H. pylori was shown to give rise to two colony forms: at normal pH the population was dominated by L colonies. One strain was chosen for further studies. Bacteria from L colonies retained VacA toxin and urease, did not invade or adhere to epithelial cells, and contained normal quantities of phosphatidylethanolamine. In a small frequency, spontaneous S colonies were formed. Bacteria from these colonies released VacA and urease, adhered to and invaded epithelial cells and contained increased amounts of lysophosphatidyl ethanolamine and phosphatidyl serine. After addition of HCl to the culture medium (pH6), almost only S colonies were formed. The results demonstrate that environmental factors, such as HCl, can change the bacterial cell wall, and thereby enhance expression of virulence factors of H. pylori in vitro. A similar in vivo variation would have implications for our understanding of the interaction between HCl secretion in the gastric mucosa and H. pylori in the development of peptic ulcer disease.

Duality gives rise to Chaplygin cosmologies with a big rip

International Nuclear Information System (INIS)

Chimento, Luis P; Lazkoz, Ruth

2006-01-01

We consider modifications to the Friedmann equation motivated by recent proposals along these lines pursuing an explanation to the observed late time acceleration. Here we show that these approaches can be framed within a theory with modified gravity, and we discuss the construction of the duals of the cosmologies generated within that framework. We then investigate the modifications required to generate extended, generalized and modified Chaplygin cosmologies, and then show that their duals belong to a larger family of cosmologies we call enlarged Chaplygin cosmologies. Finally, by letting the parameters of these models take values not earlier considered in the literature we show that some representatives of that family of cosmologies display sudden future singularities. This fact indicates that the behaviour of these spacetimes is rather different from that of generalized or modified Chaplygin gas cosmologies. This reinforces the idea that modifications of gravity can be responsible for unexpected evolutionary features in the universe

The human elements in phenomena giving rise to nuclear accidents

International Nuclear Information System (INIS)

Carnino, A.; Raggenbass, A.

1977-01-01

In its search for a high degree of safety, the nuclear industry should take into account the human parameters, which play an important role. This role is reflected in the individual records kept on incidents and analysis of these records, as has been carried out in conventional industry, represents a first attempt to allow for this factor. The first inquiries covering the background of incidents led to a series of studies and action in respect of individual staff members: on the part of operators, education of personnel in relation to their duties (for example, simulation of reactor control) and attempts to find objective selection criteria for certain specific posts; on the part of those responsible for safety, ergonomic studies and studies on human reliability. For effective prevention of accidents it is necessary to move backwards along the causality chains and therefore to study a nuclear facility as a man-machine system in order to discover the greatest number of potential accident factors. The nuclear facility is introduced into an environment which imposes its rules, constraints and checks and a full study of the human element in safety implies that they should be taken into account. The programme of the Nuclear Safety Department of the Institute of Protection and Nuclear Safety includes not only systematic updating of incident records but also special ergonomic studies (maintenance in a radioactive environment), studies of human reliability and overall studies known as safety management studies. (author)

Au/TiO2 nanobelt heterostructures for the detection of cancer cells and anticancer drug activity by potential sensing

International Nuclear Information System (INIS)

Cui, Jingjie; Xu, Ping; Li, Hong; Chen, Jing; Chen, Shaowei; Gao, Li

2016-01-01

Cancer is a cell dysfunction disease. The detection of cancer cells is extremely important for early diagnosis and clinical treatments. At present, the pretreatment for the detection of cancer cells is costly, complicated and time-consuming. As different species of the analytes may give rise to specific voltammetric signals at distinctly different potentials, simple potential sensing has the specificity to detect different cellular species. By taking advantage of the different electrochemical characteristics of normal cells, cancer cells and biointeractions between anticancer drugs and cancer cells, we develop a specific, sensitive, direct, cost-effective and rapid method for the detection of cancer cells by electrochemical potential sensing based on Au/TiO 2 nanobelt heterostructure electrodes that will be of significance in early cancer diagnosis, in vitro screening of anticancer drugs  and molecular biology research. (paper)

Determinants of cell-to-cell variability in protein kinase signaling.

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Matthias Jeschke

Full Text Available Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity' and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

microRNAs as regulators of adipogenic differentiation of mesenchymal stem cells.

Science.gov (United States)

Hamam, Dana; Ali, Dalia; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

2015-02-15

microRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel approaches for enhancing osteoblastic bone formation through inhibition of bone marrow fat formation. A number of recent studies have reported several miRNAs that enhance or inhibit adipogenic differentiation of MSCs and with potential use in microRNA-based therapy to regulate adipogenesis in the context of treating bone diseases and metabolic disorders. The current review focuses on miRNAs and their role in regulating adipogenic differentiation of MSCs.

Live-cell calcium imaging of adherent and non-adherent GL261 cells reveals phenotype-dependent differences in drug responses.

Science.gov (United States)

Strong, Averey D; Daniels, Richard L

2017-08-02

The tumor-derived GL261 cell line is used as a model for studying glioblastoma and other high-grade gliomas, and can be cultured adherently or as free-floating aggregates known as neurospheres. These different culture conditions give rise to distinct phenotypes, with increased tumorigenicity displayed by neurosphere-cultured cells. An important technique for understanding GL261 pathobiology is live cell fluorescent imaging of intracellular calcium. However, live cell imaging of GL261 neurospheres presents a technical challenge, as experimental manipulations where drugs are added to the extracellular media cause the cells to move during analysis. Here we present a method to immobilize GL261 neurospheres with low melting point agarose for calcium imaging using the fluorescent calcium sensor fura-2. GL261 cells were obtained from the NCI-Frederick Cancer Research Tumor Repository and cultured as adherent cells or induced to form neurospheres by placing freshly trypsinized cells into serum-free media containing fibroblast growth factor 2, epidermal growth factor, and B-27 supplement. Prior to experiments, adherent cells were loaded with fura-2 and cultured on 8-well chamber slides. Non-adherent neurospheres were first loaded with fura-2, placed in droplets onto an 8-well chamber slide, and finally covered with a thin layer of low melting point agarose to immobilize the cells. Ratiometric pseudocolored images were obtained during treatment with ATP, capsaicin, or vehicle control. Cells were marked as responsive if fluorescence levels increased more than 30% above baseline. Differences between treatment groups were tested using Student's t-tests and one-way ANOVA. We found that cellular responses to pharmacological treatments differ based on cellular phenotype. Adherent cells and neurospheres both responded to ATP with a rise in intracellular calcium. Notably, capsaicin treatment led to robust responses in GL261 neurospheres but not adherent cells. We demonstrate the use

SEA LEVEL RISE AND ITS POTENTIAL IMPACTS ON COASTAL URBAN AREA: A CASE OF ETI-OSA, NIGERIA

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Ayodele Michael AGBOOLA

2016-10-01

Full Text Available This study examines the spatial extent of coastal urban development and its potential sensitivity to sea-level rise. The main aim of the study is to critically examine the extent of growth in Eti-Osa over time, and the potential impacts of sea leve rise. Landsat Enhanced Thematic Mapper Plus (ETM+ imageries of years 2000 and 2015 were used to evaluate the different land use type identified. Post-classification change detection method was used to evaluate the output of the maximum likelihood supervised classification analysis done. This was also used to estimate the changes induces through urban development on the environment which accounts for the biodiversity loss. ASTER GDEM 2 imagery of 2011 was used to generate the elevation data used for the inundation analysis. Thus, both Land use map of Eti-Osa in 2015 and the down scaled Sea-level rise scenarios (at 0.5 to 15 meters were used for the inundation mapping. Results obtained from this research affirms that indeed EtiOsa has been subjected to gross urban expansion giving room for diverse forms of environmental degradation among which are huge replacement of natural land cover with built-up, reclamation of wetlands and sand filling of water bodies. This basically illustrates growth but also the risk that accompanies the advent of excessive alteration of natural ecosystem as Sea-level rise projections imply in this research.

Mesenchymal stem cell-derived microparticles: a promising therapeutic strategy.

Science.gov (United States)

Tan, Xi; Gong, Yong-Zhen; Wu, Ping; Liao, Duan-Fang; Zheng, Xi-Long

2014-08-18

Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.

