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Sample records for accessory cell function

  1. The Natural Killer Cell Cytotoxic Function Is Modulated by HIV-1 Accessory Proteins

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    Edward Barker

    2011-07-01

    Full Text Available Natural killer (NK cells’ major role in the control of viruses is to eliminate established infected cells. The capacity of NK cells to kill virus-infected cells is dependent on the interactions between ligands on the infected cell and receptors on the NK cell surface. Because of the importance of ligand-receptor interactions in modulating the NK cell cytotoxic response, HIV has developed strategies to regulate various NK cell ligands making the infected cell surprisingly refractory to NK cell lysis. This is perplexing because the HIV-1 accessory protein Vpr induces expression of ligands for the NK cell activating receptor, NKG2D. In addition, the accessory protein Nef removes the inhibitory ligands HLA-A and -B. The reason for the ineffective killing by NK cells despite the strong potential to eliminate infected cells is due to HIV-1 Vpu’s ability to down modulate the co-activation ligand, NTB-A, from the cell surface. Down modulation of NTB-A prevents efficient NK cell degranulation. This review will focus on the mechanisms through which the HIV-1 accessory proteins modulate their respective ligands, and its implication for NK cell killing of HIV-infected cells.

  2. Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis.

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    Kim, Brian S; Miyagawa, Fumi; Cho, Young-Hun; Bennett, Clare L; Clausen, Björn E; Katz, Stephen I

    2009-12-01

    The precise contribution(s) of skin dendritic cells (DCs) to immune responses in the skin has not been well delineated. We developed an intradermal (i.d.) injection model in which CD8+ T (OT-I) cells that express ovalbumin (OVA) peptide-specific TCRs (Valpha2/Vbeta5) are delivered directly to the dermis of transgenic (Tg) mice expressing OVA in the epidermis. After i.d. injection, these mice reliably develop skin graft-versus-host disease (GVHD) by day 7. To determine the relative contribution of Langerhans cells (LCs) to the ensuing GVHD-like reaction, we generated K14-OVA x Langerin-diphtheria-toxin-receptor (Langerin-DTR) Tg mice to allow conditional ablation of LCs in the epidermis. To delineate the role of dermal DCs (dDCs) in the reaction, we also generated K14-OVA Tg chimeras using beta(2)-microglobulin-deficient (beta(2)m) congenic donor bone marrow cells. Dermal DCs in these mice cannot present OVA to autoreactive T cells (OT-I cells), whereas the LCs are antigen presentation-competent. Unexpectedly, OT-I cell injection into diphtheria toxin (DT)-treated beta(2)m --> K14-OVA x Langerin-DTR Tg mice resulted in skin GVHD. Thus, in vivo, both LC and dDC appear to be dispensable for the induction of keratinocyte-directed, CD8-mediated effector immune responses. Furthermore and surprisingly, OVA-expressing epidermal cells depleted of LCs that could not initiate allogeneic epidermal lymphocyte reactions activated naive OT-I cells in vitro. These results indicate that keratinocytes may function as accessory cells competent to prime naive skin-reactive T cells.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub.

  3. Cast functional accessories for heat treatment furnaces

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    A. Drotlew

    2010-10-01

    Full Text Available The study gives examples of the cast functional accessories operating in furnaces for the heat treatment of metals and alloys. The describeddesign solutions of castings and their respective assemblies are used for charge preparation and handling. They were put in systematicorder depending on furnace design and the technological purpose of heat treatment. Basic grades of austenitic cast steel, used for castings of this type, were enumerated, and examples of general guidelines formulated for their use were stated. The functional accessories described in this study were designed and made by the Foundry Research Laboratory of West Pomeranian University of Technology.

  4. Spinal accessory nerve function following neck dissection.

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    Zibordi, F; Baiocco, F; Bascelli, C; Bini, A; Canepa, A

    1988-01-01

    Spinal accessory nerve (SAN) function was evaluated by electromyography (EMG) and muscle testing in 36 patients who underwent neck dissection with SAN preservation. The results emphasized that SAN function was relatively good after conservative neck surgery. Muscle testing findings showed better function than did EMG findings. After surgery the trapezius muscle functioned more efficiently than the sternocleidomastoid (SCM) muscle probably because of the more traumatic surgical handling of both the SCM muscle and its SAN branch. In order to obtain the functional advantages of SAN preservation, the authors suggest that the conservative procedure in radical neck dissection be used whenever warranted by oncologic diagnosis.

  5. Genetic difference in the proliferative response to T mitogens between Hi/PHA and Lo/PHA lymphocytes is independent of accessory cell function.

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    Stiffel, C; Liacopoulos-Briot, M; Decreusefond, C; Parlebas, J

    1987-01-01

    The role of the macrophage as accessory cell in the proliferative response of lymphocytes to phytohemagglutinin (PHA) was studied in two lines of mice genetically selected for high and low responsiveness to T mitogens. Adherent cell depletion of lymph node cells abrogated the low (Lo)/PHA response, but only partially inhibited the high (Hi)/PHA response. Addition of peritoneal cells provided either by Hi/PHA or by Lo/PHA mice equally restored Hi/PHA responsiveness but had only a slight reconstituting effect on the inhibited Lo/PHA response. Equivalent enhancement or suppression of proliferation of untreated lymph node cells was obtained by the addition of increasing percentages of each of the two peritoneal cell populations. However, the maximum level of the Lo/PHA response never reached that of Hi/PHA cells. These data indicate that the bidirectional selective breeding has not modified the potentialities of the macrophages as accessory cells but has resulted in an impaired response of Lo/PHA lymphocytes to the signals delivered either by accessory cells or by T mitogens.

  6. Strategies for inhibiting function of HIV-1 accessory proteins: a necessary route to AIDS therapy?

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    Richter, S N; Frasson, I; Palù, G

    2009-01-01

    The Human Immunodeficiency Virus (HIV) genome encodes three major structural proteins common to all retroviruses (Gag, Pol and Env), two regulatory proteins (Tat and Rev) that are essential for viral replication, and four accessory proteins (Nef, Vif, Vpu, Vpr). While accessory proteins were initially reported to be unnecessary for viral growth, their importance as virulence factors is now being more and more appreciated: they can dramatically alter the course and severity of viral infection, replication and disease progression. None of the HIV accessory proteins display enzymatic activity: they rather act altering cellular pathways via multiple protein-protein interactions with a number of host cell factors. All currently approved anti-HIV drugs target pol and env encoded proteins. Therefore, widening the molecular targets of HIV therapy by additionally targeting accessory proteins may expand treatment options, resulting in high impact effective new therapy. In this review we present the state of the art of compounds that target HIV accessory proteins. Most of the research has focused on the inhibition of specific accessory proteins/host cell partner interactions. Promising compounds have been found within different classes of molecules: small natural and synthetic molecules, peptides and proteins, oligonucleotides, in particular those used as RNA interference (RNAi) tools. With the assortment of compounds available, especially against Nef and Vif functions, the demonstration of the clinical efficacy of the new anti-HIV-1 drugs targeting accessory proteins is next challenge.

  7. Expression of an accessory cell phenotype by hairy cells during lymphocyte colony formation in agar culture.

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    Farcet, J P; Gourdin, M F; Testa, U; Andre, C; Jouault, H; Reyes, F

    1983-01-01

    Human T lymphocytes require the cooperation of accessory cells to generate lymphocyte colonies in agar culture under PHA stimulation. Various hairy cell enriched fractions, as well as normal monocytes, have been found to be able to initiate colony formation by normal lymphocytes. Leukemic monocytes from CMML patients were also effective, but not the leukemic lymphocytes from CLL patients. The phenotype expressed by HC in agar colonies was further studied using cell surface and enzymatic markers. We have concluded that HC in agar culture in the presence of both normal T lymphocytes and PHA lose the B phenotype that they express in vivo and function like an accessory cell in contrast to normal or leukemic B lymphocytes.

  8. CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide.

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    Saijun Zhou

    Full Text Available Ras guanine nucleotide-releasing protein-4 (RasGRP4 is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs, its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs in wild-type (WT C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein. In regard to the biologic significance of these data to innate immunity, LPS-treated splenic CD117+ DCs from WT mice induced natural killer (NK cells to produce much more interferon-γ (IFN-γ than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-γ was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117+ MCs and DCs to optimally induce acute NK cell-dependent immune responses to LPS helps explain why this signaling protein has been conserved in evolution.

  9. Accessory subunits are integral for assembly and function of human mitochondrial complex I.

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    Stroud, David A; Surgenor, Elliot E; Formosa, Luke E; Reljic, Boris; Frazier, Ann E; Dibley, Marris G; Osellame, Laura D; Stait, Tegan; Beilharz, Traude H; Thorburn, David R; Salim, Agus; Ryan, Michael T

    2016-10-06

    Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear. The incorporation of accessory subunits into the complex increases the cellular energetic cost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level.

  10. Accessory cell ability of Langerhans cells for superantigen is resistant to ultraviolet-B light

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    Tokura, Yoshiki; Yagi, Hiroaki; Hashizume, Hideo; Furukawa, Fukumi; Takigawa, Masahiro (Hamamatsu Univ. School of Medicine (Japan). Dept. of Dermatology); Yagi, Junji (Tokyo Women' s Medical Coll. (Japan). Dept. of Microbiology and Immunology)

    1994-08-01

    We examined the effects of ultraviolet-B (UVB) irradiation on the accessory cell ability of Langerhans cells (LC) to induce a T-cell response to a superantigen, staphylococcal enterotoxin B (SEB). The ability of LC-enriched epidermal cells (LC-EC) to evoke a T-cell response to SEB was retained at the doses of UVB (up to 40 mJ/cm[sup 2]) that profoundly affected the antigen-presenting function of LC-EC for a hapten, trinitrophenyl (TNP), and a protein antigen, conalbumin. Higher doses of UVB (more than 60 mJ/cm[sup 2]) reduced the accessory cell ability of LC-EC for SEB up to 50% of control. The addition of monoclonal antibodies against adhesion molecules between LC and T cells to the culture resulted in substantial suppression of the T-cell response to SEB induced by nonirradiated LC-EC, while the UVB-irradiated LC-EC induced T-cell response was not significantly blocked with these monoclonal antibodies. This suggested that the reduction of LC ability for superantigen by high doses of UVB is at least partly due to impairment of adhesion molecules on LC by UVB irradiation. (author).

  11. Chloroquine inhibits accessory cell presentation of soluble natural and synthetic protein antigens

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    Buus, S; Werdelin, O

    1984-01-01

    was time- and dose-dependent. A brief treatment solely of the accessory cells with the drug compromised their ability to stimulate primed T cells in a subsequent culture provided the accessory cells were treated with chloroquine before their exposure to the antigen. These results suggest that chloroquine......We have studied the in vitro effect of the lysosomotrophic agent, chloroquine, on the presentation of soluble protein antigens by guinea pig accessory cells. Chloroquine inhibited the capacity of antigen-pulsed accessory cells to stimulate proliferation in appropriately primed T cells. The effect...

  12. Alloactivated HLA class II-positive T-cell lines induce IL-2 reactivity but lack accessory cell function in mixed leukocyte culture

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    Odum, N; Dickmeiss, E; Hofmann, B

    1989-01-01

    in the primary mixed leukocyte reaction (median counts per minute (cpm) 5.5 x 10(3] was significantly lower than that of peripheral blood mononuclear cells (cpm: 44.0 x 10(3]. The stimulation by Ta was almost only seen when the Ta were specifically directed against the class II antigens of the responder...... peripheral blood mononuclear cells (i.e., in combinations with "backstimulation") (median cpm: 21,000). In mixed leukocyte reaction combinations without backstimulation, significantly weaker reactions were seen (median cpm: 1,000). This observation may explain previous controversies concerning...

  13. Alloactivated HLA class II-positive T-cell lines induce IL-2 reactivity but lack accessory cell function in mixed leukocyte culture

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    Odum, N; Dickmeiss, E; Hofmann, B

    1989-01-01

    ). From 70 to 90% of the Ta were HLA class II-positive as judged by the reactions with HLA class II-reactive monoclonal antibodies, and the Ta carried the DR allospecificities of the original T-cell donor when typed in the microcytotoxic test using DR-specific alloantisera. Neither irradiated nor...

  14. The gametic central cell of Arabidopsis determines the lifespan of adjacent accessory cells.

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    Kägi, Christina; Baumann, Nadine; Nielsen, Nicola; Stierhof, York-Dieter; Gross-Hardt, Rita

    2010-12-21

    Plant germ cells develop in specialized haploid structures, termed gametophytes. The female gametophyte patterns of flowering plants are diverse, with often unknown adaptive value. Here we present the Arabidopsis fiona mutant, which forms a female gametophyte that is structurally and functionally reminiscent of a phylogenetic distant female gametophyte. The respective changes include a modified reproductive behavior of one of the female germ cells (central cell) and an extended lifespan of three adjacent accessory cells (antipodals). FIONA encodes the cysteinyl t-RNA synthetase SYCO ARATH (SYCO), which is expressed and required in the central cell but not in the antipodals, suggesting that antipodal lifespan is controlled by the adjacent gamete. SYCO localizes to the mitochondria, and ultrastructural analysis of mutant central cells revealed that the protein is necessary for mitochondrial cristae integrity. Furthermore, a dominant ATP/ADP translocator caused mitochondrial cristae degeneration and extended antipodal lifespan when expressed in the central cell of wild-type plants. Notably, this construct did not affect antipodal lifespan when expressed in antipodals. Our results thus identify an unexpected noncell autonomous role for mitochondria in the regulation of cellular lifespan and provide a basis for the coordinated development of gametic and nongametic cells.

  15. The scolopidial accessory organs and Nebenorgans in orthopteroid insects: Comparative neuroanatomy, mechanosensory function, and evolutionary origin.

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    Strauß, Johannes

    2017-09-18

    Scolopidial sensilla in insects often form large sensory organs involved in proprioception or exteroception. Here the knowledge on Nebenorgans and accessory organs, two organs consisting of scolopidial sensory cells, is summarised. These organs are present in some insects which are model organisms for the physiology of mechanosensory systems (cockroaches and tettigoniids). Recent comparative studies documented the accessory organ in several taxa of Orthoptera (including tettigoniids, cave crickets, Jerusalem crickets) and the Nebenorgan in related insects (Mantophasmatodea). The accessory organ or Nebenorgan is usually a small organ of 8-15 sensilla located in the posterior leg tibia of all leg pairs. The physiological properties of the accessory organs and Nebenorgans are so far largely unknown. Taking together neuroanatomical and electrophysiological data from disparate taxa, there is considerable evidence that the accessory organ and Nebenorgan are vibrosensitive. They thus complement the larger vibrosensitive subgenual organ in the tibia. This review summarises the comparative studies of these sensory organs, in particular the arguments and criteria for the homology of the accessory organ and Nebenorgan among orthopteroid insects. Different scenarios of repeated evolutionary origins or losses of these sensory organs are discussed. Neuroanatomy allows to distinguish individual sensory organs for analysis of sensory physiology, and to infer scenarios of sensory evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Competition of chemically related antigens for presentation by accessory cells to T cells requires expenditure of metabolic energy by the accessory cells

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    Werdelin, O; Buus, S

    1983-01-01

    The immune responsiveness of guinea pigs both to dinitrophenyl-poly-L-lysine (DNP-PLL) and to the lysine-rich random copolymer of L-glutamic acid and L-lysine (GL) is controlled by the 'poly-L-lysine gene'. We have previously demonstrated that accessory cells of responder strains can be made...... incapable of presenting DNP-PLL to responsive T cells in assays for proliferation, by in vitro exposure of the cells to GL before and during their exposure to DNP-PLL. We demonstrate here that the presence of anti-Ia antibody in the cultures does not interfere with the apparent competition of the two...

  17. Note: Design and fabrication of a simple versatile microelectrochemical cell and its accessories

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    Rajan, Viswanathan; Neelakantan, Lakshman

    2015-09-01

    A microelectrochemical cell housed in an optical microscope and custom-made accessories have been designed and fabricated, which allows performing spatially resolved corrosion measurements. The cell assembly was designed to directly integrate the reference electrode close to the capillary tip to avoid air bubbles. A hard disk along with an old optical microscope was re-engineered into a microgrinder, which made the vertical grinding of glass capillary tips very easy. A stepper motor was customized into a microsyringe pump to dispense a controlled volume of electrolyte through the capillary. A force sensitive resistor was used to achieve constant wetting area. The functionality of the developed instrument is demonstrated by studying μ-electrochemical behavior of worn surface on AA2014-T6 alloy.

  18. Distribution of Neuron Cell Bodies in the Intraspinal Portion of the Spinal Accessory Nerve in Humans.

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    Boehm, Karl E; Kondrashov, Peter

    2016-01-01

    The spinal accessory nerve is often identified as a purely motor nerve innervating the trapezius and sternocleidomastoid muscles. Although it may contain proprioceptive neurons found in cervical spinal levels C2-C4, limited research has focused on the histology of the spinal accessory nerve. The objective of the present study was to examine the spinal accessory nerve to determine if there are neuronal cell bodies within the spinal accessory nerve in humans. Cervical spinal cords were dissected from eight cadavers that had previously been used for dissection in other body regions. The segmental rootlets were removed to quantify the neuron cell bodies present at each spinal level. Samples were embedded in paraffin; sectioned; stained with hematoxylin and eosin; and examined using a microscope at 4×, 10×, and 40× magnification. Digital photography was used to image the samples. Neuronal cell bodies were found in 100% of the specimens examined, with non-grossly visible ganglia found at spinal levels C1-C4. The C1 spinal level of the spinal accessory nerve had the highest number of neuron cell bodies.

  19. Versatile roles of V-ATPases accessory subunit Ac45 in osteoclast formation and function.

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    An Qin

    Full Text Available Vacuolar-type H(+-ATPases (V-ATPases are macromolecular proton pumps that acidify intracellular cargos and deliver protons across the plasma membrane of a variety of specialized cells, including bone-resorbing osteoclasts. Extracellular acidification is crucial for osteoclastic bone resorption, a process that initiates the dissolution of mineralized bone matrix. While the importance of V-ATPases in osteoclastic resorptive function is well-defined, whether V-ATPases facilitate additional aspects of osteoclast function and/or formation remains largely obscure. Here we report that the V-ATPase accessory subunit Ac45 participates in both osteoclast formation and function. Using a siRNA-based approach, we show that targeted suppression of Ac45 impairs intracellular acidification and endocytosis, both are prerequisite for osteoclastic bone resorptive function in vitro. Interestingly, we find that knockdown of Ac45 also attenuates osteoclastogenesis owing to a reduced fusion capacity of osteoclastic precursor cells. Finally, in an effort to gain more detailed insights into the functional role of Ac45 in osteoclasts, we attempted to generate osteoclast-specific Ac45 conditional knockout mice using a Cathepsin K-Cre-LoxP system. Surprisingly, however, insertion of the neomycin cassette in the Ac45-Flox(Neo mice resulted in marked disturbances in CNS development and ensuing embryonic lethality thus precluding functional assessment of Ac45 in osteoclasts and peripheral bone tissues. Based on these unexpected findings we propose that, in addition to its canonical function in V-ATPase-mediated acidification, Ac45 plays versatile roles during osteoclast formation and function.

  20. DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells.

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    Duymich, Christopher E; Charlet, Jessica; Yang, Xiaojing; Jones, Peter A; Liang, Gangning

    2016-04-28

    Promoter DNA methylation is a key epigenetic mechanism for stable gene silencing, but is correlated with expression when located in gene bodies. Maintenance and de novo DNA methylation by catalytically active DNA methyltransferases (DNMT1 and DNMT3A/B) require accessory proteins such as UHRF1 and DNMT3L. DNMT3B isoforms are widely expressed, although some do not have active catalytic domains and their expression can be altered during cell development and tumourigenesis, questioning their biological roles. Here, we show that DNMT3B isoforms stimulate gene body methylation and re-methylation after methylation-inhibitor treatment. This occurs independently of the isoforms' catalytic activity, demonstrating a similar functional role to the accessory protein DNMT3L, which is only expressed in undifferentiated cells and recruits DNMT3A to initiate DNA methylation. This unexpected role for DNMT3B suggests that it might substitute for the absent accessory protein DNMT3L to recruit DNMT3A in somatic cells.

  1. Simvastatin requires activation in accessory cells to modulate T-cell responses in asthma and COPD.

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    Knobloch, Jürgen; Yakin, Yakup; Körber, Sandra; Grensemann, Barbara; Bendella, Zeynep; Boyaci, Niyazi; Gallert, Willem-Jakob; Yanik, Sarah Derya; Jungck, David; Koch, Andrea

    2016-10-05

    T-cell-dependent airway and systemic inflammation triggers the progression of chronic obstructive pulmonary disease (COPD) and asthma. Retrospective studies suggest that simvastatin has anti-inflammatory effects in both diseases but it is unclear, which cell types are targeted. We hypothesized that simvastatin modulates T-cell activity. Circulating CD4+ and CD8+ T-cells, either pure, co-cultured with monocytes or alveolar macrophages (AM) or in peripheral blood mononuclear cells (PBMCs), were ex vivo activated towards Th1/Tc1 or Th2/Tc2 and incubated with simvastatin. Markers for Th1/Tc1 (IFNγ) and Th2/Tc2 (IL-5, IL-13) were measured by ELISA; with PBMCs this was done comparative between 11 healthy never-smokers, 11 current smokers without airflow limitation, 14 smokers with COPD and 11 never-smokers with atopic asthma. T-cell activation induced IFNγ, IL-5 and IL-13 in the presence and absence of accessory cells. Simvastatin did not modulate cytokine expression in pure T-cell fractions. β-hydroxy-simvastatin acid (activated simvastatin) suppressed IL-5 and IL-13 in pure Th2- and Tc2-cells. Simvastatin suppressed IL-5 and IL-13 in Th2-cells co-cultivated with monocytes or AM, which was partially reversed by the carboxylesterase inhibitor benzil. Simvastatin suppressed IL-5 production of Th2/Tc2-cells in PBMCs without differences between cohorts and IL-13 stronger in never-smokers and asthma compared to COPD. Simvastatin induced IFNγ in Th1/Tc1-cells in PBMCs of all cohorts except asthmatics. Simvastatin requires activation in accessory cells likely by carboxylesterase to suppress IL-5 and IL-13 in Th2/Tc2-cells. The effects on Il-13 are partially reduced in COPD. Asthma pathogenesis prevents simvastatin-induced IFNγ up-regulation. Simvastatin has anti-inflammatory effects that could be of interest for asthma therapy.

  2. Cloning, expression, and functional characterization of the equine herpesvirus 1 DNA polymerase and its accessory subunit.

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    Loregian, Arianna; Case, Alessandro; Cancellotti, Enrico; Valente, Carlo; Marsden, Howard S; Palù, Giorgio

    2006-07-01

    We report the expression and characterization of the putative catalytic subunit (pORF30) and accessory protein (pORF18) of equine herpesvirus 1 DNA polymerase, which are encoded by open reading frames 30 and 18 and are homologous to herpes simplex virus type 1 UL30 and UL42, respectively. In vitro transcription-translation of open reading frames 30 and 18 generated proteins of 136 and 45 kDa, respectively. In vitro-expressed pORF30 possessed basal DNA polymerase activity that was stimulated by pORF18, as measured by DNA polymerase assays in vitro. Purified baculovirus-expressed pORF30 exhibited DNA polymerase activity similar to that of the in vitro-expressed protein, and baculovirus-expressed pORF18 could stimulate both nucleotide incorporation and long-chain DNA synthesis by pORF30 in a dose- and time-dependent manner. The salt optima for activity of both pORF30 and the holoenzyme were substantially different from those for other herpesvirus DNA polymerases. As demonstrated by yeast two-hybrid assays, pORF30 and pORF18 could physically interact, most likely with a 1:1 stoichiometry. Finally, by mutational analysis of the 1,220-residue pORF30, we demonstrated that the extreme C terminus of pORF30 is important for physical and functional interaction with the accessory protein, as reported for UL30 and other herpesvirus DNA polymerases. In addition, a C-proximal region of pORF30, corresponding to residues 1114 to 1172, is involved in binding to, and stimulation by, pORF18. Taken together, the results indicate that pORF30 and pORF18 are the equine herpesvirus 1 counterparts of herpes simplex virus type 1 UL30 and UL42 and share many, but not all, of their characteristics.

  3. PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF

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    Satish K. Tadi

    2016-10-01

    Full Text Available In mammalian cells, classical non-homologous end joining (c-NHEJ is critical for DNA double-strand break repair induced by ionizing radiation and during V(DJ recombination in developing B and T lymphocytes. Recently, PAXX was identified as a c-NHEJ core component. We report here that PAXX-deficient cells exhibit a cellular phenotype uncharacteristic of a deficiency in c-NHEJ core components. PAXX-deficient cells display normal sensitivity to radiomimetic drugs, are proficient in transient V(DJ recombination assays, and do not shift toward higher micro-homology usage in plasmid repair assays. Although PAXX-deficient cells lack c-NHEJ phenotypes, PAXX forms a stable ternary complex with Ku bound to DNA. Formation of this complex involves an interaction with Ku70 and requires a bare DNA extension for stability. Moreover, the relatively weak Ku-dependent stimulation of LIG4/XRCC4 activity by PAXX is unmasked by XLF ablation. Thus, PAXX plays an accessory role during c-NHEJ that is largely overlapped by XLF’s function.

  4. V-ATPase-Mediated Granular Acidification Is Regulated by the V-ATPase Accessory Subunit Ac45 in POMC-Producing Cells

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    Jansen, Eric J. R.; Hafmans, Theo G. M.

    2010-01-01

    The vacuolar (H+)-ATPase (V-ATPase) is an important proton pump, and multiple critical cell-biological processes depend on the proton gradient provided by the pump. Yet, the mechanism underlying the control of the V-ATPase is still elusive but has been hypothesized to involve an accessory subunit of the pump. Here we studied as a candidate V-ATPase regulator the neuroendocrine V-ATPase accessory subunit Ac45. We transgenically manipulated the expression levels of the Ac45 protein specifically in Xenopus intermediate pituitary melanotrope cells and analyzed in detail the functioning of the transgenic cells. We found in the transgenic melanotrope cells the following: i) significantly increased granular acidification; ii) reduced sensitivity for a V-ATPase-specific inhibitor; iii) enhanced early processing of proopiomelanocortin (POMC) by prohormone convertase PC1; iv) reduced, neutral pH–dependent cleavage of the PC2 chaperone 7B2; v) reduced 7B2-proPC2 dissociation and consequently reduced proPC2 maturation; vi) decreased levels of mature PC2 and consequently reduced late POMC processing. Together, our results show that the V-ATPase accessory subunit Ac45 represents the first regulator of the proton pump and controls V-ATPase-mediated granular acidification that is necessary for efficient prohormone processing. PMID:20702583

  5. ACCESSORY SPLEEN

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    Radhika

    2016-05-01

    Full Text Available Accessory spleen is a small nodule of splenic tissue found apart from main body of spleen. Other name for accessory spleen is supernumerary spleen, splenule or splenunculus. It is usually congenital failure of fusion of splenunculus found close to hilum of spleen, greater omentum, tail of pancreas. Accessory spleen is found approximately in 10% population. MATERIALS AND METHODS The present study 100 cadaveric spleens obtained from routine dissection, specimens present in Department of Anatomy, Andhra Medical College, Vishakhapatnam in 3 years span, out of which 25 are foetal spleens, 75 are adult spleens. RESULTS We got 4 accessory spleens in adult and 1 in foetal spleen. CONCLUSION The knowledge of accessory spleen is medically significant. That they may result in interpretation errors in diagnostic imaging and symptoms may be continued after splenectomy.

  6. Sexual activity increases the number of newborn cells in the accessory olfactory bulb of male rats.

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    Wendy ePortillo

    2012-07-01

    Full Text Available In rodents, sexual behavior depends on the adequate detection of sexually relevant stimuli. The olfactory bulb (OB is a region of the adult mammalian brain undergoing constant cell renewal by continuous integration of new granular and periglomerular neurons in the accessory (AOB and main (MOB olfactory bulbs. The proliferation, migration, survival, maturation, and integration of these new cells to the OB depend on the stimulus that the subjects received. We have previously shown that 15 days after females control (paced the sexual interaction an increase in the number of cells is observed in the AOB. No changes are observed in the number of cells when females are not allowed to control the sexual interaction. In the present study we investigated if in male rats sexual behavior increases the number of new cells in the OB. Male rats were divided in five groups: 1 males that did not receive any sexual stimulation, 2 males that were exposed to female odors, 3 males that mated for 1 h and could not pace their sexual interaction, 4 males that paced their sexual interaction and ejaculated 1 time and 5 males that paced their sexual interaction and ejaculated 3 times. All males received three injections of the DNA synthesis marker bromodeoxyuridine at 1h intervals, starting 1h before the beginning of the behavioral test. Fifteen days later, males were sacrificed and the brains were processed to identify new cells and to evaluate if they differentiated into neurons. The number of newborn cells increased in the granular cell layer (also known as the internal cell layer of the AOB in males that ejaculated one or three times controlling (paced the rate of the sexual interaction. Some of these new cells were identified as neurons. In contrast, no significant differences were found in the mitral cell layer (also known as the external cell layer and glomerular cell layer of the AOB. In addition, no significant differences were found between groups in the MOB in

  7. The gametic central cell of Arabidopsis determines the lifespan of adjacent accessory cells

    OpenAIRE

    Kägi, Christina; Baumann, Nadine; Nielsen, Nicola; Stierhof, York-Dieter; Groß-Hardt, Rita

    2010-01-01

    Plant germ cells develop in specialized haploid structures, termed gametophytes. The female gametophyte patterns of flowering plants are diverse, with often unknown adaptive value. Here we present the Arabidopsis fiona mutant, which forms a female gametophyte that is structurally and functionally reminiscent of a phylogenetic distant female gametophyte. The respective changes include a modified reproductive behavior of one of the female germ cells (central cell) and an extended lifespan of th...

  8. The V-ATPase accessory protein Atp6ap1b mediates dorsal forerunner cell proliferation and left-right asymmetry in zebrafish.

    Science.gov (United States)

    Gokey, Jason J; Dasgupta, Agnik; Amack, Jeffrey D

    2015-11-01

    Asymmetric fluid flows generated by motile cilia in a transient 'organ of asymmetry' are involved in establishing the left-right (LR) body axis during embryonic development. The vacuolar-type H(+)-ATPase (V-ATPase) proton pump has been identified as an early factor in the LR pathway that functions prior to cilia, but the role(s) for V-ATPase activity are not fully understood. In the zebrafish embryo, the V-ATPase accessory protein Atp6ap1b is maternally supplied and expressed in dorsal forerunner cells (DFCs) that give rise to the ciliated organ of asymmetry called Kupffer's vesicle (KV). V-ATPase accessory proteins modulate V-ATPase activity, but little is known about their functions in development. We investigated Atp6ap1b and V-ATPase in KV development using morpholinos, mutants and pharmacological inhibitors. Depletion of both maternal and zygotic atp6ap1b expression reduced KV organ size, altered cilia length and disrupted LR patterning of the embryo. Defects in other ciliated structures-neuromasts and olfactory placodes-suggested a broad role for Atp6ap1b during development of ciliated organs. V-ATPase inhibitor treatments reduced KV size and identified a window of development in which V-ATPase activity is required for proper LR asymmetry. Interfering with Atp6ap1b or V-ATPase function reduced the rate of DFC proliferation, which resulted in fewer ciliated cells incorporating into the KV organ. Analyses of pH and subcellular V-ATPase localizations suggested Atp6ap1b functions to localize the V-ATPase to the plasma membrane where it regulates proton flux and cytoplasmic pH. These results uncover a new role for the V-ATPase accessory protein Atp6ap1b in early development to maintain the proliferation rate of precursor cells needed to construct a ciliated KV organ capable of generating LR asymmetry.

  9. A novel function for the Hox gene Abd-B in the male accessory gland regulates the long-term female post-mating response in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dragan Gligorov

    2013-03-01

    Full Text Available In insects, products of the male reproductive tract are essential for initiating and maintaining the female post-mating response (PMR. The PMR includes changes in egg laying, receptivity to courting males, and sperm storage. In Drosophila, previous studies have determined that the main cells of the male accessory gland produce some of the products required for these processes. However, nothing was known about the contribution of the gland's other secretory cell type, the secondary cells. In the course of investigating the late functions of the homeotic gene, Abdominal-B (Abd-B, we discovered that Abd-B is specifically expressed in the secondary cells of the Drosophila male accessory gland. Using an Abd-B BAC reporter coupled with a collection of genetic deletions, we discovered an enhancer from the iab-6 regulatory domain that is responsible for Abd-B expression in these cells and that apparently works independently from the segmentally regulated chromatin domains of the bithorax complex. Removal of this enhancer results in visible morphological defects in the secondary cells. We determined that mates of iab-6 mutant males show defects in long-term egg laying and suppression of receptivity, and that products of the secondary cells are influential during sperm competition. Many of these phenotypes seem to be caused by a defect in the storage and gradual release of sex peptide in female mates of iab-6 mutant males. We also found that Abd-B expression in the secondary cells contributes to glycosylation of at least three accessory gland proteins: ovulin (Acp26Aa, CG1656, and CG1652. Our results demonstrate that long-term post-mating changes observed in mated females are not solely induced by main cell secretions, as previously believed, but that secondary cells also play an important role in male fertility by extending the female PMR. Overall, these discoveries provide new insights into how these two cell types cooperate to produce and maintain a

  10. Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.

    Directory of Open Access Journals (Sweden)

    Asaph Zylbertal

    2015-12-01

    Full Text Available Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB, which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i, which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

  11. Functional anatomy of the accessory nerve studied through intraoperative electrophysiological mapping.

    Science.gov (United States)

    Brînzeu, Andrei; Sindou, Marc

    2017-03-01

    OBJECTIVE Classically the 11th cranial nerve (CN XI, or accessory nerve) is described as having a cranial and a spinal root, the latter arising from the upper segments of the spinal cord through a number of very fine rootlets. According to classical knowledge, the cranial root gives motor innervation to the vocal cords, whereas the spinal root provides the motor innervation of the sternocleidomastoid muscle (SCM) and of the upper portions of the trapezius muscle (TZ). The specific function of each of the rootlets of the spinal component is not well known. Therefore the authors aimed to map, using intraoperative direct electrical stimulation and electromyographic (EMG) recordings, the innervation territory of these rootlets in relation to their exit level from the CNS. METHODS Forty-nine patients undergoing surgery with intradural exposure at the craniocervical junction were enrolled in the study. The EMG recordings included the sternal and clavicular parts of the SCM (SCM-S and SCM-C), the superior and middle parts of the TZ (TZ-S and TZ-M), and whenever possible the vocal cords. The main trunk of CN XI, its roots (both cranial and spinal), and when possible the fine cervical rootlets, were stimulated at predetermined locations, from the jugular foramen down to the lowest cervical level exposed. The EMG responses were collected, and a map of the responses was drawn up. RESULTS Monitoring and stimulation of the spinal root were performed in all cases, whereas for the cranial root this was possible in only 19 cases. A total of 262 stimulation sites were explored: 70 at the common trunk of the nerve, 19 at the cranial root, 136 at various levels on the spinal root, and 37 at the cervical rootlets. A vocal cord response was obtained by stimulation of the cranial root in 84.2% (16/19); absence of response was considered to have a technical origin. In no case did the vocal cords respond to the stimulation of the spinal root or rootlets. Stimulation of the cervical

  12. Human pregnancy-specific glycoprotein 1a (PSG1a) induces alternative activation in human and mouse monocytes and suppresses the accessory cell-dependent T cell proliferation.

    Science.gov (United States)

    Motrán, Claudia Cristina; Díaz, Fernando López; Gruppi, Adriana; Slavin, Daniela; Chatton, Bruno; Bocco, José Luis

    2002-09-01

    It has been proposed that pregnancy-specific factors induce the suppression of a specific arm of the maternal response accompanied by activation of the nonspecific, innate immune system. The aim of this study was to determine whether pregnancy-specific glycoprotein 1a (PSG1a), the major variant of PSG polypeptides, is able to modulate the monocyte/macrophage (Mo) metabolism to regulate T cell activation and proliferation. Using the recombinant form of this glycoprotein (rec-PSG1a), expressed in mammalian cells with a vaccinia-based expression vector, we have demonstrated that human PSG1a induces arginase activity in peripheral blood human Mo and human and murine Mo cell lines. In addition, rec-PSG1a is able to induce alternative activation because it up-regulates the arginase activity and inhibits the nitric oxide production in Mo activated by lipopolysaccharides. We also observed that rec-PSG1a is an important accessory cells-dependent T cell suppressor factor that causes partial growth arrest at the S/G2/M phase of the cell cycle. Additionally, an impaired T cell proliferative response induced by mitogens and specific antigen was observed in BALB/c mice upon in vivo expression of PSG1a. Our results suggest that PSG1a function contributes to the immunomodulation during pregnancy, having opposite effects on maternal innate and adaptative systems.

  13. Dendritic Cells are Critical Accessory Cells for Thymus-Dependent Antibody Responses in Mouse and in Man

    Science.gov (United States)

    Inaba, Kayo; Steinman, Ralph M.; van Voorhis, Wesley C.; Muramatsu, Shigeru

    1983-10-01

    We report that dendritic cells (DC) are necessary and potent accessory cells for anti-sheep erythrocyte responses in both mouse and man. In mice, a small number of DC (0.3-1% of the culture) restores the response of B/T-lymphocyte mixtures to that observed in unfractionated spleen. An even lower dose (0.03-0.1% DC) is needed if the T cells have been primed to antigen. Responses are both antigen and T cell dependent. Selective depletion of DC from unfractionated spleen with the monoclonal antibody 33D1 and complement ablates the antibody response. In contrast to DC, purified spleen macrophages are weak or inactive stimulators. However, when mixed with DC, macrophages can increase the yield of antibody-secreting cells about 2-fold. In man, small numbers (0.3-1%) of blood DC stimulate antibody formation in vitro. Purified human monocytes do not stimulate but in low doses (1% of the culture) inhibit the antibody response. Likewise, selective removal of human monocytes with antibody and complement enhances or accelerates the development of antibody-secreting cells. We conclude that DC are required for the development of T-dependent antibody responses by mouse and human lymphocytes in vitro.

  14. Homology modeling, docking studies and functional analysis of various azoreductase accessory interacting proteins of Nostoc sp.PCC7120.

    Science.gov (United States)

    Philem, Priyadarshini Devi; Adhikari, Samrat

    2012-01-01

    Azo dyes have become a threat to public health because of its toxicity and carcinogenicity. Azoreductase enzyme plays a pivotal role in the degradation of azodyes released by industrial effluents and other resources. The degradation pathway has to be studied in detail for increasing the activity of azoreductase and for better degradation of azo dyes. But the data available on cyanobacterial azoreductase enzyme and its degradation pathway are still very less. Therefore the present work explored the azoreductase pathway of the cyanobacterium Nostoc sp. PCC7120 for better understanding of the degradation pathway and the other accessory interacting proteins involved. The accessory interacting proteins of azoreductase from cyanobacterium Nostoc sp. PCC7120 were obtained from STRING database. The proteins do not have a comprehensive three dimensional structure and are hypothetical. The secondary structure and functional analysis indicated that the proteins are all soluble proteins, without disulphide bonds and have alpha helices only. The structural prediction and docking study showed that alr2106, alr1063 and alr2326 have best docking result which tally with the STRING database confidence score and thus these proteins could possibly enhance the azoreductase activity and better dye degradation. These results will pave way for further increase in azoreductase activity and for better understanding of the dye degradation pathway.

  15. 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

    whether IL1RAP expression distinguishes normal (Ph(-)) and leukemic (Ph(+)) cells within the CML CD34(+)CD38(-) cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate......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...

  16. Bilateral accessory thoracodorsal artery.

    Science.gov (United States)

    Natsis, Konstantinos; Totlis, Trifon; Tsikaras, Prokopios; Skandalakis, Panagiotis

    2006-09-01

    The subscapular artery arises from the third part of the axillary artery and gives off the circumflex scapular and the thoracodorsal arteries. Although anatomical variations of the axillary artery are very common, the existence of a unilateral accessory thoracodorsal artery has been described in the literature only once. There are no reports of bilateral accessory thoracodorsal artery, in the literature. In the present study, a bilateral accessory thoracodorsal artery, originating on either side of the third part of the axillary artery, is described in a 68-year-old female cadaver. All the other branches of the axillary artery had a typical origin, course, distribution and termination. This extremely rare anatomical variation apart from the anatomical importance also has clinical significance for surgeons in this area. Especially, during the dissection or mobilization of the latissimus dorsi that is partly used for coverage problems in many regions of the body and also in dynamic cardiomyoplasty, any iatrogenic injury of this accessory artery may result in ischemia and functional loss of the graft.

  17. Distribution of lymphocytes, immunoglobulin-containing cells, macrophages, and dendritic cells in the accessory sex glands of rams experimentally infected with Actinobacillus seminis

    Directory of Open Access Journals (Sweden)

    Jorge Acosta-Dibarrat

    2016-05-01

    Full Text Available Abstract: The distribution of cells involved in the immune response in accessory sex glands of rams experimentally infected with Actinobacillus seminis was studied. Twelve one-year old rams were experimentally infected by intraurethral (IU (n=4 and intraepididymal (IE (n=4 route, and four control (CON animals were used. The animals were slaughtered 35 days post-inoculation, samples were taken from accessory sex glands, and bacteriology and histopathology tests were performed. The presence of CD4, CD8 and TCRγδ (WC1 lymphocytes, CD45RO cells, macrophages (CD14, dendritic cells (CD1b, IgA-, IgG- and IgM-containing cells (IgCC was determined. Animals of the IE group developed clinical epididymitis. No lesions were seen in rams of the IU group; two of the intraepididymal inoculated CON developed small lesions in the epididymis. A. seminis isolates were achieved from 6:16 (37.5% accessory sex glands in the IE group, but not in the IU and CON groups. In the CON group, IgA- and IgM- containing cells predominated in the bulbourethral glands and the disseminated prostate, and they were scarce or null in the vesicles and ampullae. A significant increase of IgA-, IgG- and IgM- containing cells was confirmed in the seminal vesicles, the ampullae and the bulbourethral glands in the IE group. In the IE and IU groups, an increase in CD4, CD8, WC1, CD45RO and CD14 was evidenced in the vesicles and ampullae. CD1b dendritic cells were present in the ampullae and vesicles with inflammatory processes. A. seminis triggered a local immune response in the IE and IU groups. These results indicate a different pattern of infiltrating immune cells in the accessory sex glands of infected A. seminis rams.

  18. A novel method using intranasal delivery of EdU demonstrates that accessory olfactory ensheathing cells respond to injury by proliferation.

    Science.gov (United States)

    Chehrehasa, Fatemeh; Ekberg, Jenny A K; St John, James A

    2014-03-20

    Olfactory ensheathing cells (OECs) play an important role in the continuous regeneration of the primary olfactory nervous system throughout life and for regeneration of olfactory neurons after injury. While it is known that several individual OEC subpopulations with distinct properties exist in different anatomical locations, it remains unclear how these different subpopulations respond to a major injury. We have examined the proliferation of OECs from one distinct location, the peripheral accessory olfactory nervous system, following large-scale injury (bulbectomy) in mice. We used crosses of two transgenic reporter mouse lines, S100ß-DsRed and OMP-ZsGreen, to visualise OECs, and main/accessory olfactory neurons, respectively. We surgically removed one olfactory bulb including the accessory olfactory bulb to induce degeneration, and found that accessory OECs in the nerve bundles that terminate in the accessory olfactory bulb responded by increased proliferation with a peak occurring 2 days after the injury. To label proliferating cells we used the thymidine analogue ethynyl deoxyuridine (EdU) using intranasal delivery instead of intraperitoneal injection. We compared and quantified the number of proliferating cells at different regions at one and four days after EdU labelling by the two different methods and found that intranasal delivery method was as effective as intraperitoneal injection. We demonstrated that accessory OECs actively respond to widespread degeneration of accessory olfactory axons by proliferating. These results have important implications for selecting the source of OECs for neural regeneration therapies and show that intranasal delivery of EdU is an efficient and reliable method for assessing proliferation of olfactory glia.

  19. Specific projection of displaced retinal ganglion cells upon the accessory optic system in the pigeon (Columbia livia).

    Science.gov (United States)

    Karten, J H; Fite, K V; Brecha, N

    1977-04-01

    In the pigeon, the nucleus of the basal optic root, a component of the accessory optic system, projects directly upon the vestibulo-cerebellum. This nucleus receives a prominent projection composed of large-diameter retinal axons, known as the basal optic root. The cells of origin of this tract were identified using horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) as a retrograde marker. Injections of horseradish peroxidase confined primarily to the basal optic root nucleus labeled displaced ganglion cells of the contralateral retina. Cell sizes were 18-30 micronm and the dendrites of these cells were confined to the first stratum of the inner plexiform layer. Approximately 3700 displaced ganglion cells were labeled after injections of horseradish peroxidase into basal optic root. In contrast, no displaced ganglion cells were labeled after injections of horseradish peroxidase into the optic tectum, which labeled only cells in the ganglion cell layer proper. These findings indicate that displaced ganglion cells constitute a unique population of retinal neurons that give rise to a bisynaptic pathway directed to the cerebellum via the nucleus of the basal optic root. These displaced ganglion cells may play a major role inoculomotor reflexes.