Semi-automated digital measurement as the method of choice for beta cell mass analysis.

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Violette Coppens

Full Text Available Pancreas injury by partial duct ligation (PDL activates beta cell differentiation and proliferation in adult mouse pancreas but remains controversial regarding the anticipated increase in beta cell volume. Several reports unable to show beta cell volume augmentation in PDL pancreas used automated digital image analysis software. We hypothesized that fully automatic beta cell morphometry without manual micrograph artifact remediation introduces bias and therefore might be responsible for reported discrepancies and controversy. However, our present results prove that standard digital image processing with automatic thresholding is sufficiently robust albeit less sensitive and less adequate to demonstrate a significant increase in beta cell volume in PDL versus Sham-operated pancreas. We therefore conclude that other confounding factors such as quality of surgery, selection of samples based on relative abundance of the transcription factor Neurogenin 3 (Ngn3 and tissue processing give rise to inter-laboratory inconsistencies in beta cell volume quantification in PDL pancreas.

On Capillary Rise and Nucleation

Science.gov (United States)

Prasad, R.

2008-01-01

A comparison of capillary rise and nucleation is presented. It is shown that both phenomena result from a balance between two competing energy factors: a volume energy and a surface energy. Such a comparison may help to introduce nucleation with a topic familiar to the students, capillary rise. (Contains 1 table and 3 figures.)

The fine structure of human germ layers in vivo: clues to the early differentiation of embryonic stem cells in vitro.

Science.gov (United States)

Sathananthan, Henry; Selvaraj, Kamala; Clark, Joan

2011-08-01

The fine structure of the three germ layers in human ectopic embryos (stage 7) have been documented by digital light and electron microscopy. The formation of ectoderm, endoderm and mesoderm and notochordal cells, and also the extraembryonic membranes, amnion and yolk sac, are imaged. The germ layers give rise to all the cells and tissues of the human body. Possible clues to the early differentiation of embryonic stem cells (ESC) in vitro were obtained, since these events are more or less mimicked in cultures of ESC derived from the inner cell mass of human blastocysts. The findings are discussed with reference to previous studies on the fine structure of ESC using the same technique. Copyright © 2011. Published by Elsevier Ltd.

Conditions giving rise to intense visible room temperature photoluminescence in SrWO4 thin films: the role of disorder

International Nuclear Information System (INIS)

Orhan, E.; Anicete-Santos, M.; Maurera, M.A.M.A.; Pontes, F.M.; Paiva-Santos, C.O.; Souza, A.G.; Varela, J.A.; Pizani, P.S.; Longo, E.

2005-01-01

The nature of intense visible photoluminescence at room temperature of SrWO 4 (SWO) non-crystalline thin films is discussed in the light of experimental results and theoretical calculations. The SWO thin films were synthesized by the polymeric precursors method. Their structural properties have been obtained by X-ray diffraction data and the corresponding photoluminescence (PL) spectra have been measured. The UV-vis optical spectra measurements suggest the creation of localized states in the disordered structure. The photoluminescence measurements reveal that the PL changes with the degree of disorder in the SWO thin film. To understand the origin of visible PL at room temperature in disordered SWO, we performed quantum-mechanical calculations on crystalline and disordered SWO periodic models. Their electronic structures are analyzed in terms of DOS, band dispersion and charge densities. We used DFT method with the hybrid non-local B3LYP approximation. The polarization induced by the symmetry break and the existence of localized levels favors the creation of trapped holes and electrons, giving origin to the room temperature photoluminescence phenomenon in the SWO thin films

GIVING AND RECEIVING CONSTRUCTIVE FEEDBACK

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Ірина Олійник

2015-05-01

Full Text Available The article scrutinizes the notion of feedback applicable in classrooms where team teaching is provided. The experience of giving and receiving feedback has been a good practice in cooperation between a U.S. Peace Corps volunteer and a Ukrainian counterpart. Giving and receiving feedback is an effective means of classroom observation that provides better insight into the process of teaching a foreign language. The article discusses the stages of feedback and explicates the notion of sharing experience between two teachers working simultaneously in the same classroom. The guidelines for giving and receiving feedback have been provided as well as the most commonly used vocabulary items have been listed. It has been proved that mutual feedback leads to improving teaching methods and using various teaching styles and techniques.

A Hypomorphic PALB2 Allele Gives Rise to an Unusual Form of FA-N Associated with Lymphoid Tumour Development.

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Philip J Byrd

2016-03-01

Full Text Available Patients with biallelic truncating mutations in PALB2 have a severe form of Fanconi anaemia (FA-N, with a predisposition for developing embryonal-type tumours in infancy. Here we describe two unusual patients from a single family, carrying biallelic PALB2 mutations, one truncating, c.1676_1677delAAinsG;(p.Gln559ArgfsTer2, and the second, c.2586+1G>A; p.Thr839_Lys862del resulting in an in frame skip of exon 6 (24 amino acids. Strikingly, the affected individuals did not exhibit the severe developmental defects typical of FA-N patients and initially presented with B cell non-Hodgkin lymphoma. The expressed p.Thr839_Lys862del mutant PALB2 protein retained the ability to interact with BRCA2, previously unreported in FA-N patients. There was also a large increased chromosomal radiosensitivity following irradiation in G2 and increased sensitivity to mitomycin C. Although patient cells were unable to form Rad51 foci following exposure to either DNA damaging agent, U2OS cells, in which the mutant PALB2 with in frame skip of exon 6 was induced, did show recruitment of Rad51 to foci following damage. We conclude that a very mild form of FA-N exists arising from a hypomorphic PALB2 allele.

Strategic advantages of high-rise construction

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Yaskova Natalya

2018-01-01

Full Text Available Traditional methods to assess the competitiveness of different types of real estate in the context of huge changes of new technological way of life don’t provide building solutions that would be correct from a strategic perspective. There are many challenges due to changes in the consumers’ behavior in the housing area. A multiplicity of life models, a variety of opportunities and priorities, traditions and new trends in construction should be assessed in terms of prospective benefits in the environment of the emerging new world order. At the same time, the mane discourse of high-rise construction mainly relates to its design features, technical innovations, and architectural accents. We need to clarify the criteria for economic evaluation of high-rise construction in order to provide decisions with clear and quantifiable contexts. The suggested approach to assessing the strategic advantage of high-rise construction and the prospects for capitalization of high-rise buildings poses new challenges for the economy to identify adequate quantitative assessment methods of the high-rise buildings economic efficiency, taking into account all stages of their life cycle.

Strategic advantages of high-rise construction

Science.gov (United States)

Yaskova, Natalya

2018-03-01

Traditional methods to assess the competitiveness of different types of real estate in the context of huge changes of new technological way of life don't provide building solutions that would be correct from a strategic perspective. There are many challenges due to changes in the consumers' behavior in the housing area. A multiplicity of life models, a variety of opportunities and priorities, traditions and new trends in construction should be assessed in terms of prospective benefits in the environment of the emerging new world order. At the same time, the mane discourse of high-rise construction mainly relates to its design features, technical innovations, and architectural accents. We need to clarify the criteria for economic evaluation of high-rise construction in order to provide decisions with clear and quantifiable contexts. The suggested approach to assessing the strategic advantage of high-rise construction and the prospects for capitalization of high-rise buildings poses new challenges for the economy to identify adequate quantitative assessment methods of the high-rise buildings economic efficiency, taking into account all stages of their life cycle.

SOX2 regulates acinar cell development in the salivary gland

Science.gov (United States)

Emmerson, Elaine; May, Alison J; Nathan, Sara; Cruz-Pacheco, Noel; Lizama, Carlos O; Maliskova, Lenka; Zovein, Ann C; Shen, Yin; Muench, Marcus O; Knox, Sarah M

2017-01-01

Acinar cells play an essential role in the secretory function of exocrine organs. Despite this requirement, how acinar cells are generated during organogenesis is unclear. Using the acini-ductal network of the developing human and murine salivary gland, we demonstrate an unexpected role for SOX2 and parasympathetic nerves in generating the acinar lineage that has broad implications for epithelial morphogenesis. Despite SOX2 being expressed by progenitors that give rise to both acinar and duct cells, genetic ablation of SOX2 results in a failure to establish acini but not ducts. Furthermore, we show that SOX2 targets acinar-specific genes and is essential for the survival of acinar but not ductal cells. Finally, we illustrate an unexpected and novel role for peripheral nerves in the creation of acini throughout development via regulation of SOX2. Thus, SOX2 is a master regulator of the acinar cell lineage essential to the establishment of a functional organ. DOI: http://dx.doi.org/10.7554/eLife.26620.001 PMID:28623666

Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor

DEFF Research Database (Denmark)

Shamim, Z; Spellman, S; Haagenson, M

2013-01-01

Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes...... significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis...