  20. Cone-beam computed tomography analysis of accessory maxillary ostium and Haller cells: Prevalence and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Ibrahim K.; Sansare, Kaustubh; Karjodkar, Freny R.; Vanga, Kavita; Salve, Prashant [Dept. of Oral Medicine and Radiology, Nair Hospital Dental College, Mumbai (India); Pawar, Ajinkya M. [Dept. of Conservative Dentistry and Endodontics, Nair Hospital Dental College, Mumbai (India)

    2017-03-15

    This study aimed to evaluate the prevalence of Haller cells and accessory maxillary ostium (AMO) in cone-beam computed tomography (CBCT) images, and to analyze the relationships among Haller cells, AMO, and maxillary sinusitis. Volumetric CBCT scans from 201 patients were retrieved from our institution's Digital Imaging and Communications in Medicine archive folder. Two observers evaluated the presence of Haller cells, AMO, and maxillary sinusitis in the CBCT scans. AMO was observed in 114 patients, of whom 27 (23.7%) had AMO exclusively on the right side, 26 (22.8%) only on the left side, and 61 (53.5%) bilaterally. Haller cells were identified in 73 (36.3%) patients. In 24 (32.9%) they were present exclusively on the right side, in 17 (23.3%) they were only present on the left side, and in 32 (43.8%) they were located bilaterally. Of the 73 (36.3%) patients with Haller cells, maxillary sinusitis was also present in 50 (68.5%). On using chi-square test, a significant association was observed between AMO and maxillary sinusitis in the presence of Haller cells. Our results showed AMO and Haller cells to be associated with maxillary sinusitis. This study provides evidence for the usefulness of CBCT in imaging the bony anatomy of the sinonasal complex with significantly higher precision and a smaller radiation dose.

  1. Large, but not small, antigens require time- and temperature-dependent processing in accessory cells before they can be recognized by T cells

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1986-01-01

    of antigen presentation we used the proliferative response of appropriately primed T cells during a co-culture with the paraformaldehyde-fixed and antigen-exposed presenting cells. We demonstrate that the large synthetic polypeptide antigen, dinitrophenyl-poly-L-lysine, requires processing. After an initial...... time-lag of 30 min this antigen is fully processed within 2 to 4 of culture at 37 degrees C. In contrast, the immunogenic heptapeptide, angiotensin III, can be presented by pre-fixed accessory cells, viz. without any prior processing. Antigen processing was found to be temperature...

  2. Accessory cells with a veiled morphology and movement pattern generated from monocytes after avoidance of plastic adherence and of NADPH oxidase activation. A comparison with GM-CSF/IL-4-induced monocyte-derived dendritic cells.

    Science.gov (United States)

    Ruwhof, Cindy; Canning, Martha O; Grotenhuis, Kristel; de Wit, Harm J; Florencia, Zenovia Z; de Haan-Meulman, Meeny; Drexhage, Hemmo A

    2002-07-01

    Veiled cells (VC) present in afferent lymph transport antigen from the periphery to the draining lymph nodes. Although VC in lymph form a heterogeneous population, some of the cells clearly belong on morphological grounds to the Langerhans cell (LC)/ dendritic cell (DC) series. Here we show that culturing monocytes for 24 hrs while avoiding plastic adherence (polypropylene tubes) and avoiding the activation of NADPH oxidase (blocking agents) results in the generation of a population of veiled accessory cells. The generated VC were actively moving cells like lymph-borne VC in vivo. The monocyte (mo)-derived VC population existed of CD14(dim/-) and CD14(brighT) cells. Of these the CD14(dim/-) VC were as good in stimulating allogeneic T cell proliferation as immature DC (iDC) obtained after one week of adherent culture of monocytes in granulocyte-macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. This underscores the accessory cell function of the mo-derived CD14(dim/-) VC. Although the CD14(dim/-)VC had a modest expression of the DC-specific marker CD83 and were positive for S100, expression of the DC-specific markers CD1a, Langerin, DC-SIGN, and DC-LAMP were absent. This indicates that the here generated CD14(dim/-) VC can not be considered as classical LC/DC. It was also impossible to turn the CD14(dim/-) mo-derived VC population into typical DC by culture for one week in GM-CSF/IL-4 or LPS. In fact the cells died tinder such circumstances, gaining some macrophage characteristics before dying. The IL-12 production from mo-derived CD14(dim/-) VC was lower, whereas the production of IL-10 was higher as compared to iDC. Consequently the T cells that were stimulated by these mo-derived VC produced less IFN-gamma as compared with T cells stimulated by iDC. Our data indicate that it is possible to rapidly generate a population of CD14(dim/-) veiled accessory cells from monocytes. The marker pattern and cytokine production of these VC indicate that this

  3. Function and composition of male accessory gland secretions in Anopheles gambiae: a comparison with other insect vectors of infectious diseases

    Science.gov (United States)

    Baldini, Francesco; Gabrieli, Paolo; Rogers, David W.; Catteruccia, Flaminia

    2012-01-01

    Human malaria, a major public health burden in tropical and subtropical countries, is transmitted exclusively by the bite of a female Anopheles mosquito. Malaria control strategies aimed at inducing sexual sterility in natural vector populations are an attractive alternative to the use of insecticides. However, despite their importance as disease vectors, limited information is available on the molecular mechanisms regulating fertility in Anopheles mosquitoes. In the major malaria vector, An. gambiae, the full complement of sperm and seminal fluid required for a female’s lifelong egg production is obtained from a single mating event. This single mating has important consequences for the physiology and behavior of An. gambiae females: in particular, they become refractory to further insemination, and they start laying eggs. In other insects including Drosophila, similar post-copulatory changes are induced by seminal proteins secreted by the male accessory glands and transferred to the female during mating. In this review, we analyze the current state of knowledge on the function and characterization of male seminal proteins in An. gambiae, and provide a comparative assessment of the role of these male reproductive factors in other mosquito vectors of human disease in which female post-copulatory behavior has been studied. Knowledge of the factors and mechanisms regulating fertility in An. gambiae and other vectors can help the design of novel control strategies to fight the spread of disease. PMID:22943543

  4. A method for enriching myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from human cord blood by accessory cell depletion.

    Science.gov (United States)

    Dowton, L A; Ma, D D

    1992-10-01

    Human cord blood provides a convenient alternative to bone marrow as a rich source of hemopoietic progenitor cells. This study reports a simple means for enriching a cord blood progenitor cell population by accessory cell depletion. Two methods of monocyte depletion were tested. A Cytodex 3 microcarrier system using collagen coated dextran beads was compared to the more commonly used method of plastic plate adhesion. The method of plastic plate adhesion gave a significantly higher cell recovery. T cell depletion using a recently characterized rat monoclonal antibody which fixes human complement was also investigated. A combined method of monocyte depletion by plate adhesion and T cell depletion resulted in the removal of > 96% of monocytes and > 98% of T cells. This led to a significant enrichment of myeloid (CFU-GM) and erythroid (BFU-E) colony growth. Such enriched progenitor cell populations provide a useful starting population for any study on hemopoiesis.

  5. Hemolymph circulation in insect sensory appendages: functional mechanics of antennal accessory pulsatile organs (auxiliary hearts) in the mosquito Anopheles gambiae.

    Science.gov (United States)

    Boppana, Sushma; Hillyer, Julián F

    2014-09-01

    Mosquito antennae provide sensory input that modulates host-seeking, mating and oviposition behaviors. Thus, mosquitoes must ensure the efficient transport of molecules into and out of these appendages. To accomplish this, mosquitoes and other insects have evolved antennal accessory pulsatile organs (APOs) that drive hemolymph into the antennal space. This study characterizes the structural mechanics of hemolymph propulsion throughout the antennae of Anopheles gambiae. Using intravital video imaging, we show that mosquitoes possess paired antennal APOs that are located on each side of the head's dorsal midline. They are situated between the frons and the vertex in an area that is dorsal to the antenna but ventral to the medial-most region of the compound eyes. Antennal APOs contract in synchrony at 1 Hz, which is 45% slower than the heart. By means of histology and intravital imaging, we show that each antennal APO propels hemolymph into the antenna through an antennal vessel that traverses the length of the appendage and has an effective diameter of 1-2 μm. When hemolymph reaches the end of the appendage, it is discharged into the antennal hemocoel and returns to the head. Because a narrow vessel empties into a larger cavity, hemolymph travels up the antenna at 0.2 mm s(-1) but reduces its velocity by 75% as it returns to the head. Finally, treatment of mosquitoes with the anesthetic agent FlyNap (triethylamine) increases both antennal APO and heart contraction rates. In summary, this study presents a comprehensive functional characterization of circulatory physiology in the mosquito antennae.

  6. The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia

    DEFF Research Database (Denmark)

    Gay, D; Buus, S; Pasternak, J;

    1988-01-01

    The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell...... proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T...... cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target....

  7. Accessory Proteins at ERES

    DEFF Research Database (Denmark)

    Klinkenberg, Rafael David

    proteins. Together these components co‐operate in cargo‐selection as well as forming, loading and releasing budding vesicles from specific regions on the membrane surface of the ER. Coat components furthermore convey vesicle targeting towards the Golgi. However, not much is known about the mechanisms...... that regulate the COPII assembly at the vesicle bud site. This thesis provides the first regulatory mechanism of COPII assembly in relation to ER‐membrane lipid‐signal recognition by the accessory protein p125A (Sec23IP). The aim of the project was to characterize p125A function by dissecting two main domains...... in the protein; a putative lipid‐associating domain termed the DDHD domain that is defined by the four amino acid motif that gives the domain its name; and a ubiquitously found domain termed Sterile α‐motif (SAM), which is mostly associated with oligomerization and polymerization. We first show, that the DDHD...

  8. Expression of a male accessory gland peptide of Leptinotarsa decemlineata in insect cells infected with a recombinant baculovirus.

    NARCIS (Netherlands)

    Smid, H.M.; Schooneveld, H.; Deserno, M.L.L.G.; Put, B.; Vlak, J.M.

    1998-01-01

    The male accessory glands (MAGs) of Leptinotarsa decemlineata produce an 8kDa peptide, designated Led-MAGP, that is recognized by monoclonal antibody MAC-18. The site of synthesis, amino acid sequence and the gene encoding this peptide have been documented (). The primary structure is homologous to

  9. Expression of a male accessory gland peptide of Leptinotarsa decemlineata in insect cells infected with a recombinant baculovirus.

    NARCIS (Netherlands)

    Smid, H.M.; Schooneveld, H.; Deserno, M.L.L.G.; Put, B.; Vlak, J.M.

    1998-01-01

    The male accessory glands (MAGs) of Leptinotarsa decemlineata produce an 8kDa peptide, designated Led-MAGP, that is recognized by monoclonal antibody MAC-18. The site of synthesis, amino acid sequence and the gene encoding this peptide have been documented (). The primary structure is homologous to

  10. Small Engine & Accessory Test Area

    Data.gov (United States)

    Federal Laboratory Consortium — The Small Engine and Accessories Test Area (SEATA) facilitates testaircraft starting and auxiliary power systems, small engines and accessories. The SEATA consists...

  11. [Spinal accessory nerve and lymphatic neck dissection].

    Science.gov (United States)

    Pinsolle, V; Michelet, V; Majoufre, C; Caix, P; Siberchicot, F; Pinsolle, J

    1997-09-01

    Radical neck dissection was the golden standard of treatment for cervical nodes in head and neck tumors. From the seventies, the preservation of the spinal accessory nerve has become increasingly popular in order to improve the functional result of the neck dissections. The aim of this study was to assess the degree of functional disability associated with each type of neck dissection and the value of anatomical references for dissection of the spinal accessory nerve. One hundred twenty seven patients were evaluated 1 month and 1 year after radical, functional or supraomohyoid neck dissection with a questionnaire and a physical examination. Anatomical measurements of the spinal accessory nerve were performed in 20 patients. We found considerable or severe shoulder dysfunction in 7%, 34% and 51% respectively of patients in whom supraomohyoid, functional and radical neck dissections were performed. Furthermore 49% of patients having undergone a radical neck dissection had little or no symptoms. Sacrifice of the spinal accessory nerve in radical neck dissection may lead to shoulder dysfunction. A functional disability may also be associated, although in a less extent, with any neck dissection in which the spinal accessory nerve is dissected and placed in traction. There is a large variation in the degree of functional disability and pain in patients with similar neck dissections. The course of the spinal accessory nerve in the neck makes it particularly vulnerable to injury during the dissection near the sternocleidomastoid muscle and in the posterior cervical triangle.

  12. A group-specific inhibitor of lysosomal cysteine proteinases selectively inhibits both proteolytic degradation and presentation of the antigen dinitrophenyl-poly-L-lysine by guinea pig accessory cells to T cells

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1986-01-01

    of antigens by guinea pig accessory cells. The proteinase inhibitor benzyloxycarbonyl-phenylalanylalanine-diazomethyl-ketone, which selectively inhibits cysteine proteinases, was used to block this set of enzymes in cultured cells. We demonstrate that the selective inhibition of the cysteine proteinases...... inhibitor. Another inhibitor, pepstatin A, which selectively blocks aspartic proteinases, did not block the presentation of dinitrophenyl-poly-L-lysine. The results identify cysteine proteinases, probably lysosomal, as one of the groups of enzymes involved in antigen processing....

  13. Transcriptional signature of accessory cells in the lateral line, using the Tnk1bp1:EGFP transgenic zebrafish line

    Directory of Open Access Journals (Sweden)

    Behra Martine

    2012-01-01

    Full Text Available Abstract Background Because of the structural and molecular similarities between the two systems, the lateral line, a fish and amphibian specific sensory organ, has been widely used in zebrafish as a model to study the development/biology of neuroepithelia of the inner ear. Both organs have hair cells, which are the mechanoreceptor cells, and supporting cells providing other functions to the epithelium. In most vertebrates (excluding mammals, supporting cells comprise a pool of progenitors that replace damaged or dead hair cells. However, the lack of regenerative capacity in mammals is the single leading cause for acquired hearing disorders in humans. Results In an effort to understand the regenerative process of hair cells in fish, we characterized and cloned an egfp transgenic stable fish line that trapped tnks1bp1, a highly conserved gene that has been implicated in the maintenance of telomeres' length. We then used this Tg(tnks1bp1:EGFP line in a FACsorting strategy combined with microarrays to identify new molecular markers for supporting cells. Conclusions We present a Tg(tnks1bp1:EGFP stable transgenic line, which we used to establish a transcriptional profile of supporting cells in the zebrafish lateral line. Therefore we are providing a new set of markers specific for supporting cells as well as candidates for functional analysis of this important cell type. This will prove to be a valuable tool for the study of regeneration in the lateral line of zebrafish in particular and for regeneration of neuroepithelia in general.

  14. Imaging diagnosis of accessory and cavitated uterine mass, a rare mullerian anomaly

    Directory of Open Access Journals (Sweden)

    Nishchint Jain

    2014-01-01

    Full Text Available Accessory and Cavitated Uterine Mass (ACUM is a rare form of developmental Mullerian anomaly seen in young females, which presents as chronic recurrent pelvic pain and severe dysmenorrhea. It is an accessory cavity lying within an otherwise normal uterus. It is lined by functional endometrium and surrounded by myometrium-like smooth muscle cells; hence, it bears striking macroscopic and microscopic resemblance to the uterus. Hysterosalpingography (HSG, Ultrasonography (USG, and Magnetic Resonance Imaging (MRI form the mainstay of diagnostic imaging. The entity is often under diagnosed; therefore, a high index of suspicion combined with HSG and MRI imaging can help in making an accurate diagnosis.

  15. Noradrenaline-induced enhancement of oscillatory local field potentials in the mouse accessory olfactory bulb does not depend on disinhibition of mitral cells.

    Science.gov (United States)

    Leszkowicz, Emilia; Khan, Selina; Ng, Stephanie; Ved, Nikita; Swallow, Daniel L; Brennan, Peter A

    2012-05-01

    The olfactory bulb differs from other brain regions by its use of bidirectional synaptic transmission at dendrodendritic reciprocal synapses. These reciprocal synapses provide tight coupling of inhibitory feedback from granule cell interneurons to mitral cell projection neurons in the accessory olfactory bulb (AOB), at the first stage of vomeronasal processing. It has been proposed that both the mGluR2 agonist DCG-IV and noradrenaline promote mate recognition memory formation by reducing GABAergic feedback on mitral cells. The resultant mitral cell disinhibition is thought to induce a long-lasting enhancement in the gain of inhibitory feedback from granule to mitral cells, which selectively gates the transmission of the learned chemosensory information. However, we found that local infusions of both noradrenaline and DCG-IV failed to disinhibit AOB neural activity in urethane-anaesthetised mice. DCG-IV infusion had similar effects to the GABA(A) agonist isoguvacine, suggesting that it increased GABAergic inhibition in the AOB rather than reducing it. Noradrenaline infusion into the AOB also failed to disinhibit mitral cells in awake mice despite inducing long-term increases in power of AOB local field potentials, similar to those observed following memory formation. These results suggest that mitral cell disinhibition is not essential for the neural changes in the AOB that underlie mate recognition memory formation in mice.

  16. Advanced Accessory Power Supply Topologies

    Energy Technology Data Exchange (ETDEWEB)

    Marlino, L.D.

    2010-06-15

    This Cooperative Research and Development Agreement (CRADA) began December 8, 2000 and ended September 30, 2009. The total funding provided by the Participant (General Motors Advanced Technology Vehicles [GM]) during the course of the CRADA totaled $1.2M enabling the Contractor (UT-Battelle, LLC [Oak Ridge National Laboratory, a.k.a. ORNL]) to contribute significantly to the joint project. The initial task was to work with GM on the feasibility of developing their conceptual approach of modifying major components of the existing traction inverter/drive to develop low cost, robust, accessory power. Two alternate methods for implementation were suggested by ORNL and both were proven successful through simulations and then extensive testing of prototypes designed and fabricated during the project. This validated the GM overall concept. Moreover, three joint U.S. patents were issued and subsequently licensed by GM. After successfully fulfilling the initial objective, the direction and duration of the CRADA was modified and GM provided funding for two additional tasks. The first new task was to provide the basic development for implementing a cascaded inverter technology into hybrid vehicles (including plug-in hybrid, fuel cell, and electric). The second new task was to continue the basic development for implementing inverter and converter topologies and new technology assessments for hybrid vehicle applications. Additionally, this task was to address the use of high temperature components in drive systems. Under this CRADA, ORNL conducted further research based on GM’s idea of using the motor magnetic core and windings to produce bidirectional accessory power supply that is nongalvanically coupled to the terminals of the high voltage dc-link battery of hybrid vehicles. In order not to interfere with the motor’s torque, ORNL suggested to use the zero-sequence, highfrequency harmonics carried by the main fundamental motor current for producing the accessory power

  17. Synthesis, depletion and cell-type expression of a protein from the male accessory glands of the dengue vector mosquito Aedes aegypti.

    Science.gov (United States)

    Alfonso-Parra, Catalina; Avila, Frank W; Deewatthanawong, Prasit; Sirot, Laura K; Wolfner, Mariana F; Harrington, Laura C

    2014-11-01

    Aedes aegypti males transfer sperm and seminal fluid proteins (Sfps), primarily produced by male accessory glands (AGs), to females during mating. When collectively injected or transplanted into females, AG tissues and/or seminal fluid homogenates have profound effects on Aedes female physiology and behavior. To identify targets and design new strategies for vector control, it is important to understand the biology of the AGs. Thus, we examined characteristics of AG secretion and development in A. aegypti, using the AG-specific seminal fluid protein, AAEL010824, as a marker. We showed that AAEL010824 is first detectable by 12h post-eclosion, and increases in amount over the first 3 days of adult life. We then showed that the amount of AAEL0010824 in the AG decreases after mating, with each successive mating depleting it further; by 5 successive matings with no time for recovery, its levels are very low. AAEL010824 levels in a depleted male are replenished by 48 h post-mating. In addition to examining the level of AAEL010824 protein, we also characterized the expression of its gene. We did this by making a transgenic mosquito line that carries an Enhanced Green Fluorescence Protein (EGFP) fused to the AAEL0010824 promoter that we defined here. We showed that AAEL010824 is expressed in the anterior cells of the accessory glands, and that its RNA levels also respond to mating. In addition to further characterizing AAEL010824 expression, our results with the EGFP fusion provide a promoter for driving AG expression. By providing this information on the biology of an important male reproductive tissue and the production of one of its seminal proteins, our results lay the foundation for future work aimed at identifying novel targets for mosquito population control.

  18. [Occurrence and structure of accessory adrenal glands in Wistar rats].

    Science.gov (United States)

    Schwabedal, P E; Partenheimer, U

    1983-01-01

    In complete series of histological sections through the entire abdomen of one normal Wistar-rat, one untreated and two bilaterally adrenalectomized, spontaneously hypertensive Wistar-rats accessory suprarenal glands were found in each case. The detailed findings in the various groups of animals investigated were as follows: (1) In the normal animal 10 accessory suprarenal glands were present. They consisted of tiny aggregates of cortical cells and were surrounded by a thin layer of collageneous fibers. The diameters of the accessory suprarenal complexes were in the order of 0.3 mm. (2) In the untreated, spontaneously hypertensive rat three accessory suprarenal glands were found. However, in contrast to what was seen in the normal rat, these complexes were larger and had diameters of up to 1 mm. Some of these accessory suprarenal glands consisted almost exclusively of small, chromophobe cells, whereas in others a rim of such cells was seen to surround a central core of larger and more acidophile cortical cells. There were few and collapsed capillaries. (3) In the bilaterally adrenalectomized, spontaneously hypertensive rats three, respectively four, accessory suprarenal glands were found. They were situated in the retroperitoneum and partly within the adipose capsule of the kidney but never in the place of the exstirpated main suprarenal glands. In one case an accessory gland was found within the fibrous capsule of the kidney and seen to compress the renal parenchyma. In the bilaterally adrenalectomized animals the average diameters of the accessory glands were larger than in the other groups reaching values of up to 5 mm. At least in both animals one of the accessory glands had a diameter comparable to that of the normal suprarenal gland of an untreated animal. The capillaries were dilated and their number was increased in comparison to what was seen in the other groups. In certain regions the cortical tissue of the accessory glands had an appearance resembling

  19. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae.

    Science.gov (United States)

    Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K; Hoque, Kazi Mirajul

    2015-01-01

    Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders.

  20. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace of Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Tanaya Chatterjee

    Full Text Available Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX and Accessory cholera enterotoxin (Ace secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC inhibitors, namely CaCCinh-A01, digallic acid (DGA and tannic acid. Biophysical studies indicate that the unfolding (induced by urea free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders.

  1. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

    Science.gov (United States)

    Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

    2015-01-01

    Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID:26540279

  2. Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr

    Science.gov (United States)

    Sakai, Yosuke; Doi, Naoya; Miyazaki, Yasuyuki; Adachi, Akio; Nomaguchi, Masako

    2016-01-01

    The efficiency of reverse transcription to synthesize viral DNA in infected cells greatly influences replication kinetics of retroviruses. However, viral replication in non-dividing cells such as resting T cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated SAMHD1 (sterile alpha motif and HD-domain containing protein 1). SAMHD1 reduces cellular deoxynucleoside triphosphate (dNTP) pools and affects viral reverse transcription step. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) have Vpx or Vpr to efficiently degrade SAMHD1. Interestingly, the reverse transcriptase (RT) derived from HIV-1 that encodes no anti-SAMHD1 proteins has been previously demonstrated to uniquely exhibit a high enzymatic activity. It is thus not irrational to assume that some viruses may have acquired or lost the specific RT property to better adapt themselves to the low dNTP environments confronted in non-dividing cells. This adaptation process may probably be correlated with the SAMHD1-antagonizing ability by viruses. In this report, we asked whether such adaptive events can be inferable from Vpx/Vpr and RT phylogenetic trees overlaid with SAMHD1-degrading capacity of Vpx/Vpr and with kinetic characteristics of RT. Resultant two trees showed substantially similar clustering patterns, and therefore suggested that the properties of RT and Vpx/Vpr can be linked. In other words, HIV/SIVs may possess their own RT proteins to adequately react to various dNTP circumstances in target cells. PMID:27803699

  3. Functional and computed tomography correlation of femoral and tibial tunnels in single-bundle anterior cruciate ligament reconstruction: Use of accessory anteromedial portal

    Science.gov (United States)

    Mathai, Naveen Joseph; Amaravathi, Rajkumar S; Pavan, KV; Sekaran, Padmanabhan; Sharma, Gaurav; Codanda, Belliappa

    2016-01-01

    Background: An accessory anteromedial portal (AAMP) has been shown to be effective in placing an anatomically ideal femoral tunnel. It is well known that this is due to the independent femoral drilling which is possible with the AAMP. However very little is known regarding the significance of this reconstruction technique in influencing the functional outcomes of anatomic anterior cruciate ligament reconstruction (ACLR). This study documents the influence of tibial and femoral tunnel positions on functional outcomes of anatomic ACLR using the AAMP. Materials and Methods: 41 patients who underwent anatomic ACLR between 2011 and 2013 were included in this prospective cohort study. The primary outcome involved the documentation of femoral and tibial tunnel positions with volume rendering imaging using a three-dimensional computed tomography (3D-CT) done at the end of 1 year. The tunnel position evaluations from the CT images were performed by an independent observer specializing in radiodiagnosis. Functional outcome measures included preoperative and postoperative Lysholm and International Knee Documentation Committee (IKDC) scores (subjective) documented by an independent investigator who was not involved with the surgical procedure, at the end of 1 year. Results: The minimum followup was 1 year. All patients achieved good clinical and functional outcomes postoperatively with no reported complications. Tunnel position evaluations with 3D-CT revealed the average tibial tunnel distance to be 15.5 mm (standard deviation [SD] =2.52) from the anterior border of the tibial plateau and the average femoral tunnel distance to be 14.33 mm (SD = 2.6) from the inferior margin of the medial surface of lateral femoral condyle and 13.72 mm (SD = 2.8) from the posterior margin of the medial surface of lateral femoral condyle. The average tunnel diameters were found to be 7.9 mm (SD = 0.72) for the tibial tunnels and 8.6 mm (SD = 1.07) for the femoral tunnels. Statistically

  4. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    2007-07-01

    Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

  5. Reproductive biology in Anophelinae mosquitoes (Diptera, Culicidae): Fine structure of the female accessory gland.

    Science.gov (United States)

    Laghezza Masci, Valentina; Di Luca, Marco; Gambellini, Gabriella; Taddei, Anna Rita; Belardinelli, Maria Cristina; Guerra, Laura; Mazzini, Massimo; Fausto, Anna Maria

    2015-07-01

    The morphology and ultrastructure of female accessory reproductive glands of Anopheles maculipennis s.s., Anopheles labranchiae and Anopheles stephensi were investigated by light and electron microscopy. The reproductive system in these species is characterized by two ovaries, two lateral oviducts, a single spermatheca and a single accessory gland. The gland is globular and has a thin duct which empties into the vagina, near the opening of the spermathecal duct. Significant growth of the accessory reproductive gland is observed immediately after blood meal, but not at subsequent digestion steps. At ultrastructural level, the gland consists of functional glandular units belonging to type 3 ectodermal glands. The secretory cells are elongated and goblet shaped, with most of their cytoplasm and large nucleus in the basal part, close to the basement lamella. Finely fibrous electron-transparent material occupies the secretory cavity that is in contact with the end of a short efferent duct (ductule) emerging from the gland duct. The present study is the first detailed description of female accessory gland ultrastructure in Anophelinae and provides insights into the gland's functional role in the reproductive biology of these insects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. A LysM and SH3-domain containing region of the Listeria monocytogenes p60 protein stimulates accessory cells to promote activation of host NK cells.

    Science.gov (United States)

    Schmidt, Rebecca L; Filak, Holly C; Lemon, Jack D; Potter, Terry A; Lenz, Laurel L

    2011-11-01

    Listeria monocytogenes (Lm) infection induces rapid and robust activation of host natural killer (NK) cells. Here we define a region of the abundantly secreted Lm endopeptidase, p60, that potently but indirectly stimulates NK cell activation in vitro and in vivo. Lm expression of p60 resulted in increased IFNγ production by naïve NK cells co-cultured with treated dendritic cells (DCs). Moreover, recombinant p60 protein stimulated activation of naive NK cells when co-cultured with TLR or cytokine primed DCs in the absence of Lm. Intact p60 protein weakly digested bacterial peptidoglycan (PGN), but neither muropeptide recognition by RIP2 nor the catalytic activity of p60 was required for NK cell activation. Rather, the immune stimulating activity mapped to an N-terminal region of p60, termed L1S. Treatment of DCs with a recombinant L1S polypeptide stimulated them to activate naïve NK cells in a cell culture model. Further, L1S treatment activated NK cells in vivo and increased host resistance to infection with Francisella tularensis live vaccine strain (LVS). These studies demonstrate an immune stimulating function for a bacterial LysM domain-containing polypeptide and suggest that recombinant versions of L1S or other p60 derivatives can be used to promote NK cell activation in therapeutic contexts.

  7. A LysM and SH3-domain containing region of the Listeria monocytogenes p60 protein stimulates accessory cells to promote activation of host NK cells.

    Directory of Open Access Journals (Sweden)

    Rebecca L Schmidt

    2011-11-01

    Full Text Available Listeria monocytogenes (Lm infection induces rapid and robust activation of host natural killer (NK cells. Here we define a region of the abundantly secreted Lm endopeptidase, p60, that potently but indirectly stimulates NK cell activation in vitro and in vivo. Lm expression of p60 resulted in increased IFNγ production by naïve NK cells co-cultured with treated dendritic cells (DCs. Moreover, recombinant p60 protein stimulated activation of naive NK cells when co-cultured with TLR or cytokine primed DCs in the absence of Lm. Intact p60 protein weakly digested bacterial peptidoglycan (PGN, but neither muropeptide recognition by RIP2 nor the catalytic activity of p60 was required for NK cell activation. Rather, the immune stimulating activity mapped to an N-terminal region of p60, termed L1S. Treatment of DCs with a recombinant L1S polypeptide stimulated them to activate naïve NK cells in a cell culture model. Further, L1S treatment activated NK cells in vivo and increased host resistance to infection with Francisella tularensis live vaccine strain (LVS. These studies demonstrate an immune stimulating function for a bacterial LysM domain-containing polypeptide and suggest that recombinant versions of L1S or other p60 derivatives can be used to promote NK cell activation in therapeutic contexts.

  8. Isolated spinal accessory neuropathy and intracisternal schwannomas of the spinal accessory nerve

    Directory of Open Access Journals (Sweden)

    Abdullah M. Al-Ajmi

    2015-03-01

    Full Text Available We report a 40-year-old female patient presenting with isolated left spinal accessory neuropathy that developed insidiously over 6 years. She complained of ill-defined deep neck and shoulder pain. On examination, prominent sternocleidomastoid and trapezoid muscle weakness and atrophy, shoulder instability, and lateral scapular winging were observed. MRI identified a small mass of the cisternal portion of the spinal accessory nerve. Its appearance was typical of schwannoma. Surgical treatment was not offered because of the small tumor size, lack of mass effect and the questionable functional recovery in the presence of muscular atrophy.

  9. An inducible packaging cell system for safe, efficient lentiviral vector production in the absence of HIV-1 accessory proteins.

    Science.gov (United States)

    Pacchia, A L; Adelson, M E; Kaul, M; Ron, Y; Dougherty, J P

    2001-03-30

    Lentiviral vectors based on human immunodeficiency virus type 1 (HIV-1) possess the ability to deliver exogenous genes to both dividing and nondividing cells and to subsequently establish a stable provirus in these target cells, which can allow long-term expression of the transferred gene. Herein we describe a stable packaging cell line that is devoid of HIV-1 tat, vif, vpr, vpu, and nef. In order to avoid any risk of cytotoxicity associated with constitutive expression of HIV-1 protease or the VSV-G envelope protein, transcription of the packaging and envelope constructs was tightly controlled by employing the ecdysone-inducible system. Using this cell line, we have been able to consistently generate concentrated pseudotyped vector virus stocks with titers in the range of 10(8) IU/ml, which can efficiently transduce actively dividing and growth-arrested cells in vitro. This novel packaging cell line for lentiviral vectors facilitates the production of high-titer virus stocks in the absence of replication-competent virus and provides us with an important tool for use in future gene transfer studies.

  10. The scolopidial accessory organ in the Jerusalem cricket (Orthoptera: Stenopelmatidae).

    Science.gov (United States)

    Strauß, Johannes

    2017-03-01

    Multiple mechanosensory organs form the subgenual organ complex in orthopteroid insects, located in the proximal tibia. In several Ensifera (Orthoptera), a small chordotonal organ, the so-called accessory organ, is the most posterior part of this sensory complex. In order to document the presence of this accessory organ among the Ensifera, the chordotonal sensilla and their innervation in the posterior tibia of two species of Jerusalem crickets (Stenopelmatidae: Stenopelmatus) is described. The sensory structures were stained by axonal tracing. Scolopidial sensilla occur in the posterior subgenual organ and the accessory organ in all leg pairs. The accessory organ contains 10-17 scolopidial sensilla. Both groups of sensilla are commonly spatially separated. However, in few cases neuronal fibres occurred between both organs. The two sensillum groups are considered as separate organs by the general spatial separation and innervation by different nerve branches. A functional role for mechanoreception is considered: since the accessory organ is located closely under the cuticle, sensilla may be suited to detect vibrations transferred over the leg's surface. This study extends the known taxa with an accessory organ, which occurs in several taxa of Ensifera. Comparative neuroanatomy thus suggests that the accessory organ may be conserved at least in Tettigoniidea. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. AcCNET (Accessory Genome Constellation Network): comparative genomics software for accessory genome analysis using bipartite networks.

    Science.gov (United States)

    Lanza, Val F; Baquero, Fernando; de la Cruz, Fernando; Coque, Teresa M

    2017-01-15

    AcCNET (Accessory genome Constellation Network) is a Perl application that aims to compare accessory genomes of a large number of genomic units, both at qualitative and quantitative levels. Using the proteomes extracted from the analysed genomes, AcCNET creates a bipartite network compatible with standard network analysis platforms. AcCNET allows merging phylogenetic and functional information about the concerned genomes, thus improving the capability of current methods of network analysis. The AcCNET bipartite network opens a new perspective to explore the pangenome of bacterial species, focusing on the accessory genome behind the idiosyncrasy of a particular strain and/or population.

  12. The Rcs stress response and accessory envelope proteins are required for de novo generation of cell shape in Escherichia coli.

    Science.gov (United States)

    Ranjit, Dev K; Young, Kevin D

    2013-06-01

    Interactions with immune responses or exposure to certain antibiotics can remove the peptidoglycan wall of many Gram-negative bacteria. Though the spheroplasts thus created usually lyse, some may survive by resynthesizing their walls and shapes. Normally, bacterial morphology is generated by synthetic complexes directed by FtsZ and MreBCD or their homologues, but whether these classic systems can recreate morphology in the absence of a preexisting template is unknown. To address this question, we treated Escherichia coli with lysozyme to remove the peptidoglycan wall while leaving intact the inner and outer membranes and periplasm. The resulting lysozyme-induced (LI) spheroplasts recovered a rod shape after four to six generations. Recovery proceeded via a series of cell divisions that produced misshapen and branched intermediates before later progeny assumed a normal rod shape. Importantly, mutants defective in mounting the Rcs stress response and those lacking penicillin binding protein 1B (PBP1B) or LpoB could not divide or recover their cell shape but instead enlarged until they lysed. LI spheroplasts from mutants lacking the Lpp lipoprotein or PBP6 produced spherical daughter cells that did not recover a normal rod shape or that did so only after a significant delay. Thus, to regenerate normal morphology de novo, E. coli must supplement the classic FtsZ- and MreBCD-directed cell wall systems with activities that are otherwise dispensable for growth under normal laboratory conditions. The existence of these auxiliary mechanisms implies that they may be required for survival in natural environments, where bacterial walls can be damaged extensively or removed altogether.

  13. Characterization and expression analysis of B Cell receptor accessory molecule CD79 gene in humphead snapper ( Lutjanus sanguineus)

    Science.gov (United States)

    Huang, Yucong; Yan, Xiuying; Cai, Shuanghu; Cai, Jia; Jian, Jichang; Lu, Yishan; Tang, Jufen; Wu, Zaohe

    2016-04-01

    CD79, a key component of the B cell antigen receptor complex, is composed of CD79α(Igα) and CD79β(Igβ) encoded by mb-1 and B29 respectively, and plays an important role in B cell signaling. In this study, we isolated and characterized mb-1 and B29 from humphead snapper ( Lutjanus sanguineus). Their tissue distribution and expression profiles after stimulations in vitro and in vivo were also investigated. The humphead snapper mb-1 and B29 contain open reading frames of 684 bp and 606 bp, encoding 227 amino acids and 201 amino acids, respectively. Both CD79α and CD79β possess signal peptide, extracellular Ig domain, transmembrane region and immunoreceptor tyrosine kinase activation motif (ITAM). Mb-1 is highly expressed in lymphoid organs (thymus, posterior kidney and spleen) and mucosal-associated lymphoid tissues (gill and intestine), while B29 is mainly detected in posterior kidney, spleen, gill and skin. Furthermore, transcription of mb-1 and B29 in head kidney leucocytes was up-regulated following lipopolysaccharide (LPS), pokeweed mitogen (PWM), and polyinosinic-polycytidylic acid (PolyI:C) stimulation, respectively, and their expression level in anterior kidney and spleen was also increased after challenged with formalin-inactived Vibrio harveyi. These results indicated that humphead snapper CD79 molecule might play an important role in immune response to pathogen infection.

  14. Giant Accessory Right-Sided Suprarenal Spleen in Thalassaemia

    Directory of Open Access Journals (Sweden)

    A. Arra

    2013-01-01

    Full Text Available An accessory spleen is defined as ectopic splenic tissue that develops due to failure of fusion of cells during embryonic development as they migrate from the midline to the left upper quadrant. While benign, complications may arise which include trauma, torsion, or infarction of the ectopic tissue. Additionally, patients who have had a splenectomy secondary to treatment for previous pathology such as a haematological malignancy or idiopathic thrombocytopenia purpura may experience persistent symptoms due to the accessory splenic tissue. The presence of an accessory spleen is therefore of significant diagnostic and therapeutic importance. To the best of the authors' knowledge, this case is the second and largest reported case of a giant right suprarenal accessory spleen and highlights the difficulty in differentiation of these masses from malignant adrenal tumours.

  15. Transient and sustained afterdepolarizations in accessory olfactory bulb mitral cells are mediated by distinct mechanisms that are differentially regulated by neuromodulators

    NARCIS (Netherlands)

    G. Shpak (Guy); A. Zylbertal (Asaph); S. Wagner (Shlomo)

    2015-01-01

    textabstractSocial interactions between mammalian conspecifics rely heavily on molecular communication via the main and accessory olfactory systems. These two chemosensory systems show high similarity in the organization of information flow along their early stages: social chemical cues are detected

  16. HIV-1 accessory proteins: Vpu and Vif.

    Science.gov (United States)

    Andrew, Amy; Strebel, Klaus

    2014-01-01

    HIV-1 Vif and Vpu are accessory factors involved in late stages of viral replication. Vif regulates viral infectivity by preventing virion incorporation of APOBEC3G and other members of the family of cytidine deaminases, while Vpu causes degradation of CD4 and promotes virus release by functionally inactivating the host factor BST-2. This chapter described techniques used for the characterization of Vif and Vpu and their functional interaction with host factors. Many of the techniques are, however, applicable to the functional analysis of other viral proteins.

  17. Automobile accessories: Assessment and improvement

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, M. [Univ. of Nevada, Las Vegas, NV (United States)

    1995-11-01

    With mandates and regulatory policies to meet both the California Air Resources Board (CARB) and the Partnership for a New Generation of Vehicles (PNGV), designing vehicles of the future will become a difficult task. As we look into the use of electric and hybrid vehicles, reduction of the required power demand by influential automobile components is necessary in order to obtain performance and range goals. Among those automobile components are accessories. Accessories have a profound impact on the range and mileage of future vehicles with limited amounts of energy or without power generating capabilities such as conventional vehicles. Careful assessment of major power consuming accessories helps us focus on those that need improvement and contributes to attainment of mileage and range goals for electric and hybrid vehicles.

  18. 21 CFR 878.4950 - Manual operating table and accessories and manual operating chair and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual operating table and accessories and manual... Surgical Devices § 878.4950 Manual operating table and accessories and manual operating chair and accessories. (a) Identification. A manual operating table and accessories and a manual operating chair...

  19. Bilateral accessory cleidohyoid in a human cadaver

    Directory of Open Access Journals (Sweden)

    Stark ME

    2009-10-01

    Full Text Available During routine anatomical dissection of the infrahyoid region, a muscle was found bilaterally originating from the sternal end of clavicle and inserting into the hyoid bone. The muscle coursed parallel and lateral to the sternohyoid muscle. The muscle was found in the presence of an intact omohyoid, thus being classified as an accessory cleidohyoid (cleidohyoideus accessorius muscle. While other authors have reported the presence of a unilateral cleidohyoideus accessorius muscle, to our knowledge this is the first case of a bilateral cleidohyoideus accessorius muscle in the medical literature. Anatomical variations of the infrahyoid muscles may have functional, diagnostic, surgical and pathological implications.

  20. 21 CFR 890.3910 - Wheelchair accessory.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wheelchair accessory. 890.3910 Section 890.3910...) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3910 Wheelchair accessory. (a) Identification. A wheelchair accessory is a device intended for medical purposes that is...

  1. Mfa4, an Accessory Protein of Mfa1 Fimbriae, Modulates Fimbrial Biogenesis, Cell Auto-Aggregation, and Biofilm Formation in Porphyromonas gingivalis

    OpenAIRE

    2015-01-01

    Porphyromonas gingivalis, a gram-negative obligate anaerobic bacterium, is considered to be a key pathogen in periodontal disease. The bacterium expresses Mfa1 fimbriae, which are composed of polymers of Mfa1. The minor accessory components Mfa3, Mfa4, and Mfa5 are incorporated into these fimbriae. In this study, we characterized Mfa4 using genetically modified strains. Deficiency in the mfa4 gene decreased, but did not eliminate, expression of Mfa1 fimbriae. However, Mfa3 and Mfa5 were not i...

  2. Accessory signals in T-T cell interactions between antigen- and alloantigen-specific, human memory T cells generated in vitro

    DEFF Research Database (Denmark)

    Odum, N; Ryder, L P; Georgsen, J;

    1990-01-01

    The potential of activated HLA class II-positive T cells as antigen-/alloantigen-presenting cells remains controversial. In our model system we use in vitro-primed, HLA class II-specific T cells of the memory T-cell phenotype, CD4+, CD29+ (4B4+), and CD45RO+ (UCHL-1). We have previously shown...... that alloactivated, HLA class II-positive T cells (Ta) are unable to stimulate proliferative responses in naive and primed allospecific T cells when 'back-stimulation' is avoided. The explanation of this feature of Ta is unknown, but it is due neither to suppression nor to insufficient HLA class II expression...

  3. 电生理法对豚鼠副嗅球功能分区的显示%Functional subdivisions of the guinea pig accessory olfactory bulb revealed by electrophysiology

    Institute of Scientific and Technical Information of China (English)

    余青松; 须贝外喜夫

    2001-01-01

    目的:探讨豚鼠副嗅球(AOB)是否存在多个功能分区。方法:在豚鼠副嗅球矢状位切片上,将双钨电极插入副嗅球前部或后部的犁鼻神经纤维层(VNL),以单个方波刺激传入神经纤维,用玻璃微电极记录AOB前部或后部外橄状层(EPL)细胞外场电位。结果:电刺激VNL,可在EPL记录到典型的衰减性场电位,且后EPL记录到的场电位的持续时间较前部分明显延长。刺激前VNL仅在前EPL记录到场电位,而刺激后VNL只在后EPL记录到场电位。结论:豚鼠副嗅球可分为前后两个亚区,两区存在解剖学上的差异,说明在犁鼻系统中至少存在两个不同的传入-传出通路。%Objective:To elucidate possible functional subdivisions in the guinea pig accessory olfactory bulb.Method:The guinea pig accessory olfactory bulbs were cut in sagittal slice.Bipolar tungsten electrodes were inserted into anterior or posterior vomeronasal nerve layers and single square-pulses were delivered through the eletrodes to activate afferent fibres.Glass microelectrodes were used to record extracellular field potentials of anterior or posterior external plexiform layers.Result:A single shook of the VNL provoked a characteristic damped oscillatory field potential and the oscillation in the pAOB was more distinct in wave form and longer in duration than those in the aAOB.The stimulation of anterior VNL elicited field potentials exelusively in the anterior region of EPL,whereas shocks to the posterior VNL provoked oscillatory responses only within the posterior EPL.Conclusion:The accessory olfactory bulb in the guinea-pig is distinctly segregated into the anterior and posterior subdivisions and an anatomical boundary exists in both regions.The results suggested that there are at least two different input-output pathways in vomeronasal systems.

  4. Dynamic expression pattern of kinesin accessory protein in Drosophila

    Indian Academy of Sciences (India)

    Ritu Sarpal; Krishanu Ray

    2002-09-01

    We have identified the Drosophila homologue of the non-motor accessory subunit of kinesin-II motor complex. It is homologous to the SpKAP115 of the sea urchin, KAP3A and KAP3B of the mouse, and SMAP protein in humans. In situ hybridization using a DmKAP specific cRNA probe has revealed a dynamic pattern of expression in the developing nervous system. The staining first appears in a subset of cells in the embryonic central nervous system at stage 13 and continues till the first instar larva stage. At the third instar larva stage the staining gets restricted to a few cells in the optic lobe and in the ventral ganglion region. It has also stained a subset of sensory neurons from late stage 13 and till the first instar larva stage. The DmKAP expression pattern in the nervous system corresponds well with that of Klp64D and Klp68D as reported earlier. In addition, we have found that the DmKAP gene is constitutively expressed in the germline cells and in follicle cells during oogenesis. These cells are also stained using an antibody to KLP68D protein, but mRNA in situ hybridization using KLP64D specific probe has not stained these cells. Together these results proved a basis for further analysis of tissue specific function of DmKAP in future.

  5. Myosin VIIA is a marker for the cone accessory outer segment in zebrafish

    NARCIS (Netherlands)

    Hodel, Corinne; Niklaus, Stephanie; Heidemann, Martina; Klooster, Jan; Kamermans, M.; Biehlmaier, Oliver; Gesemann, Matthias; Neuhauss, Stephan C F

    2014-01-01

    The accessory outer segment, a cytoplasmic structure running alongside the photoreceptor outer segment, has been described in teleost fishes, excluding the model organism zebrafish. So far, the function of the accessory outer segment is unknown. Here, we describe the ultrastructure of the zebrafish

  6. Building iPhone OS Accessories

    CERN Document Server

    Maskrey, Ken

    2010-01-01

    This book provides a serious, in-depth look at Apple's External Accessory Framework and the iPhone Accessories API. You'll learn how to create new, integrated solutions that combine iPhone apps with dedicated hardware. The iPhone OS Accessories API expands the opportunities for innovative iPhone developers, allowing you to control and monitor external devices, whether you've built them yourself or obtained them from a third party. What you'll learn * Develop accessories and apps for the iPhone and iPod touch. * Use Apple's External Accessory Framework to create hardware/software interaction. *

  7. Controlling Cell Function with Geometry

    Science.gov (United States)

    Mrksich, Milan

    2012-02-01

    This presentation will describe the use of patterned substrates to control cell shape with examples that illustrate the ways in which cell shape can regulate cell function. Most cells are adherent and must attach to and spread on a surface in order to survive, proliferate and function. In tissue, this surface is the extracellular matrix (ECM), an insoluble scaffold formed by the assembly of several large proteins---including fibronectin, the laminins and collagens and others---but in the laboratory, the surface is prepared by adsorbing protein to glass slides. To pattern cells, gold-coated slides are patterned with microcontact printing to create geometric features that promote cell attachment and that are surrounded by inert regions. Cells attach to these substrates and spread to adopt the shape defined by the underlying pattern and remain stable in culture for several days. Examples will be described that used a series of shapes to reveal the relationship between the shape of the cell and the structure of its cytoskeleton. These geometric cues were used to control cell polarity and the tension, or contractility, present in the cytoskeleton. These rules were further used to control the shapes of mesenchymal stem cells and in turn to control the differentiation of these cells into specialized cell types. For example, stem cells that were patterned into a ``star'' shape preferentially differentiated into bone cells whereas those that were patterned into a ``flower'' shape preferred a fat cell fate. These influences of shape on differentiation depend on the mechanical properties of the cytoskeleton. These examples, and others, reveal that shape is an important cue that informs cell function and that can be combined with the more common soluble cues to direct and study cell function.

  8. Locally vascularized pelvic accessory spleen.

    Science.gov (United States)

    Iorio, F; Frantellizzi, V; Drudi, Francesco M; Maghella, F; Liberatore, M

    2016-01-01

    Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.

  9. Immune evasion activities of accessory proteins Vpu, Nef and Vif are conserved in acute and chronic HIV-1 infection.

    Science.gov (United States)

    Mlcochova, Petra; Apolonia, Luis; Kluge, Silvia F; Sridharan, Aishwarya; Kirchhoff, Frank; Malim, Michael H; Sauter, Daniel; Gupta, Ravindra K

    2015-08-01

    Heterosexual HIV-1 transmission has been identified as a genetic bottleneck and a single transmitted/founder (T/F) variant with reduced sensitivity to type I interferon initiates productive infection in most cases. We hypothesized that particularly active accessory protein(s) may confer T/F viruses with a selective advantage in establishing HIV infection. Thus, we tested vpu, vif and nef alleles from six T/F and six chronic (CC) viruses in assays for 9 immune evasion activities involving the counteraction of interferon-stimulated genes and modulation of ligands known to activate innate immune cells. All functions were highly conserved with no significant differences between T/F and CC viruses, suggesting that these accessory protein functions are important throughout the course of infection.

  10. ``Backpack'' Functionalized Living Immune Cells

    Science.gov (United States)

    Swiston, Albert; Um, Soong Ho; Irvine, Darrell; Cohen, Robert; Rubner, Michael

    2009-03-01

    We demonstrate that functional polymeric ``backpacks'' built from polyelectrolyte multilayers (PEMs) can be attached to a fraction of the surface area of living, individual lymphocytes. Backpacks containing fluorescent polymers, superparamagnetic nanoparticles, and commercially available quantum dots have been attached to B and T-cells, which may be spatially manipulated using a magnetic field. Since the backpack does not occlude the entire cellular surface from the environment, this technique allows functional synthetic payloads to be attached to a cell that is free to perform its native functions, thereby synergistically utilizing both biological and synthetic functionalities. For instance, we have shown that backpack-modified T-cells are able to migrate on surfaces for several hours following backpack attachment. Possible payloads within the PEM backpack include drugs, vaccine antigens, thermally responsive polymers, nanoparticles, and imaging agents. We will discuss how this approach has broad potential for applications in bioimaging, single-cell functionalization, immune system and tissue engineering, and cell-based therapeutics where cell-environment interactions are critical.

  11. C4副神经移位重建斜方肌功能的实验研究%FUNCTIONAL RECONSTRUCTION OF TRAPEZIUS MUSCLE THROUGH TRANSPOSITIONAL ANASTOMOSIS OF C4 ANTERIOR TRUNK AND ACCESSORY NERVE

    Institute of Scientific and Technical Information of China (English)

    赵文; 孙坚

    2012-01-01

    Objective To investigate the feasibility of transpositional anastomosis of C4 anterior trunk and accessory nerve for functional reconstruction of the trapezius muscle so as to provide theoretical basis of repairing accessory nerve defects. Methods Thirty-six adult male Sprague-Dawley rats (weighing 200-250 g) were randomly divided into the experimental group (n=18) and control group (n=18). The transpositional anastomosis of C4 anterior trunk and accessory nerve was performed in the left sides of experimental group; the accessory nerve was transected in the left sides of control group; and the right sides of both groups were not treated as within-subject controls. The electrophysiological and histological changes of the trapezius muscle were measured. The values of the latencies and amplitudes of compound muscle action potential (CMAP) were recorded in the experimental group at 1,2, and 3 months; the latency delaying rate, amplitude recovery rate, and restoration rate of muscular tension were caculated. The counts of myelinated nerve fibers from distal to the anastomotic site were analyzed. The transverse area of the trapezius muscle was also measured and analyzed in 2 groups. Meanwhile, the muscles and nerves were harvested for transmission electron microscope observation in the experimental group at 1 and 3 months. Results As time passed by, the experimental group showed increased amplitudes of CMAP, shortened latencies of CMAP, and improved muscular tension. At 3 months, the amplitude recovery rates were 63.61% ±9.29% in upper trapezius muscle and 73.13% ±11.85% in lower trapezius muscle; the latency delaying rates were 130.45% ±37.27% and 112.62% ±19.57%, respectively, and the restoration rate of muscular tension were 77.27% ± 13.64% and 82.47% ±22.94%, respectively. The passing rate of myelinated nerve fibers was 82.55% ±5.00%. With the recovery of innervation, the transverse area of the trapezius muscle increased, showing significant differences

  12. Critical role of human T-lymphotropic virus type 1 accessory proteins in viral replication and pathogenesis.

    Science.gov (United States)

    Albrecht, Björn; Lairmore, Michael D

    2002-09-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with a diverse range of lymphoproliferative and neurodegenerative diseases, yet pathogenic mechanisms induced by the virus remain obscure. This complex retrovirus contains typical structural and enzymatic genes but also unique regulatory and accessory genes in four open reading frames (ORFs) of the pX region of the viral genome (pX ORFs I to IV). The regulatory proteins encoded by pX ORFs III and IV, Tax and Rex, respectively, have been extensively characterized. In contrast the contribution of the four accessory proteins p12(I), p27(I), p13(II), and p30(II), encoded by pX ORFs I and II, to viral replication and pathogenesis remained unclear. Proviral clones that are mutated in either pX ORF I or II, while fully competent in cell culture, are severely limited in their replicative capacity in a rabbit model. Emerging evidence indicates that the HTLV-1 accessory proteins are critical for establishment of viral infectivity, enhance T-lymphocyte activation, and potentially alter gene transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical to the viral infectivity in resting primary lymphocytes, suggesting a role for p12(I) in lymphocyte activation. The endoplasmic reticulum and cis-Golgi localizing p12(I), encoded from pX ORF I, activates NFAT, a key T-cell transcription factor, through calcium-mediated signaling pathways and may lower the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast p30(II) localizes to the nucleus and represses viral promoter activity, but may regulate cellular gene expression through p300/CBP or related coactivators of transcription. p13(II) targets mitochondrial proteins, where it alters the organelle morphology and may influence energy metabolism. Collectively, studies of the molecular functions of the HTLV-1 accessory proteins provide insight into strategies used by retroviruses that are associated with lymphoproliferative

  13. The B. subtilis Accessory Helicase PcrA Facilitates DNA Replication through Transcription Units.

    Science.gov (United States)

    Merrikh, Christopher N; Brewer, Bonita J; Merrikh, Houra

    2015-06-01

    In bacteria the concurrence of DNA replication and transcription leads to potentially deleterious encounters between the two machineries, which can occur in either the head-on (lagging strand genes) or co-directional (leading strand genes) orientations. These conflicts lead to replication fork stalling and can destabilize the genome. Both eukaryotic and prokaryotic cells possess resolution factors that reduce the severity of these encounters. Though Escherichia coli accessory helicases have been implicated in the mitigation of head-on conflicts, direct evidence of these proteins mitigating co-directional conflicts is lacking. Furthermore, the endogenous chromosomal regions where these helicases act, and the mechanism of recruitment, have not been identified. We show that the essential Bacillus subtilis accessory helicase PcrA aids replication progression through protein coding genes of both head-on and co-directional orientations, as well as rRNA and tRNA genes. ChIP-Seq experiments show that co-directional conflicts at highly transcribed rRNA, tRNA, and head-on protein coding genes are major targets of PcrA activity on the chromosome. Partial depletion of PcrA renders cells extremely sensitive to head-on conflicts, linking the essential function of PcrA to conflict resolution. Furthermore, ablating PcrA's ATPase/helicase activity simultaneously increases its association with conflict regions, while incapacitating its ability to mitigate conflicts, and leads to cell death. In contrast, disruption of PcrA's C-terminal RNA polymerase interaction domain does not impact its ability to mitigate conflicts between replication and transcription, its association with conflict regions, or cell survival. Altogether, this work establishes PcrA as an essential factor involved in mitigating transcription-replication conflicts and identifies chromosomal regions where it routinely acts. As both conflicts and accessory helicases are found in all domains of life, these results are

  14. The B. subtilis Accessory Helicase PcrA Facilitates DNA Replication through Transcription Units.

    Directory of Open Access Journals (Sweden)

    Christopher N Merrikh

    2015-06-01

    Full Text Available In bacteria the concurrence of DNA replication and transcription leads to potentially deleterious encounters between the two machineries, which can occur in either the head-on (lagging strand genes or co-directional (leading strand genes orientations. These conflicts lead to replication fork stalling and can destabilize the genome. Both eukaryotic and prokaryotic cells possess resolution factors that reduce the severity of these encounters. Though Escherichia coli accessory helicases have been implicated in the mitigation of head-on conflicts, direct evidence of these proteins mitigating co-directional conflicts is lacking. Furthermore, the endogenous chromosomal regions where these helicases act, and the mechanism of recruitment, have not been identified. We show that the essential Bacillus subtilis accessory helicase PcrA aids replication progression through protein coding genes of both head-on and co-directional orientations, as well as rRNA and tRNA genes. ChIP-Seq experiments show that co-directional conflicts at highly transcribed rRNA, tRNA, and head-on protein coding genes are major targets of PcrA activity on the chromosome. Partial depletion of PcrA renders cells extremely sensitive to head-on conflicts, linking the essential function of PcrA to conflict resolution. Furthermore, ablating PcrA's ATPase/helicase activity simultaneously increases its association with conflict regions, while incapacitating its ability to mitigate conflicts, and leads to cell death. In contrast, disruption of PcrA's C-terminal RNA polymerase interaction domain does not impact its ability to mitigate conflicts between replication and transcription, its association with conflict regions, or cell survival. Altogether, this work establishes PcrA as an essential factor involved in mitigating transcription-replication conflicts and identifies chromosomal regions where it routinely acts. As both conflicts and accessory helicases are found in all domains of life

  15. Mechanical accessories for mobile teleoperators

    Energy Technology Data Exchange (ETDEWEB)

    Feldman, M.J.; Herndon, J.N.

    1985-01-01

    The choice of optimum mechanical accessories for mobile teleoperators involves matching the criteria for emergency response with the available technology. This paper presents a general background to teleoperations, a potpourri of the manipulator systems available, and an argument for force reflecting manipulation. The theme presented is that the accomplishment of humanlike endeavors in hostile environments will be most successful when man model capabilities are utilized. The application of recent electronic technology to manipulator development has made new tools available to be applied to emergency response activities. The development activities described are products of the Consolidated Fuel Reprocessing Program at the Oak Ridge National Laboratory. 13 refs., 7 figs.

  16. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana;

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  17. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  18. Evolutionary dynamics of the accessory genome of Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Henk C den Bakker

    Full Text Available Listeria monocytogenes, a foodborne bacterial pathogen, is comprised of four phylogenetic lineages that vary with regard to their serotypes and distribution among sources. In order to characterize lineage-specific genomic diversity within L. monocytogenes, we sequenced the genomes of eight strains from several lineages and serotypes, and characterized the accessory genome, which was hypothesized to contribute to phenotypic differences across lineages. The eight L. monocytogenes genomes sequenced range in size from 2.85-3.14 Mb, encode 2,822-3,187 genes, and include the first publicly available sequenced representatives of serotypes 1/2c, 3a and 4c. Mapping of the distribution of accessory genes revealed two distinct regions of the L. monocytogenes chromosome: an accessory-rich region in the first 65° adjacent to the origin of replication and a more stable region in the remaining 295°. This pattern of genome organization is distinct from that of related bacteria Staphylococcus aureus and Bacillus cereus. The accessory genome of all lineages is enriched for cell surface-related genes and phosphotransferase systems, and transcriptional regulators, highlighting the selective pressures faced by contemporary strains from their hosts, other microbes, and their environment. Phylogenetic analysis of O-antigen genes and gene clusters predicts that serotype 4 was ancestral in L. monocytogenes and serotype 1/2 associated gene clusters were putatively introduced through horizontal gene transfer in the ancestral population of L. monocytogenes lineage I and II.

  19. A case report: accessory right renal artery

    Directory of Open Access Journals (Sweden)

    Patasi B

    2009-10-01

    Full Text Available Anatomical variations in the origin of the arteries in the abdominal area are very common. The arteries that show frequent variations include the celiac trunk, renal and gonadal arteries. During a routine dissection of a male cadaver, one main and one inferior accessory renal artery were found in the abdominal region. We discovered that the inferior accessory renal artery that originated from the right anterolateral aspect of abdominal aorta was running into the lower pole of the right kidney. The origin of the main right renal artery and the inferior accessory right renal artery were 19.8 mm and 53 mm below the superior mesenteric artery, respectively. The inferior accessory right renal artery ran directly into the inferior pole of the right kidney, in the area where the accessory right renal vein was leaving the right kidney. These anatomical variations and anomalies are important to know before any therapeutic or diagnostic procedures are performed in the abdominal area.

  20. The accessory fallopian tube: A rare anomaly

    Directory of Open Access Journals (Sweden)

    Kusum R Gandhi

    2012-01-01

    Full Text Available This paper presents a rare anatomical variation in the form of accessory fallopian tube on right side. The duplication of fallopian tube was observed in a 34-year-old female during routine undergraduate dissection in our department. Fallopian tube is the part of uterus that carries the ovum from the ovary to the uterus. Accessory fallopian tube is the congenital anomaly attached to the ampullary part of main tube. This accessory tube is common site of pyosalpinx, hydrosalpinx, cystic swelling and torsion. The ovum released by the ovary may also be captured by the blind accessory tube leading to infertility or ectopic pregnancy. Hence, all patients of infertility or pelvic inflammatory disease should be screened to rule out the presence of accessory fallopian tube and if encountered should be removed.

  1. Association between exposure to persistent organohalogen pollutants and epididymal and accessory sex gland function: Multicentre study in Inuit and European populations

    DEFF Research Database (Denmark)

    Elzanaty, Saad; Rignell-Hydbom, Anna; Jönsson, Bo A.G.;

    2006-01-01

    of epididymal [neutral-α glucosidase (NAG)], prostatic [prostate specific-antigen (PSA)] and zinc, and seminal vesicle function (fructose) were measured from 135 Swedish fishermen and fertile men from Greenland (n = 163), Warsaw, Poland (n = 167) and Kharkiv, Ukraine (n = 158). Multiple linear regression...

  2. Epifascial accessory palmaris longus muscle.

    Science.gov (United States)

    Tiengo, Cesare; Macchi, Veronica; Stecco, Carla; Bassetto, Franco; De Caro, Raffaele

    2006-09-01

    In hand reconstructive surgery the palmaris longus muscle is one of the most utilized donor site for tendon reconstruction procedures. However, its anatomic position is variable and anatomic variations may be responsible for median nerve compression. We report the case of a 40-year-old, right-handed woman, who presented with numbness and paresthesias in the palm and in the flexor aspect of the first, second, and third fingers of her right hand for the preceding 5 months, coinciding with increase of office work (typing). The clinical examination and radiological investigations (ultrasound and magnetic resonance) revealed a subcutaneous mass (15 mm x 2.3 mm x 6 cm), with a lenticular shape and definite edges at the level of the volar aspect of the distal third of the forearm. The fine-needle aspiration biopsy revealed the presence of striated muscle fibers. During surgery, a muscle belly was found in the epifascial plane. This muscle originated from subcutaneous septa in the middle forearm and inserted on to the superficial palmar aponeurosis with fine short tendon fibers. Exposure of the antebrachial fascia did not reveal any area of weakness or muscle herniation. The palmaris longus tendon, flexor digitorum superficialis tendons, and flexor carpi radialis tendon showed usual topography under the antebrachial fascia. The accessory muscle was excised and histology revealed unremarkable striated muscle fibers, limited by a thin connective sheath. The presence of an accessory palmaris longus (APL) located in the epifascial plane could be ascribed to an unusual migration of myoblasts during the morphogenesis. Although extremely rare, APL is worth bearing in mind as a possible cause of median nerve compression and etiology of a volar mass in the distal forearm.

  3. Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

    Directory of Open Access Journals (Sweden)

    Christiana Smith

    2017-04-01

    Full Text Available ObjectivesHIV-exposed uninfected (HEU infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK cell activity might occur in HEU infants and predispose them to severe infections.DesignCase–control study using cryopreserved peripheral blood mononuclear cells (PBMCs at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001 and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005. At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001 and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047, but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFNγ at birth (0.77 vs. 2.64%, p = 0.008 and at 6 months (4.12 vs. 8.39%, p = 0.001, and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008. Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory

  4. Cell elasticity determines macrophage function.

    Directory of Open Access Journals (Sweden)

    Naimish R Patel

    Full Text Available Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.

  5. Biosynthesis of Active Bacillus subtilis Urease in the Absence of Known Urease Accessory Proteins

    OpenAIRE

    Kim, Jong Kyong; Mulrooney, Scott B.; Hausinger, Robert P.

    2005-01-01

    Bacillus subtilis contains urease structural genes but lacks the accessory genes typically required for GTP-dependent incorporation of nickel. Nevertheless, B. subtilis was shown to possess a functional urease, and the recombinant enzyme conferred low levels of nickel-dependent activity to Escherichia coli. Additional investigations of the system lead to the suggestion that B. subtilis may use unidentified accessory proteins for in vivo urease activation.

  6. Prevention of Tracheal High-Dose Tolerance Induction by Granulocyte-Macrophage Colony Stimulating Factor- Dependent Restoration of Antigen-Presenting Cell Function

    Directory of Open Access Journals (Sweden)

    Kanna Haneda

    2000-01-01

    Full Text Available The intrusion of airborne allergens into airways elicits eosinophilic inflammation, as represented by bronchial asthma. It has been shown that excessive amounts of allergen in murine trachea lead to an unexpected evasion of deleterious eosinophilic inflammation by inducing T cell tolerance. In the present study, the mechanisms of tracheal high-dose tolerance are examined with regard to accessory cell functions and the effects of pro-inflammatory cytokines on tolerance. Antigen-induced tracheal eosinophilia was suppressed on instillation of high doses of antigen into the trachea, while concurrent instillation of granulocyte-macrophage colony stimulating factor (GM-CSF with the antigen restored the diminished responses. The restoration of eosinophilic infiltration by GM-CSF occurred in parallel with an increase in interleukin (IL-4 production by CD4+ T cells from the mediastinal lymph nodes. This was found to reflect the empowerment of antigen-presenting cells by GM-CSF, because the impaired ability of Ia+ cells from the tolerant mice to stimulate IL-4-producing T cells is restored by GM-CSF administration. The prevention of tolerance by up-regulating accessory cell functions is a feature unique to GM-CSF, because another pro-inflammatory cytokine, IL-iβ, failed to empower antigen-presenting cells. Thus, besides the induction of transforming growth factor-β-secreting CD4+ T cells, high-dose tolerance in the trachea includes an impairment of the accessory cell functions that support IL-4 production from T cells, which was reversed by GM-CSF. This report is the first demonstration that GM-CSF breaks the T cell tolerance of IL-4-producing T helper cells.

  7. Tumours of histiocytes and accessory dendritic cells : an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

    NARCIS (Netherlands)

    Pileri, SA; Grogan, TM; Harris, NL; Banks, P; Campo, E; Chan, JKC; Favera, RD; Delsol, G; De Wolf-Peeters, C; Falini, B; Gascoyne, RD; Gaulard, P; Gatter, KC; Isaacson, PG; Jaffe, ES; Kluin, P; Knowles, DM; Mason, DY; Mori, S; Muller-Hermelink, HK; Piris, MA; Ralfkiaer, E; Stein, H; Su, IJ; Warnke, RA; Weiss, LM

    2002-01-01

    Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasm

  8. Perioperative Identification of an Accessory Fissure of the Right Lung

    Directory of Open Access Journals (Sweden)

    Yannick Taverne

    2015-01-01

    Full Text Available Anatomical variations of lungs are common in clinical practice; however, they are sometimes overlooked in routine imaging. Surgical anatomy of the lung is complex and many variations are known to occur. A defective pulmonary development gives rise to variations in lobes and fissures. Morphological presentation is of clinical importance and profound knowledge of the organogenesis and functional anatomy is imperative for the interpretation and evaluation of lung pathophysiology and subsequent surgical intervention. However, appreciating them on radiographs and CT scans is difficult and they are therefore often either not identified or completely misinterpreted. As presented in this case report, an accessory fissure separating the superior segment of the right lower lobe from its native lobe was seen perioperatively and could only retrospectively be defined on X-rays and CT scan. It is imperative to keep in mind that accessory fissures can be missed on imaging studies and thus can make the surgical procedure more challenging.

  9. Manual therapy of the mandibular accessory ligaments for the management of temporomandibular joint disorders.

    Science.gov (United States)

    Cuccia, Antonino Marco; Caradonna, Carola; Caradonna, Domenico

    2011-02-01

    Temporomandibular joint disorders are characterized by chronic or acute musculoskeletal or myofascial pain with dysfunction of the masticatory system. Treatment modalities include occlusal splints, patient education, activity modification, muscle and joint exercises, myofascial therapy, acupuncture, and manipulative therapy. In the physiology of the temporomandibular joint, accessory ligaments limit the movement of the mandible. A thorough knowledge of the anatomy of accessory ligaments is necessary for good clinical management of temporomandibular joint disorders. Although general principles regarding the anatomy of the ligaments are relatively clear, very little substantiated information on the dimension, orientation, and function of the ligaments has been published, to the authors' knowledge. The authors review the literature concerning the accessory ligaments of the temporomandibular joint and describe treatment options, including manual techniques for mobilizing the accessory ligaments.

  10. One nose, one brain: contribution of the main and accessory olfactory system to chemosensation

    Directory of Open Access Journals (Sweden)

    Carla eMucignat

    2012-11-01

    Full Text Available The accessory olfactory system is present in most tetrapods. It is involved in the perception of chemical stimuli, being implicated also in the detection of pheromone. However, it is sensitive also to some common odorant molecules, which have no clear implication in intraspecific chemical communication. The accessory olfactory system may complement the main olfactory system, and may contribute different perceptual features to the construction of a unitary representation, which merges the different chemosensory qualities. Crosstalk between the main and accessory olfactory systems occurs at different levels of central processing, in brain areas where the inputs from the two systems converge. Interestingly, centrifugal projections from more caudal brain areas are deeply involved in modulating both main and accessory sensory processing. A high degree of interaction between the two systems may be conceived, and partial overlapping appears to occur in many functions. Therefore, the central chemosensory projections merge inputs from different organs to obtain a complex chemosensory picture.

  11. The structure and function of fungal cells

    Science.gov (United States)

    Nozawa, Y.

    1984-01-01

    The structure and function of fungal cell walls were studied with particular emphasis on dermatophytes. Extraction, isolation, analysis, and observation of the cell wall structure and function were performed. The structure is described microscopically and chemically.

  12. Intrapancreatic Accessory Spleen: Investigative Dilemmas and Role of EUS-Guided FNA for Diagnostic Confirmation

    Directory of Open Access Journals (Sweden)

    Somashekar G Krishna

    2011-11-01

    Full Text Available Context We submit a case of intrapancreatic accessory spleen. Case report A 33-year-old patient with history of dyspepsia underwent imaging studies suggestive of a neuroendocrine tumor. After referral to our institute, endoscopic ultrasound guided fine needle aspiration (EUS-FNA confirmed diagnosis as intrapancreatic accessory spleen. Discussion An accessory spleen may develop from estranged mesenchymal cells due to fusion failure of the splenic anlage. The prevalence of an accessory spleen is 10-30% with 80% of them present at the splenic hilum and 17% in the pancreatic tail. Intrapancreatic accessory spleen is commonly misdiagnosed as a pancreatic tumor. Since, the differential diagnosis includes pancreatic neuroendocrine tumors, additional investigation with EUS-FNA should be considered when radiological diagnosis is not definitive. Conclusion For diagnosis of intrapancreatic accessory spleen, radiographic imaging is useful, but lacks specificity without tissue diagnosis. Diagnosis can be safely and reliably established with EUS-FNA, leading to a benign prognosis and avoidance of unnecessary surgical intervention.

  13. Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

    Science.gov (United States)

    d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

    2015-04-16

    ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Structure and functions of fungal cell surfaces

    Science.gov (United States)

    Nozawa, Y.

    1984-01-01

    A review with 24 references on the biochemistry, molecular structure, and function of cell surfaces of fungi, especially dermatophytes: the chemistry and structure of the cell wall, the effect of polyene antibiotics on the morphology and function of cytoplasmic membranes, and the chemical structure and function of pigments produced by various fungi are discussed.

  15. The Pseudorabies Virus DNA Polymerase Accessory Subunit UL42 Directs Nuclear Transport of the Holoenzyme.

    Science.gov (United States)

    Wang, Yi-Ping; Du, Wen-Juan; Huang, Li-Ping; Wei, Yan-Wu; Wu, Hong-Li; Feng, Li; Liu, Chang-Ming

    2016-01-01

    Pseudorabies virus (PRV) DNA replication occurs in the nuclei of infected cells and requires the viral DNA polymerase. The PRV DNA polymerase comprises a catalytic subunit, UL30, and an accessory subunit, UL42, that confers processivity to the enzyme. Its nuclear localization is a prerequisite for its enzymatic function in the initiation of viral DNA replication. However, the mechanisms by which the PRV DNA polymerase holoenzyme enters the nucleus have not been determined. In this study, we characterized the nuclear import pathways of the PRV DNA polymerase catalytic and accessory subunits. Immunofluorescence analysis showed that UL42 localizes independently in the nucleus, whereas UL30 alone predominantly localizes in the cytoplasm. Intriguingly, the localization of UL30 was completely shifted to the nucleus when it was coexpressed with UL42, demonstrating that nuclear transport of UL30 occurs in an UL42-dependent manner. Deletion analysis and site-directed mutagenesis of the two proteins showed that UL42 contains a functional and transferable bipartite nuclear localization signal (NLS) at amino acids 354-370 and that K(354), R(355), and K(367) are important for the NLS function, whereas UL30 has no NLS. Coimmunoprecipitation assays verified that UL42 interacts with importins α3 and α4 through its NLS. In vitro nuclear import assays demonstrated that nuclear accumulation of UL42 is a temperature- and energy-dependent process and requires both importins α and β, confirming that UL42 utilizes the importin α/β-mediated pathway for nuclear entry. In an UL42 NLS-null mutant, the UL42/UL30 heterodimer was completely confined to the cytoplasm when UL42 was coexpressed with UL30, indicating that UL30 utilizes the NLS function of UL42 for its translocation into the nucleus. Collectively, these findings suggest that UL42 contains an importin α/β-mediated bipartite NLS that transports the viral DNA polymerase holoenzyme into the nucleus in an in vitro expression

  16. Three functions of cadherins in cell adhesion.

    Science.gov (United States)

    Maître, Jean-Léon; Heisenberg, Carl-Philipp

    2013-07-22

    Cadherins are transmembrane proteins that mediate cell-cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major functions of cadherins in cell-cell contact formation and stability. Two of those functions lead to a decrease in interfacial tension at the forming cell-cell contact, thereby promoting contact expansion--first, by providing adhesion tension that lowers interfacial tension at the cell-cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell-cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.

  17. Heterogeneity assessment of functional T cell avidity

    Science.gov (United States)

    Ioannidou, Kalliopi; Baumgaertner, Petra; Gannon, Philippe O.; Speiser, Michel F.; Allard, Mathilde; Hebeisen, Michael; Rufer, Nathalie; Speiser, Daniel E.

    2017-01-01

    The potency of cellular immune responses strongly depends on T cell avidity to antigen. Yet, functional avidity measurements are rarely performed in patients, mainly due to the technical challenges of characterizing heterogeneous T cells. The mean functional T cell avidity can be determined by the IFN-γ Elispot assay, with titrated amounts of peptide. Using this assay, we developed a method revealing the heterogeneity of functional avidity, represented by the steepness/hillslope of the peptide titration curve, documented by proof of principle experiments and mathematical modeling. Our data show that not only natural polyclonal CD8 T cell populations from cancer patients, but also monoclonal T cells differ strongly in their heterogeneity of functional avidity. Interestingly, clones and polyclonal cells displayed comparable ranges of heterogeneity. We conclude that besides the mean functional avidity, it is feasible and useful to determine its heterogeneity (hillslope) for characterizing T cell responses in basic research and patient investigation. PMID:28287160

  18. [Accessory symptomatology and therapy of Gilles de la Tourette's disease].

    Science.gov (United States)

    Achkova, M; Terziev, D

    1987-01-01

    Eight patients with Gilles de la Tourette's syndrome were examined. They had typical multiple tics and accessory disturbances--impulsive and reactive symptoms. The authors described the classification of accessory symptoms and the therapeutic approaches.

  19. Identification and functional analysis of ligands for natural killer cell activating receptors in colon carcinoma.

    Science.gov (United States)

    Zhang, Zhang; Su, Tao; He, Liang; Wang, Hongtao; Ji, Gang; Liu, Xiaonan; Zhang, Yun; Dong, Guanglong

    2012-01-01

    Natural killer (NK) cells play important roles in the immune defense against tumor cells. The function of NK cells is determined by a balance between activating and inhibitory signals. DNAX accessory molecule-1 (DNAM-1) and NK group 2 member D (NKG2D) are major NK cell activating receptors, which transduce activating signals after binding their ligands CD155, CD112 and major histocompatibility complex class I-related chains A and B (MICA/B). However, the expression and functions of these ligands in colon carcinoma are still elusive. Here, we show the higher expression of CD155, CD112 and MICA/B in colon carcinoma tissues, although no correlations between the ligands expression and patient clinicopathological parameters were found. The subsequent cytotoxicity assay indicated that NK cells effectively kill colon carcinoma cells. Functional blocking of these ligands and/or receptors with antibodies led to significant inhibition of NK cell cytotoxicity. Importantly, expression of DNAM-1 and NKG2D was reduced in NK cells of colon cancer patients, and this reduction could directly suppress the activation of NK cells. Moreover, colon cancer patients have higher serum concentrations of sCD155 and sMICA/B (soluble ligands, secreted or shed from cells) than those in healthy donors (sCD155, 127.82 ± 44.12 vs. 63.67 ± 22.30 ng/ml; sMICA, 331.51 ± 65.23 vs. 246.74 ± 20.76 pg/ml; and sMICB, 349.42 ± 81.69 vs. 52.61 ± 17.56 pg/ml). The up-regulation of these soluble ligands may down-regulate DNAM-1 and NKG2D on NK cells, ultimately leading to the inhibition of NK cytotoxicity. Colon cancer might be a promising target for NK cell-based adoptive immunotherapy.

  20. 21 CFR 878.3925 - Plastic surgery kit and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plastic surgery kit and accessories. 878.3925... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3925 Plastic surgery kit and accessories. (a) Identification. A plastic surgery kit and accessories is a device intended...

  1. 21 CFR 878.4700 - Surgical microscope and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Surgical microscope and accessories. 878.4700 Section 878.4700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microscope and accessories. (a) Identification. A surgical microscope and accessories is an AC-powered device...

  2. PIONEER POLAR STRUCTURES. SPECIFICATIONS FOR JAMESWAY SHELTER ACCESSORIES

    Science.gov (United States)

    Accessories were developed for the Jamesway in order to provide a suitable, light weight, quick-erecting shelter for use as quarters, messing, galley...wall extension kit; special entry kits; an improved electrical distribution system; and special utility accessories. Specifications for the Jamesway shelter accessories are included.

  3. HRCT evaluation of the accessory fissures of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Yildiz, Altan E-mail: ayildiz@mersin.edu.tr; Goelpinar, Fulya; Calikoglu, Mukadder; Duce, Meltem Nass; Oezer, Caner; Apaydin, F. Demir

    2004-03-01

    Introduction: The purpose of this study was to classify the accessory fissures of the lung and to assess their frequency by using high-resolution CT. Methods and patients: HRCT scans of 115 patients were prospectively reviewed. 1 mm thin sections were obtained at 10 mm intervals with a scan time of 1.9 s. The fissure and its relationship to the segmental bronchovascular structures were then evaluated on transverse sections. Results: Forty-four accessory fissures were detected in 35 of 115 patients. The most common accessory fissure was the inferior accessory fissure (12%). The second most common accessory fissure was the left minor fissure (8%). The right superior accessory fissure (5%), the accessory fissure between the medial and lateral segments of the right middle lobe (5%), and the accessory fissure between the superior and inferior segments of the lingula (5%) were seen in equal frequencies. Also, intersegmental accessory fissures, namely the fissure between the anterobasal and laterobasal of both the right (1%) and the left (2%) lower lobes were detected. We found only one subsegmental accessory fissure. Discussion and conclusion: The inferior accessory fissure and the left minor fissure were the most common accessory fissures in our study.

  4. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

  5. 21 CFR 872.4920 - Dental electrosurgical unit and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental electrosurgical unit and accessories. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4920 Dental electrosurgical unit and accessories. (a) Identification. A dental electrosurgical unit and accessories is an AC-powered...

  6. 21 CFR 872.6640 - Dental operative unit and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental operative unit and accessories. 872.6640... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6640 Dental operative unit and accessories. (a) Identification. A dental operative unit and accessories is an AC-powered device that is...

  7. 21 CFR 872.6300 - Rubber dam and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rubber dam and accessories. 872.6300 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6300 Rubber dam and accessories. (a) Identification. A rubber dam and accessories is a device composed of a thin sheet of latex with a hole in...

  8. 21 CFR 878.4160 - Surgical camera and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Surgical camera and accessories. 878.4160 Section... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4160 Surgical camera and accessories. (a) Identification. A surgical camera and accessories is a device intended to be...

  9. Spaceflight alters immune cell function and distribution

    Science.gov (United States)

    Sonnenfeld, Gerald; Mandel, Adrian D.; Konstantinova, Irina V.; Berry, Wallace D.; Taylor, Gerald R.; Lesniak, A. T.; Fuchs, Boris B.; Rakhmilevich, Alexander L.

    1992-01-01

    Experiments are described which were performed onboard Cosmos 2044 to determine spaceflight effects on immunologically important cell function and distribution. Results indicate that bone marrow cells from flown and suspended rats exhibited a decreased response to a granulocyte/monocyte colony-stimulating factor compared with the bone marrow cells from control rats. Bone marrow cells showed an increase in the percentage of cells expressing markers for helper T-cells in the myelogenous population and increased percentages of anti-asialo granulocyte/monocyte-1-bearing interleulin-2 receptor bearing pan T- and helper T-cells in the lymphocytic population.

  10. Metalloproteinases: a Functional Pathway for Myeloid Cells.

    Science.gov (United States)

    Chou, Jonathan; Chan, Matilda F; Werb, Zena

    2016-04-01

    Myeloid cells have diverse roles in regulating immunity, inflammation, and extracellular matrix turnover. To accomplish these tasks, myeloid cells carry an arsenal of metalloproteinases, which include the matrix metalloproteinases and the adamalysins. These enzymes have diverse substrate repertoires, and are thus involved in mediating proteolytic cascades, cell migration, and cell signaling. Dysregulation of metalloproteinases contributes to pathogenic processes, including inflammation, fibrosis, and cancer. Metalloproteinases also have important nonproteolytic functions in controlling cytoskeletal dynamics during macrophage fusion and enhancing transcription to promote antiviral immunity. This review highlights the diverse contributions of metalloproteinases to myeloid cell functions.

  11. Nucleolar function and size in cancer cells.

    OpenAIRE

    Derenzini, M; Trerè, D; Pession, A; Montanaro, L; Sirri, V.; Ochs, R. L.

    1998-01-01

    We have have studied the relationship between nucleolar function and size and cell doubling time in cancer cells. Seven human cancer cell lines characterized by different proliferation rates were used. Nucleolar functional activity was evaluated by measuring RNA polymerase I activity and expression of RNA polymerase I upstream binding factor (UBF), DNA topoisomerase I, and fibrillarin, three proteins involved in synthesis and processing of rRNA. Transcriptional activity of RNA polymerase I wa...

  12. Regulation of satellite cell function in sarcopenia

    Directory of Open Access Journals (Sweden)

    Stephen E Alway

    2014-09-01

    Full Text Available The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell function that is impacted by the environment (niche of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia, and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration. While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function.

  13. Ikaros in B cell development and function

    Institute of Scientific and Technical Information of China (English)

    MacLean; Sellars; Philippe; Kastner; Susan; Chan

    2011-01-01

    The zinc finger transcription factor,Ikaros,is a central regulator of hematopoiesis.It is required for the development of the earliest B cell progenitors and at later stages for VDJ recombination and B cell receptor expression.Mature B cells rely on Ikaros to set the activation threshold for various stimuli,and to choose the correct antibody isotype during class switch recombination.Thus,Ikaros contributes to nearly every level of B cell differentiation and function.

  14. Classical torus conformal block, N=2* twisted superpotential and the accessory parameter of Lame equation

    CERN Document Server

    Piatek, Marcin

    2014-01-01

    In this work the correspondence between the semiclassical limit of the DOZZ quantum Liouville theory on the torus and the Nekrasov-Shatashvili limit of the N=2* (Omega-deformed) U(2) super-Yang-Mills theory is exploited to propose new formulae for the accessory parameter of the Lame equation. It has been found that the Lame accessory parameter is determined by the classical Liouville action on the one-punctured torus or more concretely by the torus classical block evaluated on the saddle point intermediate classical weight. Moreover, as an implication of the aforementioned correspondence it has been obtained that the accessory parameter is related to the sum of all rescaled column lengths of the so-called "critical" Young diagrams extremizing the instanton "free energy". Finally, it has been pointed out that the sum over the "critical" column lengths can be rewritten in terms of a contour integral in which the integrand is built out of certain special functions.

  15. Lateral facial cleft associated with accessory mandible having teeth, absent parotid gland and peripheral facial weakness.

    Science.gov (United States)

    Ozçelik, D; Toplu, G; Türkseven, A; Senses, D A; Yiğit, B

    2014-07-01

    Transverse facial cleft is a very rare malformation. The Tessier no. 7 cleft is a lateral facial cleft which emanates from oral cavity and extends towards the tragus, involving both soft tissue and skeletal components. Here, we present a case having transverse facial cleft, accessory mandible having teeth, absent parotid gland and ipsilateral peripheral facial nerve weakness. After surgical repair of the cleft in 2-month of age, improvement of the facial nerve function was detected in 3-year of age. Resection of the accessory mandible was planned in 5-6 years of age.

  16. A peptide from the male accessory gland in Leptinotarsa decemlineata: Purification, characterization and molecular cloning.

    NARCIS (Netherlands)

    Smid, H.M.; Koopmanschap, A.B.; Kort, de C.A.D.; Schooneveld, H.

    1997-01-01

    Our interest in the male accessory glands (MAGs) of Leptinotarsa decemlineata was raised recently by our finding that certain cells produce a secretory substance that is recognized by one of our monoclonal antibodies (MAC-18), developed for the immunohistochemical demonstration of peptidergic

  17. A peptide from the male accessory gland in Leptinotarsa decemlineata: Purification, characterization and molecular cloning.

    NARCIS (Netherlands)

    Smid, H.M.; Koopmanschap, A.B.; Kort, de C.A.D.; Schooneveld, H.

    1997-01-01

    Our interest in the male accessory glands (MAGs) of Leptinotarsa decemlineata was raised recently by our finding that certain cells produce a secretory substance that is recognized by one of our monoclonal antibodies (MAC-18), developed for the immunohistochemical demonstration of peptidergic neuron

  18. Physiological functions of plant cell coverings.

    Science.gov (United States)

    Hoson, Takayuki

    2002-08-01

    The cell coverings of plants have two important functions in plant life. Plant cell coverings are deeply involved in the regulation of the life cycle of plants: each stage of the life cycle, such as germination, vegetative growth, reproductive growth, and senescence, is strongly influenced by the nature of the cell coverings. Also, the apoplast, which consists of the cell coverings, is the field where plant cells first encounter the outer environment, and so becomes the major site of plant responses to the environment. In the regulation of each stage of the life cycle and the response to each environmental signal, some specific constituents of the cell coverings, such as xyloglucans in dicotyledons and 1,3,1,4-beta-glucans in Gramineae, act as the key component. The physiological functions of plant cell coverings are sustained by the metabolic turnover of these components. The components of the cell coverings are supplied from the symplast, but then they are modified or degraded in the apoplast. Thus, the metabolism of the cell coverings is regulated through the cross-talk between the symplast and the apoplast. The understanding of physiological functions of plant cell coverings will be greatly advanced by the use of genomic approaches. At the same time, we need to introduce nanobiological techniques for clarifying the minute changes in the cell coverings that occur in a small part within each cell.

  19. Generation of functional eyes from pluripotent cells.

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2009-08-01

    Full Text Available Pluripotent cells such as embryonic stem (ES and induced pluripotent stem (iPS cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

  20. Delay estimation for CMOS functional cells

    DEFF Research Database (Denmark)

    Madsen, Jan

    1991-01-01

    Presents a new RC tree network model for delay estimation of CMOS functional cells. The model is able to reflect topological changes within a cell, which is of particular interest when doing performance driven layout synthesis. Further, a set of algorithms to perform worst case analysis on arbitr......Presents a new RC tree network model for delay estimation of CMOS functional cells. The model is able to reflect topological changes within a cell, which is of particular interest when doing performance driven layout synthesis. Further, a set of algorithms to perform worst case analysis...... on arbitrary CMOS functional cells using the proposed delay model, is presented. Both model and algorithms have been implemented as a part of a cell compiler (CELLO) working in an experimental silicon compiler environment....

  1. Accessory spine of the foramen ovale.

    Science.gov (United States)

    Skrzat, J; Walocha, J; Zawiliński, J

    2012-11-01

    The objective of this study was to provide morphometric analysis of an accessory spine that was found within the lumen of the foramen ovale, as well as to find out whether this structure could mechanically irritate the mandibular nerve. A bifid spine was perceived in the macerated skull of an adult individual. It was located in the anterior part of the left foramen ovale. The overall length of the spine was found to be 1.8 mm. The spine had a homogenous structure, and showed high levels of mineralisation. We conclude that the accessory spine did not compress the mandibular nerve, and that the foramen ovale provided enough space for passage of the nerve. In all likelihood, these structures remained in anatomical accordance without causing any neurological symptoms.