Fully Solution-Processed Inverted Polymer Solar Cells with Laminated Nanowire Electrodes

KAUST Repository

Gaynor, Whitney

2010-01-26

We demonstrate organic photovoltaic cells in which every layer is deposited by solution processing on opaque metal substrates, with efficiencies similar to those obtained in conventional device structures on transparent substrates. The device architecture is enabled by solution-processed, laminated silver nanowire films serving as the top transparent anode. The cells are based on the regioregular poly(3- hexylthiophene) and C 61 butyric acid methyl ester bulk heterojunction and reach an efficiency of 2.5% under 100 mW/cm 2 of AM 1.5G illumination. The metal substrates are adequate barriers to moisture and oxygen, in contrast to transparent plastics that have previously been used, giving rise to the possibility of roll-to-roll solutionprocessed solar cells that are packaged by lamination to glass substrates, combining the cost advantage of roll-toroll processing with the barrier properties of glass and metal foil. © 2010 American Chemical Society.

Fully Solution-Processed Inverted Polymer Solar Cells with Laminated Nanowire Electrodes

KAUST Repository

Gaynor, Whitney; Lee, Jung-Yong; Peumans, Peter

2010-01-01

We demonstrate organic photovoltaic cells in which every layer is deposited by solution processing on opaque metal substrates, with efficiencies similar to those obtained in conventional device structures on transparent substrates. The device architecture is enabled by solution-processed, laminated silver nanowire films serving as the top transparent anode. The cells are based on the regioregular poly(3- hexylthiophene) and C 61 butyric acid methyl ester bulk heterojunction and reach an efficiency of 2.5% under 100 mW/cm 2 of AM 1.5G illumination. The metal substrates are adequate barriers to moisture and oxygen, in contrast to transparent plastics that have previously been used, giving rise to the possibility of roll-to-roll solutionprocessed solar cells that are packaged by lamination to glass substrates, combining the cost advantage of roll-toroll processing with the barrier properties of glass and metal foil. © 2010 American Chemical Society.

Human Development VIII: A Theory of “Deep” Quantum Chemistry and Cell Consciousness: Quantum Chemistry Controls Genes and Biochemistry to Give Cells and Higher Organisms Consciousness and Complex Behavior

Directory of Open Access Journals (Sweden)

Søren Ventegodt

2006-01-01

Full Text Available Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it “sees”, and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam’s razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules’ orbitals make one huge “cell-orbital”, which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology.

Science.gov (United States)

Gerweck, Leo E; Wakimoto, Hiroaki

2016-03-01

Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers have led to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflect the response of the sensitive rather than the resistant tumorigenic cell population. The reports further suggest that the marker-based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers, and drugs that specifically target the resistant tumorigenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells that sustain tumor growth and that the marker-identified population is radioresistant relative to the marker-negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony-forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability. ©2016 American Association for Cancer Research.

Analysis gives sensibility two models gives migration and transport gives radionuclides in the geosphere

International Nuclear Information System (INIS)

Torres Berdeguez, M. B.; Gil Castillo, R.; Peralta Vidal, J.L.

1998-01-01

An sensibility analysis it was applied two models, the first one, a model compressible for the near field (I finish source) The second, a simple model gives migration and transport radionuclides in the geosphere. The study was developed varying the securities ed simultaneously at the same time each parameter and observing the results in changes in the output and input. The intention in analysis it is to determine the parameter that but it influences in the variation the concentration. The statistical technique Regression it was employee in the study. This statistical method is used to analyze the dependence between a dependent variable and an or but independent variables

The Impact of the Rise in Vegetable Prices on Vegetable Producer Behavior–Based on the survey of vegetable producers in Jiayu, Hubei Province

Directory of Open Access Journals (Sweden)

Liu Pan

2015-01-01

Full Text Available In order to study the impact of the rise in prices of vegetables on vegetable producers, and to increase the revenue of vegetable producers, this paper does a survey by anonymous sampling questionnaire. Results shows that: most vegetable growers think that vegetable prices should rise and would continue to rise, and that vegetable prices would increase their revenue, thus in the coming year they would expand the planting scale of vegetable variety whose increase rate is the largest in this year. But because of the increase of logistics costs and production costs, some farmers benefit very little from the rising trend of vegetable prices. Most farmers expect too much in the trend estimation of the prices of vegetables and also lack of planning and forward-looking in production, thus the planting area of single variety is often decided by the market of previous year. According to analysis of the impact of the rise in vegetable prices on vegetable producer behavior, this paper gives the following suggestions to increase revenue of vegetable producers: change the mode of thinking, improve rural information platform, and increase capital investment for vegetable production base.

Mathematical modeling of the Phoenix Rising pathway.

Directory of Open Access Journals (Sweden)

Chad Liu

2014-02-01

Full Text Available Apoptosis is a tightly controlled process in mammalian cells. It is important for embryogenesis, tissue homoeostasis, and cancer treatment. Apoptosis not only induces cell death, but also leads to the release of signals that promote rapid proliferation of surrounding cells through the Phoenix Rising (PR pathway. To quantitatively understand the kinetics of interactions of different molecules in this pathway, we developed a mathematical model to simulate the effects of various changes in the PR pathway on the secretion of prostaglandin E2 (PGE2, a key factor for promoting cell proliferation. These changes include activation of caspase 3 (C3, caspase 7 (C7, and nuclear factor κB (NFκB. In addition, we simulated the effects of cyclooxygenase-2 (COX2 inhibition and C3 knockout on the level of secreted PGE2. The model predictions on PGE2 in MEF and 4T1 cells at 48 hours after 10-Gray radiation were quantitatively consistent with the experimental data in the literature. Compared to C7, the model predicted that C3 activation was more critical for PGE2 production. The model also predicted that PGE2 production could be significantly reduced when COX2 expression was blocked via either NFκB inactivation or treatment of cells with exogenous COX2 inhibitors, which led to a decrease in the rate of conversion from arachidonic acid to prostaglandin H2 in the PR pathway. In conclusion, the mathematical model developed in this study yielded new insights into the process of tissue regrowth stimulated by signals from apoptotic cells. In future studies, the model can be used for experimental data analysis and assisting development of novel strategies/drugs for improving cancer treatment or normal tissue regeneration.

How to Give a Good Talk?

OpenAIRE

Legout , Arnaud

2013-01-01

Why should you give great talks? How to make great slides? How to give a talk? How to make good presentations?; 3rd cycle; Warning: download the powerpoint version to get animations. Animated slides in the PDF version may look cluttered.

Feedback dynamics and cell function: Why systems biology is called Systems Biology.

Science.gov (United States)

Wolkenhauer, Olaf; Mesarovic, Mihajlo

2005-05-01

A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

Effect of liquid gate bias rising time in pH sensors based on Si nanowire ion sensitive field effect transistors

Science.gov (United States)

Jang, Jungkyu; Choi, Sungju; Kim, Jungmok; Park, Tae Jung; Park, Byung-Gook; Kim, Dong Myong; Choi, Sung-Jin; Lee, Seung Min; Kim, Dae Hwan; Mo, Hyun-Sun

2018-02-01

In this study, we investigate the effect of rising time (TR) of liquid gate bias (VLG) on transient responses in pH sensors based on Si nanowire ion-sensitive field-effect transistors (ISFETs). As TR becomes shorter and pH values decrease, the ISFET current takes a longer time to saturate to the pH-dependent steady-state value. By correlating VLG with the internal gate-to-source voltage of the ISFET, we found that this effect occurs when the drift/diffusion of mobile ions in analytes in response to VLG is delayed. This gives us useful insight on the design of ISFET-based point-of-care circuits and systems, particularly with respect to determining an appropriate rising time for the liquid gate bias.