  2. The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes.

    Science.gov (United States)

    Dedeurwaerder, Annelike; Desmarets, Lowiese M; Olyslaegers, Dominique A J; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

    2013-03-23

    The ability to productively infect monocytes/macrophages is the most important difference between the low virulent feline enteric coronavirus (FECV) and the lethal feline infectious peritonitis virus (FIPV). In vitro, the replication of FECV in peripheral blood monocytes always drops after 12h post inoculation, while FIPV sustains its replication in the monocytes from 45% of the cats. The accessory proteins of feline coronaviruses have been speculated to play a prominent role in virulence as deletions were found to be associated with attenuated viruses. Still, no functions have been ascribed to them. In order to investigate if the accessory proteins of FIPV are important for sustaining its replication in monocytes, replication kinetics were determined for FIPV 79-1146 and its deletion mutants, lacking either accessory protein open reading frame 3abc (FIPV-Δ3), 7ab (FIPV-Δ7) or both (FIPV-Δ3Δ7). Results showed that the deletion mutants FIPV-Δ7 and FIPV-Δ3Δ7 could not maintain their replication, which was in sharp contrast to wt-FIPV. FIPV-Δ3 could still sustain its replication, but the percentage of infected monocytes was always lower compared to wt-FIPV. In conclusion, this study showed that ORF7 is crucial for FIPV replication in monocytes/macrophages, giving an explanation for its importance in vivo, its role in the development of FIP and its conservation in field strains. The effect of an ORF3 deletion was less pronounced, indicating only a supportive role of ORF3 encoded proteins during the infection of the in vivo target cell by FIPVs.

  3. Membrane elastic properties and cell function.

    Directory of Open Access Journals (Sweden)

    Bruno Pontes

    Full Text Available Recent studies indicate that the cell membrane, interacting with its attached cytoskeleton, is an important regulator of cell function, exerting and responding to forces. We investigate this relationship by looking for connections between cell membrane elastic properties, especially surface tension and bending modulus, and cell function. Those properties are measured by pulling tethers from the cell membrane with optical tweezers. Their values are determined for all major cell types of the central nervous system, as well as for macrophage. Astrocytes and glioblastoma cells, which are considerably more dynamic than neurons, have substantially larger surface tensions. Resting microglia, which continually scan their environment through motility and protrusions, have the highest elastic constants, with values similar to those for resting macrophage. For both microglia and macrophage, we find a sharp softening of bending modulus between their resting and activated forms, which is very advantageous for their acquisition of phagocytic functions upon activation. We also determine the elastic constants of pure cell membrane, with no attached cytoskeleton. For all cell types, the presence of F-actin within tethers, contrary to conventional wisdom, is confirmed. Our findings suggest the existence of a close connection between membrane elastic constants and cell function.

  4. Instruments and accessories for neutron scattering research

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Yoshinobu; Morii, Yukio [eds.] [Advanced Science Research Center (Tokai Site), Japan Atomic Energy Research Institute, Tokai, Ibaraki (Japan)

    2000-04-01

    This report describes neutron scattering instruments and accessories installed by four neutron scattering research groups at the ASRC (Advanced Science Research Center) of the JAERI and the recent topics of neutron scattering research using these instruments. The specifications of nine instruments (HRPD, BIX-I, TAS-1 and PNO in the reactor hall, RESA, BIX-II, TAS-2, LTAS and SANS-J in the guide hall of the JRR-3M) are summarized in this booklet. (author)

  5. Bilateral accessory cleidohyoid in a human cadaver

    OpenAIRE

    Stark ME; Wu B; Bluth BE; Wisco JJ

    2009-01-01

    During routine anatomical dissection of the infrahyoid region, a muscle was found bilaterally originating from the sternal end of clavicle and inserting into the hyoid bone. The muscle coursed parallel and lateral to the sternohyoid muscle. The muscle was found in the presence of an intact omohyoid, thus being classified as an accessory cleidohyoid (cleidohyoideus accessorius) muscle. While other authors have reported the presence of a unilateral cleidohyoideus accessorius muscle, to our know...

  6. REGULATORY T–CELLS: ORIGIN AND FUNCTION

    Directory of Open Access Journals (Sweden)

    I. S. Freidlin

    2005-01-01

    Full Text Available Abstract. Over the past decade a population of so–called “regulatory T cells” (Treg cells has been linked to the prevention of autoimmunity. In this review we discuss the molecular mechanisms of Treg cells development and function including the identification of the unique molecular marker of Treg cells – the transcription factor Foxp3. We discuss also the mechanisms of suppression, which include the direct cell contact through binding of cell surface molecules CTLA–4 on Treg cells to CD80/CD86 molecules of effector T cells and the local secretion of cytokines (IL–10, TGFβ. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. These cells are a good target for designing ways to induce or abrogate immunological tolerance to self and non–self antigens. (Med. Immunol., 2005, vol.7, № 4, pp. 347–354

  7. Shoulder complaints after neck dissection; is the spinal accessory nerve involved?

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; van der Laan, B.F.; Plukker, J.T.; Roodenburg, J.L.

    The purpose of the current study was to investigate the relation between shoulder morbidity (pain and range of motion), and the function of the spinal accessory nerve after neck dissection. Identifying dysfunction of the nerve gives insight in the mechanisms of post-operative shoulder complaints. In

  8. The ulcerative colitis marker protein WAFL interacts with accessory proteins in endocytosis

    Directory of Open Access Journals (Sweden)

    You Fu Pan, Ing-Marie Viklund, Heng Hang Tsai, Sven Pettersson, Ichiro N. Maruyama

    2010-01-01

    Full Text Available Ulcerative colitis (UC is one of the major forms of inflammatory bowel disease with unknown cause. A molecular marker, WAFL, has recently been found to be up-regulated in the inflamed colonic mucosa of UC patients. Towards understanding biological function of WAFL, we analyzed proteins interacting with WAFL in HEK-293 cells by immunoprecipitation and mass spectrometry. Among four proteins found to specifically interact with WAFL, both KIAA0196 and KIAA1033 bind to α-appendage of the adaptor protein complex 2 (AP2, which acts as an interaction hub for accessory proteins in endocytosis mediated by clathrin-coated vesicle (CCV. The specific interaction between WAFL and KIAA0196 was also confirmed in human colorectal carcinoma HCT-116 cells by co-immunoprecipitation with specific antibodies. Meta-analyses of the databases of expressed genes suggest that the three genes are co-expressed in many tissues and cell types, and that their molecular function may be classified in the category of 'membrane traffic protein'. Therefore, these results suggest that WAFL may play an important role in endocytosis and subsequent membrane trafficking by interacting with AP2 through KIAA0196 and KIAA1033.

  9. Mast Cell: A Multi-Functional Master Cell.

    Science.gov (United States)

    Krystel-Whittemore, Melissa; Dileepan, Kottarappat N; Wood, John G

    2015-01-01

    Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On the other hand, mast cells have also been implicated in the pathophysiology of many diseases, including allergy, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, and cardiovascular diseases. This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions.

  10. CD83 modulates B cell function in vitro: increased IL-10 and reduced Ig secretion by CD83Tg B cells.

    Directory of Open Access Journals (Sweden)

    Birte Kretschmer

    Full Text Available The murine transmembrane glycoprotein CD83 is an important regulator for both thymic T cell maturation and peripheral T cell responses. Recently, we reported that CD83 also has a function on B cells: Ubiquitous transgenic (Tg expression of CD83 interfered with the immunoglobulin (Ig response to infectious agents and to T cell dependent as well as T cell independent model antigen immunization. Here we compare the function of CD83Tg B cells that overexpress CD83 and CD83 mutant (CD83mu B cells that display a drastically reduced CD83 expression. Correlating with CD83 expression, the basic as well as the lipopolysaccharide (LPS induced expression of the activation markers CD86 and MHC-II are significantly increased in CD83Tg B cells and reciprocally decreased in CD83mu B cells. Wild-type B cells rapidly upregulate CD83 within three hours post BCR or TLR engagement by de novo protein synthesis. The forced premature overexpression of CD83 on the CD83Tg B cells results in reduced calcium signaling, reduced Ig secretion and a reciprocally increased IL-10 production upon in vitro activation. This altered phenotype is mediated by CD83 expressed on the B cells themselves, since it is observed in the absence of accessory cells. In line with this finding, purified CD83mu B cells displayed a reduced IL-10 production and slightly increased Ig secretion upon LPS stimulation in vitro. Taken together, our data strongly suggest that CD83 is expressed by B cells upon activation and contributes to the regulation of B cell function.

  11. Connexins and beta-cell functions

    NARCIS (Netherlands)

    Cigliola, V.; Chellakudam, V.; Arabi Eter, W.; Meda, P.

    2013-01-01

    Proper functioning of pancreatic islets requires that numerous beta-cells are properly coordinated. With evolution, many mechanisms have converged, which now allow individual beta-cells to sense the state of activity of their neighbors as well as the changes taking place in the extracellular medium,

  12. Functions of proteoglycans at the cell surface

    DEFF Research Database (Denmark)

    Höök, M; Woods, A; Johansson, S;

    1986-01-01

    Proteoglycans (primarily heparan sulphate proteoglycans) are found at the surface of most adherent eukaryotic cells. Earlier studies suggest that these molecules can be associated with the cell surface principally by two different mechanisms. Proteoglycans may occur as membrane......-intercalated glycoproteins, where the core protein of the proteoglycan is anchored in the lipid interior of the plasma membrane, or they may be bound via the polysaccharide components of the molecule to specific anchoring proteins present at the cell surface. A number of functions have been proposed for cell surface......-associated proteoglycans, including: regulation of cell-substrate adhesion; regulation of cell proliferation; participation in the binding and uptake of extracellular components; and participation in the regulation of extracellular matrix formation. Evidence is discussed suggesting that the cell-associated heparan...

  13. Study on reduction of accessory horsepower requirements. Program summary report

    Energy Technology Data Exchange (ETDEWEB)

    Lefferts, C.H.

    1977-06-15

    The objective of this program was to define, evaluate and develop automotive accessory systems to minimize engine power consumption and significantly improve fuel economy. All tasks have been completed and the program objectives have been accomplished. Information is presented on each phase of the program which involved: conceptual design to recommended component improvement and accessory drive systems; performance and sizing analyses; detail design and specifications; fabrication, and performance testing; evaluation of integrated hybrid drive, improved accessories; and an advanced air conditioning concept.

  14. Structure and diversity in mammalian accessory olfactory bulb.

    Science.gov (United States)

    Meisami, E; Bhatnagar, K P

    1998-12-15

    The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory-like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well-developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species-specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of

  15. Adipose tissue: cell heterogeneity and functional diversity.

    Science.gov (United States)

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  16. Induction of Functional Hair-Cell-Like Cells from Mouse Cochlear Multipotent Cells

    Directory of Open Access Journals (Sweden)

    Quanwen Liu

    2016-01-01

    Full Text Available In this paper, we developed a two-step-induction method of generating functional hair cells from inner ear multipotent cells. Multipotent cells from the inner ear were established and induced initially into progenitor cells committed to the inner ear cell lineage on the poly-L-lysine substratum. Subsequently, the committed progenitor cells were cultured on the mitotically inactivated chicken utricle stromal cells and induced into hair-cell-like cells containing characteristic stereocilia bundles. The hair-cell-like cells exhibited rapid permeation of FM1-43FX. The whole-cell patch-clamp technique was used to measure the membrane currents of cells differentiated for 7 days on chicken utricle stromal cells and analyze the biophysical properties of the hair-cell-like cells by recording membrane properties of cells. The results suggested that the hair-cell-like cells derived from inner ear multipotent cells were functional following differentiation in an enabling environment.

  17. Accessory sperm: a biomonitor of boar sperm fertilization capacity.

    Science.gov (United States)

    Ardón, Florencia; Evert, Meike; Beyerbach, Martin; Weitze, Karl-Fritz; Waberski, Dagmar

    2005-04-15

    The number of accessory sperm found in the zona pellucida of porcine embryos was correlated to their individual quality and to the embryo quality range found within a single sow. Our goal was to determine whether accessory sperm counts provide semen evaluation with additional, useful information. Accessory sperm count was highest when only normal embryos were found in a given sow and diminished if oocytes or degenerated embryos were present (P<0.01). Within a given sow, normal embryos had higher (P<0.05) accessory sperm counts than degenerated embryos, although not when oocytes were also present. Fertilization capacity of sperm is optimal when only normal embryos are found in a given sow; this capacity is indicated by high accessory sperm counts. A decrease in fertilization capacity is reflected in diminishing accessory sperm counts. The boar had a significant effect (P<0.01) on accessory sperm count, but not on the percentage of normal embryos; this suggests that accessory sperm may be more sensitive indicators of the fertilization capacity of sperm than the percentage of normal embryos. We conclude that accessory sperm count can be used for the detection of compensable defects in sperm and is a valid parameter for assessing sperm fertilization capacity.

  18. Decontamination of minimally invasive surgical endoscopes and accessories.

    Science.gov (United States)

    Ayliffe, G

    2000-08-01

    lung function testing by spirometry. (7) Possible alternative disinfectants to glutaraldehyde include peracetic acid (0.2-0.35%), chlorine dioxide (700-1100 ppm) and superoxidized water. These are very effective, killing vegetative bacteria, including mycobacteria, and viruses in 5 min and bacterial spores in 10 min. An endorsement of compatibility with endoscopes, accessories and processing equipment is required from both the solution/device manufacturer and the endoscope manufacturer. Other important considerations are stability, cost and safety from the user and environmental standpoints. (8) Cleaning and disinfection or sterilization should be undertaken by trained staff in a dedicated area, e.g., SSD or TSSU. A suitable training programme is described. (9) If endoscopes are processed by immersion in disinfectants, harmful residues must be removed by thorough rinsing. Sterile or bacteria free water is essential for rinsing all invasive endoscopes and accessories to prevent recontamination. (10) If an automated washer disinfector is used it must be effective, non-damaging, reliable, easy to use and its performance regularly monitored. (11) If used, washer disinfectors and other processing equipment should be disinfected on a regular basis, i.e., between patients or at the start of each session. This will prevent biofilm formation and recontamination of instruments during rinsing. Disinfection should include the water treatment system, if present. (12) To comply with the Medical Devices Directive, manufacturers are obliged to provide full details on how to decontaminate the reusable devices they supply. This should include details of compatibility with heat, pressure, moisture, processing chemicals and ultrasonics. (13) The Infection Control Team should always be involved in the formulation and implementation of decontamination policies. Wherever possible, the national good practice guidelines produced by the Medical Devices Agency and/or professional societies shoul

  19. ACCESSORY RENAL ARTERYAND ITS CLINICAL IMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Rachna Magotra

    2013-12-01

    Full Text Available Origin of the Testicular Artery variations were found during routine dissection of abdomen of the middle aged cadaver in the Dept of Anatomy, Govt. Medical College Jammu. On the left side there were two renal arteries, One of them was the main Renal artery which was originating from the anterolateral aspect of abdominal aorta and running to the hilum of the kidney in front of the renal vein The other was the Accessory Renal artery which was originating from anterolateral aspect of aorta 5mm above origin of main renal artery and going to the upper pole of the kidney. The origin of accessory renal artery and main renal artery was 4.2 and 9.2mm below the level of origin of superior mesentric artery. The left testicular artery was originating from the accessory renal artery and crossing the renal artery and the renal vein anteriorly before following its usual course in the posterior abdominal wall. Only one renal artery was seen on the right side arising from the anterolateral aspect of aorta. The right testicular artery originated 52mm below the origin of right renal artery and followed its normal course This anomaly is explained by embryological development of both kidneys and gonads from intermediate mesoderm of mesonephric crest. Further the vasculature of kidneys and gonads is derived from lateral mesonephric branches of dorsal aorta .Even though the condition presents as a silent renal anomaly (Undiagnosed throughout life and revealed only on autopsy the surgical implications are noteworthy, which too have been highlighted in this report.

  20. Non‑Azygos Accessory Fissure in Right Upper Lobe Associated with Superior and Inferior Accessory Fissures in Right Lower Lobe

    Directory of Open Access Journals (Sweden)

    Thomas Jose Eluvathingal Muttikkal

    2012-01-01

    Full Text Available Accessory fissures in the lungs are common congenital variations, usually detected as incidental findings in radiographs or CT scan. Accessory fissures can act as an anatomic barrier to the spread of inflammatory or neoplastic disease, as well as due to the variant anatomy, mimic lesions. It is important to recognize the presence of accessory fissures, as they affect surgical planning of pulmonary lobectomy and segmentectomy. Accessory fissure in the right upper lobe other than due to the anomalous course of azygos vein is very rare. We report a case of non-azygos accessory fissure, between the apical and the anterior segments of right upper lobe, along with superior and inferior accessory fissures in the right lower lobe.

  1. Cell functional enviromics: Unravelling the function of environmental factors

    Directory of Open Access Journals (Sweden)

    Alves Paula M

    2011-06-01

    Full Text Available Abstract Background While functional genomics, focused on gene functions and gene-gene interactions, has become a very active field of research in molecular biology, equivalent methodologies embracing the environment and gene-environment interactions are relatively less developed. Understanding the function of environmental factors is, however, of paramount importance given the complex, interactive nature of environmental and genetic factors across multiple time scales. Results Here, we propose a systems biology framework, where the function of environmental factors is set at its core. We set forth a "reverse" functional analysis approach, whereby cellular functions are reconstructed from the analysis of dynamic envirome data. Our results show these data sets can be mapped to less than 20 core cellular functions in a typical mammalian cell culture, while explaining over 90% of flux data variance. A functional enviromics map can be created, which provides a template for manipulating the environmental factors to induce a desired phenotypic trait. Conclusion Our results support the feasibility of cellular function reconstruction guided by the analysis and manipulation of dynamic envirome data.

  2. Mast cell function: a new vision of an old cell.

    Science.gov (United States)

    da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia; Oliver, Constance

    2014-10-01

    Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.

  3. Impaired Leydig cell function in infertile men

    DEFF Research Database (Denmark)

    Andersson, A-M; Jørgensen, N; Frydelund-Larsen, L

    2004-01-01

    To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E(2)/T ratio...... of the fertile levels.Thus, the group of infertile men showed significant signs of impaired Leydig cell function in parallel to their impaired spermatogenesis. The association of decreased spermatogenesis and impaired Leydig cell function might reflect a disturbed paracrine communication between the seminiferous......, and calculated free T index (cFT) were compared between the two groups.A shift toward lower serum T levels, cFT, and T/LH ratio and higher serum LH, E(2), and E(2)/T levels was observed in the group of infertile men. On average, the infertile men had 18, 26, and 34% lower serum T, cFT, and T/LH levels...

  4. A multi-scale mathematical modeling framework to investigate anti-viral therapeutic opportunities in targeting HIV-1 accessory proteins.

    Science.gov (United States)

    Suryawanshi, Gajendra W; Hoffmann, Alexander

    2015-12-07

    Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus. Two HIV-1 proteins counter these cellular restriction factors: Vpu, which reduces surface BST2, and Vif, which degrades cellular A3G. The contest between these host and viral proteins influences whether HIV-1 infection is established and progresses towards AIDS. In this work, we present an age-structured multi-scale viral dynamics model of in vivo HIV-1 infection. We integrated the intracellular dynamics of anti-viral activity of the host factors and their neutralization by HIV-1 accessory proteins into the virus/cell population dynamics model. We calculate the basic reproductive ratio (Ro) as a function of host-viral protein interaction coefficients, and numerically simulated the multi-scale model to understand HIV-1 dynamics following host factor-induced perturbations. We found that reducing the influence of Vpu triggers a drop in Ro, revealing the impact of BST2 on viral infection control. Reducing Vif׳s effect reveals the restrictive efficacy of A3G in blocking RT and in inducing lethal hypermutations, however, neither of these factors alone is sufficient to fully restrict HIV-1 infection. Interestingly, our model further predicts that BST2 and A3G function synergistically, and delineates their relative contribution in limiting HIV-1 infection and disease progression. We provide a robust modeling framework for devising novel combination therapies that target

  5. Stem cell function during plant vascular development.

    Science.gov (United States)

    Miyashima, Shunsuke; Sebastian, Jose; Lee, Ji-Young; Helariutta, Yka

    2013-01-23

    The plant vascular system, composed of xylem and phloem, evolved to connect plant organs and transport various molecules between them. During the post-embryonic growth, these conductive tissues constitutively form from cells that are derived from a lateral meristem, commonly called procambium and cambium. Procambium/cambium contains pluripotent stem cells and provides a microenvironment that maintains the stem cell population. Because vascular plants continue to form new tissues and organs throughout their life cycle, the formation and maintenance of stem cells are crucial for plant growth and development. In this decade, there has been considerable progress in understanding the molecular control of the organization and maintenance of stem cells in vascular plants. Noticeable advance has been made in elucidating the role of transcription factors and major plant hormones in stem cell maintenance and vascular tissue differentiation. These studies suggest the shared regulatory mechanisms among various types of plant stem cell pools. In this review, we focus on two aspects of stem cell function in the vascular cambium, cell proliferation and cell differentiation.

  6. Phosphorylation regulates human T-cell leukemia virus type 1 Rex function

    Directory of Open Access Journals (Sweden)

    Ward Michael

    2009-11-01

    Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 is a pathogenic complex deltaretrovirus, which is the causative agent of adult T-cell leukemia/lymphoma (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to the structural and enzymatic viral gene products, HTLV-1 encodes the positive regulatory proteins Tax and Rex along with viral accessory proteins. Tax and Rex proteins orchestrate the timely expression of viral genes important in viral replication and cellular transformation. Rex is a nucleolar-localizing shuttling protein that acts post-transcriptionally by binding and facilitating the export of the unspliced and incompletely spliced viral mRNAs from the nucleus to the cytoplasm. HTLV-1 Rex (Rex-1 is a phosphoprotein and general protein kinase inhibition correlates with reduced function. Therefore, it has been proposed that Rex-1 function may be regulated through site-specific phosphorylation. Results We conducted a phosphoryl mapping of Rex-1 over-expressed in transfected 293 T cells using a combination of affinity purification and liquid chromatography tandem mass spectrometry. We achieved 100% physical coverage of the Rex-1 polypeptide and identified five novel phosphorylation sites at Thr-22, Ser-36, Thr-37, Ser-97, and Ser-106. We also confirmed evidence of two previously identified residues, Ser-70 and Thr-174, but found no evidence of phosphorylation at Ser-177. The functional significance of these phosphorylation events was evaluated using a Rex reporter assay and site-directed mutational analysis. Our results indicate that phosphorylation at Ser-97 and Thr-174 is critical for Rex-1 function. Conclusion We have mapped completely the site-specific phosphorylation of Rex-1 identifying a total of seven residues; Thr-22, Ser-36, Thr-37, Ser-70, Ser-97, Ser-106, and Thr-174. Overall, this work is the first to completely map the phosphorylation sites in Rex-1 and provides important insight into

  7. Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection.

    Directory of Open Access Journals (Sweden)

    Jennifer Martinez

    2010-03-01

    Full Text Available Natural killer (NK cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s underlying NK cell activation and function in response to poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV, the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR 2-myeloid differentiating factor 88 (MyD88 pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs, was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K-extracellular signal-regulated kinase (ERK pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections.

  8. Reviewing prescription spending and accessory usage.

    Science.gov (United States)

    Oxenham, Julie

    This article aims to explore the role of the stoma nurse specialist in the community and how recent initiatives within the NHS have impacted on the roles in stoma care to react to the rising prescription costs in the specialty. The article will explore how the stoma care nurse conducted her prescription reviews within her own clinical commissioning group (CCG). The findings of the reviews will be highlighted by a small case history and a mini audit that reveals that some stoma patients may be using their stoma care accessories inappropriately, which may contribute to the rise in stoma prescription spending. To prevent the incorrect use of stoma appliances it may necessitate an annual review of ostomates (individuals who have a stoma), as the author's reviews revealed that inappropriate usage was particularly commonplace when a patient may have not been reviewed by a stoma care specialist for some considerable amount of time. Initial education of the ostomate and ongoing education of how stoma products work is essential to prevent the misuse of stoma appliances, particularly accessories, as the reviews revealed that often patients were not always aware of how their products worked in practice.

  9. [An accessory muscle and additional variants of the forearm].

    Science.gov (United States)

    Arnold, G; Zech, M

    1977-01-01

    A report is given on an accessory muscle of the forearm. The muscle originates from the medial epicondyle and the fascia of the forearm and inserts into the pisiform bone and retinaculum. The accessory muscle has a great similarity with the flexor carpi ulnaris muscle.

  10. 21 CFR 884.1175 - Endometrial suction curette and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial suction curette and accessories. 884... Diagnostic Devices § 884.1175 Endometrial suction curette and accessories. (a) Identification. An endometrial suction curette is a device used to remove material from the uterus and from the mucosal lining of the...

  11. High association between accessory soleus muscle and achilles tendonopathy

    Energy Technology Data Exchange (ETDEWEB)

    Luck, Michael D.; Gordon, Andrew G.; Blebea, Judy S.; Dalinka, Murray K. [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

    2008-12-15

    This study investigated the association between accessory soleus muscle and abnormalities of the Achilles tendon. The authors reviewed 15 consecutive cases with a diagnosis of accessory soleus muscle from a computerized database of ankle magnetic resonance (MR) examinations reported between January 1998 and January 2007. On review, two cases were eliminated because of an incorrect initial diagnosis: One patient had a low lying soleus attachment to the Achilles tendon, while the other had a prominent flexor hallucis longus tendon partially obliterating Kager's fat. The remaining 13 cases with accessory soleus muscles were evaluated for Achilles tendon abnormalities. There were 13 cases of accessory soleus muscles in 11 patients; two patients had bilateral accessory soleus muscles (the only study patients with bilateral MR examinations in our sample). There were five male and six female patients ranging from 15 to 81 years of age (mean 48). There were nine cases (69.2%) in which Achilles tendonopathy was associated with accessory soleus muscle, including tendonopathy of each Achilles tendon in the two patients with bilateral accessory muscles. In our small patient population, there was a high association between accessory soleus muscle and Achilles tendonopathy. (orig.)

  12. 21 CFR 876.5630 - Peritoneal dialysis system and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Peritoneal dialysis system and accessories. 876... Peritoneal dialysis system and accessories. (a) Identification. (1) A peritoneal dialysis system and... peritoneal dialysis, a source of dialysate, and, in some cases, a water purification mechanism. After...

  13. 21 CFR 884.5350 - Contraceptive diaphragm and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive diaphragm and accessories. 884.5350 Section 884.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Devices § 884.5350 Contraceptive diaphragm and accessories. (a) Identification. A contraceptive...

  14. 46 CFR 98.25-40 - Valves, fittings, and accessories.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Valves, fittings, and accessories. 98.25-40 Section 98... Anhydrous Ammonia in Bulk § 98.25-40 Valves, fittings, and accessories. (a) All valves, flanges, fittings... Engineering) of this chapter. Valves shall be fitted with noncorrosive material suitable for ammonia...

  15. Brugada syndrome in a patient with accessory pathway.

    Science.gov (United States)

    Bodegas, A I; Arana, J I; Vitoria, Y; Arriandiaga, J R; Barrenetxea, J I

    2002-01-01

    Brugada syndrome in a patient with Wolff-Parkinson-White syndrome. We report a 32-year-old man with orthodromic atrioventricular (AV) reciprocating tachycardia using a right posterior accessory pathway. However, his ECG showed ST segment elevation in leads V1 to V3. After successful radiofrequency ablation of his accessory pathway a cardioverter defibrillator was implanted.

  16. 21 CFR 884.2740 - Perinatal monitoring system and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Perinatal monitoring system and accessories. 884.2740 Section 884.2740 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Monitoring Devices § 884.2740 Perinatal monitoring system and accessories. (a) Identification. A...

  17. Eicosanoids, β-cell function, and diabetes.

    Science.gov (United States)

    Luo, Pengcheng; Wang, Mong-Heng

    2011-08-01

    Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes into eicosanoids, which are involved in diverse diseases, including type 1 and type 2 diabetes. During the last 30 years, evidence has been accumulated that suggests important functions for eicosanoids in the control of pancreatic β-cell function and destruction. AA metabolites of the COX pathway, especially prostaglandin E(2) (PGE(2)), appear to be significant factors to β-cell dysfunction and destruction, participating in the pathogenesis of diabetes and its complications. Several elegant studies have contributed to the sorting out of the importance of 12-LOX eicosanoids in cytokine-mediated inflammation in pancreatic β cells. The role of CYP eicosanoids in diabetes is yet to be explored. A recent publication has demonstrated that stabilizing the levels of epoxyeicosatrienoic acids (EETs), CYP eicosanoids, by inhibiting or deleting soluble epoxide hydrolase (sEH) improves β-cell function and reduces β-cell apoptosis in diabetes. In this review we summarize recent findings implicating these eicosanoid pathways in diabetes and its complications. We also discuss the development of animal models with targeted gene deletion and specific enzymatic inhibitors in each pathway to identify potential targets for the treatment of diabetes and its complications.

  18. Stem Cells in Functional Bladder Engineering

    Science.gov (United States)

    Smolar, Jakub; Salemi, Souzan; Horst, Maya; Sulser, Tullio; Eberli, Daniel

    2016-01-01

    Conditions impairing bladder function in children and adults, such as myelomeningocele, posterior urethral valves, bladder exstrophy or spinal cord injury, often need urinary diversion or augmentation cystoplasty as when untreated they may cause severe bladder dysfunction and kidney failure. Currently, the gold standard therapy of end-stage bladder disease refractory to conservative management is enterocystoplasty, a surgical enlargement of the bladder with intestinal tissue. Despite providing functional improvement, enterocystoplasty is associated with significant long-term complications, such as recurrent urinary tract infections, metabolic abnormalities, stone formation, and malignancies. Therefore, there is a strong clinical need for alternative therapies for these reconstructive procedures, of which stem cell-based tissue engineering (TE) is considered to be the most promising future strategy. This review is focused on the recent progress in bladder stem cell research and therapy and the challenges that remain for the development of a functional bladder wall.

  19. Algal Accessory Pigment Detection Using AVIRIS Image-Derived Spectral Radiance Data

    Science.gov (United States)

    Richardson, Laurie L.; Ambrosia, Vincent G.

    1996-01-01

    Visual and derivative analyses of AVIRIS spectral data can be used to detect algal accessory pigments in aquatic communities. This capability extends the use of remote sensing for the study of aquatic ecosystems by allowing detection of taxonomically significant pigment signatures which yield information about the type of algae present. Such information allows remote sensing-based assessment of aquatic ecosystem health, as in the detection of nuisance blooms of cyanobacteria or toxic blooms of dinoflagellates. Remote sensing of aquatic systems has traditionally focused on quantification of chlorophyll a, a photoreactive (and light-harvesting) pigment which is common to all algae as well as cyanobacteria (bluegreen algae). Due to the ubiquitousness of this pigment within algae, chl a is routinely measured to estimate algal biomass both during ground-truthing and using various airborne or satellite based sensors, including AVIRIS. Within the remote sensing and aquatic sciences communities, ongoing research has been performed to detect algal accessory pigments for assessment of algal population composition. This research is based on the fact that many algal accessory pigments are taxonomically significant, and all are spectrally unique. Aquatic scientists have been refining pigment analysis techniques, primarily high performance liquid chromatography, or HPLC, to detect specific pigments as a time-saving alternative to individual algal cell identifications and counts. Remote sensing scientists are investigating the use of pigment signatures to construct pigment libraries analogous to mineral spectral libraries used in geological remote sensing applications. The accessory pigment approach has been used successfully in remote sensing using data from the Thematic Mapper, low-altitude, multiple channel scanners, field spectroradiometers and the AVIRIS hyperspectral scanner. Due to spectral and spatial resolution capabilities, AVIRIS is the sensor of choice for such

  20. Function of laccases in cell wall biosynthesis

    DEFF Research Database (Denmark)

    Larsen, Anders; Holm, Preben Bach; Andersen, Jeppe Reitan

    2011-01-01

    substrate specificities and expression patterns. As part of the strategic research centre Bio4Bio, the present project deals with laccase functions in relation to cell wall formation in grasses based on a study of the model species Brachypodium distachyon. Thirty-one isozymes have been retrieved from......Laccases are multicopper oxidases capable of polymerizing monolignols. Histochemical assays have shown temporal and spatial correlation with secondary cell wall formation in both herbs and woody perennials. However, in plants laccases constitutes a relatively large group of isoenzymes with unique...... hybridization. Specific isozymes that show high correlation with the process of secondary cell wall formation will be further studied in a reverse genetic study in which candidates will be knocked out using RNA interference. Phenotypes of knock-out mutants are to be described in relation to cell wall...

  1. Optimizing cell arrays for accurate functional genomics

    Directory of Open Access Journals (Sweden)

    Fengler Sven

    2012-07-01

    Full Text Available Abstract Background Cellular responses emerge from a complex network of dynamic biochemical reactions. In order to investigate them is necessary to develop methods that allow perturbing a high number of gene products in a flexible and fast way. Cell arrays (CA enable such experiments on microscope slides via reverse transfection of cellular colonies growing on spotted genetic material. In contrast to multi-well plates, CA are susceptible to contamination among neighboring spots hindering accurate quantification in cell-based screening projects. Here we have developed a quality control protocol for quantifying and minimizing contamination in CA. Results We imaged checkered CA that express two distinct fluorescent proteins and segmented images into single cells to quantify the transfection efficiency and interspot contamination. Compared with standard procedures, we measured a 3-fold reduction of contaminants when arrays containing HeLa cells were washed shortly after cell seeding. We proved that nucleic acid uptake during cell seeding rather than migration among neighboring spots was the major source of contamination. Arrays of MCF7 cells developed without the washing step showed 7-fold lower percentage of contaminant cells, demonstrating that contamination is dependent on specific cell properties. Conclusions Previously published methodological works have focused on achieving high transfection rate in densely packed CA. Here, we focused in an equally important parameter: The interspot contamination. The presented quality control is essential for estimating the rate of contamination, a major source of false positives and negatives in current microscopy based functional genomics screenings. We have demonstrated that a washing step after seeding enhances CA quality for HeLA but is not necessary for MCF7. The described method provides a way to find optimal seeding protocols for cell lines intended to be used for the first time in CA.

  2. Impaired mastication reduced newly generated neurons at the accessory olfactory bulb and pheromonal responses in mice.

    Science.gov (United States)

    Utsugi, Chizuru; Miyazono, Sadaharu; Osada, Kazumi; Matsuda, Mitsuyoshi; Kashiwayanagi, Makoto

    2014-12-01

    A large number of neurons are generated at the subventricular zone (SVZ) even during adulthood. In a previous study, we have shown that a reduced mastication impairs both neurogenesis in the SVZ and olfactory functions. Pheromonal signals, which are received by the vomeronasal organ, provide information about reproductive and social states. Vomeronasal sensory neurons project to the accessory olfactory bulb (AOB) located on the dorso-caudal surface of the main olfactory bulb. Newly generated neurons at the SVZ migrate to the AOB and differentiate into granule cells and periglomerular cells. This study aimed to explore the effects of changes in mastication on newly generated neurons and pheromonal responses. Bromodeoxyuridine-immunoreactive (BrdU-ir; a marker of DNA synthesis) and Fos-ir (a marker of neurons excited) structures in sagittal sections of the AOB after exposure to urinary odours were compared between the mice fed soft and hard diets. The density of BrdU-ir cells in the AOB in the soft-diet-fed mice after 1 month was essentially similar to that of the hard-diet-fed mice, while that was lower in the soft-diet-fed mice for 3 or 6 months than in the hard-diet-fed mice. The density of Fos-ir cells in the soft-diet-fed mice after 2 months was essentially similar to that in the hard-diet-fed mice, while that was lower in the soft-diet-fed mice for 4 months than in the hard-diet-fed mice. The present results suggest that impaired mastication reduces newly generated neurons at the AOB, which in turn impairs olfactory function at the AOB. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Physician accessories: Doctor, what you carry is every patient′s worry?

    Directory of Open Access Journals (Sweden)

    Pandey Anita

    2010-10-01

    Full Text Available Background: Nosocomial infections are on the rise worldwide and many a times they are carried by the health care personnel. Accessories used by physicians and healthcare personnel can be a potential source of nosocomial infection. Materials and Methods: We designed a survey with the aim to investigate the prevalence of microbial flora of accessories such as pens, stethoscopes, cell phones and white coat used by the physicians working in a tertiary care hospital. Observations: It was observed that 66% of the pens, 55% of the stethoscopes, 47.61% of the cell phones and 28.46% of the white coats used by the doctors were colonized with various microorganisms. Staphylococcus spp. was the predominant isolate followed by Escherichia coli. Methicillin resistance in Staphylococcus aureus was also found, which was a matter of concern. Conclusions: Awareness of appropriate hand hygiene is important in order to prevent potential transmission to patients.

  4. Cell cycle phase regulates glucocorticoid receptor function.

    Directory of Open Access Journals (Sweden)

    Laura Matthews

    Full Text Available The glucocorticoid receptor (GR is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. In contrast to many other nuclear receptors, GR is thought to be exclusively cytoplasmic in quiescent cells, and only translocate to the nucleus on ligand binding. We now demonstrate significant nuclear GR in the absence of ligand, which requires nuclear localisation signal 1 (NLS1. Live cell imaging reveals dramatic GR import into the nucleus through interphase and rapid exclusion of the GR from the nucleus at the onset of mitosis, which persists into early G(1. This suggests that the heterogeneity in GR distribution is reflective of cell cycle phase. The impact of cell cycle-driven GR trafficking on a panel of glucocorticoid actions was profiled. In G2/M-enriched cells there was marked prolongation of glucocorticoid-induced ERK activation. This was accompanied by DNA template-specific, ligand-independent GR transactivation. Using chimeric and domain-deleted receptors we demonstrate that this transactivation effect is mediated by the AF1 transactivation domain. AF-1 harbours multiple phosphorylation sites, which are consensus sequences for kinases including CDKs, whose activity changes during the cell cycle. In G2/M there was clear ligand independent induction of GR phosphorylation on residues 203 and 211, both of which are phosphorylated after ligand activation. Ligand-independent transactivation required induction of phospho-S211GR but not S203GR, thereby directly linking cell cycle driven GR modification with altered GR function. Cell cycle phase therefore regulates GR localisation and post-translational modification which selectively impacts GR activity. This suggests that cell cycle phase is an important determinant in the cellular response to Gc, and that mitotic index contributes to tissue Gc sensitivity.

  5. Controlling Functional Group Architecture in Artificial Cells

    Science.gov (United States)

    2015-07-02

    further enable enzyme encapsulation to improve the efficiency of light-driven hydrogen fuel production. 5. Changes in key personnel, if applicable : -None ...Controlling Functional Group Architecture in Artificial Cells 5a. CONTRACT NUMBER W9132T-14-2-0002 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...cycloadditions to modify reactive groups within the phospholipid membrane structure and how the nature of the reactive elements, the copper catalyst

  6. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

    Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

  7. Successful treatment of accessory breast cancer with endocrine therapy().

    Science.gov (United States)

    Wang, Chun-Xi; Guo, Shu-Li; Han, Li-Na

    Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient with an accessory breast cancer reported in the Chinese Hospital Knowledge Database and PubMed literature from 1975 to 2015.

  8. Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

    Science.gov (United States)

    Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

    2011-08-01

    Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

  9. Transcriptional activation of melanocortin 2 receptor accessory protein by PPARγ in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam Soo; Kim, Yoon-Jin [Department of Biology, Research Institute for Basic Science, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Cho, Si Young [R and D Center, Amore Pacific Corporation, Yongin-si, Gyeonggi-do 446-729 (Korea, Republic of); Lee, Tae Ryong, E-mail: trlee@amorepacific.com [R and D Center, Amore Pacific Corporation, Yongin-si, Gyeonggi-do 446-729 (Korea, Republic of); Kim, Sang Hoon, E-mail: shkim@khu.ac.kr [Department of Biology, Research Institute for Basic Science, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2013-09-27

    Highlights: •MRAP enhanced HSL expression. •ACTH-mediated MRAP reduced glycerol release. •PPARγ induced MRAP expression. •PPARγ bound to the MRAP promoter. -- Abstract: Adrenocorticotropic hormone (ACTH) in rodents decreases lipid accumulation and body weight. Melanocortin receptor 2 (MC2R) and MC2R accessory protein (MRAP) are specific receptors for ACTH in adipocytes. Peroxisome proliferator-activated receptor γ (PPARγ) plays a role in the transcriptional regulation of metabolic pathways such as adipogenesis and β-oxidation of fatty acids. In this study we investigated the transcriptional regulation of MRAP expression during differentiation of 3T3-L1 cells. Stimulation with ACTH affected lipolysis in murine mature adipocytes via MRAP. Putative peroxisome proliferator response element (PPRE) was identified in the MRAP promoter region. In chromatin immunoprecipitation and reporter assays, we observed binding of PPARγ to the MRAP promoter. The mutagenesis experiments showed that the −1209/−1198 region of the MRAP promoter could function as a PPRE site. These results suggest that PPARγ is required for transcriptional activation of the MRAP gene during adipogenesis, which contributes to understanding of the molecular mechanism of lipolysis in adipocytes.

  10. Design of a marine sediment trap and accessories

    Digital Repository Service at National Institute of Oceanography (India)

    Janakiraman, G.; Fernando, V.; Venkatesan, R.; Rajaraman, V.S.

    The marine sediment trap and the mooring accessories were developed indigenously and were used successfully for the collection of settling sediments in the Arabian Sea The experience gained in using sediment trap and further improvements...

  11. 21 CFR 872.6010 - Abrasive device and accessories.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... disk, guard for an abrasive disk, abrasive point, polishing agent strip, and polishing wheel....

  12. ISO and EIGA standards for cryogenic vessels and accessories

    CERN Document Server

    CERN. Geneva

    2016-01-01

    The EIGA/WG 6’s scope is cryogenic vessels and accessories, including their design, material compatibility, operational requirements and periodical inspection. The specific responsibilities include monitoring international standardization (ISO, CEN) and regulations (UN, TPED, PED...

  13. Creep Function of a Single Living Cell

    Science.gov (United States)

    Desprat, Nicolas; Richert, Alain; Simeon, Jacqueline; Asnacios, Atef

    2005-01-01

    We used a novel uniaxial stretching rheometer to measure the creep function J(t) of an isolated living cell. We show, for the first time at the scale of the whole cell, that J(t) behaves as a power-law J(t) = Atα. For N = 43 mice myoblasts (C2-7), we find α = 0.24 ± 0.01 and A = (2.4 ± 0.3) 10−3 Pa−1 s−α. Using Laplace Transforms, we compare A and α to the parameters G0 and β of the complex modulus G*(ω) = G0ωβ measured by other authors using magnetic twisting cytometry and atomic force microscopy. Excellent agreement between A and G0 on the one hand, and between α and β on the other hand, indicated that the power-law is an intrinsic feature of cell mechanics and not the signature of a particular technique. Moreover, the agreement between measurements at very different size scales, going from a few tens of nanometers to the scale of the whole cell, suggests that self-similarity could be a central feature of cell mechanical structure. Finally, we show that the power-law behavior could explain previous results first interpreted as instantaneous elasticity. Thus, we think that the living cell must definitely be thought of as a material with a large and continuous distribution of relaxation time constants which cannot be described by models with a finite number of springs and dash-pots. PMID:15596508

  14. A New Integrated Onboard Charger and Accessory Power Converter for Plug-in Electric Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Su, Gui-Jia [ORNL; Tang, Lixin [ORNL

    2014-01-01

    In this paper, a new approach is presented for integrating the function of onboard battery charging into the traction drive system and accessory dc-dc converter of a plug-in electric vehicle (PEV). The idea is to utilize the segmented traction drive system of a PEV as the frond converter of the charging circuit and the transformer and high voltage converter of the 14 V accessory dc-dc converter to form a galvanically isolated onboard charger. Moreover, a control method is presented for suppressing the battery current ripple component of twice the grid frequency with the reduced dc bus capacitor in the segmented inverter. The resultant integrated charger has lower cost, weight, and volume than a standalone charger due to a substantially reduced component count. The proposed integrated charger topology was verified by modeling and experimental results on a 5.8 kW charger prototype.

  15. Accessory gland as a site for prothoracicotropic hormone controlled ecdysone synthesis in adult male insects

    DEFF Research Database (Denmark)

    Hentze, Julie Lilith; Møller, Morten Erik; Jørgensen, Anne

    2013-01-01

    Insect steroid hormones (ecdysteroids) are important for female reproduction in many insect species and are required for the initiation and coordination of vital developmental processes. Ecdysteroids are also important for adult male physiology and behavior, but their exact function and site...... of synthesis remains unclear, although previous studies suggest that the reproductive system may be their source. We have examined expression profiles of the ecdysteroidogenic Halloween genes, during development and in adults of the flour beetle Tribolium castaneum. Genes required for the biosynthesis...... melanogaster and the gene for its receptor Torso seems to be expressed specifically in the accessory glands of males. The composite results suggest strongly that the accessory glands of adult male insects are the main source of E, but not 20E. The finding of a possible male-specific source of E raises...