How thoughts give rise to action - conscious motor intention increases the excitability of target-specific motor circuits.

Directory of Open Access Journals (Sweden)

Volker R Zschorlich

Full Text Available The present study shows evidence for conscious motor intention in motor preparation prior to movement execution. We demonstrate that conscious motor intention of directed movement, combined with minimally supra-threshold transcranial magnetic stimulation (TMS of the motor cortex, determines the direction and the force of resulting movements, whilst a lack of intention results in weak and omni-directed muscle activation. We investigated changes of consciously intended goal directed movements by analyzing amplitudes of motor-evoked potentials of the forearm muscle, flexor carpi radialis (FCR, and extensor carpi radialis (ECR, induced by transcranial magnetic stimulation over the right motor cortex and their motor outcome. Right-handed subjects were asked to develop a strong intention to move their left wrist (flexion or extension, without any overt motor output at the wrist, prior to brain stimulation. Our analyses of hand acceleration and electromyography showed that during the strong motor intention of wrist flexion movement, it evoked motor potential responses that were significantly larger in the FCR muscle than in the ECR, whilst the opposite was true for an extension movement. The acceleration data on flexion/extension corresponded to this finding. Under no-intention conditions again, which served as a reference for motor evoked potentials, brain stimulation resulted in undirected and minimally simultaneous extension/flexion innervation and virtually no movement. These results indicate that conscious intentions govern motor function, which in turn shows that a neuronal activation representing an "intention network" in the human brain pre-exists, and that it functionally represents target specific motor circuits. Until today, it was unclear whether conscious motor intention exists prior to movement, or whether the brain constructs such an intention after movement initiation. Our study gives evidence that motor intentions become aware before

How Thoughts Give Rise to Action - Conscious Motor Intention Increases the Excitability of Target-Specific Motor Circuits

Science.gov (United States)

Zschorlich, Volker R.; Köhling, Rüdiger

2013-01-01

The present study shows evidence for conscious motor intention in motor preparation prior to movement execution. We demonstrate that conscious motor intention of directed movement, combined with minimally supra-threshold transcranial magnetic stimulation (TMS) of the motor cortex, determines the direction and the force of resulting movements, whilst a lack of intention results in weak and omni-directed muscle activation. We investigated changes of consciously intended goal directed movements by analyzing amplitudes of motor-evoked potentials of the forearm muscle, flexor carpi radialis (FCR), and extensor carpi radialis (ECR), induced by transcranial magnetic stimulation over the right motor cortex and their motor outcome. Right-handed subjects were asked to develop a strong intention to move their left wrist (flexion or extension), without any overt motor output at the wrist, prior to brain stimulation. Our analyses of hand acceleration and electromyography showed that during the strong motor intention of wrist flexion movement, it evoked motor potential responses that were significantly larger in the FCR muscle than in the ECR, whilst the opposite was true for an extension movement. The acceleration data on flexion/extension corresponded to this finding. Under no-intention conditions again, which served as a reference for motor evoked potentials, brain stimulation resulted in undirected and minimally simultaneous extension/flexion innervation and virtually no movement. These results indicate that conscious intentions govern motor function, which in turn shows that a neuronal activation representing an “intention network” in the human brain pre-exists, and that it functionally represents target specific motor circuits. Until today, it was unclear whether conscious motor intention exists prior to movement, or whether the brain constructs such an intention after movement initiation. Our study gives evidence that motor intentions become aware before any motor

Roles of bHLH genes in neural stem cell differentiation

International Nuclear Information System (INIS)

Kageyama, Ryoichiro; Ohtsuka, Toshiyuki; Hatakeyama, Jun; Ohsawa, Ryosuke

2005-01-01

Neural stem cells change their characteristics over time during development: they initially proliferate only and then give rise to neurons first and glial cells later. In the absence of the repressor-type basic helix-loop-helix (bHLH) genes Hes1, Hes3 and Hes5, neural stem cells do not proliferate sufficiently but prematurely differentiate into neurons and become depleted without making the later born cell types such as astrocytes and ependymal cells. Thus, Hes genes are essential for maintenance of neural stem cells to make cells not only in correct numbers but also in full diversity. Hes genes antagonize the activator-type bHLH genes, which include Mash1, Math and Neurogenin. The activator-type bHLH genes promote the neuronal fate determination and induce expression of Notch ligands such as Delta. These ligands activate Notch signaling and upregulate Hes1 and Hes5 expression in neighboring cells, thereby maintaining these cells undifferentiated. Thus, the activator-type and repressor-type bHLH genes regulate each other, allowing only subsets of cells to undergo differentiation while keeping others to stay neural stem cells. This regulation is essential for generation of complex brain structures of appropriate size, shape and cell arrangement

The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

Energy Technology Data Exchange (ETDEWEB)

Silva Meirelles, Lindolfo da, E-mail: lindolfomeirelles@gmail.com [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Laboratory for Stem Cells and Tissue Engineering, PPGBioSaúde, Lutheran University of Brazil, Av. Farroupilha 8001, 92425-900 Canoas, RS (Brazil); Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre [Laboratory of Large-Scale Functional Biology (LLSFBio), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); and others

2016-12-10

Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

International Nuclear Information System (INIS)

Silva Meirelles, Lindolfo da; Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana; Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre

2016-01-01

Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

Correlation between membrane fluidity cellular development and stem cell differentiation

KAUST Repository

Noutsi, Pakiza

2016-12-01

Cell membranes are made up of a complex structure of lipids and proteins that diffuse laterally giving rise to what we call membrane fluidity. During cellular development, such as neuronal differentiation, cell membranes undergo dramatic structural changes induced by proteins such as ARC and Cofilin among others in the case of synaptic modification. In this study we used the generalized polarization (GP) property of fluorescent probe Laurdan using two-photon microscopy to determine membrane fluidity as a function of time and for various cell lines. A low GP value corresponds to a higher fluidity and a higher GP value is associated with a more rigid membrane. Four different cell lines were monitored such as hN2, NIH3T3, HEK293 and L6 cells. As expected, NIH3T3 cells have more rigid membrane at earlier stages of their development. On the other hand neurons tend to have the highest membrane fluidity early in their development emphasizing its correlation with plasticity and the need for this malleability during differentiation. This study sheds light on the involvement of membrane fluidity during neuronal differentiation and development of other cell lines.

The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

Energy Technology Data Exchange (ETDEWEB)

Blom, Magdalena; Reis, Katarina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Heldin, Johan [Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala SE-751 22 Uppsala (Sweden); Kreuger, Johan [Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala (Sweden); Aspenström, Pontus, E-mail: pontus.aspenstrom@ki.se [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

2017-03-15

RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

International Nuclear Information System (INIS)

Blom, Magdalena; Reis, Katarina; Heldin, Johan; Kreuger, Johan; Aspenström, Pontus

2017-01-01

RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

Socioecological Aspects of High-rise Construction

Science.gov (United States)

Eichner, Michael; Ivanova, Zinaida

2018-03-01

In this article, the authors consider the socioecological problems that arise in the construction and operation of high-rise buildings. They study different points of view on high-rise construction and note that the approaches to this problem are very different. They also analyse projects of modern architects and which attempts are made to overcome negative impacts on nature and mankind. The article contains materials of sociological research, confirming the ambivalent attitude of urban population to high-rise buildings. In addition, one of the author's sociological survey reveals the level of environmental preparedness of the university students, studying in the field of "Construction of unique buildings and structures", raising the question of how future specialists are ready to take into account socioecological problems. Conclusion of the authors: the construction of high-rise buildings is associated with huge social and environmental risks, negative impact on the biosphere and human health. This requires deepened skills about sustainable design methods and environmental friendly construction technologies of future specialists. Professor M. Eichner presents in the article his case study project results on implementation of holistic eco-sustainable construction principles for mixed-use high-rise building in the metropolis of Cairo.

New insights in oncology: Epi-genetics and cancer stem cells

International Nuclear Information System (INIS)

Krutovskikh, V.; Partensky, C.

2011-01-01

Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either 'gain' (oncogenes) or 'lose' (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ('epi-mutations') turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms. (authors)

B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS

Science.gov (United States)

Pedersen, Gabriel K.; Àdori, Monika; Khoenkhoen, Sharesta; Dosenovic, Pia; Beutler, Bruce; Karlsson Hedestam, Gunilla B.

2014-01-01

B-1 cells mediate early protection against infection by responding to T cell-independent (TI) antigens found on the surface of various pathogens. Mice with impaired expression of the atypical IκB protein IκBNS have markedly reduced frequencies of B-1 cells. We used a mouse strain with dysfunctional IκBNS derived from an N-ethyl-N-nitrosourea (ENU) screen, named bumble, to investigate the point in the development of B-1 cells where IκBNS is required. The presence of wild-type (wt) peritoneal cells in mixed wt/bumble chimeras did not rescue the development of bumble B-1 cells, but wt peritoneal cells transferred to bumble mice restored natural IgM levels and response to TI antigens. The bumble and wt mice displayed similar levels of fetal liver B-1 progenitors and splenic neonatal transitional B (TrB) cells, both of which were previously shown to give rise to B-1 cells. Interestingly, we found that a subset of wt neonatal TrB cells expressed common B-1a markers (TrB-1a) and that this cell population was absent in the bumble neonatal spleen. Sorted TrB-1a (CD93+IgM+CD5+) cells exclusively generated B-1a cells when adoptively transferred, whereas sorted CD93+IgM+CD5− cells gave rise to B-2 cells and, to a lesser extent, B-1b and B-1a cells. This study identifies a phenotypically distinct splenic population of TrB-1a cells and establishes that the development of B-1a cells is blocked before this stage in the absence of IκBNS. PMID:25228759

Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry

DEFF Research Database (Denmark)

Leth-Larsen, Rikke; Lund, Rikke; Hansen, Helle V

2009-01-01

The spread of cancer cells from a primary tumor to form metastasis at distant sites is a complex multi-step process. The cancer cell proteins, and plasma membrane proteins in particular, involved in this process are poorly defined and a study of the very early events of the metastatic process using...... clinical samples or in vitro assays is not feasible. We have used a unique model system consisting of two isogenic human breast cancer cell lines that are equally tumorigenic in mice, but while one gives rise to metastasis, the other disseminates single cells that remain dormant at distant organs. Membrane...... purification and comparative quantitative LC-MS/MS proteomic analysis identified 13 membrane proteins that were expressed at higher levels and 3 that were under-expressed in the metastatic compared to the non-metastatic cell line from a total of 1919 identified protein entries. Among the proteins were ecto-5...

Gamma delta T-cell differentiation and effector function programming, TCR signal strength, when and how much?

Science.gov (United States)

Zarin, Payam; Chen, Edward L Y; In, Tracy S H; Anderson, Michele K; Zúñiga-Pflücker, Juan Carlos

2015-07-01

γδ T-cells boast an impressive functional repertoire that can paint them as either champions or villains depending on the environmental and immunological cues. Understanding the function of the various effector γδ subsets necessitates tracing the developmental program of these subsets, including the point of lineage bifurcation from αβ T-cells. Here, we review the importance of signals from the T-cell receptor (TCR) in determining αβ versus γδ lineage fate, and further discuss how the molecular components of this pathway may influence the developmental programming of γδ T-cells functional subsets. Additionally, we discuss the role of temporal windows in restricting the development of IL-17 producing γδ T-cell subtypes, and explore whether fetal and adult hematopoietic progenitors maintain the same potential for giving rise to this important subset. Copyright © 2015 Elsevier Inc. All rights reserved.

Sea-level rise: towards understanding local vulnerability

Science.gov (United States)

Rahmstorf, Stefan

2012-06-01

Projections of global sea-level rise into the future have become more pessimistic over the past five years or so. A global rise by more than one metre by the year 2100 is now widely accepted as a serious possibility if greenhouse gas emissions continue unabated. That is witnessed by the scientific assessments that were made since the last IPCC report was published in 2007. The Delta Commission of the Dutch government projected up to 1.10 m as a 'high-end' scenario (Vellinga et al 2009). The Scientific Committee on Antarctic Research (SCAR) projected up to 1.40 m (Scientific Committee on Antarctic Research 2009), and the Arctic Monitoring and Assessment Programme (AMAP) gives a range of 0.90-1.60 m in its 2011 report (Arctic Monitoring and Assessment Programme 2011). And recently the US Army Corps of Engineers recommends using a 'low', an 'intermediate' and a 'high' scenario for global sea-level rise when planning civil works programmes, with the high one corresponding to a 1.50 m rise by 2100 (US Army Corps of Engineers 2011). This more pessimistic view is based on a number of observations, most importantly perhaps the fact that sea level has been rising at least 50% faster in the past decades than projected by the IPCC (Rahmstorf et al 2007, IPCC 2007). Also, the rate of rise (averaged over two decades) has accelerated threefold, from around 1 mm yr-1 at the start of the 20th century to around 3 mm yr-1 over the past 20 years (Church and White 2006), and this rate increase closely correlates with global warming (Rahmstorf et al 2011). The IPCC projections, which assume almost no further acceleration in the 20th century, thus look less plausible. And finally the observed net mass loss of the two big continental ice sheets (Van den Broeke et al 2011) calls into question the assumption that ice accumulation in Antarctica would largely balance ice loss from Greenland in the course of further global warming (IPCC 2007). With such a serious sea-level rise on the horizon

Induction of RNA interference in dendritic cells.

Science.gov (United States)

Li, Mu; Qian, Hua; Ichim, Thomas E; Ge, Wei-Wen; Popov, Igor A; Rycerz, Katarzyna; Neu, John; White, David; Zhong, Robert; Min, Wei-Ping

2004-01-01

Dendritic cells (DC) reside at the center of the immunological universe, possessing the ability both to stimulate and inhibit various types of responses. Tolerogenic/regulatory DC with therapeutic properties can be generated through various means of manipulations in vitro and in vivo. Here we describe several attractive strategies for manipulation of DC using the novel technique of RNA interference (RNAi). Additionally, we overview some of our data regarding yet undescribed characteristics of RNAi in DC such as specific transfection strategies, persistence of gene silencing, and multi-gene silencing. The advantages of using RNAi for DC genetic manipulation gives rise to the promise of generating tailor-made DC that can be used effectively to treat a variety of immunologically mediated diseases.

Effects of an oil price rise on inflation, output, and the exchange rate in the case of subsidization policy

Energy Technology Data Exchange (ETDEWEB)

Zandi, F R

1982-01-01

Since the Organization of Petroleum Exporting Countries raised the price of oil by 400% in 1974, the theory of supply inflation has received a great deal of attention. This study analyses the short and long run effects of an oil price rise on output, inflation, and the exchange rate. The study also analyses dynamic adjustments to the oil price rise in cases where oil-price subsidies are provided and where no subsidies are provided. In the no-subsidy case it is shown that the oil price rise can be inflationary or deflationary. The implications of the policy of subsidizing the price of oil is highlighted by taking account of a government budget constraint which in turn leads to the possibility of monetization as a source of financing the deficit, and thereby to higher output relative to the no subsidy case. As to the price level, the possibility is illustrated that subsidization can actually be more inflationary. The important element giving rise to the above possibility is the subsidy induced increase in the money supply. Exchange-rate flexibility is shown not to insulate the domestic price level against an oil price rise. In the long run the rate of inflation and exchange-rate variations are determined by the rate of growth of the money supply. The dynamic adjustment path of price and output is shown to be determined by the rate of adjustment of inflationary expectations.

Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration.