  16. Main and accessory olfactory bulbs and their projections in the brain anticipate feeding in food-entrained rats.

    Science.gov (United States)

    Caba, Mario; Pabello, Marcela; Moreno, Maria Luisa; Meza, Enrique

    2014-10-01

    The olfactory bulb (OB) has a circadian clock independent of the suprachiasmatic nucleus, but very little is known about the functional significance of its oscillations. The OB plays a major role in food intake as it contributes to the evaluation of the hedonic properties of food, it is necessary for a normal pattern of locomotor behavior and their ablation disrupts feeding patterns. Previously we demonstrated that OB of rabbit pups can be entrained by periodic nursing but it was not clear whether food was the entraining signal. Here we hypothesized that OB can be entrained by a food pulse during the day in adult rats under a restricted feeding schedule. Then we expect that OB will have a high activation before food presentation when animals show food anticipatory activity (FAA). To this aim we determined by immunohistochemistry the expression of FOS protein, as an indicator of neural activation, in the mitral and granular cell layers of the main and accessory OB. Additionally we also explored two of the OB brain targets, the piriform cortex (PC) and bed nuclei of the accessory olfactory tract (BAOT), in three groups: ad libitum (ALF), restricted feeding (RF), and fasted rats after restricted feeding (RF-F). In ALF group FOS levels in both main and accessory OB were low during the day and high during the night at the normal onset of the increase of activity, in agreement with previous reports. On the contrary in RF and RF-F groups FOS was high at the time of FAA, just before food presentation, when animals are in a state of high arousal and during food consumption but was low during the night. In their brain targets, we observed a similar pattern as OB in all groups with the only difference being that FOS levels remained high during the night in RF-F group. We conclude that the OB is entrained by food restriction by showing high activation at the time of food presentation, which persists during fasting and impose a similar FOS pattern to the two brain targets

  17. Review of accessory tragus with highlights of its associated syndromes.

    Science.gov (United States)

    Bahrani, Bahar; Khachemoune, Amor

    2014-12-01

    Accessory tragus is a developmental defect involving malformation of part of the external ear. It is a moderately rare congenital condition reported in 1858 by Birkett for the first time. Histological features of accessory tragus include a thin layer of stratum corneum with a rugated epidermis, presence of eccrine glands, and irregular spatial positioning of vellus hair follicles accompanied by sebaceous glands. Accessory tragus is commonly a limited deformity; however, it can be a sign of associated congenital syndromes. It has been shown to be associated with Goldenhar syndrome, Townes-Brocks syndrome, Treacher-Collins syndrome, VACTERL syndrome, and Wolf-Hirschhron syndrome. Surgical excision, the most common form of management of accessory tragus lesions, typically leads to a positive outcome. An extensive search was performed using pubmed.gov, Embase, MedLine, and Googlescholar.com using key words: accessory tragus, congenital malformations of ear, first branchial arch, and embryology. In this paper, we review the clinical and histological presentation, associated syndromes, management, and outcome of accessory tragus.

  18. Origins of Protein Functions in Cells

    Science.gov (United States)

    Seelig, Burchard; Pohorille, Andrzej

    2011-01-01

    In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis and in vitro evolution of very large libraries of random amino acid sequences. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions yet, important clues have been uncovered. In one example (Keefe and Szostak, 2001), novel ATP binding proteins were identified that appear to be unrelated in both sequence and structure to any known ATP binding proteins. One of these proteins was subsequently redesigned computationally to bind GTP through introducing several mutations that introduce targeted structural changes to the protein, improve its binding to guanine and prevent water from accessing the active center. This study facilitates further investigations of individual evolutionary steps that lead to a change of function in primordial proteins. In a second study (Seelig and Szostak, 2007), novel enzymes were generated that can join two pieces of RNA in a reaction for which no natural enzymes are known

  19. Restoration of shoulder abduction by transfer of the spinal accessory nerve to suprascapular nerve through dorsal approach: a clinical study

    Institute of Scientific and Technical Information of China (English)

    GUAN Shi-bing; HOU Chun-lin; CHEN De-song; GU Yu-dong

    2006-01-01

    Background In recent years, transfer of the spinal accessory nerve to suprascapular nerve has become a routine procedure for restoration of shoulder abduction. However, the operation via the traditional supraclavicular anterior approach often leads to partial denervation of the trapezius muscle. The purpose of the study was to introduce transfer of the spinal accessory nerve through dorsal approach, using distal branch of the spinal accessory nerve, to repair the suprascapular nerve for restoration of shoulder abduction, and to observe its therapeutic effect.Methods From January to October 2003, a total of 11 patients with a brachial plexus injury and an intact or nearly intact spinal accessory nerve were treated by transferring the spinal accessory nerve to the suprascapular nerve through dorsal approach. The patients were followed up for 18 to 26 months [mean (23.5 ±5.2) months] to evaluate their shoulder abduction and function of the trapezius muscle. The outcomes were compared with those of 26 patients treated with traditional anterior approach. And the data were analyzed by Student's t test using SPSS 10.5.Results In the 11 patients, the spinal accessory nerves were transferred to the suprascapular nerve through the dorsal approach successfully. Intact function of the upper trapezius was achieved in all of them. In the patients,the location of the two nerves was relatively stable at the level of superior margin of the scapula, the mean distance between them was (4.2±1.4) cm, both the nerves could be easily dissected and end-to-end anastomosed without any tension. During the follow-up, the first electrophysiological sign of recovery of the infraspinatus appeared at (6.8±2.7) months and the first sign of restoration of the shoulder abduction at (7.6±2.9) months after the operation, which were earlier than that after the traditional operation [(8.7±2.4) months and (9.9±2.8)months, respectively; P<0.05]. The postoperative shoulder abduction was 62.8°± 12

  20. The need to accessorize: Molecular roles of HTLV-1 p30 and HTLV-2 p28 accessory proteins in the viral life cycle

    Directory of Open Access Journals (Sweden)

    Rajaneesh eAnupam

    2013-09-01

    Full Text Available Extensive studies of HTLV-1 and HTLV-2 over the last three decades have provided detailed knowledge on viral transformation, host-viral interactions and pathogenesis. HTLV-1 is the etiological agent of adult T cell leukemia (ATL and multiple neurodegenerative and inflammatory diseases while HTLV-2 disease association remains elusive, with few infected individuals displaying neurodegenerative diseases similar to HTLV-1. The HTLV group of oncoretroviruses has a genome that encodes structural and enzymatic proteins Gag, Pro and Env, regulatory proteins Tax and Rex, and several accessory proteins from the pX region. Of these proteins, HTLV-1 p30 and HTLV-2 p28 are encoded by the open reading frame (ORF II of the pX region. Like most other accessory proteins, p30 and p28 are dispensable for in vitro viral replication and transformation but are required for efficient viral replication and persistence in vivo. Both p30 and p28 regulate viral gene expression at the post-transcriptional level whereas p30 can also function at the transcriptional level. Recently, several reports have implicated p30 and p28 in multiple cellular processes, which provide novel insight into HTLV spread and survival and ultimately pathogenesis. In this review we summarize and compare what is known about p30 and p28, highlighting their roles in viral replication and viral pathogenesis.

  1. ACCESSORY FISSURE OF RIGHT LUNG: A REPORT OF TWO CASES

    Directory of Open Access Journals (Sweden)

    Sarita Behera

    2014-06-01

    Full Text Available Right lung is divided into upper (superior, middle and lower (Inferior lobes by an oblique and a horizontal fissure.Oblique fissure passes spirally from posterior border to inferior border deep into the lung separating the lower lobe from upper and middle lobes. A short horizontal fissure passes horizontally forwards from the oblique fissure at midaxillary line to meet the anterior border at 4th costochondral junction. This separates the upper lobe from the middle lobe. During routine dissection in 2010-11 undergraduate batch, we came across two cases of right lungs where an accessory fissure was extending horizontally backwards from the oblique fissure at mid axillary line towards the vertebral part of medial surface. In the 1st case, this accessory fissure was not meeting the normal horizontal fissure where as in the 2nd case it was meeting. This accessory fissure separates the lower lobe into a superior and an inferior segment. Knowledge of different types of accessory fissures is important because it may mislead the radiological findings, may act as a barrier to spread of infection creating a sharply marginated pneumonia which can wrongly be interpretated as atelectasis or consolidation. Identification of completeness of fissure is important prior to lobectomy, because individuals with incomplete fissures are more prone to develop postoperative air leak. Considering the clinical importance of such anomalies, anatomical knowledge and prior awareness of accessory fissures in the lungs may be important for clinicians and radiologists.

  2. Accessory costs of seed production and the evolution of angiosperms.

    Science.gov (United States)

    Lord, Janice M; Westoby, Mark

    2012-01-01

    Accessory costs of reproduction frequently equal or exceed direct investment in offspring, and can limit the evolution of small offspring sizes. Early angiosperms had minimum seed sizes, an order of magnitude smaller than their contemporaries. It has been proposed that changes to reproductive features at the base of the angiosperm clade reduced accessory costs thus removing the fitness disadvantage of small seeds. We measured accessory costs of reproduction in 25 extant gymnosperms and angiosperms, to test whether angiosperms can produce small seeds more economically than gymnosperms. Total accessory costs scaled isometrically to seed mass for angiosperms but less than isometrically for gymnosperms, so that smaller seeds were proportionally more expensive for gymnosperms to produce. In particular, costs of abortions and packaging structures were significantly higher in gymnosperms. Also, the relationship between seed:ovule ratio and seed size was negative in angiosperms but positive in gymnosperms. We argue that the carpel was a key evolutionary innovation reducing accessory costs in angiosperms by allowing sporophytic control of pre- and postzygotic mate selection and timing of resource allocation. The resulting reduction in costs of aborting unfertilized ovules or genetically inferior embryos would have lowered total reproductive costs enabling early angiosperms to evolve small seed sizes and short generation times. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution.

  3. Accessory bones of the feet: Radiological analysis of frequency

    Directory of Open Access Journals (Sweden)

    Vasiljević Vladica

    2010-01-01

    Full Text Available Background/Aim. Accessory bones are most commonly found on the feet and they represent an anatomic variant. They occur when there is a failure in the formation of a unique bone from separated centre of ossification. The aim of this study was to establish their frequency and medical significance. Methods. Anteroposterior and lateral foot radiography was performed in 270 patients aged of 20-80 years with a history of trauma (180 and rheumatology disease (90. The presence and distribution of accessory bones was analysed in relation to the total number of patients and their gender. The results are expressed in numeric values and in terms of percentage. Results. Accessory bones were identified in 62 (22.96% patients: 29 (10.74% of them were found in female patients and 33 (12.22% in males. The most common accessory bones were as follows: os tibiale externum 50%, os peroneum 29.03%, ostrigonum 11.29%, os vaselianum 9.68%. Conclusion. Accessory bones found in 23% of patients with trauma and some of rheumatological diseases. Their significance is demonstrated in the differential diagnosis among degenerative diseases, avulsion fractures, muscle and tendon trauma and other types of injuries which can cause painful affection of the foot, as well as in forensic practice.

  4. Metabolic regulation of regulatory T cell development and function

    Directory of Open Access Journals (Sweden)

    David John Coe

    2014-11-01

    Full Text Available It is now well established that the effector T cell (Teff response is regulated by a series of metabolic switches. Quiescent T cells predominantly require ATP-generating processes, whereas proliferating Teff require high metabolic flux through growth-promoting pathways, such as glycolysis. Pathways that control metabolism and immune cell function are intimately linked, and changes in cell metabolism at both the cell and system levels have been shown to enhance or suppress specific T cell effector functions. Furthermore, functionally distinct T cell subsets have been shown to require distinct energetic and biosynthetic pathways to support their specific functional needs. In particular, naturally occurring regulatory T cells (Treg are characterized by a unique metabolic signature distinct to that of conventional Teff cells. We here briefly review the signaling pathways that control Treg metabolism and how this metabolic phenotype integrates their differentiation and function. Ultimately, these metabolic features may provide new opportunities for the therapeutic modulation of unwanted immune responses.

  5. Accessory left gastric artery: angiographic anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Soo; Lim, Hyung Guhn; Kim, Hong Soo; Jeon, Doo Sung [Presbyterian Medical Center, Chunju (Korea, Republic of); Chung, Jin Wook; Park, Jae Hyung [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Song, Soon Young [Myongji Hospital, College of Medicine, Kwandong University, Seoul (Korea, Republic of)

    2000-09-01

    To evaluate the angiographic anatomy of the accessory left gastric artery (accLGA). We evaluated the angiographic findings of the accLGA in 50 patients (Angiostar; Siemens, Erlangen, Germany). Performing celiac and selective angiography in 50 and 34 patients, respectively. By means of celiac angiography, (1) site of origin, (2) anatomical course, (3) diameter, (4) degree of tortuosity, and (5) distal tapering were evaluated, while selective angiography was used to determine (1) arterial branching, (2) area of blood supply, and (3) patterns of gastric wall stain. Celiac angiography showed that the accLGA arose from the left hepatic artery (LHA) in 45 cases (90%) and from the proper hepatic artery in five (10%). If the accLGA arose from the LHA, its origin entirely depended on the branching pattern of the latter. It always arose from the lateral branch of the LHA furthest to the left and uppermost, and proximal to its umbilical point. The most common anatomical course of the accLGA, seen in 27 cases (54%), was between the S2 and S3 segmental branch. The diameter and degree of tortuosity of the accLGA were similar to those of adjacent intrahepatic branches in 21 (42%) and 33 cases (66%), respectively. The degree of tapering was less than that of adjacent intrahepatic vessel in 28 (56%). Selective angiography demonstrated esophageal branching of the acc LGA in 27 cases (79%), inferior phrenic arterial branching in three (9%), a mediastinal branch in one (3%), and hypervascularity of the lung in one (3%). In 15 cases (44%), bifurcation of the accLGA was recognized. The vascular territory of the accLGA was the gastric fundus together with the distal esophagus in 21 cases (62%), mainly the gastric fundus in six (18%), and mainly the distal esophagus in four (12%). The pattern of gastric mucosal stain was curvilinear wall in 31 cases (91%) and nodular in three (9%). A knowledge of the angiographic anatomy of the accLGA facilitates accurate recognition of this artery on

  6. Cell Phone’s Functions on Language Learning

    Institute of Scientific and Technical Information of China (English)

    伍文忠; 王娜

    2012-01-01

      With the time passing by and development of this society, almost everyone has a cell phone, we may see that cell phone as a new fifth medium after computer, having its own characters and advantages, many learners research the communica⁃tive function of cell phone and some from the technological level. This thesis aims at trying to reveal cultural functions of culture, aiming at improve cell phone’ s learning and culture functions in a more proper way.

  7. Expression and function of nicotinic acetylcholine receptors in stem cells

    Directory of Open Access Journals (Sweden)

    Herman S. Cheung

    2016-07-01

    Full Text Available Nicotinic acetylcholine receptors are prototypical ligand gated ion channels typically found in muscular and neuronal tissues. Functional nicotinic acetylcholine receptors, however, have also recently been identified on other cell types, including stem cells. Activation of these receptors by the binding of agonists like choline, acetylcholine, or nicotine has been implicated in many cellular changes. In regards to stem cell function, nicotinic acetylcholine receptor activation leads to changes in stem cell proliferation, migration and differentiation potential. In this review we summarize the expression and function of known nicotinic acetylcholine receptors in different classes of stem cells including: pluripotent stem cells, mesenchymal stem cells, periodontal ligament derived stem cells, and neural progenitor cells and discuss the potential downstream effects of receptor activation on stem cell function.

  8. Impact of genomic damage and ageing on stem cell function

    Science.gov (United States)

    Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

    2014-01-01

    Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

  9. [Surgical treatment strategy for flatfoot related with accessory navicular].

    Science.gov (United States)

    Deng, Yin-shuan; Gao, Qiu-ming; Zhen, Ping; Tang, Kang-lai

    2015-02-01

    Accessory navicular source flatfoot is one of the foot deformity of clinical common disease,its treatment method is more controversial, differences in clinical efficacy of different surgical methods, according to accessory navicular source flatfoot symptoms of surgical treatment,there is no uniform standard, around a pair of accessory navicular excision how to reconstruct the arch produced a series of operation methods, the clinical curative effect of different operative methods produce also different, how to develop the operation strategy, choose operation method, and after acessory navicular excision whether to rebuild posterior tibial tendon, how to rebuild, the problems such as how to rebuild is the research hotspot and difficulty, looking forward to further research.

  10. Immunosurveillance function of human mast cell?

    Institute of Scientific and Technical Information of China (English)

    (O)ner (O)zdemir

    2005-01-01

    Mast cell (MC) is so widely recognized as a critical effector in allergic disorders that it can be difficult to think of MC in any other context. Indeed, MCs are multifunctional and recently shown that MCs can also act as antigen presenters as well as effector elements of human immune system. First observations of their possible role as anti-tumor cells in peri- or intra-tumoral tissue were mentioned five decades ago and a high content of MCs is considered as a favorable prognosis,consistent with this study. Believers of this hypothesis assumed them to be inhibitors of tumor development through their pro-apoptotic and -necrolytic granules e.g.,granzymes and TNF-α. However, some still postulate them to be enhancers of tumor development through their effects on angiogenesis due to mostly tryptase.There are also some data suggesting increased MC density causes tumor development and indicates bad prognosis. Furthermore, since MC-associated mediators have shown to influence various aspects of tumor biology, the net effect of MCs on the development/progression of tumors has been difficult to evaluate. For instance, chymase induces apoptosis in targets; yet,tryptase, another MC protease, is a well-known mitogen.MCs with these various enzyme expression patterns may mediate different functions and the predominant MC type in tissues may be determined by the environmental needs. The coexistence of tryptase-expressing MCs(MCT) and chymase and tryptase-expressing MCs (MCTC)in physiological conditions reflects a naturally occurring balance that contributes to tissue homeostasis. We have recently discussed the role and relevance of MC serine proteases in different bone marrow diseases.

  11. Mechanisms of T regulatory cell function.

    Science.gov (United States)

    Askenasy, Nadir; Kaminitz, Ayelet; Yarkoni, Shai

    2008-05-01

    Regulatory T cells (Treg) play a pivotal role in tolerance to self-antigens and tissue grafts, and suppression of autoimmune reactions. These cells modulate the intensity and quality of immune reactions through attenuation of the cytolytic activities of reactive immune cells. Treg cells operate primarily at the site of inflammation where they modulate the immune reaction through three major mechanisms: a) direct killing of cytotoxic cells through cell-to-cell contact, b) inhibition of cytokine production by cytotoxic cells, in particular interleukin-2, c) direct secretion of immunomodulatory cytokines, in particular TGF-beta and interleukin-10. In addition to differential contributions of these mechanisms under variable inflammatory conditions, mechanistic complexity and diversity evolves from the diverse tasks performed by various Treg cell subsets in different stages of the immune reaction. Here we attempt to integrate the current experimental evidence to delineate the major suppressive pathways of Treg cells.

  12. ACCESSORY LOBE OF RIGHT LUNG: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    A.K. Manicka Vasuki

    2015-12-01

    Full Text Available Anatomical variations of lungs in the form of Accessory lobe and abnormality in the fissures are important for the surgeons to avoid possible injuries to the neighbouring structures. We report a case of Accessory lobe of right lung between middle and lower lobe in a male cadaver which was found during routine dissection in the Anatomy department, PSG IMS & R. Fissure and lobes of left lung was normal. Anatomical knowledge of such variations are helpful for Cardiothoracic surgeons in lobectomies, surgical resections involving individual segments and for Radiologists for interpreting X – rays,CT & MRI scans.

  13. Aplasia of the parotid glands with accessory parotid tissue

    Energy Technology Data Exchange (ETDEWEB)

    Higley, Meghan J.; Walkiewicz, Thomas W.; Miller, Jeffrey H.; Curran, John G.; Towbin, Richard B. [Phoenix Children' s Hospital, Department of Radiology, Phoenix, AZ (United States)

    2010-03-15

    Congenital absence of the parotid gland is a rare entity. Absence is most commonly unilateral, and is not associated with accessory glandular tissue. In the majority of reported cases, parotid gland aplasia is seen with craniofacial abnormalities or hypoplasia of other ectodermal structures, particularly the lacrimal glands. We present a 14-year-old male with bilateral parotid gland aplasia detected incidentally on MRI of the brain and then confirmed on neck CT. The studies also revealed accessory parotid tissue superficial to the left masseter muscle. There were no associated craniofacial abnormalities. The lacrimal glands and submandibular glands were normal. (orig.)

  14. Beyond growth: novel functions for bacterial cell wall hydrolases.

    Science.gov (United States)

    Wyckoff, Timna J; Taylor, Jennifer A; Salama, Nina R

    2012-11-01

    The peptidoglycan cell wall maintains turgor pressure and cell shape of most bacteria. Cell wall hydrolases are essential, together with synthases, for growth and daughter cell separation. Recent work in diverse organisms has uncovered new cell wall hydrolases that act autonomously or on neighboring cells to modulate invasion of prey cells, cell shape, innate immune detection, intercellular communication, and competitor lysis. The hydrolases involved in these processes catalyze the cleavage of bonds throughout the sugar and peptide moities of peptidoglycan. Phenotypes associated with these diverse hydrolases reveal new functions of the bacterial cell wall beyond growth and division.

  15. Accessory wandering spleen: Report of a case of laparoscopic approach in an asymptomatic patient

    Directory of Open Access Journals (Sweden)

    Alessandro Perin

    2014-01-01

    CONCLUSION: We suggest performing surgery with a laparoscopic approach in patients with accessory wandering spleen, though asymptomatic, because of the risk of serious complications in case of accessory spleen torsion.

  16. Colicin Killing: Foiled Cell Defense and Hijacked Cell Functions

    Science.gov (United States)

    de Zamaroczy, Miklos; Chauleau, Mathieu

    , which help to advance our understanding of the molecular events governing colicin import. In particular, our review includes the following: (1) Structural data on the tripartite interaction of a colicin with the outer membrane receptor and the translocation machinery, (2) Comparison of the normal cellular functions of the Tol and Ton systems of the inner membrane with their "hijacked" roles during colicin import, (3) An analysis of the interaction of a nuclease-type colicin with its cognate immunity protein in the context of the immunity of producer cells, and of the dissociation of this complex in the context of the attack of the colicin on target cells, (4) Information on the endoproteolytic cleavage, which presumably accompanies the penetration of nuclease-type colicins into the cytoplasm. The new data presented here provides further insight into cellular functions "hijacked" or "borrowed" by colicins to permit their entry into target cells.

  17. Impacts of Humanized Mouse Models on the Investigation of HIV-1 Infection: Illuminating the Roles of Viral Accessory Proteins in Vivo

    Directory of Open Access Journals (Sweden)

    Eri Yamada

    2015-03-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 encodes four accessory genes: vif, vpu, vpr, and nef. Recent investigations using in vitro cell culture systems have shed light on the roles of these HIV-1 accessory proteins, Vif, Vpr, Vpu, and Nef, in counteracting, modulating, and evading various cellular factors that are responsible for anti-HIV-1 intrinsic immunity. However, since humans are the exclusive target for HIV-1 infection, conventional animal models are incapable of mimicking the dynamics of HIV-1 infection in vivo. Moreover, the effects of HIV-1 accessory proteins on viral infection in vivo remain unclear. To elucidate the roles of HIV-1 accessory proteins in the dynamics of viral infection in vivo, humanized mouse models, in which the mice are xenotransplanted with human hematopoietic stem cells, has been utilized. This review describes the current knowledge of the roles of HIV-1 accessory proteins in viral infection, replication, and pathogenicity in vivo, which are revealed by the studies using humanized mouse models.

  18. 21 CFR 876.1500 - Endoscope and accessories.

    Science.gov (United States)

    2010-04-01

    ..., and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optical system for conveying an image to the user's eye and their accessories may assist in gaining...

  19. 21 CFR 884.6120 - Assisted reproduction accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Assisted reproduction accessories. 884.6120 Section 884.6120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction Devices §...

  20. Accessory breast on the posterior thigh of a man.

    Science.gov (United States)

    Camisa, C

    1980-11-01

    An elderly man with a mass that clinically resembles the normal female breast on the posterior portion of his left thigh is presented. We believe this is an unusual case of accessory breast tissue occurring in a location remote from the embryonic mammary line.

  1. ABC transporter architecture and regulatory roles of accessory domains

    NARCIS (Netherlands)

    Biemans-Oldehinkel, E; Doeven, MK; Poolman, B

    2006-01-01

    We present an overview of the architecture of ATP-binding cassette (ABC) transporters and dissect the systems in core and accessory domains. The ABC transporter core is formed by the transmembrane domains (TMDs) and the nucleotide binding domains (NBDs) that constitute the actual translocator. The a

  2. The benefits of using bluetooth accessories with hearing aids.

    Science.gov (United States)

    Smith, Pauline; Davis, Adrian

    2014-10-01

    To investigate the benefits in reported outcomes after providing bluetooth accessories for established hearing aid users. Prospective observational study using validated quantitative outcome measures and detailed patient narrative before and two months after patients were provided with bluetooth accessories. Twelve patients with bilateral NHS hearing aids participated. They had a wide range of ages and hearing loss. After two months, 10 patients reported substantial additional benefit and kept the accessories; two returned them for various reasons. Statistically significant changes were seen in two validated outcome measures: the Glasgow Hearing Aid Benefit Profile and the International Outcome Inventory - Hearing Aids, but not in the Speech, Spatial and Qualities of Hearing Scale. Two notable benefits were reported: some described hearing the emotion and mood in a voice for the first time; others were amazed to report an improved ability to hear film or to hold conversations over the telephone. The provision of bluetooth accessories can give additional reported benefit for some patients - we need better knowledge about who benefits, and whether further support/training to individuals would make a difference.

  3. Validated Competency Task Lists for Apparel and Accessories Marketing.

    Science.gov (United States)

    Selke-Kern, Barbara E.

    Developed by a project that validated task lists by a variety of teachers and apparel marketing business persons, this guide contains task lists for occupations in the field of apparel and accessories marketing. The guide is organized in three sections. Section 1 includes the following: (1) notes on using the information in the guide; (2) a…

  4. 21 CFR 876.5010 - Biliary catheter and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Biliary catheter and accessories. 876.5010 Section 876.5010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... healing, or for preventing stricture of the bile duct. This generic type of device may include a bile...

  5. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Science.gov (United States)

    2010-04-01

    ... sufficiently low permeability to water that an ultrafiltration controller is not required to prevent excessive... the disposable inserts (Kiil type) (§ 876.5830) or dialyzers of high permeability (§ 876.5860). (3... dialysate delivery system of the peritoneal dialysis system and accessories (§ 876.5630), or the controlled...

  6. Accessory enzymes from Aspergillus involved in xylan and pectin degradation

    NARCIS (Netherlands)

    Vries, de R.P.

    1999-01-01

    The xylanolytic and pectinolytic enzyme systems from Aspergillus have been the subject of study for many years. Although the main chain cleaving enzymes and their encoding genes have been studied in detail, little information is available about most of the accessory enzymes and their corresponding g

  7. 21 CFR 890.3025 - Prosthetic and orthotic accessory.

    Science.gov (United States)

    2010-04-01

    ... intended for medical purposes to support, protect, or aid in the use of a cast, orthosis (brace), or prosthesis. Examples of prosthetic and orthotic accessories include the following: A pelvic support band and belt, a cast shoe, a cast bandage, a limb cover, a prosthesis alignment device, a postsurgical pylon,...

  8. Accessory proteins of SARS-CoV and other coronaviruses.

    Science.gov (United States)

    Liu, Ding Xiang; Fung, To Sing; Chong, Kelvin Kian-Long; Shukla, Aditi; Hilgenfeld, Rolf

    2014-09-01

    The huge RNA genome of SARS coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. Although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. Notably, some SARS-CoV accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. The structural information on these proteins is also limited, with only two (p7a and p9b) having their structures determined by X-ray crystallography. This review makes an attempt to summarize the published knowledge on SARS-CoV accessory proteins, with an emphasis on their involvement in virus-host interaction. The accessory proteins of other coronaviruses are also briefly discussed. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses" (see Introduction by Hilgenfeld and Peiris (2013)). Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 21 CFR 876.4890 - Urological table and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urological table and accessories. 876.4890 Section 876.4890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Surgical Devices § 876.4890 Urological table...

  10. 21 CFR 876.5130 - Urological catheter and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urological catheter and accessories. 876.5130 Section 876.5130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5130...

  11. The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

    Directory of Open Access Journals (Sweden)

    María Guadalupe Reyes García

    2013-01-01

    Full Text Available T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95% are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

  12. Accessory veins in nonmaturing autogenous arteriovenous fistulae: analysis of anatomic features and impact on fistula maturation.

    Science.gov (United States)

    Engstrom, Bjorn I; Grimm, Lars J; Ronald, James; Smith, Tony P; Kim, Charles Y

    2015-01-01

    The appropriate management of nonmaturing arteriovenous (AV) fistulae continues to be a controversial issue. While coil embolization of accessory side-branch veins can be performed to encourage maturation of nonmaturing AV fistulae, the true efficacy and optimal patient population are not well understood. Fistulagrams performed on nonmaturing AV fistulae were retrospectively reviewed in 145 patients (86 males, median age 63 years) for the presence of accessory veins. Fistula and accessory vein measurements were obtained, as were rates of eventual fistula maturation after accessory vein coil embolization. Of 145 nonmaturing fistulae, 49 (34%) had a stenosis without any accessory veins, 76 (52%) had a stenosis and one or more accessory veins, and 20 (14%) had an accessory vein without concurrent stenosis. Eighteen AV fistulae had one or more accessory veins without coexisting stenosis. Nine fistulae had a caliber decrease immediately downstream from the accessory vein. Coil embolization of dominant accessory veins with a caliber decrease immediately downstream (n = 6) resulted in a 100% eventual fistula maturation rate versus 67% for fistulae without this configuration (n = 6, p = 0.15). Accessory vein size was not correlated with maturation rates (p = 0.51). The majority of nonmaturing fistulae with accessory veins had a coexisting stenosis. Higher maturation rates may result with selected anatomic parameters, although additional studies with more robust sample sizes are needed prior to definitive conclusions. © 2014 Wiley Periodicals, Inc.

  13. Deficient natural killer cell function in preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  14. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    Science.gov (United States)

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2016-01-01

    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  15. Cell size control - a mechanism for maintaining fitness and function.

    Science.gov (United States)

    Miettinen, Teemu P; Caldez, Matias J; Kaldis, Philipp; Björklund, Mikael

    2017-09-01

    The maintenance of cell size homeostasis has been studied for years in different cellular systems. With the focus on 'what regulates cell size', the question 'why cell size needs to be maintained' has been largely overlooked. Recent evidence indicates that animal cells exhibit nonlinear cell size dependent growth rates and mitochondrial metabolism, which are maximal in intermediate sized cells within each cell population. Increases in intracellular distances and changes in the relative cell surface area impose biophysical limitations on cells, which can explain why growth and metabolic rates are maximal in a specific cell size range. Consistently, aberrant increases in cell size, for example through polyploidy, are typically disadvantageous to cellular metabolism, fitness and functionality. Accordingly, cellular hypertrophy can potentially predispose to or worsen metabolic diseases. We propose that cell size control may have emerged as a guardian of cellular fitness and metabolic activity. © 2017 WILEY Periodicals, Inc.

  16. N-Acetylglucosamine Functions in Cell Signaling

    Directory of Open Access Journals (Sweden)

    James B. Konopka

    2012-01-01

    Full Text Available The amino sugar N-acetylglucosamine (GlcNAc is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli responds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.

  17. Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells.

    Science.gov (United States)

    Maître, Jean-Léon; Berthoumieux, Hélène; Krens, Simon Frederik Gabriel; Salbreux, Guillaume; Jülicher, Frank; Paluch, Ewa; Heisenberg, Carl-Philipp

    2012-10-12

    Differential cell adhesion and cortex tension are thought to drive cell sorting by controlling cell-cell contact formation. Here, we show that cell adhesion and cortex tension have different mechanical functions in controlling progenitor cell-cell contact formation and sorting during zebrafish gastrulation. Cortex tension controls cell-cell contact expansion by modulating interfacial tension at the contact. By contrast, adhesion has little direct function in contact expansion, but instead is needed to mechanically couple the cortices of adhering cells at their contacts, allowing cortex tension to control contact expansion. The coupling function of adhesion is mediated by E-cadherin and limited by the mechanical anchoring of E-cadherin to the cortex. Thus, cell adhesion provides the mechanical scaffold for cell cortex tension to drive cell sorting during gastrulation.

  18. Dental enamel cells express functional SOCE channels.

    Science.gov (United States)

    Nurbaeva, Meerim K; Eckstein, Miriam; Concepcion, Axel R; Smith, Charles E; Srikanth, Sonal; Paine, Michael L; Gwack, Yousang; Hubbard, Michael J; Feske, Stefan; Lacruz, Rodrigo S

    2015-10-30

    Dental enamel formation requires large quantities of Ca(2+) yet the mechanisms mediating Ca(2+) dynamics in enamel cells are unclear. Store-operated Ca(2+) entry (SOCE) channels are important Ca(2+) influx mechanisms in many cells. SOCE involves release of Ca(2+) from intracellular pools followed by Ca(2+) entry. The best-characterized SOCE channels are the Ca(2+) release-activated Ca(2+) (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca(2+) uptake mechanism in enamel cells. Investigating primary murine enamel cells, we found that key components of CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the maturation stage of enamel development. Furthermore, inositol 1,4,5-trisphosphate receptor (IP3R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP3Rs are the main ER Ca(2+) release mechanism. Passive depletion of ER Ca(2+) stores with thapsigargin resulted in a significant raise in [Ca(2+)]i consistent with SOCE. In cells pre-treated with the CRAC channel blocker Synta-66 Ca(2+) entry was significantly inhibited. These data demonstrate that enamel cells have SOCE mediated by CRAC channels and implicate them as a mechanism for Ca(2+) uptake in enamel formation.

  19. Generation of functional organs from stem cells

    Directory of Open Access Journals (Sweden)

    Yunying Liu

    2013-01-01

    Full Text Available We are now well entering the exciting era of stem cells. Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, diabetes, and etc. It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue. In fact, organ transplantation has been successfully practiced in clinics for liver or kidney failure. However, the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs. Toward that direction, generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists. Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells, a blastocyst complementation system, tissue decellularization/recellularization and a combination of stem cells and tissue engineering.

  20. The staphylococcal accessory regulator, SarA, is an RNA-binding protein that modulates the mRNA turnover properties of late-exponential and stationary phase Staphylococcus aureus cells

    Directory of Open Access Journals (Sweden)

    John M Morrison

    2012-03-01

    Full Text Available The modulation of mRNA turnover is gaining recognition as a mechanism by which Staphylococcus aureus regulates gene expression, but the factors that orchestrate alterations in transcript degradation are poorly understood. In that regard, we previously found that 138 mRNA species, including the virulence factors protein A (spa and collagen binding protein (cna, are stabilized in a sarA-dependent manner during exponential phase growth, suggesting that SarA protein may directly or indirectly effect the RNA turnover properties of these transcripts. Herein, we expanded our characterization of the effects of sarA on mRNA turnover during late exponential and stationary phases of growth. Results revealed that the locus affects the RNA degradation properties of cells during both growth phases. Further, using gel mobility shift assays and RIP-ChIP, it was found that SarA protein is capable of binding mRNA species that it stabilizes both in vitro and within bacterial cells. Taken together, these results suggest that SarA post-transcriptionally regulates S. aureus gene expression in a manner that involves binding to and consequently altering the mRNA turnover properties of target transcripts.

  1. Molecular structure and biological function of proliferating cell nuclear antigen

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proliferating cell nuclear antigen (PCNA) is the core component of replication complex in eukaryote.As a processive factor of DNA polymerase delta, PCNA coordinates the replication process by interacting with various replication proteins. PCNA appears to play an essential role in many cell events, such as DNA damage repair, cell cycle regulation, and apoptosis, through the coordination or organization of different partners. PCNA is an essential factor in cell proliferation, and has clinical significance in tumor research. In this article we review the functional structure of PCNA, which acts as a function switch in different cell events.

  2. IL1RAPL1基因多态性与秦巴山区儿童精神运动功能的相关性%Correlation between interleukin 1 receptor accessory protein-like, gene 1 polymorphism and children's psychomotor function in Qinba mountain area

    Institute of Scientific and Technical Information of China (English)

    高晓彩; 牛银波; 张淑苗; 李静; 张富昌

    2009-01-01

    Objective To investigate the effect of mental retardation related gene on psychomotor function, thereby offering the evidence for availability of psychomotor function disability to sub-cretin diagnosis. Methods Four genetic marker sites, i.e., DXS1218, DXS9896, rs6526806 and rs12847959 on interleukin 1 receptor accessory protein-like, gene 1 (IL1RAPL1) were genotyped by PCR, PCR-SSCP and PAGE for 220 Qinba mountain area children aged 7-14. Meanwhile, a psychomotor function test was performed to study their relationship. Results DXS1218, DXS9896 and rs12847959 of IL1RAPL1 gene had high heterozygosis degree(Het) in the children. The Het was 0.8941,0.8674,0.4872, respectively. The rs6526806 showed lower heterozygosis degree (Het=0.1804). The DXS1218, DXS9896, rs6526806 and rs12847959 did not correlate with children's psychomotor function(F=0.909,0.279,0.725,1.982, all P > 0.05). Conclusions IL1RAPL1 gene polymorphism does not affect human psychomotor controlling ability. Maybe psychomotor function is less affected by genetic factor, thereby it is a available assistant index for sub-cretin diagnosis.%目的 探讨精神发育迟滞相关基因(IL1RAPL1)对人类精神运动功能的影响,为精神运动功能障碍对亚克汀病诊断的有效性提供证据.方法 采用传统PCR、单链构象多态PCR(PCR-SSCP)、聚丙烯酰胺凝胶电泳等分子生物学方法,对秦巴山区220名7~14岁儿童IL1RAPL1基因的DXS1218、DXS9896、rs6526806,rs12847959共4个遗传标记位点进行多态性检测,并进行精神运动功能测验,对多态性检测结果与儿童精神运动功能测验成绩进行关联分析.结果 DXS1218、DXS9896、rs12847959 3个遗传标记在受检儿童中均有较高杂合度(Het),分别为0.8941、0.8674、0.4872,rs6526806有较低的Het,为0.1804;4个遗传标记多态性均未显示出与儿童精神运动功能的相关性(F值分别为0.909、0.279、0.725、1.982,P均>0.05).结论 IL1RAPL1基因多态性对人的精神运动

  3. Attaching Accessory Devices to the Replisome.

    Science.gov (United States)

    Sutani, Takashi; Shirahige, Katsuhiko

    2016-08-04

    Evidence mounts, via two studies published in Molecular Cell (Villa et al. 2016; Samora et al. 2016), that Ctf4 recruits to the replisome various factors that play diverse roles in chromosome duplication, by acting as an interaction hub.

  4. [Surgical treatment of the accessory navicular syndrome with simple excision].

    Science.gov (United States)

    Chi, Lei-Ting; Li, Cheng; Zhang, Dong; Li, Zhi; Huang, Bo; Zhang, Ting-Jiu; Yu, Ming; Wang, Ping-Xi

    2009-12-01

    To observe and evaluate the clinical effects of surgical treatment for the accessory navicular syndrome with simple excision. From November 2006 to December 2008, 23 patients (twenty-five feet) with accessory navicular syndrome received simple excision of the accessory navicular bone. The chief complains were intermittent pain of feet after running or walking. Physical examination showed local tenderness on palpation in the region of the navicular bone. X-ray or CT showed there was an accessory navicular bone. The present history ranged from 6 months to 12 years. There were 14 males and 9 females. The mean age was 14.6 years, ranging from 8 to 35 years. About 2 cm long incision was made at the tip of the medial prominence of the navicular bone. After partial dissection of the posterior tibial tendon, the accesssory navicular bone was exposed and excisied. The prominence of the tuberosity of the navicular bone was cut and shaved. The posterior tibial tenden was repaired before closing the wound. The foot was immobilized with cast or brace in inversion position and no weight-bearing for 2 weeks. Strenuous jumping or dancing must be avoided in 3 months after surgery. The patients with residual symptoms and signs received physical therapy and an arch support for shoes without flatfoot deformity. The average clinical follow-up during was 12 month (ranged, 3 to 18 months). The excellent results in 21 feet and good in 4 feet (3 feet with mild flat deformity and 1 foot with old sprain injury). The average hospital stay was 5 days and no wound infection occurred. All patients resumed the normal life and study after operation. Surgical treatment of the accessory navicular syndrome with simple excision has the advantages of less invasive to the posterior tibial tenden and the medial longitudinal arch of the foot, shorter time of immobilization of the foot and stay in hospital, small incision and good clinical results. This procedure is one of the best selective treatments for

  5. Peripheral NK cell phenotypes: multiple changing of faces of an adapting, developing cell.

    Science.gov (United States)

    Perussia, Bice; Chen, Yingying; Loza, Matthew J

    2005-02-01

    We have defined the existence of developmental relationships among human peripheral NK cells with distinct phenotypic and functional characteristics. These findings closely parallel the changes that occur in vivo during NK cell development, and in vitro in experimental culture systems supporting NK cell generation from hematopoietic progenitors. These new insights provide a simplified framework to understand NK cell immunobiology and the cellular bases for their roles in innate immunity, initiation and maintenance of immune responses via regulation of adaptive and accessory cell functions, and immune pathologies.

  6. Functional neutrophils from human ES cells

    OpenAIRE

    Sweeney, Colin L; Malech, Harry L.

    2009-01-01

    In this issue of Blood, Yokoyama and colleagues demonstrate in vitro differentiation of hESCs into mature neutrophils with functional capabilities (chemotaxis, phagocytosis, microbicidal oxidase activity, and bacterial killing) approaching or equal to that of normal peripheral blood neutrophils.

  7. 半胱亚磺酸脱羧酶在成年小鼠副性腺器官中的表达%Expression of Cysteine Sulfinate Decarboxylase in Male Accessory Organs of Adult Mice

    Institute of Scientific and Technical Information of China (English)

    范晶晶; 庞立义

    2012-01-01

    We conducted semi-quantitative reverse transcription polymerase chain reaction(RT-PCR),western blott and immunohistochemical analysis in order to examine CSD mRNA and protein expression in the accessory organs of male mice.The results show that CSD is expressed both at the mRNA and protein levels in the organs.Immunohistochemical analysis reveals that CSD is expressed in the tall columnar cells of the seminal vesicle,the glandular epithelium of the bulbourethral gland,and the epithelial cells of the prostate gland.These results suggest that male accessory organs have the function to produce taurine through the CSD pathway.%采用RT-PCR、Western blot、免疫组织化学方法检测了CSD在小鼠副性腺器官中mRNA和蛋白水平的表达。结果显示,CSD在小鼠副性腺器官中都有mRNA和蛋白水平的表达。CSD主要定位于精囊腺的高柱状上皮细胞、前列腺的腺上皮细胞和尿道球腺的腺上皮细胞中。结果表明雄性副性腺器官可以通过CSD合成通路参与牛磺酸的合成。

  8. The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

    Science.gov (United States)

    McBride, Ruth; Fielding, Burtram C.

    2012-01-01

    A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies. PMID:23202509

  9. Impact of infection on the secretory capacity of the male accessory glands

    Directory of Open Access Journals (Sweden)

    M. Marconi

    2009-06-01

    Full Text Available INTRODUCTION: Studies that compare the impact of different infectious entities of the male reproductive tract (MRT on the male accessory gland function are controversial. MATERIAL AND METHODS: Semen analyses of 71 patients with proven infections of the MRT were compared with the results of 40 healthy non-infected volunteers. Patients were divided into 3 groups according to their diagnosis: chronic prostatitis NIH type II (n = 38, chronic epididymitis (n = 12, and chronic urethritis (n = 21. RESULTS: The bacteriological analysis revealed 9 different types of microorganisms, considered to be the etiological agents, isolated in different secretions, including: urine, expressed prostatic secretions, semen and urethral smears: E. Coli (n = 20, Klebsiella (n = 2, Proteus spp. (n = 1, Enterococcus (n = 20, Staphylococcus spp. (n = 1, M. tuberculosis (n = 2, N. gonorrhea (n = 8, Chlamydia tr. (n = 16 and, Ureaplasma urealyticum (n = 1. The infection group had significantly (p < 0.05 lower: semen volume, alpha-glucosidase, fructose, and zinc in seminal plasma and, higher pH than the control group. None of these parameters was sufficiently accurate in the ROC analysis to discriminate between infected and non-infected men. CONCLUSION: Proven bacterial infections of the MRT impact negatively on all the accessory gland function parameters evaluated in semen, suggesting impairment of the secretory capacity of the epididymis, seminal vesicles and prostate. These findings were associated with an infectious related significant increase of semen pH. None of the semen parameters evaluated can be suggested as a diagnostic tool for infection.

  10. Regulation of Natural Killer Cell Function by STAT3

    Directory of Open Access Journals (Sweden)

    Nicholas eCacalano

    2016-04-01

    Full Text Available Natural killer (NK cells, key members of a distinct hempatopoietic lineage, innate lymphoid cells (ILCs, are critical effectors that mediate cytotoxicity toward tumor and virally-infected cells but also regulate inflammation, antigen presentation and the adaptive immune response. It has been shown that NK cells can regulate the development and activation of many other components of the immune response such as dendritic cells, which in turn, modulate the function of NK cells in multiple synergistic feed back loops driven by cell-cell contact and the secretion of cytokines and chemokines that control effector function and migration of cells to sites of immune activation. The Signal Transducer and Activator of Transcription (STAT-3 is involved in driving almost all of the pathways that control NK cytolytic activity as well as the reciprocal regulatory interactions between NK cells and other components of the immune system. In the context of tumor immunology, NK cells are a first line of defense that eliminates pre-cancerous and transformed cells early in the process of carcinogenesis, through a mechanism of immune surveillance. Even after tumors become established, NK cells are critical components of anti-cancer immunity: dysfunctional NK cells are often found in the peripheral blood of cancer patients and the lack of NK cells in the tumor microenvironment often correlates with poor prognosis. The pathways and soluble factors activated in tumor-associated NK cells, cancer cells, and regulatory myeloid cells which determine the outcome of cancer immunity are all critically regulated by STAT3. Using the tumor microenvironment as a paradigm, we present here an overview of the research that has revealed fundamental mechanisms through which STAT3 regulates all aspects of natural killer cell biology, including NK development, activation, target cell killing, and fine tuning of the innate and adaptive immune responses.