Science.gov (United States)

Yasui, T; Mabuchi, Y; Toriumi, H; Ebine, T; Niibe, K; Houlihan, D D; Morikawa, S; Onizawa, K; Kawana, H; Akazawa, C; Suzuki, N; Nakagawa, T; Okano, H; Matsuzaki, Y

2016-02-01

Human dental pulp stem/progenitor cells (hDPSCs) are attractive candidates for regenerative therapy because they can be easily expanded to generate colony-forming unit-fibroblasts (CFU-Fs) on plastic and the large cell numbers required for transplantation. However, isolation based on adherence to plastic inevitably changes the surface marker expression and biological properties of the cells. Consequently, little is currently known about the original phenotypes of tissue precursor cells that give rise to plastic-adherent CFU-Fs. To better understand the in vivo functions and translational therapeutic potential of hDPSCs and other stem cells, selective cell markers must be identified in the progenitor cells. Here, we identified a dental pulp tissue-specific cell population based on the expression profiles of 2 cell-surface markers LNGFR (CD271) and THY-1 (CD90). Prospectively isolated, dental pulp-derived LNGFR(Low+)THY-1(High+) cells represent a highly enriched population of clonogenic cells--notably, the isolated cells exhibited long-term proliferation and multilineage differentiation potential in vitro. The cells also expressed known mesenchymal cell markers and promoted new bone formation to heal critical-size calvarial defects in vivo. These findings suggest that LNGFR(Low+)THY-1(High+) dental pulp-derived cells provide an excellent source of material for bone regenerative strategies. © International & American Associations for Dental Research 2015.

MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

DEFF Research Database (Denmark)

Yin, Hang; Pasut, Alessandra; Soleimani, Vahab D

2013-01-01

Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells...... (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism...... of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels...

Review: the role of neural crest cells in the endocrine system.

Science.gov (United States)

Adams, Meghan Sara; Bronner-Fraser, Marianne

2009-01-01

The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

Plasmonic Nanostructure for Enhanced Light Absorption in Ultrathin Silicon Solar Cells

Directory of Open Access Journals (Sweden)

Jinna He

2012-01-01

Full Text Available The performances of thin film solar cells are considerably limited by the low light absorption. Plasmonic nanostructures have been introduced in the thin film solar cells as a possible solution around this issue in recent years. Here, we propose a solar cell design, in which an ultrathin Si film covered by a periodic array of Ag strips is placed on a metallic nanograting substrate. The simulation results demonstrate that the designed structure gives rise to 170% light absorption enhancement over the full solar spectrum with respect to the bared Si thin film. The excited multiple resonant modes, including optical waveguide modes within the Si layer, localized surface plasmon resonance (LSPR of Ag stripes, and surface plasmon polaritons (SPP arising from the bottom grating, and the coupling effect between LSPR and SPP modes through an optimization of the array periods are considered to contribute to the significant absorption enhancement. This plasmonic solar cell design paves a promising way to increase light absorption for thin film solar cell applications.

Multipotent versus differentiated cell fate selection in the developing Drosophila airways

Science.gov (United States)

Matsuda, Ryo; Hosono, Chie; Samakovlis, Christos; Saigo, Kaoru

2015-01-01

Developmental potentials of cells are tightly controlled at multiple levels. The embryonic Drosophila airway tree is roughly subdivided into two types of cells with distinct developmental potentials: a proximally located group of multipotent adult precursor cells (P-fate) and a distally located population of more differentiated cells (D-fate). We show that the GATA-family transcription factor (TF) Grain promotes the P-fate and the POU-homeobox TF Ventral veinless (Vvl/Drifter/U-turned) stimulates the D-fate. Hedgehog and receptor tyrosine kinase (RTK) signaling cooperate with Vvl to drive the D-fate at the expense of the P-fate while negative regulators of either of these signaling pathways ensure P-fate specification. Local concentrations of Decapentaplegic/BMP, Wingless/Wnt, and Hedgehog signals differentially regulate the expression of D-factors and P-factors to transform an equipotent primordial field into a concentric pattern of radially different morphogenetic potentials, which gradually gives rise to the distal-proximal organization of distinct cell types in the mature airway. DOI: http://dx.doi.org/10.7554/eLife.09646.001 PMID:26633813

The Insulin-like Growth Factor (IGF)-I E-Peptides Modulate Cell Entry of the Mature IGF-I Protein

OpenAIRE

Pfeffer, Lindsay A.; Brisson, Becky K.; Lei, Hanqin; Barton, Elisabeth R.

2009-01-01

Insulin-like growth factor (IGF)-I is a critical protein for cell development and growth. Alternative splicing of the igf1 gene gives rise to multiple isoforms. In rodents, proIGF-IA and proIGF-IB have different carboxy-terminal extensions called the E-peptides (EA and EB) and upon further posttranslational processing, produce the identical mature IGF-I protein. Rodent EB has been reported to have mitogenic and motogenic effects independent of IGF-I. However, effects of EA or EB on mature IGF...

Cell lineage mapping of taste bud cells and keratinocytes in the mouse tongue and soft palate.

Science.gov (United States)

Okubo, Tadashi; Clark, Cheryl; Hogan, Brigid L M

2009-02-01

The epithelium of the mouse tongue and soft palate consists of at least three distinct epithelial cell populations: basal cells, keratinized cells organized into filiform and fungiform papillae, and taste receptor cells present in tight clusters known as taste buds in the fungiform and circumvallate papillae and soft palate. All three cell types develop from the simple epithelium of the embryonic tongue and palate, and are continually replaced in the adult by cell turnover. Previous studies using pulse-chase tritiated thymidine labeling in the adult mouse provided evidence for a high rate of cell turnover in the keratinocytes (5-7 days) and taste buds (10 days). However, little is known about the localization and phenotype of the long-term stem or progenitor cells that give rise to the mature taste bud cells and surrounding keratinocytes in these gustatory tissues. Here, we make use of a tamoxifen-inducible K14-CreER transgene and the ROSA26 LacZ reporter allele to lineage trace the mature keratinocytes and taste bud cells of the early postnatal and adult mouse tongue and soft palate. Our results support the hypothesis that both the pore keratinocytes and receptor cells of the taste bud are derived from a common K14(+)K5(+)Trp63(+)Sox2(+) population of bipotential progenitor cells located outside the taste bud. The results are also compatible with models in which the keratinocytes of the filiform and fungiform papillae are derived from basal progenitor cells localized at the base of these structures.

Maximal Fluctuations of Confined Actomyosin Gels: Dynamics of the Cell Nucleus.

Science.gov (United States)

Rupprecht, J-F; Singh Vishen, A; Shivashankar, G V; Rao, M; Prost, J

2018-03-02

We investigate the effect of stress fluctuations on the stochastic dynamics of an inclusion embedded in a viscous gel. We show that, in nonequilibrium systems, stress fluctuations give rise to an effective attraction towards the boundaries of the confining domain, which is reminiscent of an active Casimir effect. We apply this generic result to the dynamics of deformations of the cell nucleus, and we demonstrate the appearance of a fluctuation maximum at a critical level of activity, in agreement with recent experiments [E. Makhija, D. S. Jokhun, and G. V. Shivashankar, Proc. Natl. Acad. Sci. U.S.A. 113, E32 (2016)PNASA60027-842410.1073/pnas.1513189113].

The Impact of Sea Level Rise on Geodetic Vertical Datum of Peninsular Malaysia

Science.gov (United States)

Din, A. H. M.; Abazu, I. C.; Pa'suya, M. F.; Omar, K. M.; Hamid, A. I. A.

2016-09-01

Sea level rise is rapidly turning into major issues among our community and all levels of the government are working to develop responses to ensure these matters are given the uttermost attention in all facets of planning. It is more interesting to understand and investigate the present day sea level variation due its potential impact, particularly on our national geodetic vertical datum. To determine present day sea level variation, it is vital to consider both in-situ tide gauge and remote sensing measurements. This study presents an effort to quantify the sea level rise rate and magnitude over Peninsular Malaysia using tide gauge and multi-mission satellite altimeter. The time periods taken for both techniques are 32 years (from 1984 to 2015) for tidal data and 23 years (from 1993 to 2015) for altimetry data. Subsequently, the impact of sea level rise on Peninsular Malaysia Geodetic Vertical Datum (PMGVD) is evaluated in this study. the difference between MSL computed from 10 years (1984 - 1993) and 32 years (1984 - 2015) tidal data at Port Kelang showed that the increment of sea level is about 27mm. The computed magnitude showed an estimate of the long-term effect a change in MSL has on the geodetic vertical datum of Port Kelang tide gauge station. This will help give a new insight on the establishment of national geodetic vertical datum based on mean sea level data. Besides, this information can be used for a wide variety of climatic applications to study environmental issues related to flood and global warming in Malaysia.