  11. Molecular regulation of pancreatic stellate cell function

    Directory of Open Access Journals (Sweden)

    Jaster Robert

    2004-10-01

    Full Text Available Abstract Until now, no specific therapies are available to inhibit pancreatic fibrosis, a constant pathological feature of chronic pancreatitis and pancreatic cancer. One major reason is the incomplete knowledge of the molecular principles underlying fibrogenesis in the pancreas. In the past few years, evidence has been accumulated that activated pancreatic stellate cells (PSCs are the predominant source of extracellular matrix (ECM proteins in the diseased organ. PSCs are vitamin A-storing, fibroblast-like cells with close morphological and biochemical similarities to hepatic stellate cells (also known as Ito-cells. In response to profibrogenic mediators such as various cytokines, PSCs undergo an activation process that involves proliferation, exhibition of a myofibroblastic phenotype and enhanced production of ECM proteins. The intracellular mediators of activation signals, and their antagonists, are only partially known so far. Recent data suggest an important role of enzymes of the mitogen-activated protein kinase family in PSC activation. On the other hand, ligands of the nuclear receptor PPARγ (peroxisome proliferator-activated receptor γ stimulate maintenance of a quiescent PSC phenotype. In the future, targeting regulators of the PSC activation process might become a promising approach for the treatment of pancreatic fibrosis.

  12. Multiparameter fluorescence spectroscopic imaging of cell function

    Science.gov (United States)

    Bright, Gary R.

    1994-08-01

    The ability to quantitate physiological parameters in single living cells using fluorescence spectroscopic imaging has expanded our understanding of many cell regulatory processes. Previous studies have focussed on the measurement of single parameters, such as the concentration of calcium, and more recently two parameters, such as calcium and pH using fluorescence ratio imaging. The complexity of the interrelationships among cell biochemical reactions suggests a need to extend the measurement scheme to several parameters. Expansion of the number of parameters involves several complexities associated with fluorescent probe selection and instrumentation design as well as the processing and management of the data. A system has been assembled which provides maximum flexibility in multiparameter fluorescence imaging measurements. The system provides multiple combinations of excitation, dichroic mirror, and emission wavelengths. It has automatic acquisition of any number of parameters. The number of parameters is primarily limited by the selection of fluorescent probes with nonoverlapping spectra. We demonstrate the utility of the system by the coordinated monitoring of stimulated changes in the concentrations of calcium, magnesium, and pH using fluorescence ratio imaging coupled with a conventional transmitted light image of single smooth muscle cells. The results demonstrate coordinated changes in some instances but uncoordinated changes in others.

  13. Scaffold functions of 14-3-3 adaptors in B cell immunoglobulin class switch DNA recombination.

    Science.gov (United States)

    Lam, Tonika; Thomas, Lisa M; White, Clayton A; Li, Guideng; Pone, Egest J; Xu, Zhenming; Casali, Paolo

    2013-01-01

    Class switch DNA recombination (CSR) of the immunoglobulin heavy chain (IgH) locus crucially diversifies antibody biological effector functions. CSR involves the induction of activation-induced cytidine deaminase (AID) expression and AID targeting to switch (S) regions by 14-3-3 adaptors. 14-3-3 adaptors specifically bind to 5'-AGCT-3' repeats, which make up for the core of all IgH locus S regions. They selectively target the upstream and downstream S regions that are set to undergo S-S DNA recombination. We hypothesized that 14-3-3 adaptors function as scaffolds to stabilize CSR enzymatic elements on S regions. Here we demonstrate that all seven 14-3-3β, 14-3-3ε, 14-3-3γ, 14-3-3η, 14-3-3σ, 14-3-3τ and 14-3-3ζ adaptors directly interacted with AID, PKA-Cα (catalytic subunit) and PKA-RIα (regulatory inhibitory subunit) and uracil DNA glycosylase (Ung). 14-3-3 adaptors, however, did not interact with AID C-terminal truncation mutant AIDΔ(180-198) or AIDF193A and AIDL196A point-mutants (which have been shown not to bind to S region DNA and fail to mediate CSR). 14-3-3 adaptors colocalized with AID and replication protein A (RPA) in B cells undergoing CSR. 14-3-3 and AID binding to S region DNA was disrupted by viral protein R (Vpr), an accessory protein of human immunodeficiency virus type-1 (HIV-1), which inhibited CSR without altering AID expression or germline IH-CH transcription. Accordingly, we demonstrated that 14-3-3 directly interact with Vpr, which in turn, also interact with AID, PKA-Cα and Ung. Altogether, our findings suggest that 14-3-3 adaptors play important scaffold functions and nucleate the assembly of multiple CSR factors on S regions. They also show that such assembly can be disrupted by a viral protein, thereby allowing us to hypothesize that small molecule compounds that specifically block 14-3-3 interactions with AID, PKA and/or Ung can be used to inhibit unwanted CSR.

  14. Scaffold functions of 14-3-3 adaptors in B cell immunoglobulin class switch DNA recombination.

    Directory of Open Access Journals (Sweden)

    Tonika Lam

    Full Text Available Class switch DNA recombination (CSR of the immunoglobulin heavy chain (IgH locus crucially diversifies antibody biological effector functions. CSR involves the induction of activation-induced cytidine deaminase (AID expression and AID targeting to switch (S regions by 14-3-3 adaptors. 14-3-3 adaptors specifically bind to 5'-AGCT-3' repeats, which make up for the core of all IgH locus S regions. They selectively target the upstream and downstream S regions that are set to undergo S-S DNA recombination. We hypothesized that 14-3-3 adaptors function as scaffolds to stabilize CSR enzymatic elements on S regions. Here we demonstrate that all seven 14-3-3β, 14-3-3ε, 14-3-3γ, 14-3-3η, 14-3-3σ, 14-3-3τ and 14-3-3ζ adaptors directly interacted with AID, PKA-Cα (catalytic subunit and PKA-RIα (regulatory inhibitory subunit and uracil DNA glycosylase (Ung. 14-3-3 adaptors, however, did not interact with AID C-terminal truncation mutant AIDΔ(180-198 or AIDF193A and AIDL196A point-mutants (which have been shown not to bind to S region DNA and fail to mediate CSR. 14-3-3 adaptors colocalized with AID and replication protein A (RPA in B cells undergoing CSR. 14-3-3 and AID binding to S region DNA was disrupted by viral protein R (Vpr, an accessory protein of human immunodeficiency virus type-1 (HIV-1, which inhibited CSR without altering AID expression or germline IH-CH transcription. Accordingly, we demonstrated that 14-3-3 directly interact with Vpr, which in turn, also interact with AID, PKA-Cα and Ung. Altogether, our findings suggest that 14-3-3 adaptors play important scaffold functions and nucleate the assembly of multiple CSR factors on S regions. They also show that such assembly can be disrupted by a viral protein, thereby allowing us to hypothesize that small molecule compounds that specifically block 14-3-3 interactions with AID, PKA and/or Ung can be used to inhibit unwanted CSR.

  15. KNOW-BLADE Task-2 report: Aerodynamic accessories

    DEFF Research Database (Denmark)

    Johansen, J.; Sørensen, Niels N.; Zahle, Frederik

    2004-01-01

    of a pulsating jet placed at the leading edge in order to enhance mean lift. The general trend is that increased pulsation frequency is beneficial, in that it reduces the oscillation amplitude and raisesthe mean lift level while lowering the mean drag level. An increased jet exit velocity has a tendency...... the airfoil geometry. In general the 7mm stallstrips placed at P00 and P-02 had the greatest effect on the max lift followed by stall strip P02. Unfortunately, there was not sufficient agreement between the experimental results and the simulations to draw any conclusions of optimum position andgeometry......In the EC project KNOW-BLADE a work package has been defined to investigate the possibility to numerically model aerodynamic accessories in existing Navier-Stokes solvers. Four different aerodynamic accessories have been investigated. Firstly, thepotential of applying active flow control by means...

  16. Spinal accessory nerve schwannomas masquerading as a fourth ventricular lesion

    Directory of Open Access Journals (Sweden)

    Shyam Sundar Krishnan

    2015-01-01

    Full Text Available Schwannomas are benign lesions that arise from the nerve sheath of cranial nerves. The most common schwannomas arise from the 8 th cranial nerve (the vestibulo-cochlear nerve followed by trigeminal and facial nerves and then from glossopharyngeal, vagus, and spinal accessory nerves. Schwannomas involving the oculomotor, trochlear, abducens and hypoglossal nerves are very rare. We report a very unusual spinal accessory nerve schwannoma which occupied the fourth ventricle and extended inferiorly to the upper cervical canal. The radiological features have been detailed. The diagnostic dilemma was due to its midline posterior location mimicking a fourth ventricular lesion like medulloblastoma and ependymoma. Total excision is the ideal treatment for these tumors. A brief review of literature with tabulations of the variants has been listed.

  17. Spinal accessory neuropathy, droopy shoulder, and thoracic outlet syndrome.

    Science.gov (United States)

    Al-Shekhlee, Amer; Katirji, Bashar

    2003-09-01

    Droopy shoulder has been proposed as a cause of thoracic outlet syndrome. Two patients developed manifestations of neurovascular compression upon arm abduction, associated with unilateral droopy shoulder and trapezius muscle weakness caused by iatrogenic spinal accessory neuropathies following cervical lymph node biopsies. The first patient developed a cold, numb hand with complete axillary artery occlusion when his arm was abducted to 90 degrees. The second patient complained of paresthesias in digits 4 and 5 of the right hand, worsened by elevation of the arm, with nerve conduction findings of right lower trunk plexopathy (low ulnar and medial antebrachial cutaneous sensory nerve action potentials). Spinal accessory nerve grafting (in the first patient) coupled with shoulder strengthening physical exercises in both patients resulted in gradual improvement of symptoms in 2 years. These two cases demonstrate that unilateral droopy shoulder secondary to trapezius muscle weakness may cause compression of the thoracic outlet structures.

  18. Live cell imaging to understand monocyte, macrophage, and dendritic cell function in atherosclerosis.

    Science.gov (United States)

    McArdle, Sara; Mikulski, Zbigniew; Ley, Klaus

    2016-06-27

    Intravital imaging is an invaluable tool for understanding the function of cells in healthy and diseased tissues. It provides a window into dynamic processes that cannot be studied by other techniques. This review will cover the benefits and limitations of various techniques for labeling and imaging myeloid cells, with a special focus on imaging cells in atherosclerotic arteries. Although intravital imaging is a powerful tool for understanding cell function, it alone does not provide a complete picture of the cell. Other techniques, such as flow cytometry and transcriptomics, must be combined with intravital imaging to fully understand a cell's phenotype, lineage, and function.

  19. Natural killer cells: Biology, functions and clinical relevance

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction. Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1 killer immunoglobulin like receptors-KIR, 2 C-type lectin receptors,3natural citotoxicity receptors-NCR and 4 Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

  20. Headgear Accessories Classification Using an Overhead Depth Sensor

    Science.gov (United States)

    Luna, Carlos A.; Marron-Romera, Marta; Mazo, Manuel; Luengo-Sanchez, Sara; Macho-Pedroso, Roberto

    2017-01-01

    In this paper, we address the generation of semantic labels describing the headgear accessories carried out by people in a scene under surveillance, only using depth information obtained from a Time-of-Flight (ToF) camera placed in an overhead position. We propose a new method for headgear accessories classification based on the design of a robust processing strategy that includes the estimation of a meaningful feature vector that provides the relevant information about the people’s head and shoulder areas. This paper includes a detailed description of the proposed algorithmic approach, and the results obtained in tests with persons with and without headgear accessories, and with different types of hats and caps. In order to evaluate the proposal, a wide experimental validation has been carried out on a fully labeled database (that has been made available to the scientific community), including a broad variety of people and headgear accessories. For the validation, three different levels of detail have been defined, considering a different number of classes: the first level only includes two classes (hat/cap, and no hat/cap), the second one considers three classes (hat, cap and no hat/cap), and the last one includes the full class set with the five classes (no hat/cap, cap, small size hat, medium size hat, and large size hat). The achieved performance is satisfactory in every case: the average classification rates for the first level reaches 95.25%, for the second one is 92.34%, and for the full class set equals 84.60%. In addition, the online stage processing time is 5.75 ms per frame in a standard PC, thus allowing for real-time operation. PMID:28796177

  1. Testicular dysgenesis syndrome and Leydig cell function

    DEFF Research Database (Denmark)

    Joensen, Ulla Nordström; Jørgensen, Niels; Rajpert-De Meyts, Ewa

    2008-01-01

    originating in early foetal life. TDS comprises various aspects of impaired gonadal development and function, including testicular cancer. A growing body of evidence, including animal models and research in human beings, points to lifestyle factors and endocrine disrupters as risk factors for TDS. We present...

  2. Endocrine disruptors and Leydig cell function.

    Science.gov (United States)

    Svechnikov, K; Izzo, G; Landreh, L; Weisser, J; Söder, O

    2010-01-01

    During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  3. [Structure and function of fungal cell wall].

    Science.gov (United States)

    Ohno, Naohito

    2008-12-01

    Cell wall glycans of fungi/yeasts are reviewed. Fungi/yeasts produce various kinds of polysaccharides. As part of the cell wall they are interlinked with other components forming a huge network. The insolubility and complex with multiple components makes the research very tough. Studies on beta-glucan have been performed from various views, such as chemistry, conformation, solubility, tissue distribution and metabolism, biological activity, clinical application, receptor, biosynthesis, and antibody. Studies on mannan focus on immunotoxicity, such as anaphylactoid reaction and coronary arteritis induction. alpha-glucan, chitin, and capsular polysaccharide were also mentioned in relation to structure and genes. Compared with human and animal polysaccharides, fungi/yeasts polysaccharides have very characteristic properties.

  4. The vitamin d receptor and T cell function

    DEFF Research Database (Denmark)

    Kongsbak, Martin; Levring, Trine B; Geisler, Carsten

    2013-01-01

    ultimately to increase their chance of survival. Immune modulatory therapies that enhance VDR expression and activity are therefore considered in the clinic today to a greater extent. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies...... have been engaged investigating the impact of VDR expression in T cells and found that VDR expression and activity plays an important role in both T cell development, differentiation and effector function. In this review we will analyze current knowledge of VDR regulation and function in T cells...

  5. Functional genomics of vascular endothelial cells

    OpenAIRE

    Wallgard, Elisabet

    2008-01-01

    Angiogenesis, the formation of new blood vessels from preexisting ones, is a process involved in normal development as well as in several pathological conditions, such as cancer, ischemic heart disease, wound healing and certain retinal complications. Antiangiogenic targeting is therefore a promising new therapeutic principle. However, few blood vessel-specific drug targets have been identified, and information is still limited about endothelial cell (EC)-specific molecular ...

  6. Phenotype and functions of memory Tfh cells in human blood.

    Science.gov (United States)

    Schmitt, Nathalie; Bentebibel, Salah-Eddine; Ueno, Hideki

    2014-09-01

    Our understanding of the origin and functions of human blood CXCR5(+) CD4(+) T cells found in human blood has changed dramatically in the past years. These cells are currently considered to represent a circulating memory compartment of T follicular helper (Tfh) lineage cells. Recent studies have shown that blood memory Tfh cells are composed of phenotypically and functionally distinct subsets. Here, we review the current understanding of human blood memory Tfh cells and the subsets within this compartment. We present a strategy to define these subsets based on cell surface profiles. Finally, we discuss how increased understanding of the biology of blood memory Tfh cells may contribute insight into the pathogenesis of autoimmune diseases and the mode of action of vaccines.

  7. Impairment of B-cell functions during HIV-1 infection.

    Science.gov (United States)

    Amu, Sylvie; Ruffin, Nicolas; Rethi, Bence; Chiodi, Francesca

    2013-09-24

    A variety of B-cell dysfunctions are manifested during HIV-1 infection, as reported early during the HIV-1 epidemic. It is not unusual that the pathogenic mechanisms presented to elucidate impairment of B-cell responses during HIV-1 infection focus on the impact of reduced T-cell numbers and functions, and lack of germinal center formation in lymphoid tissues. To our understanding, however, perturbation of B-cell phenotype and function during HIV-1 infection may begin at several different B-cell developmental stages. These impairments can be mediated by intrinsic B-cell defects as well as by the lack of proper T-cell help. In this review, we will highlight some of the pathways and molecular interactions leading to B-cell impairment prior to germinal center formation and B-cell activation mediated through the B-cell receptor in response to HIV-1 antigens. Recent studies indicate a regulatory role for B cells on T-cell biology and immune responses. We will discuss some of these novel findings and how these regulatory mechanisms could potentially be affected by the intrinsic defects of B cells taking place during HIV-1 infection.

  8. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  9. Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging.

    Science.gov (United States)

    Sage, Peter T; Tan, Catherine L; Freeman, Gordon J; Haigis, Marcia; Sharpe, Arlene H

    2015-07-14

    Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice.

  10. Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging

    Directory of Open Access Journals (Sweden)

    Peter T. Sage

    2015-07-01

    Full Text Available Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR cells to stimulatory T follicular helper (TFH cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice.

  11. Modulation of Vascular Cell Function by Bim Expression

    Directory of Open Access Journals (Sweden)

    Margaret E. Morrison

    2013-01-01

    Full Text Available Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim−/− mice. Bim−/− endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim−/− endothelial cells with Bim−/− pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

  12. Modulation of vascular cell function by bim expression.

    Science.gov (United States)

    Morrison, Margaret E; Palenski, Tammy L; Jamali, Nasim; Sheibani, Nader; Sorenson, Christine M

    2013-01-01

    Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-) pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

  13. Developmental and Functional Control of Natural Killer Cells by Cytokines

    Science.gov (United States)

    Wu, Yang; Tian, Zhigang; Wei, Haiming

    2017-01-01

    Natural killer (NK) cells are effective in combating infections and tumors and as such are tempting for adoptive transfer therapy. However, they are not homogeneous but can be divided into three main subsets, including cytotoxic, tolerant, and regulatory NK cells, with disparate phenotypes and functions in diverse tissues. The development and functions of such NK cells are controlled by various cytokines, such as fms-like tyrosine kinase 3 ligand (FL), kit ligand (KL), interleukin (IL)-3, IL-10, IL-12, IL-18, transforming growth factor-β, and common-γ chain family cytokines, which operate at different stages by regulating distinct signaling pathways. Nevertheless, the specific roles of each cytokine that regulates NK cell development or that shapes different NK cell functions remain unclear. In this review, we attempt to describe the characteristics of each cytokine and the existing protocols to expand NK cells using different combinations of cytokines and feeder cells. A comprehensive understanding of the role of cytokines in NK cell development and function will aid the generation of better efficacy for adoptive NK cell treatment. PMID:28824650

  14. Functional identification of islet cell types by electrophysiological fingerprinting

    Science.gov (United States)

    Zhang, Quan; Vergari, Elisa; Kellard, Joely A.; Rodriguez, Blanca; Ashcroft, Frances M.; Rorsman, Patrik

    2017-01-01

    The α-, β- and δ-cells of the pancreatic islet exhibit different electrophysiological features. We used a large dataset of whole-cell patch-clamp recordings from cells in intact mouse islets (N = 288 recordings) to investigate whether it is possible to reliably identify cell type (α, β or δ) based on their electrophysiological characteristics. We quantified 15 electrophysiological variables in each recorded cell. Individually, none of the variables could reliably distinguish the cell types. We therefore constructed a logistic regression model that included all quantified variables, to determine whether they could together identify cell type. The model identified cell type with 94% accuracy. This model was applied to a dataset of cells recorded from hyperglycaemic βV59M mice; it correctly identified cell type in all cells and was able to distinguish cells that co-expressed insulin and glucagon. Based on this revised functional identification, we were able to improve conductance-based models of the electrical activity in α-cells and generate a model of δ-cell electrical activity. These new models could faithfully emulate α- and δ-cell electrical activity recorded experimentally. PMID:28275121

  15. Synthetic protein interactions reveal a functional map of the cell

    Science.gov (United States)

    Berry, Lisa K; Ólafsson, Guðjón; Ledesma-Fernández, Elena; Thorpe, Peter H

    2016-01-01

    To understand the function of eukaryotic cells, it is critical to understand the role of protein-protein interactions and protein localization. Currently, we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations – a key requirement for the evolution of new protein functions. To answer this question, we fused every protein in the yeast Saccharomyces cerevisiae with a partner from each of the major cellular compartments and quantitatively assessed the effects upon growth. This analysis reveals that cells have a remarkable and unanticipated tolerance for forced protein associations, even if these associations lead to a proportion of the protein moving compartments within the cell. Furthermore, the interactions that do perturb growth provide a functional map of spatial protein regulation, identifying key regulatory complexes for the normal homeostasis of eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.13053.001 PMID:27098839

  16. Ascaris lumbricoides and its invasion of the accessory cystic duct: an unusual presentation.

    Science.gov (United States)

    Majid, Zain; Masood, Irfan; Pirzada, Muhammad Taqi

    2015-04-01

    Around the world, Ascaris lumbricoides is the most common helminthic infection. We describe the case of a 25-year-old woman, known to have had Ascaris infestation, presenting with abdominal pain, constipation and jaundice together with fever and tachycardia. There was tenderness in the right hypochondrium and liver function tests confirmed cholestatic jaundice. An abdominal ultrasound showed multiple linear echogenic foci in the distal small intestine along with cholelithiasis and a thick-walled gall bladder with a single stone compressing the common bile duct (Mirizzi syndrome). The patient underwent exploratory laparotomy; more than 100 worms were found inside the small intestine and they were removed by enterotomy and manual decompression. No worm could be palpated within the common bile duct (CBD). Cholecystectomy was performed, during which an accessory cystic duct was noted opening into the common bile duct superiorly to the main cystic duct. A 10 cm live worm was found coming out of it and was removed via forceps. Later on an endoscopic retrograde cholangio-pancreatogram (ERCP) showed a widened ampulla, a mildly dilated common bile duct, but without any filling defects. The patient made an uneventful postoperative recovery being discharged on the ninth day. Worms in an accessory cystic duct have not been report in the medical literature so far.

  17. Mesenchymal stem cells support hepatocyte function in engineered liver grafts.

    Science.gov (United States)

    Kadota, Yoshie; Yagi, Hiroshi; Inomata, Kenta; Matsubara, Kentaro; Hibi, Taizo; Abe, Yuta; Kitago, Minoru; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

    2014-01-01

    Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology. In this context, the use of mesenchymal stem cells (MSC) is an option meeting the criteria for therapeutic organ engineering. Ideally, supportive cells are required to (1) reduce the hepatic cell mass needed in an engineered liver by enhancing hepatocyte function, (2) modulate hepatic regeneration in a paracrine fashion or by direct contact, and (3) enhance the preservability of parenchymal cells during storage. Here, we describe enhanced hepatic function achieved using a strategy of sequential infusion of cells and illustrate the advantages of co-cultivating bone marrow-derived MSCs with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSCs and hepatocytes were transplanted into live animals. After blood flow was established, we show that expression of adhesion molecules and proangiogenic factors was upregulated in the graft.

  18. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and functio...

  19. Experience-Dependent Plasticity in Accessory Olfactory Bulb Interneurons following Male-Male Social Interaction.

    Science.gov (United States)

    Cansler, Hillary L; Maksimova, Marina A; Meeks, Julian P

    2017-07-26

    Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early gene Arc after male-male social experience. Following the resident-intruder paradigm, Arc-expressing IGCs in acute AOB slices from resident males displayed stronger excitation than nonexpressing neighbors when sensory inputs were stimulated. The increased excitability of Arc-expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated IH currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident-intruder encounters. These results reveal that nonmating behaviors drive AOB inhibitory plasticity and indicate that increased MC inhibition involves intrinsic excitability changes in Arc-expressing interneurons.SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male-male social chemosensory encounters. We show that the plasticity

  20. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  1. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Science.gov (United States)

    Sonoyama, Wataru; Liu, Yi; Fang, Dianji; Yamaza, Takayoshi; Seo, Byoung-Moo; Zhang, Chunmei; Liu, He; Gronthos, Stan; Wang, Cun-Yu; Wang, Songlin; Shi, Songtao

    2006-12-20

    Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  2. Testicular dysgenesis syndrome and Leydig cell function

    DEFF Research Database (Denmark)

    Joensen, U.N.; Jorgensen, N.; Rajpert-De, Meyts E.

    2008-01-01

    originating in early foetal life. TDS comprises various aspects of impaired gonadal development and function, including testicular cancer. A growing body of evidence, including animal models and research in human beings, points to lifestyle factors and endocrine disrupters as risk factors for TDS. We present......Fertility among human beings appear to be on the decline in many Western countries, and part of the explanation may be decreasing male fecundity. A hypothesis has been put forward that decreasing semen quality may be associated with a testicular dysgenesis syndrome (TDS), a spectrum of disorders...

  3. Investigating evolutionary conservation of dendritic cell subset identity and functions

    Directory of Open Access Journals (Sweden)

    Thien-Phong eVu Manh

    2015-06-01

    Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

  4. Adult neural stem cells-Functional potential and therapeutic applications

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; ZHU Jianhong

    2004-01-01

    The adult brain has been thought traditionally as a structure with a very limited regenerative capacity. It is now evident that neurogenesis in adult mammalian brain is a prevailing phenomenon. Neural stem cells with the ability to self-renew, differentiate into neurons, astrocytes and oligodendrocytes reside in some regions of the adult brain. Adult neurogenesis can be stimulated by many physiological factors including pregnancy. More strikingly, newborn neurons in hippocampus integrally function with local neurons, thus neural stem cells might play important roles in memory and learning function. It seems that neural stem cells could transdifferentiate into other tissues, such as blood cells and muscles. Although there are some impediments in this field, some attempts have been made to employ adult neural stem cells in the cell replacement therapy for traumatic and ischemic brain injuries.

  5. The selection and function of cell type-specific enhancers.

    Science.gov (United States)

    Heinz, Sven; Romanoski, Casey E; Benner, Christopher; Glass, Christopher K

    2015-03-01

    The human body contains several hundred cell types, all of which share the same genome. In metazoans, much of the regulatory code that drives cell type-specific gene expression is located in distal elements called enhancers. Although mammalian genomes contain millions of potential enhancers, only a small subset of them is active in a given cell type. Cell type-specific enhancer selection involves the binding of lineage-determining transcription factors that prime enhancers. Signal-dependent transcription factors bind to primed enhancers, which enables these broadly expressed factors to regulate gene expression in a cell type-specific manner. The expression of genes that specify cell type identity and function is associated with densely spaced clusters of active enhancers known as super-enhancers. The functions of enhancers and super-enhancers are influenced by, and affect, higher-order genomic organization.

  6. Smooth muscle cells largely develop independently of functional hemogenic endothelium

    Directory of Open Access Journals (Sweden)

    Monika Stefanska

    2014-01-01

    Full Text Available Vascular smooth muscle cells represent a major component of the cardiovascular system. In vitro studies have shown that FLK1+ cells derived from embryonic stem (ES cells can differentiate into both endothelial and smooth muscle cells. These FLK1+ cells also contain a mesodermal precursor, the hemangioblast, able to produce endothelial, blood and smooth muscle cells. The generation of blood precursors from the hemangioblast was recently shown to occur through a transient cell population of specialised endothelium, a hemogenic endothelium. To date, the lineage relationship between this cell population and smooth muscle cell progenitors has not been investigated. In this study, we generated a reporter ES cell line in which expression of the fluorescent protein H2B-VENUS is driven by the α-smooth muscle actin (α-SMA regulatory sequences. We demonstrated that this reporter cell line efficiently trace smooth muscle development during ES cell differentiation. Although some smooth muscle cells are associated with broad endothelial development, we established that smooth muscle cells are mostly generated independently from a specialised functional hemogenic endothelium. This study provides new and important insights into hematopoietic and vascular development, which may help in driving further progress towards the development of bioengineered vascular grafts for regenerative medicine.

  7. Selective Function of PKC-θ in T cells

    Institute of Scientific and Technical Information of China (English)

    Santhakumar Manicassamy; Sonal Gupta; Zuoming Sun

    2006-01-01

    T cell activation is a critical process in initiating adaptive immune response since only through this process the na(i)ve antigen specific T cells differentiate into armed effector T cells that mediate the actual immune response.During T cell activation, na(i)ve T cells undergo clonal expansion and acquire the capability to kill target cells infected with pathogens or produce cytokines essential for regulating immune response. Inappropriate activation or inactivation of T cells leads to autoimmunity or severe immunodeficiencies. PKC-θ is selectively expressed in T cells and required for mediating T cell activation process. Mice deficient in PKC-θ exhibit defects in T cell activation, survival and activation-inducedcell death. PKC-θ selectively translocates to immunological synapse and mediates the signals required for activation of NF-κB, AP1 and NFAT that are essential for T cell activation.Furthermore, PKC-θ-/- mice displayed multiple defects in the development of T cell-mediated immune responses in vivo. PKC-θ is thus a critical molecule that regulates T cell function at multiple stages in T cell-mediated immune responses in vivo. Cellular & Molecular Immunology. 2006;3(4):263-270.

  8. Regulation of pituitary cell function by adiponectin.

    Science.gov (United States)

    Rodriguez-Pacheco, Francisca; Martinez-Fuentes, Antonio J; Tovar, Sulay; Pinilla, Leonor; Tena-Sempere, Manuel; Dieguez, Carlos; Castaño, Justo P; Malagon, María M

    2007-01-01

    Adiponectin is a member of the family of adipose tissue-related hormones known as adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and antiangiogenic properties. Adiponectin actions are primarily mediated through binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2. Likewise, adiponectin expression has been detected in adipocytes as well as in a variety of extra-adipose tissues, including the chicken pituitary. Interestingly, adiponectin secretion and adiponectin receptor expression in adipocytes have been shown to be regulated by pituitary hormones. These observations led us to investigate whether adiponectin, like the adipokine leptin, regulates pituitary hormone production. Specifically, we focused our analysis on somatotrophs and gonadotrophs because of the relationship between the control of energy metabolism, growth and reproduction. To this end, the effects of adiponectin on both GH and LH secretion as well as its interaction with major stimulatory regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat pituitary cell cultures. Results show that adiponectin inhibits GH and LH release as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH-R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we demonstrate that the pituitary expresses both adiponectin and adiponectin receptors under the regulation of the adipokine. In sum, our data indicate that adiponectin, either locally produced or from other sources, may play a neuroendocrine role in the control of both somatotrophs and gonadotrophs.

  9. Molecular Mechanisms Regulating Human Dendritic Cell Development, Survival and Function

    NARCIS (Netherlands)

    L. van de Laar (Lianne)

    2011-01-01

    textabstractDendritic cells (DC) are professional antigen presenting cells (APC) with a dual function in the immune system. On the one hand, these specialized leukocytes are equipped to alert the immune system to invading pathogens or other danger signals. On the other, DC can promote tolerogenic re

  10. Human CD8 T cells generated in vitro from hematopoietic stem cells are functionally mature

    Directory of Open Access Journals (Sweden)

    Zúñiga-Pflücker Juan

    2011-03-01

    Full Text Available Abstract Background T cell development occurs within the highly specialized thymus. Cytotoxic CD8 T cells are critical in adaptive immunity by targeting virally infected or tumor cells. In this study, we addressed whether functional CD8 T cells can be generated fully in vitro using human umbilical cord blood (UCB hematopoietic stem cells (HSCs in coculture with OP9-DL1 cells. Results HSC/OP9-DL1 cocultures supported the differentiation of CD8 T cells, which were TCR/CD3hi CD27hi CD1aneg and thus phenotypically resembled mature functional CD8 single positive thymocytes. These in vitro-generated T cells also appeared to be conventional CD8 cells, as they expressed high levels of Eomes and low levels of Plzf, albeit not identical to ex vivo UCB CD8 T cells. Consistent with the phenotypic and molecular characterization, upon TCR-stimulation, in vitro-generated CD8 T cells proliferated, expressed activation markers (MHC-II, CD25, CD38, secreted IFN-γ and expressed Granzyme B, a cytotoxic T-cell effector molecule. Conclusion Taken together, the ability to direct human hematopoietic stem cell or T-progenitor cells towards a mature functional phenotype raises the possibility of establishing cell-based treatments for T-immunodeficiencies by rapidly restoring CD8 effector function, thereby mitigating the risks associated with opportunistic infections.

  11. Neural progenitor cells regulate microglia functions and activity.

    Science.gov (United States)

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  12. Functional transcriptomics of a migrating cell in Caenorhabditis elegans.

    Science.gov (United States)

    Schwarz, Erich M; Kato, Mihoko; Sternberg, Paul W

    2012-10-02

    In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi-treated L4 larvae. We observed expression of 8,000-10,000 genes in the linker cell, 22-25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67-dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.

  13. Amine-functionalized polypyrrole: Inherently cell adhesive conducting polymer.

    Science.gov (United States)

    Lee, Jae Y; Schmidt, Christine E

    2015-06-01

    Electrically conducting polymers (CPs) have been recognized as novel biomaterials that can electrically communicate with biological systems. For their tissue engineering applications, CPs have been modified to promote cell adhesion for improved interactions between biomaterials and cells/tissues. Conventional approaches to improve cell adhesion involve the surface modification of CPs with biomolecules, such as physical adsorption of cell adhesive proteins and polycationic polymers, or their chemical immobilization; however, these approaches require additional multiple modification steps with expensive biomolecules. In this study, as a simple and effective alternative to such additional biomolecule treatment, we synthesized amine-functionalized polypyrrole (APPy) that inherently presents cell adhesion-supporting positive charges under physiological conditions. The synthesized APPy provides electrical activity in a moderate range and a hydrophilic surface compared to regular polypyrrole (PPy) homopolymers. Under both serum and serum-free conditions, APPy exhibited superior attachment of human dermal fibroblasts and Schwann cells compared to PPy homopolymer controls. Moreover, Schwann cell adhesion onto the APPy copolymer was at least similar to that on poly-l-lysine treated PPy controls. Our results indicate that amine-functionalized CP substrates will be useful to achieve good cell adhesion and potentially electrically stimulate various cells. In addition, amine functionality present on CPs can further serve as a novel and flexible platform to chemically tether various bioactive molecules, such as growth factors, antibodies, and chemical drugs. © 2014 Wiley Periodicals, Inc.

  14. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

  15. Male Age Affects Female Mate Preference, Quantity of Accessory Gland Proteins, and Sperm Traits and Female Fitness in D. melanogaster.

    Science.gov (United States)

    Rezaei, Abolhasan; Krishna, Mysore Siddaiah; Santhosh, Hassan T

    2015-01-01

    For species in which mating is resource-independent and offspring do not receive parental care, theoretical models of age-based female mate preference predict that females should prefer to mate with older males as they have demonstrated ability to survive. Thus, females should obtain a fitness benefit from mating with older males. However, male aging is often associated with reductions in quantity of sperm. The adaptive significance of age-based mate choice is therefore unclear. Various hypotheses have made conflicting predictions concerning this issue, because published studies have not investigated the effect of age on accessory gland proteins and sperm traits. D. melanogaster exhibits resource-independent mating, and offspring do not receive parental care, making this an appropriate model for studying age-based mate choice. In the present study, we found that D. melanogaster females of all ages preferred to mate with the younger of two competing males. Young males performed significantly greater courtship attempts and females showed least rejection for the same than middle-aged and old males. Young males had small accessory glands that contained very few main cells that were larger than average. Nevertheless, compared with middle-aged or old males, the young males transferred greater quantities of accessory gland proteins and sperm to mated females. As a result, females that mated with young male produced more eggs and progeny than those that mated with older males. Furthermore, mating with young male reduced female's lifespan. These studies indicate that quantity of accessory gland proteins and sperm traits decreased with male age and females obtain direct fitness benefit from mating with preferred young males.

  16. Microfluidics as a functional tool for cell mechanics.

    Science.gov (United States)

    Vanapalli, Siva A; Duits, Michel H G; Mugele, Frieder

    2009-01-05

    Living cells are a fascinating demonstration of nature's most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax-thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both controlling and manipulating the cell microenvironment and measuring the resulting mechanical response. In this review, the power of microfluidics as a functional tool for research in cell mechanics is highlighted. In particular, current literature is discussed to show that microfluidics powered by soft lithographic techniques offers the following capabilities that are of significance for understanding the mechanical behavior of cells: (i) Microfluidics enables the creation of in vitro models of physiological environments in which cell mechanics can be probed. (ii) Microfluidics is an excellent means to deliver physical cues that affect cell mechanics, such as cell shape, fluid flow, substrate topography, and stiffness. (iii) Microfluidics can also expose cells to chemical cues, such as growth factors and drugs, which alter their mechanical behavior. Moreover, these chemical cues can be delivered either at the whole cell or subcellular level. (iv) Microfluidic devices offer the possibility of measuring the intrinsic mechanical properties of cells in a high throughput fashion. (v) Finally, microfluidic methods provide exquisite control over drop size, generation, and manipulation. As a result, droplets are being increasingly used to control the physicochemical environment of cells and as biomimetic analogs of living cells. These powerful attributes of microfluidics should further stimulate novel means of investigating the link between physicochemical cues and the biomechanical

  17. Melatonin signaling in T cells: Functions and applications.

    Science.gov (United States)

    Ren, Wenkai; Liu, Gang; Chen, Shuai; Yin, Jie; Wang, Jing; Tan, Bie; Wu, Guoyao; Bazer, Fuller W; Peng, Yuanyi; Li, Tiejun; Reiter, Russel J; Yin, Yulong

    2017-04-01

    Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status, and immune function. Importantly, melatonin significantly influences T-cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T-cell biology and the beneficial effects of melatonin in T-cell response-based diseases. In addition to expressing both membrane and nuclear receptors for melatonin, T cells have the four enzymes required for the synthesis of melatonin and produce high levels of melatonin. Meanwhile, melatonin is highly effective in modulating T-cell activation and differentiation, especially for Th17 and Treg cells, and also memory T cells. Mechanistically, the influence of melatonin in T-cell biology is associated with membrane and nuclear receptors as well as receptor-independent pathways, for example, via calcineurin. Several cell signaling pathways, including ERK1/2-C/EBPα, are involved in the regulatory roles of melatonin in T-cell biology. Through modulation in T-cell responses, melatonin exerts beneficial effects in various inflammatory diseases, such as type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. These findings highlight the importance of melatonin signaling in T-cell fate determination, and T cell-based immune pathologies.

  18. Salivary gland NK cells are phenotypically and functionally unique.

    Science.gov (United States)

    Tessmer, Marlowe S; Reilly, Emma C; Brossay, Laurent

    2011-01-13

    Natural killer (NK) cells and CD8(+) T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV) infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg) cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

  19. Salivary gland NK cells are phenotypically and functionally unique.

    Directory of Open Access Journals (Sweden)

    Marlowe S Tessmer

    2011-01-01

    Full Text Available Natural killer (NK cells and CD8(+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV. However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

  20. Xylem cell death: emerging understanding of regulation and function.

    Science.gov (United States)

    Bollhöner, Benjamin; Prestele, Jakob; Tuominen, Hannele

    2012-02-01

    Evolutionary, as well as genetic, evidence suggests that vascular development evolved originally as a cell death programme that allowed enhanced movement of water in the extinct protracheophytes, and that secondary wall formation in the water-conducting cells evolved afterwards, providing mechanical support for effective long-distance transport of water. The extant vascular plants possess a common regulatory network to coordinate the different phases of xylem maturation, including secondary wall formation, cell death, and finally autolysis of the cell contents, by the action of recently identified NAC domain transcription factors. Consequently, xylem cell death is an inseparable part of the xylem maturation programme, making it difficult to uncouple cell death mechanistically from secondary wall formation, and thus identify the key factors specifically involved in regulation of cell death. Current knowledge suggests that the necessary components for xylem cell death are produced early during xylem differentiation, and cell death is prevented through the action of inhibitors and storage of hydrolytic enzymes in inactive forms in compartments such as the vacuole. Bursting of the central vacuole triggers autolytic hydrolysis of the cell contents, which ultimately leads to cell death. This cascade of events varies between the different xylem cell types. The water-transporting tracheary elements rely on a rapid cell death programme, with hydrolysis of cell contents taking place for the most part, if not entirely, after vacuolar bursting, while the xylem fibres disintegrate cellular contents at a slower pace, well before cell death. This review includes a detailed description of cell morphology, function of plant growth regulators, such as ethylene and thermospermine, and the action of hydrolytic nucleases and proteases during cell death of the different xylem cell types.

  1. Study on reduction of accessory-horsepower requirements. Third quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    1975-04-23

    The objective of this study program is to minimize automotive accessory horsepower consumption, and thereby maximize overall vehicle fuel economy, by utilizing continuously variable speed drives or auxiliary power units (APUs) in a standard passenger automobile. As an aid to definitizing accessory performance, load requirements and fuel economy, a baseline vehicle has beeen established. This vehicle is a conventional intermediate size 5- or 6-passenger automobile with a 4.1 to 5.7 liter (250 to 350 cubic inch) displacement, spark ignition engine. Accessories to be considered are the alternator, power steering system, power brakes, air conditioner, cooling fan, water pump and emission control air pump. A program summary of major accomplishments is presented including: accessory drive devices analyses; vehicle computer model fuel economy analyses; improved accessory efficiency analysis; resized engine fuel economy analysis; accessory evaluation matrix completed; drive-systems trade-study completed and the prime concept presented; and variable-speed belt-drive concepts reviewed.

  2. Accessory spleen presenting as acute abdomen: A case report and operative management

    Directory of Open Access Journals (Sweden)

    A. Landmann

    2016-09-01

    Full Text Available Accessory spleens are found in 10–30% of patients and are asymptomatic. Rarely, torsion of an accessory spleen can cause abdominal pain and acute abdomen. We present the case of an 8-year-old girl who arrives to the emergency room with left upper quadrant abdominal pain. CT scan revealed a non-enhancing soft tissue mass and multiple small splenules. Laparoscopy revealed a torsed accessory spleen and malrotation. Accessory spleen is a common congenital anomaly that is frequently asymptomatic. Rarely, an accessory spleen may become torsed around its vascular pedicle resulting in severe abdominal pain. Treatment is surgical resection. Torsion of accessory splenic tissue is a rare cause of acute abdomen in pediatric patients.

  3. Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function.

    Directory of Open Access Journals (Sweden)

    Venkateswara Rao Simhadri

    Full Text Available NKp30, a natural cytotoxicity receptor expressed on NK cells is critically involved in direct cytotoxicity against various tumor cells and directs both maturation and selective killing of dendritic cells. Recently the intracellular protein BAT3, which is involved in DNA damage induced apoptosis, was identified as a ligand for NKp30. However, the mechanisms underlying the exposure of the intracellular ligand BAT3 to surface NKp30 and its role in NK-DC cross talk remained elusive. Electron microscopy and flow cytometry demonstrate that exosomes released from 293T cells and iDCs express BAT3 on the surface and are recognized by NKp30-Ig. Overexpression and depletion of BAT3 in 293T cells directly correlates with the exosomal expression level and the activation of NK cell-mediated cytokine release. Furthermore, the NKp30-mediated NK/DC cross talk resulting either in iDC killing or maturation was BAT3-dependent. Taken together this puts forward a new model for the activation of NK cells through intracellular signals that are released via exosomes from accessory cells. The manipulation of the exosomal regulation may offer a novel strategy to induce tumor immunity or inhibit autoimmune diseases caused by NK cell-activation.

  4. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    Science.gov (United States)

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  5. Mitochondrial function in Müller cells - Does it matter?

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Svare, Alicia

    2017-01-01

    Growing evidence suggests that mitochondrial dysfunction might play a key role in the pathogenesis of age-related neurodegenerative inner retinal diseases such as diabetic retinopathy and glaucoma. Therefore, the present review provides a perspective on the impact of functional mitochondria...... energy production and previous literature has primarily emphasized glycolysis as the main energy provider. However, recent studies highlight the need of mitochondrial ATP production to upheld Müller cell functions. Therefore, the present review aims to provide an overview of the current evidence...... on the impact of mitochondrial functions in Müller cells....

  6. Osmotic stress affects functional properties of human melanoma cell lines

    CERN Document Server

    La Porta, Caterina A M; Pasini, Maria; Laurson, Lasse; Alava, Mikko J; Zapperi, Stefano; Amar, Martine Ben

    2015-01-01

    Understanding the role of microenvironment in cancer growth and metastasis is a key issue for cancer research. Here, we study the effect of osmotic pressure on the functional properties of primary and metastatic melanoma cell lines. In particular, we experimentally quantify individual cell motility and transmigration capability. We then perform a circular scratch assay to study how a cancer cell front invades an empty space. Our results show that primary melanoma cells are sensitive to a low osmotic pressure, while metastatic cells are less. To better understand the experimental results, we introduce and study a continuous model for the dynamics of a cell layer and a stochastic discrete model for cell proliferation and diffusion. The two models capture essential features of the experimental results and allow to make predictions for a wide range of experimentally measurable parameters.

  7. Derivation and Utilization of Functional CD8(+) Dendritic Cell Lines.

    Science.gov (United States)

    Pigni, Matteo; Ashok, Devika; Acha-Orbea, Hans

    2016-01-01

    It is notoriously difficult to obtain large quantities of non-activated dendritic cells ex vivo. For this reason, we produced and characterized a mouse model expressing the large T oncogene under the CD11c promoter (Mushi mice), in which CD8α(+) dendritic cells transform after 4 months. We derived a variety of stable cell lines from these primary lines. These cell lines reproducibly share with freshly isolated dendritic cells most surface markers, mRNA and protein expression, and all tested biological functions. Cell lines can be derived from various strains and knockout mice and can be easily transduced with lentiviruses. In this article, we describe the derivation, culture, and lentiviral transduction of these dendritic cell lines.

  8. Multiple layers of B cell memory with different effector functions.

    Science.gov (United States)

    Dogan, Ismail; Bertocci, Barbara; Vilmont, Valérie; Delbos, Frédéric; Mégret, Jérome; Storck, Sébastien; Reynaud, Claude-Agnès; Weill, Jean-Claude

    2009-12-01

    Memory B cells are at the center of longstanding controversies regarding the presence of antigen for their survival and their re-engagement in germinal centers after secondary challenge. Using a new mouse model of memory B cell labeling dependent on the cytidine deaminase AID, we show that after immunization with a particulate antigen, B cell memory appeared in several subsets, comprising clusters of immunoglobulin M-positive (IgM(+)) and IgG1(+) B cells in germinal center-like structures that persisted up to 8 months after immunization, as well as IgM(+) and IgG1(+) B cells with a memory phenotype outside of B cell follicles. After challenge, the IgG subset differentiated into plasmocytes, whereas the IgM subset reinitiated a germinal center reaction. This model, in which B cell memory appears in several layers with different functions, reconciles previous conflicting propositions.

  9. Transplantation of mouse fetal liver cells for analyzing the function of hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Gudmundsson, Kristbjorn Orri; Stull, Steven W; Keller, Jonathan R

    2012-01-01

    Hematopoietic stem cells are defined by their ability to self-renew and differentiate through progenitor cell stages into all types of mature blood cells. Gene-targeting studies in mice have demonstrated that many genes are essential for the generation and function of hematopoietic stem and progenitor cells. For definitively analyzing the function of these cells, transplantation studies have to be performed. In this chapter, we describe methods to isolate and transplant fetal liver cells as well as how to analyze donor cell reconstitution. This protocol is tailored toward mouse models where embryonic lethality precludes analysis of adult hematopoiesis or where it is suspected that the function of fetal liver hematopoietic stem and progenitor cells is compromised.

  10. Characterization and functionality of proliferative human Sertoli cells.

    Science.gov (United States)

    Chui, Kitty; Trivedi, Alpa; Cheng, C Yan; Cherbavaz, Diana B; Dazin, Paul F; Huynh, Ai Lam Thu; Mitchell, James B; Rabinovich, Gabriel A; Noble-Haeusslein, Linda J; John, Constance M

    2011-01-01

    It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2'-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility

  11. A Case Report on Unilateral Accessory Humeral Head of Pronator Teres

    OpenAIRE

    Verma, Suman; Sakthivel, Sulochana

    2016-01-01

    The presence of an accessory muscle in the forearm is likely to compress on the neurovascular structures and has clinical implications. We encountered an accessory humeral head of pronator teres during routine dissection of left upper limb in a male cadaver. The accessory head had fleshy origin from medial supracondylar line, medial intermuscular septum and brachialis fascia. It coursed downwards in the cubital region covering brachial artery and median nerve. Further, it narrowed becoming mo...

  12. Total laparoscopic removal of accessory gallbladder: A case report and review of literature

    OpenAIRE

    2015-01-01

    Accessory gallbladder is a rare congenital anomaly occurring in 1 in 4000 births, that is not associated with any specific symptoms. Usually this cannot be diagnosed on ultrasonography and hence they are usually not diagnosed preoperatively. Removal of the accessory gallbladder is necessary to avoid recurrence of symptoms. H-type accessory gallbladder is a rare anomaly. Once identified intra-operatively during laparoscopic cholecystectomy, the surgery is usually converted to open. By using th...

  13. Accessory Genes Confer a High Replication Rate to Virulent Feline Immunodeficiency Virus

    OpenAIRE

    Troyer, Ryan M.; Thompson, Jesse; Elder, John H.; VandeWoude, Sue

    2013-01-01

    Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS in domestic cats, similar to human immunodeficiency virus (HIV)/AIDS in humans. The FIV accessory protein Vif abrogates the inhibition of infection by cat APOBEC3 restriction factors. FIV also encodes a multifunctional OrfA accessory protein that has characteristics similar to HIV Tat, Vpu, Vpr, and Nef. To examine the role of vif and orfA accessory genes in FIV replication and pathogenicity, we generated chimeras between tw...

  14. Extraperitoneal Pelvic laparoscopic disconnection of accessory urethra from normal urethra in a case of urethral duplication.

    Science.gov (United States)

    Pant, Nitin; Aggarwal, Satish Kumar

    2014-04-01

    We report an extraperitoneal pelvic laparoscopic approach to disconnect accessory urethra from normal urethra in complete urethral duplication. First stage consisted of chordee correction, partial excision of the accessory urethra and glansplasty. In the second stage the remaining accessory urethra was disconnected from the normal urethra through a pre-peritoneal minimal access approach to the retropubic space. The remaining distal mucosa was ablated using monopolar cautery.

  15. Extraperitoneal Pelvic laparoscopic disconnection of accessory urethra from normal urethra in a case of urethral duplication

    Directory of Open Access Journals (Sweden)

    Nitin Pant

    2014-01-01

    Full Text Available We report an extraperitoneal pelvic laparoscopic approach to disconnect accessory urethra from normal urethra in complete urethral duplication. First stage consisted of chordee correction, partial excision of the accessory urethra and glansplasty. In the second stage the remaining accessory urethra was disconnected from the normal urethra through a pre-peritoneal minimal access approach to the retropubic space. The remaining distal mucosa was ablated using monopolar cautery.

  16. Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable.

    Science.gov (United States)

    Maben, Zachary J; Malik, Sundeep; Jiang, Liyi H; Hinkle, Patricia M

    2016-01-01

    Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling. MRAP is a single transmembrane domain protein that forms antiparallel homodimers. These studies ask when MRAP first acquires this dual topology, whether MRAP architecture is static or stable, and whether the accessory protein undergoes rapid turnover. To answer these questions, we developed an approach that capitalizes on the specificity of bacterial biotin ligase, which adds biotin to lysine in a short acceptor peptide sequence; the distinct mobility of MRAP protomers of opposite orientations based on their N-linked glycosylation; and the ease of identifying biotin-labeled proteins. We inserted biotin ligase acceptor peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins in mammalian cells together with either cytoplasmic or endoplasmic reticulum-targeted biotin ligase. MRAP assumed dual topology early in biosynthesis in both CHO and OS3 adrenal cells. Once established, MRAP orientation was stable. Despite its conformational stability, MRAP displayed a half-life of under 2 h in CHO cells. The amount of MRAP was increased by the proteasome inhibitor MG132 and MRAP underwent ubiquitylation on lysine and other amino acids. Nonetheless, when protein synthesis was blocked with cycloheximide, MRAP was rapidly degraded even when MG132 was included and all lysines were replaced by arginines, implicating non-proteasomal degradation pathways. The results show that although MRAP does not change orientations during trafficking, its synthesis and degradation are dynamically regulated.

  17. Functional motor microdomains of the outer hair cell lateral membrane.

    Science.gov (United States)

    Santos-Sacchi, Joseph

    2002-12-01

    The outer hair cell (OHC) of the mammalian inner ear is a highly partitioned neuroepithelial cell whose lateral membrane is devoted to electromotility, a fast mechanical length change owing to the motor protein, prestin. Spatially restricted measures of prestin-derived nonlinear capacitance or gating charge, using either electrical amputation or discrete membrane mechanical deformation, were used to determine that functional variation exists within the extensive lateral membrane of the cell. This was evidenced by variation in the motor's operating voltage range and sensitivity among microdomains within the lateral membrane. That is, localized regions of the membrane evidenced Boltzmann distributions of motor charge whose midpoint voltage and slope differed from those obtained for the whole cell. These data highlight the functional independence of microdomains and imply that measured whole cell characteristics may differ from the microscopic characteristics of elementary motors.

  18. Analysis of the pharmacological properties of chicken melanocortin-2 receptor (cMC2R) and chicken melanocortin-2 accessory protein 1 (cMRAP1).

    Science.gov (United States)

    Barlock, Travis K; Gehr, Deshae T; Dores, Robert M

    2014-09-01

    The chicken (Gallus gallus) melanocortin-2 receptor (cMC2R) can be functionally expressed in CHO cells when chicken melanocortin-2 receptor accessory protein 1 (cMRAP1) is co-expressed. The transiently transfected CHO cells responded in a robust manner to stimulation by hACTH(1-24) (EC50 value=2.7 × 10(-12)M +/- 1.3 × 10(-12)), but the transfected CHO cells could not be stimulated by NDP-MSH at concentrations as high as 10(-7)M. Incubation of cMC2R/cMRAP1 transfected cells with alanine substituted analogs of hACTH(1-24) at amino acid positions F(7) or W(9) completely blocked stimulation of the transfected cells. Similarly, incubation of cMC2R/cMRAP1 transfected cells with an analog of hACTH(1-24) with alanine substitutions at amino acid positions R(17)R(18)P(19) resulted in a 276 fold shift in EC50 value relative to the positive control (pHFRW motif and KKRRP motif of hACTH(1-24), and both motifs are required for full activation of the receptor. While previous studies had shown that Anolis carolinensis MC2R and Xenopus tropicalis MC2R could be functionally expressed in CHO cells that co-expressed mouse MRAP1, co-expression of these non-mammalian tetrapod MC2Rs with cMRAP1 resulted in a significant increase in sensitivity to hACTH(1-24), as measured by EC50 value, for A. carolinensis MC2R (p<0.005) and X. tropicalis MC2R (p<0.007). The implications of these observations are discussed.

  19. Expression and function of FERMT genes in colon carcinoma cells.

    Science.gov (United States)

    Kiriyama, Kenji; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Kubo, Terufumi; Tamura, Yasuaki; Kanaseki, Takayuki; Takahashi, Akari; Nakazawa, Emiri; Saka, Eri; Ragnarsson, Charlotte; Nakatsugawa, Munehide; Inoda, Satoko; Asanuma, Hiroko; Takasu, Hideo; Hasegawa, Tadashi; Yasoshima, Takahiro; Hirata, Koichi; Sato, Noriyuki

    2013-01-01

    Invasion into the matrix is one of hallmarks of malignant diseases and is the first step for tumor metastasis. Thus, analysis of the molecular mechanisms of invasion is essential to overcome tumor cell invasion. In the present study, we screened for colon carcinoma-specific genes using a cDNA microarray database of colon carcinoma tissues and normal colon tissues, and we found that fermitin family member-1 (FERMT1) is overexpressed in colon carcinoma cells. FRRMT1, FERMT2 and FERMT3 expression was investigated in colon carcinoma cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that only FERMT1 had cancer cell-specific expression. Protein expression of FERMT1 was confirmed by western blotting and immunohistochemical staining. To address the molecular functions of FERMT genes in colon carcinoma cells, we established FERMT1-, FERMT2- and FERMT3-overexpressing colon carcinoma cells. FERMT1-overexpressing cells exhibited greater invasive ability than did FERMT2- and FERMT3-overexpressing cells. On the other hand, FERMT1-, FERMT2- and FERMT3-overexpressing cells exhibited enhancement of cell growth. Taken together, the results of this study indicate that FERMT1 is expressed specifically in colon carcinoma cells, and has roles in matrix invasion and cell growth. These findings indicate that FERMT1 is a potential molecular target for cancer therapy.

  20. Bilateral Tensor Fasciae Suralis Muscles in a Cadaver with Unilateral Accessory Flexor Digitorum Longus Muscle

    Directory of Open Access Journals (Sweden)

    Logan S. W. Bale

    2017-01-01

    Full Text Available Muscle variants are routinely encountered in the dissection laboratory and in clinical practice and therefore anatomists and clinicians need to be aware of their existence. Here we describe two different accessory muscles identified while performing educational dissection of a 51-year-old male cadaver. Tensor fasciae suralis, a rare muscle variant, was identified bilaterally and accessory flexor digitorum longus, a more common muscle variant, was present unilaterally. Tensor fasciae suralis and accessory flexor digitorum longus are clinically relevant muscle variants. To our knowledge, the coexistence of tensor fasciae suralis and accessory flexor digitorum longus in the same individual has not been reported in either cadaveric or imaging studies.

  1. Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features.

    Science.gov (United States)

    Zhu, Wangyong; Hu, Fengchun; Liu, Xingguang; Guo, Songcan; Tao, Qian

    2016-01-01

    This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student's t test was used to compare the length of Stensen's duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen's duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen's duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen's duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis.

  2. Incomplete and accessory fissures of the lung evaluated by high-resolution computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Heřmanová, Zuzana, E-mail: zuzana.hermanova2@fnol.cz; Čtvrtlík, Filip, E-mail: filip.ctvrtlik@fnol.cz; Heřman, Miroslav, E-mail: herman@fnol.cz

    2014-03-15

    Purpose: The aim of our study was to assess incomplete and accessory interlobar fissures using volumetric thin-section high-resolution computed tomography (HRCT). Materials and methods: Retrospective assessment of HRCT examinations of 250 patients was performed. We assessed the localization, extension, and type of the incompleteness of fissures as well as the presence and localization of accessory fissures. We searched for possible correlation among the localization of interlobar fissures, the presence of incompleteness, and accessory fissures. Results: On the left side, an incomplete oblique fissure was found in 24%. The discontinuity was present in the parahilar region and the area of the incompleteness was most frequently between 21% and 40%. The right oblique fissure was incomplete in 35%, mostly parahilarly, with the most frequent discontinuity below 20%. An incomplete horizontal fissure was found in 74%. Accessory fissures were identified in 16% of patients, with the same frequency on both sides. The most frequent finding was accessory horizontal fissure with 8.0% on the left side, superior accessory fissure (7.2%) and inferior accessory fissure (5.2%) on the right side. No correlation was found among the localization of interlobar fissures, the presence of incompleteness, and accessory fissures. Conclusion: Incomplete and accessory fissures are frequent anatomic variations of interlobar fissures.

  3. Ras proteins have multiple functions in vegetative cells of Dictyostelium.

    Science.gov (United States)

    Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

    2010-11-01

    During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG⁻ cells are only partially deficient in chemotaxis, whereas rasC⁻/rasG⁻ cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG⁻, rasC⁻, and rasC⁻/rasG⁻ cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG⁻ and rasC⁻/rasG⁻ cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG⁻ and rasC⁻/rasG⁻ cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells.

  4. Role of liver functions on liver cell mitosis

    Directory of Open Access Journals (Sweden)

    Takata,Tameyuki

    1974-06-01

    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  5. GSM accessories now available from the CERN Stores

    CERN Multimedia

    Labo Telecom

    2001-01-01

    As of 1st October you can order and receive GSM accessories from the CERN stores like any other article. The CERN stores also manage GSM telephones but, for technical reasons, only the Labo Telecom shop (Building 31, Room S026) is able to make the standard sales, repairs and exchanges for authorised persons with a CERN subscription. Labo Telecom will thus become a specialist shop, open from 11 a.m. to 12 a.m., and will apply the usual rules and authorisation procedures of the stores. The paper form for requests for GSM subscriptions is being computerized and will be available on EDH in the near future.

  6. Accessory breast tissue in axilla masquerading as breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Goyal Shikha

    2008-01-01

    Full Text Available Ectopic or accessory breast tissue is most commonly located in the axilla, though it may be present anywhere along the milk line. Development is hormone dependent, similar to normal breast tissue. These lesions do not warrant any intervention unless they produce discomfort, thus their identification and distinction from other breast pathologies, both benign and malignant, is essential. We report a case with locally advanced breast cancer who presented with an ipsilateral axillary mass following surgery, radiotherapy, and chemotherapy. Subsequent evaluation with excision biopsy showed duct ectasia in axillary breast tissue and the patient was continued on hormone therapy with tamoxifen.

  7. MyosinV controls PTEN function and neuronal cell size.

    Science.gov (United States)

    van Diepen, Michiel T; Parsons, Maddy; Downes, C Peter; Leslie, Nicholas R; Hindges, Robert; Eickholt, Britta J

    2009-10-01

    The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types. PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P(3) to PtdIns(4,5)P(2), thereby antagonizing PI(3)K (phosphoinositide 3-kinase) and its established downstream effector pathways. However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P(3) (Refs 3, 4, 5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Förster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV-transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss, required PI(3)K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

  8. Structure and function of endosomes in plant cells.

    Science.gov (United States)

    Contento, Anthony L; Bassham, Diane C

    2012-08-01

    Endosomes are a heterogeneous collection of organelles that function in the sorting and delivery of internalized material from the cell surface and the transport of materials from the Golgi to the lysosome or vacuole. Plant endosomes have some unique features, with an organization distinct from that of yeast or animal cells. Two clearly defined endosomal compartments have been studied in plant cells, the trans-Golgi network (equivalent to the early endosome) and the multivesicular body (equivalent to the late endosome), with additional endosome types (recycling endosome, late prevacuolar compartment) also a possibility. A model has been proposed in which the trans-Golgi network matures into a multivesicular body, which then fuses with the vacuole to release its cargo. In addition to basic trafficking functions, endosomes in plant cells are known to function in maintenance of cell polarity by polar localization of hormone transporters and in signaling pathways after internalization of ligand-bound receptors. These signaling functions are exemplified by the BRI1 brassinosteroid hormone receptor and by receptors for pathogen elicitors that activate defense responses. After endocytosis of these receptors from the plasma membrane, endosomes act as a signaling platform, thus playing an essential role in plant growth, development and defense responses. Here we describe the key features of plant endosomes and their differences from those of other organisms and discuss the role of these organelles in cell polarity and signaling pathways.

  9. Cell viability and functionality of probiotic bacteria in dairy products

    Directory of Open Access Journals (Sweden)

    Gabriel eVinderola

    2011-05-01

    Full Text Available Probiotic bacteria, according to the definition adopted by the World Health Organization in 2002, are live microorganisms, which when administered in adequate amounts confer a health benefit to the host. Recent studies show that the same probiotic strain produced and/or preserved under different storage conditions, may present different responses regarding their susceptibility to the adverse conditions of the gastrointestinal tract, its capacity to adhere to the intestinal epithelium, or its immunomodulating capacity, being the functionality affected without changes in cell viability. This could imply that the control of cell viability is not always enough to guarantee the functionality (probiotic capacity of a strain. Therefore, a new challenge arises for food technologists and microbiologists when it comes to designing and monitoring probiotic food: to be able to monitor the cell functionality a probiotic microorganism along all the stages the strain goes through from the moment it is produced and included into the food vehicle until to the moment of consumption. Conventional methodological tools or others still to be developed must be used. The application of cell membrane functionality markers, the use of tests of resistence to intestinal barriers, the study of surface properties and the application of in vivo models comes together as complementary tools to assess the actual capacity of a probiotic into a specific food to exert functional effects regardless the number of viable cells present at the moment of consumption.

  10. Serotonin of mast cell origin contributes to hippocampal function.

    Science.gov (United States)

    Nautiyal, Katherine M; Dailey, Christopher A; Jahn, Jaquelyn L; Rodriquez, Elizabeth; Son, Nguyen Hong; Sweedler, Jonathan V; Silver, Rae

    2012-08-01

    In the central nervous system, serotonin, an important neurotransmitter and trophic factor, is synthesized by both mast cells and neurons. Mast cells, like other immune cells, are born in the bone marrow and migrate to many tissues. We show that they are resident in the mouse brain throughout development and adulthood. Measurements based on capillary electrophoresis with native fluorescence detection indicate that a significant contribution of serotonin to the hippocampal milieu is associated with mast cell activation. Compared with their littermates, mast cell-deficient C57BL/6 Kit(W-sh/W-sh) mice have profound deficits in hippocampus-dependent spatial learning and memory and in hippocampal neurogenesis. These deficits are associated with a reduction in cell proliferation and in immature neurons in the dentate gyrus, but not in the subventricular zone - a neurogenic niche lacking mast cells. Chronic treatment with fluoxetine, a selective serotonin reuptake inhibitor, reverses the deficit in hippocampal neurogenesis in mast cell-deficient mice. In summary, the present study demonstrates that mast cells are a source of serotonin, that mast cell-deficient C57BL/6 Kit(W-sh/W-sh) mice have disrupted hippocampus-dependent behavior and neurogenesis, and that elevating serotonin in these mice, by treatment with fluoxetine, reverses these deficits. We conclude that mast cells contribute to behavioral and physiological functions of the hippocampus and note that they play a physiological role in neuroimmune interactions, even in the absence of inflammatory responses.

  11. Altered effector function of peripheral cytotoxic cells in COPD

    Directory of Open Access Journals (Sweden)

    Corne Jonathan M

    2009-06-01

    Full Text Available Abstract Background There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD. We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3- cells and NKT-like (CD56+CD3+ cells. Methods Peripheral blood mononuclear cells (PBMCs were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3- and NKT-like (CD56+CD3+ cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies. Results The proportion of peripheral blood NKT-like (CD56+CD3+ cells in smokers with COPD (COPD subjects was significantly lower (0.6% than in healthy smokers (smokers (2.8%, p +CD3- cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p +CD3+ cells (16.7% vs 52.4% specific lysis, p +CD3- and NKT-like (CD56+CD3+ cells from smokers and HNS. Conclusion In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3- and NKT-like (CD56+CD3+ cells in COPD subjects are reduced and that their cytotoxic effector function is defective.

  12. Invited article: inhibition of B cell functions: implications for neurology.

    Science.gov (United States)

    Dalakas, Marinos C

    2008-06-01

    B cells are involved in the pathophysiology of many neurologic diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. B cells are clonally expanded in various CNS disorders, such as multiple sclerosis (MS), paraneoplastic CNS disorders, or stiff-person syndrome, and are activated to produce pathogenic autoantibodies in demyelinating neuropathies and myasthenia. B cell activating factor (BAFF) and a proliferating inducing ligand (APRIL), key cytokines for B cell survival, are strongly unregulated in MS brain and in muscles of inflammatory myopathies. Modulation of B cell functions using a series of monoclonal antibodies against CD20+ B cells or the molecules that increase B cell survival, such as BAFF/APRIL and their receptors BAFF-R, TACI, and BCMA, provide a rational approach to the treatment of the aforementioned neurologic disorders. In controlled studies, rituximab, a B cell-depleting monoclonal antibody, has been encouraging in MS and paraproteinemic anti-MAG demyelinating neuropathy, exerting long-lasting remissions. In uncontrolled series, benefit has been reported in several disorders. B cell depletion is a well-tolerated therapeutic option currently explored in the treatment of several autoimmune neurologic disorders.

  13. Functional analysis of spontaneous cell movement under different physiological conditions.

    Directory of Open Access Journals (Sweden)

    Hiroaki Takagi

    Full Text Available Cells can show not only spontaneous movement but also tactic responses to environmental signals. Since the former can be regarded as the basis to realize the latter, playing essential roles in various cellular functions, it is important to investigate spontaneous movement quantitatively at different physiological conditions in relation to a cell's physiological functions. For that purpose, we observed a series of spontaneous movements by Dictyostelium cells at different developmental periods by using a single cell tracking system. Using statistical analysis of these traced data, we found that cells showed complex dynamics with anomalous diffusion and that their velocity distribution had power-law tails in all conditions. Furthermore, as development proceeded, average velocity and persistency of the movement increased and as too did the exponential behavior in the velocity distribution. Based on these results, we succeeded in applying a generalized Langevin model to the experimental data. With this model, we discuss the relation of spontaneous cell movement to cellular physiological function and its relevance to behavioral strategies for cell survival.

  14. Impairment of T cell function in parasitic infections.

    Directory of Open Access Journals (Sweden)

    Vasco Rodrigues

    2014-02-01

    Full Text Available In mammals subverted as hosts by protozoan parasites, the latter and/or the agonists they release are detected and processed by sensors displayed by many distinct immune cell lineages, in a tissue(s-dependent context. Focusing on the T lymphocyte lineage, we review our present understanding on its transient or durable functional impairment over the course of the developmental program of the intracellular parasites Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Trypanosoma cruzi in their mammalian hosts. Strategies employed by protozoa to down-regulate T lymphocyte function may act at the initial moment of naïve T cell priming, rendering T cells anergic or unresponsive throughout infection, or later, exhausting T cells due to antigen persistence. Furthermore, by exploiting host feedback mechanisms aimed at maintaining immune homeostasis, parasites can enhance T cell apoptosis. We will discuss how infections with prominent intracellular protozoan parasites lead to a general down-regulation of T cell function through T cell anergy and exhaustion, accompanied by apoptosis, and ultimately allowing pathogen persistence.

  15. Overexpression of neurofilament H disrupts normal cell structure and function

    Science.gov (United States)

    Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

    2002-01-01

    Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

  16. Novel immunomodulatory effects of adiponectin on dendritic cell functions.

    Science.gov (United States)

    Tsang, Julia Yuen Shan; Li, Daxu; Ho, Derek; Peng, Jiao; Xu, Aimin; Lamb, Jonathan; Chen, Yan; Tam, Paul Kwong Hang

    2011-05-01

    Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms.

  17. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Wen Jing Sim

    2016-01-01

    Full Text Available Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

  18. Human Embryonic Stem Cells Form Functional Thyroid Follicles

    Science.gov (United States)

    Latif, Rauf; Davies, Terry F.

    2015-01-01

    Objective: The molecular events that lead to human thyroid cell speciation remain incompletely characterized. It has been shown that overexpression of the regulatory transcription factors Pax8 and Nkx2-1 (ttf-1) directs murine embryonic stem (mES) cells to differentiate into thyroid follicular cells by initiating a transcriptional regulatory network. Such cells subsequently organized into three-dimensional follicular structures in the presence of extracellular matrix. In the current study, human embryonic stem (hES) cells were studied with the aim of recapitulating this scenario and producing functional human thyroid cell lines. Methods: Reporter gene tagged pEZ-lentiviral vectors were used to express human PAX8-eGFP and NKX2-1-mCherry in the H9 hES cell line followed by differentiation into thyroid cells directed by Activin A and thyrotropin (TSH). Results: Both transcription factors were expressed efficiently in hES cells expressing either PAX8, NKX2-1, or in combination in the hES cells, which had low endogenous expression of these transcription factors. Further differentiation of the double transfected cells showed the expression of thyroid-specific genes, including thyroglobulin (TG), thyroid peroxidase (TPO), the sodium/iodide symporter (NIS), and the TSH receptor (TSHR) as assessed by reverse transcription polymerase chain reaction and immunostaining. Most notably, the Activin/TSH-induced differentiation approach resulted in thyroid follicle formation and abundant TG protein expression within the follicular lumens. On stimulation with TSH, these hES-derived follicles were also capable of dose-dependent cAMP generation and radioiodine uptake, indicating functional thyroid epithelial cells. Conclusion: The induced expression of PAX8 and NKX2-1 in hES cells was followed by differentiation into thyroid epithelial cells and their commitment to form functional three-dimensional neo-follicular structures. The data provide proof of principal that hES cells can be

  19. Comparison of hemihypoglossal- and accessory-facial neurorrhaphy for treating facial paralysis in rats.

    Science.gov (United States)

    Li, Dezhi; Wan, Hong; Feng, Jie; Wang, Shiwei; Su, Diya; Hao, Shuyu; Schumacher, Michael; Liu, Song

    2014-12-15

    The aim of this study was to determine the effectiveness of hypoglossal-facial nerve "side"-to-end (HemiHN-FN) and accessory-facial nerve end-to-end (AN-FN) neurorrhaphy using a predegenerated nerve graft (PNG) for reanimating facial paralysis in a rat FN injury model. A total of 25 rats with complete unilateral facial paralysis resulting from section of the right FN were divided into 5 groups (n=5 each) that were submitted to immediate, delayed (3 months after FN injury) or no (control) FN reconstruction procedures involving HemiHN-FN or AN-FN neurorrhaphy. Approximately 3 months after FN reconstruction, cholera toxin subunit B conjugate Alexa 555 (CTB-Alexa 555) was injected into the ipsilateral whisker pad muscle and CTB-Alexa 555-labeled neurons were observed in the hypoglossal or accessory nuclei of all the FN reconstruction rats, but none of these neurons were found in the controls. There were numerous myelinated and nonmyelinated axons in both PNG and repaired FN of the FN reconstruction rats. No differences were found for these numbers between the two neurorrhaphy methods for each of the treatment time points, indicating the equal effectiveness of axon regeneration. However, a significantly higher number of CTB-Alexa 555-labeled neurons was observed in the hypoglossal nucleus of the immediate HemiHN-FN neurorrhaphy-treated rats when compared to that in the accessory nucleus of the immediate AN-FN neurorrhaphy-treated rats, consistent with the surface values of the recorded MAPs at the whisker pad muscle while electro-stimulating the FN. These results suggest that HemiHN-FN neurorrhaphy produces more efficient innervation of the paralyzed facial muscles than AN-FN neurorrhaphy without sacrificing ipsilateral hypoglossal function. Taking into consideration the clinical relevance of these findings for postoperative complications and functional reanimation in relation to the central plasticity, we suggest that HemiHN-FN neurorrhaphy may be the preferable facial

  20. A functional genomic analysis of cell morphology using RNA interference

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    Jones MR

    2003-10-01

    Full Text Available Abstract Background The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. Results We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. Conclusions Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology.

  1. The Angiotensin-(1-7)/Mas Axis Improves Pancreatic β-Cell Function in Vitro and in Vivo.

    Science.gov (United States)

    Sahr, Anika; Wolke, Carmen; Maczewsky, Jonas; Krippeit-Drews, Peter; Tetzner, Anja; Drews, Gisela; Venz, Simone; Gürtler, Sarah; van den Brandt, Jens; Berg, Sabine; Döring, Paula; Dombrowski, Frank; Walther, Thomas; Lendeckel, Uwe

    2016-12-01

    The angiotensin-converting enzyme 2/angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system often opposes the detrimental effects of the angiotensin-converting enzyme/Ang II/Ang II type 1 receptor axis and has been associated with beneficial effects on glucose homeostasis, whereas underlying mechanisms are mostly unknown. Here we investigate the effects of Ang-(1-7) and its receptor Mas on β-cell function. Isolated islets from Mas-deficient and wild-type mice were stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion determined. Islets' cytoplasmic calcium and cAMP concentrations, mRNA amounts of Ins1, Ins2, Pdx1, and Mafa and effects of inhibitors of cAMP downstream signaling were determined. Ang-(1-7) was also applied to mice by osmotic pumps for 14 days and effects on glucose tolerance and insulin secretion were assessed. Ang-(1-7) increased insulin secretion from wild-type islets, whereas antagonists and genetic Mas deficiency led to reduced insulin secretion. The Mas-dependent effects of Ang-(1-7) on insulin secretion did not result from changes in insulin gene expression or changes in the excitation-secretion coupling but from increased intracellular cAMP involving exchange protein activated directly by cAMP. Administration of Ang-(1-7) in vivo had only marginal effects on glucose tolerance in wild-type mice but still resulted in improved insulin secretion from islets isolated of these mice. Interestingly, although less pronounced than in wild types, Ang-(1-7) still affected insulin secretion in Mas-deficient islets. The data indicate a significant function of Ang-(1-7) in the regulation of insulin secretion from mouse islets in vitro and in vivo, mainly, but not exclusively, by Mas-dependent signaling, modulating the accessory pathway of insulin secretion via increase in cAMP.

  2. Abnormal red cell structure and function in neuroacanthocytosis.

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    Judith C A Cluitmans

    Full Text Available Panthothenate kinase-associated neurodegeneration (PKAN belongs to a group of hereditary neurodegenerative disorders known as neuroacanthocytosis (NA. This genetically heterogeneous group of diseases is characterized by degeneration of neurons in the basal ganglia and by the presence of deformed red blood cells with thorny protrusions, acanthocytes, in the circulation.The goal of our study is to elucidate the molecular mechanisms underlying this aberrant red cell morphology and the corresponding functional consequences. This could shed light on the etiology of the neurodegeneration.We performed a qualitative and semi-quantitative morphological, immunofluorescent, biochemical and functional analysis of the red cells of several patients with PKAN and, for the first time, of the red cells of their family members.We show that the blood of patients with PKAN contains not only variable numbers of acanthocytes, but also a wide range of other misshapen red cells. Immunofluorescent and immunoblot analyses suggest an altered membrane organization, rather than quantitative changes in protein expression. Strikingly, these changes are not limited to the red blood cells of PKAN patients, but are also present in the red cells of heterozygous carriers without neurological problems. Furthermore, changes are not only present in acanthocytes, but also in other red cells, including discocytes. The patients' cells, however, are more fragile, as observed in a spleen-mimicking device.These morphological, molecular and functional characteristics of red cells in patients with PKAN and their family members offer new tools for diagnosis and present a window into the pathophysiology of neuroacanthocytosis.

  3. Biogenesis and function of T cell-derived exosomes

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    Miguel Angel Alonso

    2016-08-01

    Full Text Available Exosomes are a particular type of extracellular vesicle, characterized by their endosomal origin as intraluminal vesicles present in large endosomes with a multivesicular structure. After these endosomes fuse with the plasma membrane, exosomes are secreted into the extracellular space. The ability of exosomes to carry and selectively deliver bioactive molecules (e.g., lipids, proteins and nucleic acids confers on them the capacity to modulate the activity of receptor cells, even if these cells are located in distant tissues or organs. Since exosomal cargo depends on cell type, a detailed understanding of the mechanisms that regulate the biochemical composition of exosomes is fundamental to a comprehensive view of exosome function. Here, we review the latest advances concerning exosome function and biogenesis in T cells, with particular focus on the mechanism of protein sorting at multivesicular endosomes. Exosomes secreted by specific T-cell subsets can modulate the activity of immune cells, including other T-cell subsets. Ceramide, tetraspanins and MAL have been revealed to be important in exosome biogenesis by T cells. These molecules, therefore, constitute potential molecular targets for artificially modulating exosome production and, hence, the immune response for therapeutic purposes.

  4. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

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    Qian-Kun Yang

    2013-01-01

    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  5. Plant organelle proteomics: collaborating for optimal cell function.

    Science.gov (United States)

    Agrawal, Ganesh Kumar; Bourguignon, Jacques; Rolland, Norbert; Ephritikhine, Geneviève; Ferro, Myriam; Jaquinod, Michel; Alexiou, Konstantinos G; Chardot, Thierry; Chakraborty, Niranjan; Jolivet, Pascale; Doonan, John H; Rakwal, Randeep

    2011-01-01

    Organelle proteomics describes the study of proteins present in organelle at a particular instance during the whole period of their life cycle in a cell. Organelles are specialized membrane bound structures within a cell that function by interacting with cytosolic and luminal soluble proteins making the protein composition of each organelle dynamic. Depending on organism, the total number of organelles within a cell varies, indicating their evolution with respect to protein number and function. For example, one of the striking differences between plant and animal cells is the plastids in plants. Organelles have their own proteins, and few organelles like mitochondria and chloroplast have their own genome to synthesize proteins for specific function and also require nuclear-encoded proteins. Enormous work has been performed on animal organelle proteomics. However, plant organelle proteomics has seen limited work mainly due to: (i) inter-plant and inter-tissue complexity, (ii) difficulties in isolation of subcellular compartments, and (iii) their enrichment and purity. Despite these concerns, the field of organelle proteomics is growing in plants, such as Arabidopsis, rice and maize. The available data are beginning to help better understand organelles and their distinct and/or overlapping functions in different plant tissues, organs or cell types, and more importantly, how protein components of organelles behave during development and with surrounding environments. Studies on organelles have provided a few good reviews, but none of them are comprehensive. Here, we present a comprehensive review on plant organelle proteomics starting from the significance of organelle in cells, to organelle isolation, to protein identification and to biology and beyond. To put together such a systematic, in-depth review and to translate acquired knowledge in a proper and adequate form, we join minds to provide discussion and viewpoints on the collaborative nature of organelles in

  6. Alternative mitochondrial functions in cell physiopathology: beyond ATP production

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    Kowaltowski A.J.

    2000-01-01

    Full Text Available It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology.

  7. Sertoli cell only syndrome: Status of sertoli cell maturation and function

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    Manish Jain

    2012-01-01

    Full Text Available Background of the study: Mature and functional Sertoli cells are essential for the survival of germ cells in testes. In Sertoli cell only syndrome (SCOS, there is no germ cells. Then, question arises whether absence of germ cells in SCOS secondary to Sertoli cells immaturity or mal function. Sertoli cells maturational and functional status is unclear in SCOS. This study investigated status of maturation and function of Sertoli cells in patients with SCOS. Materials and Methods: The present study was comprised of 37 cases of SCOS and 50 normal control males. Detailed clinical examination and investigation were carried out as per pre-determined proforma. Semen analysis, hormonal analysis (FSH, LH, testosterone, etc., and fine needle aspiration cytology (FNAC of testes (bilateral were performed. Fluorescence in situ hybridization (FISH with XY probes was carried out in addition to conventional chromosome analysis to find out chromosomal abnormalities, in particular sex chromosome aneuploidy, including mosaicism. Yq microdeletion status was also investigated. The anti-mullerian hormone (AMH, inhibin B, and seminal lactate were estimated by ELISA methods. Results: The study did not find any case of high AMH. About 78% cases had low inhibin B, and 60% had low AMH. FSH was high in about 78% cases. Low level of lactate was found in 49% cases. There was one case of high level of inhibin B. There were 6 (16.2% cases of chromosomal abnormality (2 mosaic Klinefelter and 4 Klinefelter syndrome and 4 (10.8% cases of Yq microdeletion. Conclusion: We conclude that Sertoli cell immaturity does not play any role in SCOS (no case of high AMH. It seems, in majority cases, Sertoli cells are functionally- and/or numerically-deficient (low inhibin B, AMH and lactate. However, in about 22% cases, Sertoli cell function and/or number remains normal (normal inhibin B, AMH. Inhibin B and FSH seems best predictor/marker of Sertoli cell function.

  8. Reducing bone cancer cell functions using selenium nanocomposites.

    Science.gov (United States)

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects.

  9. Invariant NKT cells: regulation and function during viral infection.

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    Jennifer A Juno

    Full Text Available Natural killer T cells (NKT cells represent a subset of T lymphocytes that express natural killer (NK cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT, express a highly restricted T cell receptor (TCR and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

  10. The accessory coracobrachialis muscle: ultrasound and MR features

    Energy Technology Data Exchange (ETDEWEB)

    Bauones, Salem [Centre hospitalier de l' Universite de Montreal (CHUM), Department of Radiology, Hopital Saint-Luc, Montreal, Quebec (Canada); Moraux, Antoine [Imagerie Medicale Jacquemars Gielee, Lille (France)

    2015-09-15

    To present the prevalence, clinical relevance, and ultrasound (US) and magnetic resonance imaging (MRI) appearances of the accessory coracobrachialis (ACB) muscle. We present an US prospective study of the ACB muscle over a 2-year period. Five of the eight patients with suspected ACB on US were subsequently examined by MRI. An ACB muscle was demonstrated by US in eight patients (eight shoulders), including seven females, one male, with mean age 39 years, over 770 (664 patients) consecutive shoulder US examinations referred to our institution yielding a prevalence of 1.04 %. In dynamic US assessment, one case of subcoracoid impingement secondary to a bulky ACB was diagnosed. No thoracic outlet syndrome was encountered in the remaining cases. MRI confirmed the presence of the accessory muscle in five cases. ACB muscle is a rarely reported yet not uncommon anatomic variation of the shoulder musculature encountered only in eight of 664 patients referred for shoulder US study. Its US and MRI appearance is described. One of our patients presented with subcoracoid impingement related to the presence of an ACB. (orig.)

  11. Behaviour of bentonite accessory minerals during the thermal stage

    Energy Technology Data Exchange (ETDEWEB)

    Arcos, David; Bruno, Jordi [Enviros-QuantiSci, Barcelona (Spain); Benbow, Steven; Takase, Hiro [Quintessa Limited, Henley-on-Thames (United Kingdom)

    2000-03-15

    This report discusses in a quantitative manner the evolution of the accessory minerals in the bentonite as a result of the thermal event exerted by the spent fuel in the near field. Three different modelling approaches have been used and the results compared between them. The three different approaches have been calculated using two Differential Algebraic Equation (DAE) solver: DYLAN (Model-1) and the Nag DAE solver, d02ngf (Model-2) and the third approach (Model-3) using the last version of PHREEQC. The results from these calculations indicate the feasibility of the modelling approach to model the migration of bentonite accessory minerals and relevant aqueous species throughout the thermal gradient. These calculations indicate that the migration of quartz and quartz polymorphs is a lesser problem. The aqueous speciation of Ca in the bentonite pore water is fundamental in order to define the potential migration of anhydrite during the thermal stage. If CaSO{sub 4}(aq) is the predominant aqueous species, then anhydrite dissolves at the initial groundwater migration times through bentonite. However, if Ca{sup 2+} is considered to be the dominant Ca species at the bentonite pore water, then anhydrite migrates towards the clay/granite interface. This is the main difference in the chemical systems considered in the three model approaches used in this work. The main process affecting the trace mineral behaviour in bentonite is cation exchange. This process controls the concentration of calcium, which results in a direct control of the calcite precipitation-dissolution.

  12. Digital dermatitis of the accessory digits of dairy cows

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    Celso A. Rodrigues

    2010-03-01

    Full Text Available This report characterizes the digital dermatitis (DD lesions in the accessory digits of dairy cows and presents data on the applied therapy. Fifteen Holstein cattle with DD affecting the accessory digits of the hindlimbs from four dairy farms with previous history of DD were evaluated. Lesions were excised, the wounds were sutured, and a topical application of oxytetracycline powder covered by bandaging was associated with a single parenteral administration of long acting oxytetracycline IM (20mg/kg. Tissue samples were obtained for histopathology and transmission electronic microscopy (TEM. Lesions from all the animals were recuperated 15 days after surgical procedure. Overal, most DD lesions were papillomatous epidermal projections or wartlike verrucous lesions. Histopathologically, samples revealed hyperplasia of epidermis with hyperkeratosis, several mitoses in the stratum basale and elongated rete ridges in the superficial and middle dermis. TEM revealed long, thin spirochete-like bacteria. Morphologic features of lesions and its response to therapy were comparable to those described for DD.

  13. Generation of functional thyroid from embryonic stem cells.

    Science.gov (United States)

    Antonica, Francesco; Kasprzyk, Dominika Figini; Opitz, Robert; Iacovino, Michelina; Liao, Xiao-Hui; Dumitrescu, Alexandra Mihaela; Refetoff, Samuel; Peremans, Kathelijne; Manto, Mario; Kyba, Michael; Costagliola, Sabine

    2012-11-01

    The primary function of the thyroid gland is to metabolize iodide by synthesizing thyroid hormones, which are critical regulators of growth, development and metabolism in almost all tissues. So far, research on thyroid morphogenesis has been missing an efficient stem-cell model system that allows for the in vitro recapitulation of the molecular and morphogenic events regulating thyroid follicular-cell differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2-1 and PAX8 is sufficient to direct mouse embryonic stem-cell differentiation into thyroid follicular cells that organize into three-dimensional follicular structures when treated with thyrotropin. These in vitro-derived follicles showed appreciable iodide organification activity. Importantly, when grafted in vivo into athyroid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mouse embryonic stem cells can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.

  14. Microfluidics as a functional tool for cell mechanics

    OpenAIRE

    Vanapalli, Siva A.; Duits, Michel H.G.; Mugele, Frieder

    2009-01-01

    Living cells are a fascinating demonstration of nature’s most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax—thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both c...

  15. A functional profile of gene expression in ARPE-19 cells

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    Johnson Dianna A

    2005-11-01

    Full Text Available Abstract Background Retinal pigment epithelium cells play an important role in the pathogenesis of age related macular degeneration. Their morphological, molecular and functional phenotype changes in response to various stresses. Functional profiling of genes can provide useful information about the physiological state of cells and how this state changes in response to disease or treatment. In this study, we have constructed a functional profile of the genes expressed by the ARPE-19 cell line of retinal pigment epithelium. Methods Using Affymetrix MAS 5.0 microarray analysis, genes expressed by ARPE-19 cells were identified. Using GeneChip® annotations, these genes were classified according to their known functions to generate a functional gene expression profile. Results We have determined that of approximately 19,044 unique gene sequences represented on the HG-U133A GeneChip® , 6,438 were expressed in ARPE-19 cells irrespective of the substrate on which they were grown (plastic, fibronectin, collagen, or Matrigel. Rather than focus our subsequent analysis on the identity or level of expression of each individual gene in this large data set, we examined the number of genes expressed within 130 functional categories. These categories were selected from a library of HG-U133A GeneChip® annotations linked to the Affymetrix MAS 5.0 data sets. Using this functional classification scheme, we were able to categorize about 70% of the expressed genes and condense the original data set of over 6,000 data points into a format with 130 data points. The resulting ARPE-19 Functional Gene Expression Profile is displayed as a percentage of ARPE-19-expressed genes. Conclusion The Profile can readily be compared with equivalent microarray data from other appropriate samples in order to highlight cell-specific attributes or treatment-induced changes in gene expression. The usefulness of these analyses is based on the assumption that the numbers of genes

  16. NK cell subgroups, phenotype and functions after autologous stem cell transplantation

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    Benedikt eJacobs

    2015-11-01

    Full Text Available High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotypes and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl following autoSCT, CD56++ NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and KIR compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly up-regulated KIR2DL2/3 and KIR3DL1, whereas KIR2DL1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration.In conclusion, we describe an unusual up-regulation of CD57 and KIRs on CD56++ NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.

  17. Functional cell types in taste buds have distinct longevities.

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    Isabel Perea-Martinez

    Full Text Available Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

  18. Cell-selective metabolic labeling of biomolecules with bioorthogonal functionalities.

    Science.gov (United States)

    Xie, Ran; Hong, Senlian; Chen, Xing

    2013-10-01

    Metabolic labeling of biomolecules with bioorthogonal functionalities enables visualization, enrichment, and analysis of the biomolecules of interest in their physiological environments. This versatile strategy has found utility in probing various classes of biomolecules in a broad range of biological processes. On the other hand, metabolic labeling is nonselective with respect to cell type, which imposes limitations for studies performed in complex biological systems. Herein, we review the recent methodological developments aiming to endow metabolic labeling strategies with cell-type selectivity. The cell-selective metabolic labeling strategies have emerged from protein and glycan labeling. We envision that these strategies can be readily extended to labeling of other classes of biomolecules.