THE IMPACT OF SEA LEVEL RISE ON GEODETIC VERTICAL DATUM OF PENINSULAR MALAYSIA

Directory of Open Access Journals (Sweden)

A. H. M. Din

2016-09-01

Full Text Available Sea level rise is rapidly turning into major issues among our community and all levels of the government are working to develop responses to ensure these matters are given the uttermost attention in all facets of planning. It is more interesting to understand and investigate the present day sea level variation due its potential impact, particularly on our national geodetic vertical datum. To determine present day sea level variation, it is vital to consider both in-situ tide gauge and remote sensing measurements. This study presents an effort to quantify the sea level rise rate and magnitude over Peninsular Malaysia using tide gauge and multi-mission satellite altimeter. The time periods taken for both techniques are 32 years (from 1984 to 2015 for tidal data and 23 years (from 1993 to 2015 for altimetry data. Subsequently, the impact of sea level rise on Peninsular Malaysia Geodetic Vertical Datum (PMGVD is evaluated in this study. the difference between MSL computed from 10 years (1984 – 1993 and 32 years (1984 – 2015 tidal data at Port Kelang showed that the increment of sea level is about 27mm. The computed magnitude showed an estimate of the long-term effect a change in MSL has on the geodetic vertical datum of Port Kelang tide gauge station. This will help give a new insight on the establishment of national geodetic vertical datum based on mean sea level data. Besides, this information can be used for a wide variety of climatic applications to study environmental issues related to flood and global warming in Malaysia.

Temporal variation of accumulation rates on a natural salt marsh in the 20th century determined by 137Cs chronologies – the impact of sea level rise and increased inundation frequency

DEFF Research Database (Denmark)

Andersen, Thorbjørn Joest; Svinth, Steffen; Pejrup, Morten

2011-01-01

Salt marshes are potentially threatened by sea level rise if sediment supply is unable to balance the rising sea. A rapid sea level rise is one of the pronounced effects of global warming and global sea level is at present rising at an elevated rate of about 3.4 mm y-1 on average. This increasing...... in sediment deposition is significant and gives reason for concern as it may be the first sign of a sedimentation deficiency which could be threatening this and other salt marshes in the case of a rapidly rising sea level. Our work demonstrates that the assumption of a constant relationship between salt marsh...... with salt marsh accretion is most probably not valid in the present case study and it may well be that this is also the case for many other salt marshes, especially if sea level continues to rise rapidly as indicated by some climate change scenarios....

Socioecological Aspects of High-rise Construction

Directory of Open Access Journals (Sweden)

Eichner Michael

2018-01-01

Full Text Available In this article, the authors consider the socioecological problems that arise in the construction and operation of high-rise buildings. They study different points of view on high-rise construction and note that the approaches to this problem are very different. They also analyse projects of modern architects and which attempts are made to overcome negative impacts on nature and mankind. The article contains materials of sociological research, confirming the ambivalent attitude of urban population to high-rise buildings. In addition, one of the author’s sociological survey reveals the level of environmental preparedness of the university students, studying in the field of "Construction of unique buildings and structures", raising the question of how future specialists are ready to take into account socioecological problems. Conclusion of the authors: the construction of high-rise buildings is associated with huge social and environmental risks, negative impact on the biosphere and human health. This requires deepened skills about sustainable design methods and environmental friendly construction technologies of future specialists. Professor M. Eichner presents in the article his case study project results on implementation of holistic eco-sustainable construction principles for mixed-use high-rise building in the metropolis of Cairo.

Rising Long-term Interest Rates

DEFF Research Database (Denmark)

Hallett, Andrew Hughes

Rather than chronicle recent developments in European long-term interest rates as such, this paper assesses the impact of increases in those interest rates on economic performance and inflation. That puts us in a position to evaluate the economic pressures for further rises in those rates......, the first question posed in this assignment, and the scope for overshooting (the second question), and then make some illustrative predictions of future interest rates in the euro area. We find a wide range of effects from rising interest rates, mostly small and mostly negative, focused on investment...... till the emerging European recovery is on a firmer basis and capable of overcoming increases in the cost of borrowing and shrinking fiscal space. There is also an implication that worries about rising/overshooting interest rates often reflect the fact that inflation risks are unequally distributed...

Influence of dump voltage and allowable temperature rise on stabilizer requirements in superconducting coils

International Nuclear Information System (INIS)

Schwenterly, S.W.

1988-01-01

A superconducting winding must have enough stabilizer to satisfy two sets of criteria. During normal operation, the amount of stabilizer must be large enough either to make the coil unconditionally stable or to give a certain desired stability margin. Once a dump occurs, the amount of stabilizer must be large enough to carry the current without generating excessive dump voltages or allowing the winding to exceed a certain maximum temperature (and maximum pressure, in the case of force-cooled coils). The voltage criterion often dominates for very large coil systems, but it is frequently ignored in initial design studies. This paper gives some simple relations between the dump voltage and the stored energy, temperature rise, and coil geometry that are useful in scooping the required amount of stabilizer. Comparison with some recently proposed fusion magnet system designs indicates that excessive dump voltages could result in some cases. High-temperature superconductors may require more stabilizer than the conventional alloys. Calculations with simple model coil systems indicate how trade-offs between various coil parameters affect the dump voltage. 12 refs., 1 fig., 1 tab

SU-F-T-683: Cancer Stem Cell Hypothesis and Radiation Treatments

International Nuclear Information System (INIS)

Fourkal, E

2016-01-01

Purpose: The tumor control probability in radiation therapy allows comparing different radiation treatments to each other by means of calculating the probability that a prescribed dose of radiation eradicates or controls the tumor. In the conventional approach, all cancer cells can divide unlimited number of times and the tumor control often means eradicating every malignant cell by the radiation. In recent years however, there is a mounting consensus that in a given tumor volume there is a sub-population of cells, known as cancer stem cells (CSCs) that are responsible for tumor initiation and growth. Other or progenitor cancer cells can only divide limited number of times. This entails that only cancer stem cells may nned to be eliminated in order to control the tumor. Thus one may define TCP as the probability of eliminating CSCs for the given dose of radiation. Methods: Using stochastic methods, specifically the birth-and-death Markov processes, an infinite system of equations is set for probabilities of having m cancer stem cells at time t after the start of radiation. The TCP is calculated as the probability of no cancer stem cells surviving the radiation. Two scenarios are studied. In the first situation, the TCP is calculated for a unidirectional case when CSC gives birth to another CSC or a progenitor cell. In the second scenario, a bidirectional model is studied where the progenitor cell gives rise to CSC. Results: The proposed calculations show that the calculated TCP for CSC depends on whether one adopts unidirectional or bidirectional conversion models. The bidirectional model shows significantly lower TCP values for the given dose delivered to the tumor. Conclusion: Incorporating CSC hypothesis into the TCP modeling may notably influence the dose prescription as well as the concept of the expected TCP after the radiation treatments.

SU-F-T-683: Cancer Stem Cell Hypothesis and Radiation Treatments

Energy Technology Data Exchange (ETDEWEB)

Fourkal, E [Pinnacle Health Cancer Center, Harrisburg, PA (United States)

2016-06-15

Purpose: The tumor control probability in radiation therapy allows comparing different radiation treatments to each other by means of calculating the probability that a prescribed dose of radiation eradicates or controls the tumor. In the conventional approach, all cancer cells can divide unlimited number of times and the tumor control often means eradicating every malignant cell by the radiation. In recent years however, there is a mounting consensus that in a given tumor volume there is a sub-population of cells, known as cancer stem cells (CSCs) that are responsible for tumor initiation and growth. Other or progenitor cancer cells can only divide limited number of times. This entails that only cancer stem cells may nned to be eliminated in order to control the tumor. Thus one may define TCP as the probability of eliminating CSCs for the given dose of radiation. Methods: Using stochastic methods, specifically the birth-and-death Markov processes, an infinite system of equations is set for probabilities of having m cancer stem cells at time t after the start of radiation. The TCP is calculated as the probability of no cancer stem cells surviving the radiation. Two scenarios are studied. In the first situation, the TCP is calculated for a unidirectional case when CSC gives birth to another CSC or a progenitor cell. In the second scenario, a bidirectional model is studied where the progenitor cell gives rise to CSC. Results: The proposed calculations show that the calculated TCP for CSC depends on whether one adopts unidirectional or bidirectional conversion models. The bidirectional model shows significantly lower TCP values for the given dose delivered to the tumor. Conclusion: Incorporating CSC hypothesis into the TCP modeling may notably influence the dose prescription as well as the concept of the expected TCP after the radiation treatments.

C-V Calculations in CdS/CdTe Thin Films Solar Cells with a CdSxTe1-x Interlayer

Directory of Open Access Journals (Sweden)

A. Gonzalez-Cisneros

2013-01-01

Full Text Available In CdS/CdTe solar cells, chemical interdiffusion at the interface gives rise to the formation of an interlayer of the ternary compound CdSxCdTe1-x. In this work, we evaluate the effects of this interlayer in CdS/CdTe photovoltaic cells in order to improve theoretical results describing experimental C-V (capacitance versus voltage characteristics. We extended our previous theoretical methodology developed on the basis of three cardinal equations (Castillo-Alvarado et al., 2010. The present results provide a better fit to experimental data obtained from CdS/CdTe solar cells grown in our laboratory by the chemical bath deposition (for CdS film and the close-spaced vapor transport (for CdTe film techniques.

Rethinking the social and cultural dimensions of charitable giving

DEFF Research Database (Denmark)

Bajde, Domen

2009-01-01

-giving and focuses on charitable gifts as an emblem of postmodern gift-giving to distant others. Historical evidence and sociological theory on postmodern solidarity are combined to shed light on the fluid duality of contemporary giving and the importance of the imaginary in charitable giving. The outlined socially...... symbolic dimensions of charitable giving are critically examined in light of postmodern consumer culture and the recent social corporate responsibility trends. By openly engaging the proposed complexities of gift-giving, our vocabulary and understanding of postmodern giving can be revised so as to invite...

Molecular and Microenvironmental Determinants of Glioma Stem-Like Cell Survival and Invasion

Directory of Open Access Journals (Sweden)

Alison Roos

2017-06-01

Full Text Available Glioblastoma multiforme (GBM is the most frequent primary brain tumor in adults with a 5-year survival rate of 5% despite intensive research efforts. The poor prognosis is due, in part, to aggressive invasion into the surrounding brain parenchyma. Invasion is a complex process mediated by cell-intrinsic pathways, extrinsic microenvironmental cues, and biophysical cues from the peritumoral stromal matrix. Recent data have attributed GBM invasion to the glioma stem-like cell (GSC subpopulation. GSCs are slowly dividing, highly invasive, therapy resistant, and are considered to give rise to tumor recurrence. GSCs are localized in a heterogeneous cellular niche, and cross talk between stromal cells and GSCs cultivates a fertile environment that promotes GSC invasion. Pro-migratory soluble factors from endothelial cells, astrocytes, macrophages, microglia, and non-stem-like tumor cells can stimulate peritumoral invasion of GSCs. Therefore, therapeutic efforts designed to target the invasive GSCs may enhance patient survival. In this review, we summarize the current understanding of extrinsic pathways and major stromal and immune players facilitating GSC maintenance and survival.

Assessment of the cathode contribution to the degradation of anode-supported solid oxide fuel cells

DEFF Research Database (Denmark)

Hagen, Anke; Liu, Yi-Lin; Barfod, Rasmus

2008-01-01

The degradation of anode-supported cells was studied over 1500 h as a function of cell polarization either in air or oxygen on the cathode side. Based on impedance analysis, contributions of the anode and cathode to the increase of total resistance were assigned. Accordingly, the degradation rates...... of the cathode were strongly dependent on the pO(2). Microstructural analysis of the cathode/electrolyte interface carried out after removal of the cathode showed craters on the electrolyte surface where the lanthanum strontium manganite (LSM) particles had been located. The changes of shape and size...... of these craters observed after testing correlated with the cell voltage degradation rates. The results can be interpreted in terms of element redistribution at the cathode/electrolyte interface and formation of foreign phases giving rise to a weakening of local contact points of the LSM cathode and yttria...

In situ monitoring of molecular changes during cell differentiation processes in marine macroalgae through mass spectrometric imaging.

Science.gov (United States)

Kessler, Ralf W; Crecelius, Anna C; Schubert, Ulrich S; Wichard, Thomas

2017-08-01

Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was employed to discriminate between cell differentiation processes in macroalgae. One of the key developmental processes in the algal life cycle is the production of germ cells (gametes and zoids). The gametogenesis of the marine green macroalga Ulva mutabilis (Chlorophyta) was monitored by metabolomic snapshots of the surface, when blade cells differentiate synchronously into gametangia and giving rise to gametes. To establish MSI for macroalgae, dimethylsulfoniopropionate (DMSP), a known algal osmolyte, was determined. MSI of the surface of U. mutabilis followed by chemometric data analysis revealed dynamic metabolomic changes during cell differentiation. DMSP and a total of 55 specific molecular biomarkers, which could be assigned to important stages of the gametogenesis, were detected. Our research contributes to the understanding of molecular mechanisms underlying macroalgal cell differentiation. Graphical abstract Molecular changes during cell differentiation of the marine macroalga Ulva were visualized by matrix assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI).

Systematic aging of commercial LiFePO4|Graphite cylindrical cells including a theory explaining rise of capacity during aging

Science.gov (United States)

Lewerenz, Meinert; Münnix, Jens; Schmalstieg, Johannes; Käbitz, Stefan; Knips, Marcus; Sauer, Dirk Uwe

2017-03-01

The contribution introduces a new theory explaining the capacity increase that is often observed in early stages of life of lithium-ion batteries. This reversible and SOC-depending capacity rise is explained by the passive electrode effect in this work. The theory assumes a slow, compensating flow of active lithium between the passive and the active part of the anode, where the passive part represents the geometric excess anode with respect to the cathode. The theory is validated using a systematic test of 50 cylindrical 8 Ah LiFePO4|Graphite battery cells analyzed during cyclic and calendaric aging. The cyclic aging has been performed symmetrically at 40 °C cell temperature, varying current rates and DODs. The calendar aging is executed at three temperatures and up to four SOCs. The aging is dominated by capacity fade while the increase of internal resistance is hardly influenced. Surprisingly shallow cycling between 45 and 55% SOC shows stronger aging than aging at higher DOD and tests at 4 C exhibit less aging than aging at lower C-rates. Aging mechanisms at 60 °C seem to deviate from those at 40 °C or lower. The data of this aging matrix is used for further destructive and non-destructive characterization in future contributions.

Three-dimensional epithelial tissues generated from human embryonic stem cells.

Science.gov (United States)

Hewitt, Kyle J; Shamis, Yulia; Carlson, Mark W; Aberdam, Edith; Aberdam, Daniel; Garlick, Jonathan A

2009-11-01

The use of pluripotent human embryonic stem (hES) cells for tissue engineering may provide advantages over traditional sources of progenitor cells because of their ability to give rise to multiple cell types and their unlimited expansion potential. We derived cell populations with properties of ectodermal and mesenchymal cells in two-dimensional culture and incorporated these divergent cell populations into three-dimensional (3D) epithelial tissues. When grown in specific media and substrate conditions, two-dimensional cultures were enriched in cells (EDK1) with mesenchymal morphology and surface markers. Cells with a distinct epithelial morphology (HDE1) that expressed cytokeratin 12 and beta-catenin at cell junctions became the predominant cell type when EDK1 were grown on surfaces enriched in keratinocyte-derived extracellular matrix proteins. When these cells were incorporated into the stromal and epithelial tissue compartments of 3D tissues, they generated multilayer epithelia similar to those generated with foreskin-derived epithelium and fibroblasts. Three-dimensional tissues demonstrated stromal cells with morphologic features of mature fibroblasts, type IV collagen deposition in the basement membrane, and a stratified epithelium that expressed cytokeratin 12. By deriving two distinct cell lineages from a common hES cell source to fabricate complex tissues, it is possible to explore environmental cues that will direct hES-derived cells toward optimal tissue form and function.