  19. Stem cell-derived hepatocytes for functional liver replacement

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    Bruno eChrist

    2012-06-01

    Full Text Available Mesenchymal stem cells (MSC represent an alternate cell source to substitute for primary hepatocytes in hepatocyte transplantation because of their multiple differentiation potential and nearly unlimited availability. They may differentiate into hepatocyte-like cells in vitro and maintain specific hepatocyte functions also after transplantation into the regenerating livers of mice or rats both under injury and non-injury conditions. Depending on the underlying liver disease their mode of action is either to replace the diseased liver tissue or to support liver regeneration through their anti-inflammatory and anti-apoptotic as well as their pro-proliferative action.

  20. Lipid-laden dendritic cells fail to function

    Institute of Scientific and Technical Information of China (English)

    Philip C Calder

    2010-01-01

    @@ Dendritic cells(DCs)are professional antigen-acquiring,-processing and-presenting cells[1-4].As such,DCs form the key link between the innate and acquired immune responses playing a role in host defence and in immune tolerance[1-4].Accordingly,defects in the ability of DCs to function can lead to increased susceptibility to infection,loss of tolerance,autoimmunity and tumour growth[1-4].Sub-classes of DCs are defined and discriminated by the expression of different cell surface markers.

  1. Plant and algal cell walls: diversity and functionality.

    Science.gov (United States)

    Popper, Zoë A; Ralet, Marie-Christine; Domozych, David S

    2014-10-01

    Although plants and many algae (e.g. the Phaeophyceae, brown, and Rhodophyceae, red) are only very distantly related they are united in their possession of carbohydrate-rich cell walls, which are of integral importance being involved in many physiological processes. Furthermore,wall components have applications within food, fuel, pharmaceuticals, fibres (e.g. for textiles and paper) and building materials and have long been an active topic of research. As shown in the 27 papers in this Special Issue, as the major deposit of photosynthetically fixed carbon, and therefore energy investment, cell walls are of undisputed importance to the organisms that possess them, the photosynthetic eukaryotes ( plants and algae). The complexities of cell wall components along with their interactions with the biotic and abiotic environment are becoming increasingly revealed. The importance of plant and algal cell walls and their individual components to the function and survival of the organism, and for a number of industrial applications, are illustrated by the breadth of topics covered in this issue, which includes papers concentrating on various plants and algae, developmental stages, organs, cell wall components, and techniques. Although we acknowledge that there are many alternative ways in which the papers could be categorized (and many would fit within several topics), we have organized them as follows: (1) cell wall biosynthesis and remodelling, (2) cell wall diversity, and (3) application of new technologies to cell walls. Finally, we will consider future directions within plant cell wall research. Expansion of the industrial uses of cell walls and potentially novel uses of cell wall components are both avenues likely to direct future research activities. Fundamentally, it is the continued progression from characterization (structure, metabolism, properties and localization) of individual cell wall components through to defining their roles in almost every aspect of plant

  2. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and functio...... a common mechanism for modulating innate or adaptive immunity.......). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially...... and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents...

  3. Involvement of distinct PKC gene products in T cell functions

    Directory of Open Access Journals (Sweden)

    Gottfried eBaier

    2012-08-01

    Full Text Available It is well established that members of the Protein kinase C(PKC family seem to have important roles in T cells. Focusing on the physiological and non-redundant PKC functions established in primary mouse T cells via germline gene-targeting approaches, our current knowledge defines two particularly critical PKC gene products, PKCθ and PKCα, as the flavor of PKC in T cells that appear to have a positive role in signaling pathways that are necessary for full antigen receptor-mediated T cell activation ex vivo and T cell-mediated immunity in vivo. Consistently, in spite of the current dogma that PKCθ inhibition might be sufficient to achieve complete immunosuppressive effects, more recent results have indicated that the pharmacological inhibition of PKCθ, and additionally, at least PKCα, appears to be needed to provide a successful approach for the prevention of allograft rejection and treatment of autoimmune diseases.

  4. New developments in goblet cell mucus secretion and function.

    Science.gov (United States)

    Birchenough, G M H; Johansson, M E V; Gustafsson, J K; Bergström, J H; Hansson, G C

    2015-07-01

    Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell that can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example, after endocytosis or in response to acetyl choline. However, despite much progress in recent years, our understanding of goblet cell function and regulation is still in its infancy.

  5. Kicking against the PRCs - A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2.

    Directory of Open Access Journals (Sweden)

    Shih Chieh Liang

    2015-12-01

    Full Text Available The Polycomb group (PcG and trithorax group (trxG genes play crucial roles in development by regulating expression of homeotic and other genes controlling cell fate. Both groups catalyse modifications of chromatin, particularly histone methylation, leading to epigenetic changes that affect gene activity. The trxG antagonizes the function of PcG genes by activating PcG target genes, and consequently trxG mutants suppress PcG mutant phenotypes. We previously identified the ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN1 (ALP1 gene as a genetic suppressor of mutants in the Arabidopsis PcG gene LIKE HETEROCHROMATIN PROTEIN1 (LHP1. Here, we show that ALP1 interacts genetically with several other PcG and trxG components and that it antagonizes PcG silencing. Transcriptional profiling reveals that when PcG activity is compromised numerous target genes are hyper-activated in seedlings and that in most cases this requires ALP1. Furthermore, when PcG activity is present ALP1 is needed for full activation of several floral homeotic genes that are repressed by the PcG. Strikingly, ALP1 does not encode a known chromatin protein but rather a protein related to PIF/Harbinger class transposases. Phylogenetic analysis indicates that ALP1 is broadly conserved in land plants and likely lost transposase activity and acquired a novel function during angiosperm evolution. Consistent with this, immunoprecipitation and mass spectrometry (IP-MS show that ALP1 associates, in vivo, with core components of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2, a widely conserved PcG protein complex which functions as a H3K27me3 histone methyltransferase. Furthermore, in reciprocal pulldowns using the histone methyltransferase CURLY LEAF (CLF, we identify not only ALP1 and the core PRC2 components but also plant-specific accessory components including EMBRYONIC FLOWER 1 (EMF1, a transcriptional repressor previously associated with PRC1-like complexes. Taken together our data suggest that ALP1

  6. Oct4 targets regulatory nodes to modulate stem cell function.

    Directory of Open Access Journals (Sweden)

    Pearl A Campbell

    Full Text Available Stem cells are characterized by two defining features, the ability to self-renew and to differentiate into highly specialized cell types. The POU homeodomain transcription factor Oct4 (Pou5f1 is an essential mediator of the embryonic stem cell state and has been implicated in lineage specific differentiation, adult stem cell identity, and cancer. Recent description of the regulatory networks which maintain 'ES' have highlighted a dual role for Oct4 in the transcriptional activation of genes required to maintain self-renewal and pluripotency while concomitantly repressing genes which facilitate lineage specific differentiation. However, the molecular mechanism by which Oct4 mediates differential activation or repression at these loci to either maintain stem cell identity or facilitate the emergence of alternate transcriptional programs required for the realization of lineage remains to be elucidated. To further investigate Oct4 function, we employed gene expression profiling together with a robust statistical analysis to identify genes highly correlated to Oct4. Gene Ontology analysis to categorize overrepresented genes has led to the identification of themes which may prove essential to stem cell identity, including chromatin structure, nuclear architecture, cell cycle control, DNA repair, and apoptosis. Our experiments have identified previously unappreciated roles for Oct4 for firstly, regulating chromatin structure in a state consistent with self-renewal and pluripotency, and secondly, facilitating the expression of genes that keeps the cell poised to respond to cues that lead to differentiation. Together, these data define the mechanism by which Oct4 orchestrates cellular regulatory pathways to enforce the stem cell state and provides important insight into stem cell function and cancer.

  7. Evidence for the presence of urease apoprotein complexes containing UreD, UreF, and UreG in cells that are competent for in vivo enzyme activation.

    OpenAIRE

    I. S. Park; Hausinger, R P

    1995-01-01

    In vivo activation of Klebsiella aerogenes urease, a nickel-containing enzyme, requires the presence of functional UreD, UreF, and UreG accessory proteins and is further facilitated by UreE. These accessory proteins are proposed to be involved in metallocenter assembly (M. H. Lee, S. B. Mulrooney, M. J. Renner, Y. Markowicz, and R. P. Hausinger, J. Bacteriol. 174:4324-4330, 1992). A series of three UreD-urease apoprotein complexes are present in cells that express ureD at high levels, and the...

  8. Crystallization of accessory phases in magmas by local saturation adjacent to phenocrysts

    Science.gov (United States)

    Bacon, C.R.

    1989-01-01

    Accessory minerals commonly occur attached to or included in the major crystalline phases of felsic and some intermediate igneous rocks. Apatite is particularly common as inclusions, but Fe-Ti oxides, pyrrhotite, zircon, monazite, chevkinite and xenotime are also known from silicic rocks. Accessories may nucleate near the host crystal/ liquid interface as a result of local saturation owing to formation of a differentiated chemical boundary layer in which accessory mineral solubility would be lower than in the surrounding liquid. Differentiation of this boundary layer would be greatest adjacent to ferromagnesian phenocrysts, especially Fe-Ti oxides; it is with oxides that accessories are most commonly associated in rocks. A boundary layer may develop if the crystal grows more rapidly than diffusion can transport incorporated and rejected elements to and from the phenocryst. Diffusion must dominate over convection as a mode of mass transfer near the advancing crystal/liquid interface in order for a boundary layer to exist. Accumulation of essential structural constituent elements of accessory minerals owing to their slow diffusion in evolved silicate melt also may force local saturation, but this is not a process that applies to all cases. Local saturation is an attractive mechanism for enhancing fractionation during crystallization differentiation. If accessory minerals attached to or included in phenocrysts formed because of local saturation, their host phenocrysts must have grown rapidly when accessories nucleated in comparison to lifetimes of magma reservoirs. Some inconsistencies remain in a local saturation origin for accessory phases that cannot be evaluated without additional information. ?? 1989.

  9. 21 CFR 884.6190 - Assisted reproductive microscopes and microscope accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Assisted reproductive microscopes and microscope... Devices § 884.6190 Assisted reproductive microscopes and microscope accessories. (a) Identification. Assisted reproduction microscopes and microscope accessories (excluding microscope stage warmers, which are...

  10. 21 CFR 876.4730 - Manual gastroenterology-urology surgical instrument and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual gastroenterology-urology surgical... Devices § 876.4730 Manual gastroenterology-urology surgical instrument and accessories. (a) Identification. A manual gastroenterology-urology surgical instrument and accessories is a device designed to...

  11. 77 FR 15390 - Certain Handbags, Luggage, Accessories, and Packaging Thereof; Notice of Request for Statements...

    Science.gov (United States)

    2012-03-15

    ... COMMISSION Certain Handbags, Luggage, Accessories, and Packaging Thereof; Notice of Request for Statements on... interest issues raised by the ] recommended relief, specifically issuance of a general exclusion order covering handbags, luggage, accessories, and packaging thereof that infringe U.S. Trademark...

  12. 48 CFR 52.247-13 - Accessorial Services-Moving Contracts.

    Science.gov (United States)

    2010-10-01

    ...-Moving Contracts. 52.247-13 Section 52.247-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.247-13 Accessorial Services—Moving Contracts. As prescribed in 47.207-5(c), insert a clause... furniture: Accessorial Services—Moving Contracts (APR 1984) (a) Packing and/or crating and padding....

  13. 21 CFR 878.4200 - Introduction/drainage catheter and accessories.

    Science.gov (United States)

    2010-04-01

    ... catheters (including dialysis), and other general surgical catheters. An introduction/drainage catheter... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Introduction/drainage catheter and accessories... Introduction/drainage catheter and accessories. (a) Identification. An introduction/drainage catheter is a...

  14. 21 CFR 878.4400 - Electrosurgical cutting and coagulation device and accessories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrosurgical cutting and coagulation device and accessories. 878.4400 Section 878.4400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....4400 Electrosurgical cutting and coagulation device and accessories. (a) Identification. An...

  15. 46 CFR 38.10-1 - Valves, fittings, and accessories-TB/ALL.

    Science.gov (United States)

    2010-10-01

    ... valves to close in case of fire. The quick-closing shutoff valves shall be capable of local manual... 46 Shipping 1 2010-10-01 2010-10-01 false Valves, fittings, and accessories-TB/ALL. 38.10-1... GASES Piping, Valves, Fittings, and Accessory Equipment § 38.10-1 Valves, fittings, and accessories—TB...

  16. A peptide from the male accessory glands of the Colorado potato beetle.

    NARCIS (Netherlands)

    Smid, H.M.

    1998-01-01

    This thesis describes a study of the male accessory glands of the Colorado potato beetle, Leptinotarsa decemlineata (Say). These glands add various substances to the ejaculate. On mating, the ejaculate is transferred to the female, together with the substances from the male accessory glands. The fun

  17. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  18. Matrigel improves functional properties of primary human salivary gland cells.

    Science.gov (United States)

    Maria, Ola M; Zeitouni, Anthony; Gologan, Olga; Tran, Simon D

    2011-05-01

    Currently, there is no effective treatment available to patients with irreversible loss of functional salivary acini caused by Sjogren's syndrome or after radiotherapy for head and neck cancer. A tissue-engineered artificial salivary gland would help these patients. The graft cells for this device must establish tight junctions in addition to being of fluid-secretory nature. This study analyzed a graft source from human salivary glands (huSG) cultured on Matrigel. Cells were obtained from parotid and submandibular glands, expanded in vitro, and then plated on either Matrigel-coated (2 mg/mL) or uncoated culture dish. Immunohistochemistry, transmission electron microscopy, quantitative real-time-polymerase chain reaction, Western blot, and transepithelial electrical resistance were employed. On Matrigel, huSG cells adopted an acinar phenotype by forming three-dimensional acinar-like units (within 24 h of plating) as well as a monolayer of cells. On uncoated surfaces (plastic), huSG cells only formed monolayers of ductal cells. Both types of culture conditions allowed huSG cells to express tight junction proteins (claudin-1, -2, -3, -4; occludin; JAM-A; and ZO-1) and adequate transepithelial electrical resistance. Importantly, 99% of huSG cells on Matrigel expressed α-amylase and the water channel protein Aquaporin-5, as compared to cells on plastic. Transmission electron microscopy confirmed an acinar phenotype with many secretory granules. Matrigel increased the secretion of α-amylase two to five folds into the media, downregulated certain salivary genes, and regulated the translation of acinar proteins. This three-dimensional in vitro serum-free cell culture method allows the organization and differentiation of huSG cells into salivary cells with an acinar phenotype.

  19. [Differentiation of functional cells from iPS cells by efficient gene transfer].

    Science.gov (United States)

    Kawabata, Kenji; Tashiro, Katsuhisa; Mizuguchi, Hiroyuki

    2010-11-01

    Induced pluripotent stem (iPS) cells, which are generated from somatic cells by transducing four genes, are expected to have broad application to regenerative medicine. Although establishment of an efficient gene transfer system for iPS cells is considered to be essential for differentiating them into functional cells, the detailed transduction characteristics of iPS cells have not been examined. By using an adenovirus (Ad) vector containing the cytomegalovirus enhancer/beta-actin (CA) promoters, we have developed an efficient transduction system for mouse mesenchymal stem cells and embryonic stem (ES) cells. Also, we applied our transduction system to mouse iPS cells and investigated whether efficient differentiation could be achieved by Ad vector-mediated transduction of a functional gene. As in the case of ES cells, the Ad vector could efficiently transduce transgenes into mouse iPS cells. We found that the CA promoter had potent transduction ability in iPS cells. Moreover, exogenous expression of a PPARγ gene or a Runx2 gene into mouse iPS cells by an optimized Ad vector enhanced adipocyte or osteoblast differentiation, respectively. These results suggest that Ad vector-mediated transient transduction is sufficient to promote cellular differentiation and that our transduction methods would be useful for therapeutic applications based on iPS cells.

  20. Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies

    Institute of Scientific and Technical Information of China (English)

    Susumu; Kohno; Shunsuke; Kitajima; Nobunari; Sasaki; Chiaki; Takahashi

    2016-01-01

    Carcinogenic transformation of somatic cells resembles nuclear reprogramming toward the generation of pluripotent stem cells.These events share eternal escape from cellular senescence,continuous self-renewal in limited but certain population of cells,and refractoriness to terminal differentiation while maintaining the potential to differentiate into cells of one or multiple lineages.As represented by several oncogenes those appeared to be first keys to pluripotency,carcinogenesis and nuclear reprogramming seem to share a number of core mechanisms.The retinoblastoma tumor suppressor product retinoblastoma(RB)seems to be critically involved in both events in highly complicated manners.However,disentangling such complicated interactions has enabled us to better understand how stem cell strategies are shared by cancer cells.This review covers recent findings on RB functions related to stem cells and stem cell-like behaviors of cancer cells.

  1. Functional Implications of Neuroendocrine Differentiated Cells in Prostate Cancer

    NARCIS (Netherlands)

    J. Jongsma (Johan)

    2000-01-01

    textabstractThis thesis focuses on NE differentiation in prostate cancer, especially in prostate cancer models. We studied the effects of androgen depletion on the NE differentiated status of in vivo and in vitro prostatic tumor models. Knowledge concerning the function of NE cells in the normal hum

  2. Hypoxia, hormones, and red blood cell function in chick embryos.

    Science.gov (United States)

    Dragon, Stefanie; Baumann, Rosemarie

    2003-04-01

    The red blood cell function of avian embryos is regulated by cAMP. Adenosine A(2A) and beta-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO(2) transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.

  3. Microfluidics as a functional tool for cell mechanics

    NARCIS (Netherlands)

    Vanapalli, Siva A.; Duits, Michel H.G.; Mugele, Frieder

    2009-01-01

    Living cells are a fascinating demonstration of nature’s most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax—thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remod

  4. Functional Implications of Neuroendocrine Differentiated Cells in Prostate Cancer

    NARCIS (Netherlands)

    J. Jongsma (Johan)

    2000-01-01

    textabstractThis thesis focuses on NE differentiation in prostate cancer, especially in prostate cancer models. We studied the effects of androgen depletion on the NE differentiated status of in vivo and in vitro prostatic tumor models. Knowledge concerning the function of NE cells in the normal

  5. Generation of functional thyroid from embryonic stem cells

    Science.gov (United States)

    Antonica, Francesco; Kasprzyk, Dominika Figini; Opitz, Robert; Iacovino, Michelina; Liao, Xiao-Hui; Dumitrescu, Alexandra Mihaela; Refetoff, Samuel; Peremans, Kathelijne; Manto, Mario; Kyba, Michael; Costagliola, Sabine

    2013-01-01

    The primary function of thyroid gland is to metabolize iodide by synthesizing thyroid hormones that are critical regulators of growth, development and metabolism in virtually all tissues. To date, research on thyroid morphogenesis was missing an efficient stem-cell model system which allows to recapitulate in vitro the molecular and morphogenic events regulating thyroid follicular cells differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2.1 and PAX8 is sufficient to direct mouse embryonic stem-cells (mESC) differentiation into thyroid follicular cells which organized into three-dimensional follicular structures when treated with thyrotropin. Those in vitro derived follicles showed significant iodide organification activity. Importantly, when grafted in vivo into athyreoid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mESC can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue. PMID:23051751

  6. Function of mesenchymal stem cells following loading of gold nanotracers

    Directory of Open Access Journals (Sweden)

    et al

    2011-02-01

    Full Text Available Laura M Ricles1, Seung Yun Nam1,2, Konstantin Sokolov3,1, Stanislav Y Emelianov1,3, Laura J Suggs11Department of Biomedical Engineering, 2Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, TX, USA; 3Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USABackground: Stem cells can differentiate into multiple cell types, and therefore can be used for cellular therapies, including tissue repair. However, the participation of stem cells in tissue repair and neovascularization is not well understood. Therefore, implementing a noninvasive, long-term imaging technique to track stem cells in vivo is needed to obtain a better understanding of the wound healing response. Generally, we are interested in developing an imaging approach to track mesenchymal stem cells (MSCs in vivo after delivery via a polyethylene glycol modified fibrin matrix (PEGylated fibrin matrix using MSCs loaded with gold nanoparticles as nanotracers. The objective of the current study was to assess the effects of loading MSCs with gold nanoparticles on cellular function.Methods: In this study, we utilized various gold nanoparticle formulations by varying size and surface coatings and assessed the efficiency of cell labeling using darkfield microscopy. We hypothesized that loading cells with gold nanotracers would not significantly alter cell function due to the inert and biocompatible characteristics of gold. The effect of nanoparticle loading on cell viability and cytotoxicity was analyzed using a LIVE/DEAD stain and an MTT assay. The ability of MSCs to differentiate into adipocytes and osteocytes after nanoparticle loading was also examined. In addition, nanoparticle loading and retention over time was assessed using inductively coupled plasma mass spectrometry (ICP-MS.Conclusion: Our results demonstrate that loading MSCs with gold nanotracers does not alter cell function and, based on the ICP

  7. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K. H.; Schjødt, I.; Syrjala, K. L.

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction......). Assessment included descriptive data, Sexual Functioning Questionnaire, Body Image Scale and Hospital Anxiety and Depression Scale. The results showed a significant decline in overall sexual function in both men and women (P=.... Forty-seven percent of men and 60% of women reported at least one physical sexual problem 1 year after HSCT. Patients with chronic GVHD trended toward reporting lower levels of sexual function. Finally, women with chronic GVHD scored lower than those without chronic GVHD on the sexual function problem...

  8. [Functional surgery for head and neck squamous cell carcinoma].

    Science.gov (United States)

    Janot, François; Julieron, Morbize

    2002-12-01

    Surgery for head and neck squamous cell carcinoma can alter speech, swallowing, and cosmoses. Recent tendency is to avoid mutilating surgery unless the tumour is aggressive or resistant to chemotherapy and or radiotherapy. Functional surgery is being widely employed, and for example it may vary between conventional partial surgery and endoscopic laser surgery for small sized vocal cord cancers. Various new reconstructive procedures have been developed to help early functional restoration. Loco-regional flaps can be used to replace gums and avoid dental extractions. Free flaps with micro-vascular anastomosis can be employed for immediate reconstruction of extensive surgical defects involving pharyngeal wall, tongue, mandible and mid-face to restore better function and cosmoses. Few recently developed techniques can be also employed in selected cases of laryngo-pharyngeal cancers to avoid permanent laryngeal mutilation. Another goal of functional surgery is to decrease the postoperative radiotherapy or chemo-radiotherapy sequelae, and obtain successful postoperative functional rehabilitation.

  9. Mysterious Myofibroblast: A Cell with Diverse Origin and Multiple Functions

    Directory of Open Access Journals (Sweden)

    Sowmya Rao

    2017-03-01

    Full Text Available Myofibroblasts are one of the most controversial cells in recent times. Ever since its first discovery, numerous discussions have been done on its illusive nature and functions. They are commonly considered as smooth muscle like fibroblasts. Their presence and distribution in normal and pathological conditions are still not clear since they are difficult to identify with the routine histological techniques. Recent studies have shown their ubiquitous presence in the body tissues hence suggesting their important role in both physiological functioning and pathological conditions. This review discusses briefly the cell in terms of its definition, possible precursors; mechanism involved in its modulation, most importantly how to differentiate it from its nearest counterparts such as fibroblasts and smooth muscle cells and finally its fundamental role in physiology and pathology. [J Interdiscipl Histopathol 2017; 5(1.000: 12-17

  10. The functional diversity of retinal ganglion cells in the mouse.

    Science.gov (United States)

    Baden, Tom; Berens, Philipp; Franke, Katrin; Román Rosón, Miroslav; Bethge, Matthias; Euler, Thomas

    2016-01-21

    In the vertebrate visual system, all output of the retina is carried by retinal ganglion cells. Each type encodes distinct visual features in parallel for transmission to the brain. How many such 'output channels' exist and what each encodes are areas of intense debate. In the mouse, anatomical estimates range from 15 to 20 channels, and only a handful are functionally understood. By combining two-photon calcium imaging to obtain dense retinal recordings and unsupervised clustering of the resulting sample of more than 11,000 cells, here we show that the mouse retina harbours substantially more than 30 functional output channels. These include all known and several new ganglion cell types, as verified by genetic and anatomical criteria. Therefore, information channels from the mouse eye to the mouse brain are considerably more diverse than shown thus far by anatomical studies, suggesting an encoding strategy resembling that used in state-of-the-art artificial vision systems.

  11. Fast Image Retrieval of Textile Industrial Accessory Based on Multi-Feature Fusion

    Institute of Scientific and Technical Information of China (English)

    沈文忠; 杨杰

    2004-01-01

    A hierarchical retrieval scheme of the accessory image database is proposed based on textile industrial accessory contour feature and region feature. At first smallest enclosed rectangle[1] feature (degree of accessory coordination) is used to filter the image database to decouple the image search scope. After the accessory contour information and region information are extracted, the fusion multi-feature of the centroid distance Fourier descriptor and distance distribution histogram is adopted to finish image retrieval accurately. All the features above are invariable under translation, scaling and rotation. Results from the test on the image database including 1,000 accessory images demonstrate that the method is effective and practical with high accuracy and fast speed.

  12. Successful accessory renal artery denervation in a patient with resistant hypertension

    Directory of Open Access Journals (Sweden)

    Halil Atas

    2014-01-01

    Full Text Available Renal sympathetic denervation is safe and effective in patients with resistant hypertension. In all of the studies of renal artery denervation, patients with accessory renal arteries are excluded. So there is not any data regarding renal sympathetic denervation applied to the accessory renal arteries. We present a young female patient with resistant hypertension despite use of five different antihypertensive drugs. The patient had a well developed (diameter >4 mm left renal accessory. We believe that if we omitted the well developed accessory renal artery, we would not have maintained adequate blood pressure control. Thus, we applied radiofrequency ablation to both renal arteries and left accessory artery. Immediately after the procedure, the patient′s blood pressure was reduced to 110/60 mmHg and this effect was continued during the first month of follow-up.

  13. Carcinoid tumor of the duodenum and accessory papilla associated with polycythemia vera

    Institute of Scientific and Technical Information of China (English)

    Horng-Yuan Wang; Ming-Jen Chen; Tsen-Long Yang; Ming-Chih Chang; Yu-Jan Chan

    2005-01-01

    Carcinoid tumors have been reported in a wide range of organs but most frequently involve the gastrointestinal tract; however, duodenal carcinoid tumors are rare. We report a 50-year-old male patient complaining of multiple melenas for 3 wk. The panendoscopy and endoscopic retrograde cholangiopancreaticography revealed swelling accessory papilla with an ulcer. The biopsy taken showed a carcinoid tumor. The lesion was removed by wide resection. Patient was found to have an abnormal blood cell count during the follow-up period with elevated levels of hemoglobin and hematocrit of 21.2 g/dL and 63.5%,respectively, thrombocytosis of 501 000/μL, and leukocytosis of 20 410/μL. He was diagnosed as a polycythemia vera by a hematologist after further evaluation. He received periodic phlebotomy and hydroxyurea treatment. The response was good and his hematocrit was stabilized by periodic phlebotomy in the range of 44-49% during the last 2 years. The possible origin of UGI bleeding by a duodenal carcinoid tumor, although rare, should be considered. There has been one case report of a duodenal carcinoid tumor that involved accessory papilla of the pancreas divisum and one case report of metastatic carcinoid tumor associated with polycythemia vera. It is different in our patient as compared with the latter report, which mentioned a polycythemia vera patient who was found to have a metastatic carcinoid in the 17 years follow-up period. Chemotherapy had been given before the carcinoid tumor was revealed. Our patient had no previous chemotherapy for polycythemia vera before he was found to have duodenal carcinoid tumor; this excludes the possibility of chemotherapy induced carcinoid tumor, although it had been suspected in the previous report. In our patient, the existence of both diseases may be by predisposition of each other since both diseases have an increased incidence of other neoplasm, or they may be coexistent incidentally.

  14. PEDF improves mitochondrial function in RPE cells during oxidative stress.

    Science.gov (United States)

    He, Yuan; Leung, Kar Wah; Ren, Yuan; Pei, Jinzhi; Ge, Jian; Tombran-Tink, Joyce

    2014-09-11

    Oxidative stress plays an important role in health and aging. We have shown that oxidative stress impairs mitochondrial function and promotes RPE cell death in an age-dependent manner. This study investigates the role of pigment epithelium-derived factor (PEDF) in limiting oxidative stress-induced damage to RPE cells through mitochondrial pathways. Three groups of early-passaged RPE cells from donors 50 to 55, 60 to 65, and 70 to 75 years old (yo) were either preconditioned with PEDF followed by exposure to sublethal doses of hydrogen peroxide (H2O2) or post-treated with PEDF after H2O2 treatment. Effects of PEDF on mitochondrial function and cell viability were examined. Oxidative stress induced an age-dependent increase in LDH release, reactive oxygen species (ROS) levels, and cell death and a decrease in adenosine triphosphate (ATP) production and mitochondrial membrane potential (ΔΨm) in human RPE cells. Preconditioning or poststressed treatment with PEDF resulted in increased cell viability, inhibition of cytochrome c release and caspase 3 cleavage, and improved mitochondria function denoted by a decrease in ROS generation and increases in ATP production and ΔΨm. Oxidative stress also disrupted the reticular network, trafficking, and distribution of the mitochondria and blocked activation of phosphatidylinositol 3 kinase (PI3K), Akt, and Erk signaling in the cells. These effects were more pronounced in RPE cells from individuals>60 yo compared to the 50 to 55 yo age group. Pigment epithelium-derived factor mitigated negative effects of oxidative stress on mitochondrial remodeling and cellular distribution and unblocked its control of PI3K/Akt and mitogen-activated protein kinase (MAPK) signaling. Although PEDF potentiated both PI3K/Akt and MAPK signaling in the cells, stabilization of mitochondrial networks and function was dependent on its activation of PI3K/Akt. Specificity of PEDF's activity was confirmed using the pharmacological inhibitors LY294002

  15. Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells.

    Science.gov (United States)

    Reynolds, S D; Hong, K U; Giangreco, A; Mango, G W; Guron, C; Morimoto, Y; Stripp, B R

    2000-06-01

    The neuroepithelial body (NEB) is a highly dynamic structure that responds to chronic airway injury through hyperplasia of associated pulmonary neuroendocrine (PNE) cells. Although NEB dysplasia is correlated with preneoplastic conditions and PNE cells are thought to serve as a precursor for development of small cell lung carcinoma, mechanisms regulating expansion of the PNE cell population are not well understood. Based on studies performed in animal models, it has been suggested that NEB-associated progenitor cells that are phenotypically distinct from PNE cells contribute to PNE cell hyperplasia. We have previously used a Clara cell-specific toxicant, naphthalene, to induce airway injury in mice and have demonstrated that naphthalene-resistant Clara cells, characterized by their expression of Clara cell secretory protein (CCSP), and PNE cells contribute to airway repair and associated hyperplasia of NEBs. This study was conducted to define the contribution of NEB-associated CCSP-expressing progenitor cells to PNE cell hyperplasia after Clara cell ablation. Transgenic (CCtk) mice were generated in which herpes simplex virus thymidine kinase was expressed within all CCSP-expressing cells of the conducting airway epithelium through the use of transcriptional regulatory elements from the mouse CCSP promoter. Chronic administration of ganciclovir (GCV) to CCtk transgenic mice resulted in selective ablation of CCSP-expressing cells within conducting airways. Proliferation and hyperplasia of PNE cells occurred in the absence of detectable proliferation among any other residual airway epithelial cell populations. These results demonstrate that PNE cells function as a self-renewing progenitor population and that NEB-associated Clara cells are not necessary for PNE cell hyperplasia.

  16. Genetic and Functional Diversity of Propagating Cells in Glioblastoma

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    Sara G.M. Piccirillo

    2015-01-01

    Full Text Available Glioblastoma (GBM is a lethal malignancy whose clinical intransigence has been linked to extensive intraclonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies the implicit assumption that cancer stem cells or tumor-propagating cells are themselves genetically and functionally diverse. To test this, we screened primary GBM tumors by SNP array to identify copy number alterations (a minimum of three that could be visualized in single cells by multicolor fluorescence in situ hybridization. Interrogation of neurosphere-derived cells (from four patients and cells derived from secondary transplants of these same cells in NOD-SCID mice allowed us to infer the clonal and phylogenetic architectures. Whole-exome sequencing and single-cell genetic analysis in one case revealed a more complex clonal structure. This proof-of-principle experiment revealed that subclones in each GBM had variable regenerative or stem cell activity, and highlighted genetic alterations associated with more competitive propagating activity in vivo.

  17. Generation of functional podocytes from human induced pluripotent stem cells

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    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  18. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    Science.gov (United States)

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

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    Christian Kosan

    2016-01-01

    Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

  20. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    Science.gov (United States)

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-05

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  1. A Cell-Based Assay to Assess Hemichannel Function

    Science.gov (United States)

    Krishnan, Srinivasan; Fiori, Mariana C.; Cuello, Luis G.; Altenberg, Guillermo A.

    2017-01-01

    Activation of connexin hemichannels is involved in the pathophysiology of disorders that include deafness, stroke, and cardiac infarct. This aspect makes hemichannels an attractive therapeutic target. Unfortunately, most available inhibitors are not selective or isoform specific, which hampers their translational application. The absence of a battery of useful inhibitors is due in part to the absence of simple screening assays for the discovery of hemichannel-active drugs. Here, we present an assay that we have recently developed to assess hemichannel function. The assay is based on the expression of functional human connexins in a genetically modified bacterial strain deficient in K+ uptake. These modified cells do not grow in low-K+ medium, but functional expression of connexin hemichannels allows K+ uptake and growth. This cell-growth-based assay is simple, robust, and easily scalable to high-throughput multi-well platforms.

  2. Fatty acids, lipid mediators, and T-cell function.

    Science.gov (United States)

    de Jong, Anja J; Kloppenburg, Margreet; Toes, René E M; Ioan-Facsinay, Andreea

    2014-01-01

    Research toward the mechanisms underlying obesity-linked complications has intensified during the last years. As a consequence, it has become clear that metabolism and immunity are intimately linked. Free fatty acids and other lipids acquired in excess by current feeding patterns have been proposed to mediate this link due to their immune modulatory capacity. The functional differences between saturated and unsaturated fatty acids, in combination with their dietary intake are believed to modulate the outcome of immune responses. Moreover, unsaturated fatty acids can be oxidized in a tightly regulated and specific manner to generate either potent pro-inflammatory or pro-resolving lipid mediators. These oxidative derivatives of fatty acids have received detailed attention during the last years, as they have proven to have strong immune modulatory capacity, even in pM ranges. Both fatty acids and oxidized fatty acids have been studied especially in relation to macrophage and T-cells functions. In this review, we propose to focus on the effect of fatty acids and their oxidative derivatives on T-cells, as it is an active area of research during the past 5 years. The effect of fatty acids and their derivatives on activation and proliferation of T-cells, as well as the delicate balance between stimulation and lipotoxicity will be discussed. Moreover, the receptors involved in the interaction between free fatty acids and their derivatives with T-cells will be summarized. Finally, the mechanisms involved in modulation of T-cells by fatty acids will be addressed, including cellular signaling and metabolism of T-cells. The in vitro results will be placed in context of in vivo studies both in humans and mice. In this review, we summarize the latest findings on the immune modulatory function of lipids on T-cells and will point out novel directions for future research.

  3. Fatty Acids, Lipid Mediators, and T-Cell Function

    Science.gov (United States)

    de Jong, Anja J.; Kloppenburg, Margreet; Toes, René E. M.; Ioan-Facsinay, Andreea

    2014-01-01

    Research toward the mechanisms underlying obesity-linked complications has intensified during the last years. As a consequence, it has become clear that metabolism and immunity are intimately linked. Free fatty acids and other lipids acquired in excess by current feeding patterns have been proposed to mediate this link due to their immune modulatory capacity. The functional differences between saturated and unsaturated fatty acids, in combination with their dietary intake are believed to modulate the outcome of immune responses. Moreover, unsaturated fatty acids can be oxidized in a tightly regulated and specific manner to generate either potent pro-inflammatory or pro-resolving lipid mediators. These oxidative derivatives of fatty acids have received detailed attention during the last years, as they have proven to have strong immune modulatory capacity, even in pM ranges. Both fatty acids and oxidized fatty acids have been studied especially in relation to macrophage and T-cells functions. In this review, we propose to focus on the effect of fatty acids and their oxidative derivatives on T-cells, as it is an active area of research during the past 5 years. The effect of fatty acids and their derivatives on activation and proliferation of T-cells, as well as the delicate balance between stimulation and lipotoxicity will be discussed. Moreover, the receptors involved in the interaction between free fatty acids and their derivatives with T-cells will be summarized. Finally, the mechanisms involved in modulation of T-cells by fatty acids will be addressed, including cellular signaling and metabolism of T-cells. The in vitro results will be placed in context of in vivo studies both in humans and mice. In this review, we summarize the latest findings on the immune modulatory function of lipids on T-cells and will point out novel directions for future research. PMID:25352844

  4. Successful catheter ablation of a left anterior accessory pathway from the non-coronary cusp of the aortic valve.

    Science.gov (United States)

    Laranjo, Sérgio; Oliveira, Mário; Trigo, Conceição

    2015-08-01

    Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp.

  5. LACHESIS restricts gametic cell fate in the female gametophyte of Arabidopsis.

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    Rita Gross-Hardt

    2007-03-01

    Full Text Available In flowering plants, the egg and sperm cells form within haploid gametophytes. The female gametophyte of Arabidopsis consists of two gametic cells, the egg cell and the central cell, which are flanked by five accessory cells. Both gametic and accessory cells are vital for fertilization; however, the mechanisms that underlie the formation of accessory versus gametic cell fate are unknown. In a screen for regulators of egg cell fate, we isolated the lachesis (lis mutant which forms supernumerary egg cells. In lis mutants, accessory cells differentiate gametic cell fate, indicating that LIS is involved in a mechanism that prevents accessory cells from adopting gametic cell fate. The temporal and spatial pattern of LIS expression suggests that this mechanism is generated in gametic cells. LIS is homologous to the yeast splicing factor PRP4, indicating that components of the splice apparatus participate in cell fate decisions.

  6. The impact of extracellular acidosis on dendritic cell function.

    Science.gov (United States)

    Vermeulen, Mónica Elba; Gamberale, Romina; Trevani, Analía Silvina; Martínez, Diego; Ceballos, Ana; Sabatte, Juan; Giordano, Mirta; Geffner, Jorge Raúl

    2004-01-01

    Dendritic cells (DCs) are the most efficient antigen-presenting cells. They are activated in the periphery by conserved pathogen molecules and by inflammatory mediators produced by a variety of cell types in response to danger signals. It is widely appreciated that inflammatory responses in peripheral tissues are usually associated with the development of acidic microenvironments. Surprisingly, there are relatively few studies directed to analyze the effect of extracellular acidosis on the immune response. We focus on the influence of extracellular acidosis on the function of immature DCs. The results presented here show that acidosis activates DCs. It increases the acquisition of extracellular antigens for MHC class I-restricted presentation and the ability of antigen-pulsed DCs to induce both specific CD8+ CTL and B-cell responses. These findings may have important implications to our understanding of the mechanisms through which DCs sense the presence of infection or inflammation in nonlymphoid tissues.

  7. Relationship between development of accessory maxillary sinus and chronic sinusitis

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    Caner Sahin

    2015-01-01

    Full Text Available Background: We aimed to investigate whether there is a relationship between development of accessory maxillary osmium (AMO and chronic sinusitis. Material and Methods: A total of 100 patients who had endoscopic sinus surgery for chronic rhinosinusitis (CRS constituted the study group while 100 patients who had septoplasty were taken as the control group. The patients were examined for the presence of AMO using rigid endoscope. Results: The prevalence of AMO was 14% in the rhinosinusitis group and 9% in the control group. The difference between the groups was statistically significant (P < 0.05. Conclusion: Our study revealed that AMO prevalence is significantly higher in patients with CRS when compared with the controls. CRS may enhance perforation of fontanelle and formation of AMO.

  8. Morphology and protein patterns of honey bee drone accessory glands.

    Science.gov (United States)

    Cruz-Landim, Carminda da; Dallacqua, Rodrigo Pires

    2005-09-30

    We used light and transmission electron microscopy to examine the morphology of the accessory glands of immature and mature adult males of Apis mellifera L. We also made an electrophoretic analysis of the protein content of the mature gland. The glands of the immature male actively secrete a mucous substance that can be seen in the lumen of the gland of the mature male. This secretion stains with mercury bromophenol blue and with periodic acid-Schiff reaction, which stain glyconjugates. The protein content was higher in the lumen secretion than in the gland wall extracts. The electrophoresis patterns of the wall extracts were different from those of the secretion found in the gland lumen.

  9. Development of Heat-resistant XLPE Cable and Accessories

    Science.gov (United States)

    Yamada, Hiroyuki; Nakagawa, Shinichi; Murata, Yoshinao; Kishi, Kouji; Katakai, Shoshi

    We have developed heat-resistant XLPE cable and accessories that can be operated at 105°C as the maximum permissible conductor temperature in normal operation. Through this cable system, greater transmission capacity can be achieved using existing cable ducts and without increasing the conductor size of the cable. We have developed heat-resistant XLPE insulation material which has a higher melting point than that of conventional XLPE. The breakdown strength of heat-resistant XLPE cable at 105°C is almost the same as that of conventional XLPE cable at 90°C. The heat deformation of the new cable at 105°C is almost the same as that of conventional XLPE cable at 90°C. Conventional self-pressurized rubber joints can be applied to heat-resistant cable lines with the new waterproof joint compound with low heat resistivity.

  10. B Cell Function in Severe Combined Immunodeficiency after Stem Cell or Gene Therapy: A Review

    Science.gov (United States)

    Buckley, Rebecca H.

    2010-01-01

    While bone marrow transplantation has resulted in life-saving T cell reconstitution in infants with severe combined immunodeficiency (SCID), correction of B cell function has been more problematic. This review examines B cell reconstitution results presented in 19 reports from the United States and Europe on post-transplantation immune reconstitution in SCID over the past two decades. The analysis considered whether pre-transplantation conditioning regimens were used, the overall survival rate, the percentage with donor B cell chimerism, the percentage with B cell function, and the percentage of survivors requiring immunoglobulin (IG) replacement. The survival rates were higher at those Centers that did not use pre-transplant conditioning or post-transplantation graft-versus-host disease prophylaxis. The percentage of survivors with B cell chimerism and/or function was higher and the percentage requiring IG replacement was lower at those Centers that used pre-transplant conditioning. However there were substantial numbers of patients requiring IG replacement at all Centers. Thus, pre-transplant conditioning does not guarantee that B cell function will develop. Since most infants with SCID either present with serious infections or are diagnosed as newborns, one must decide whether there is justification for using agents that compromise innate immunity and have intrinsic toxicities to gain B cell immune reconstitution. PMID:20371393

  11. Sirt1 deficiency attenuates spermatogenesis and germ cell function.

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    Matthew Coussens

    Full Text Available In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration. The initial investigations of Sirt1 deficient mice have revealed a phenotype that includes a reduced lifespan, small size, and an increased frequency of abnormal sperm. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/- mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Numbers of mature sperm and spermatogenic precursors, as early as d15.5 of development, are significantly reduced ( approximately 2-10-fold less; Pfunction of Sirt1 deficient germ cells, we compared the efficiency of generating embryos and viable offspring in in vitro fertilization (IVF experiments using gametes from Sirt1-/- and sibling Sirt1+/- mice. While viable animals were derived in both Sirt1-/- X wild type and Sirt1-/- X Sirt1-/- crosses, the efficiency of producing both 2-cell zygotes and viable offspring was diminished when IVF was performed with Sirt1-/- sperm and/or oocytes. Together, these data support an important role for Sirt1 in spermatogenesis, including spermatogenic stem cells, as well as germ cell

  12. Functional Reconstitution Of Natural Killer Cells In Allogeneic Hematopoietic Stem Cell Transplantation

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    Md Ashik eUllah

    2016-04-01

    Full Text Available Natural killer (NK cells are the first lymphocyte population to reconstitute following allogeneic hematopoietic stem cell transplantation (HSCT and are important in mediating immunity against both leukemia and pathogens. Although NK cell numbers generally reconstitute within a month, the acquisition of mature NK cell phenotype and full functional competency can take 6 months or more, and is influenced by graft composition, concurrent pharmacologic immunosuppression, graft-versus-host disease and other clinical factors. In addition, cytomegalovirus infection and reactivation have a dominant effect on NK cell memory imprinting following allogeneic HSCT just as it does in healthy individuals. Our understanding of NK cell education and licensing has evolved in the years since the ‘missing self’ hypothesis for NK-mediated graft-versus-leukemia effect was first put forward. For example, we now know that NK cell ‘re-education’ can occur, and that unlicensed NK cells can be more protective than licensed NK cells in certain settings, thus raising new questions about how best to harness graft-versus-leukemia effect. Here we review current understanding of the functional reconstitution of NK cells and NK cell education following allogeneic HSCT, highlighting a conceptual framework for future research.

  13. Functional integration of human neural precursor cells in mouse cortex.

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    Fu-Wen Zhou

    Full Text Available This study investigates the electrophysiological properties and functional integration of different phenotypes of transplanted human neural precursor cells (hNPCs in immunodeficient NSG mice. Postnatal day 2 mice received unilateral injections of 100,000 GFP+ hNPCs into the right parietal cortex. Eight weeks after transplantation, 1.21% of transplanted hNPCs survived. In these hNPCs, parvalbumin (PV-, calretinin (CR-, somatostatin (SS-positive inhibitory interneurons and excitatory pyramidal neurons were confirmed electrophysiologically and histologically. All GFP+ hNPCs were immunoreactive with anti-human specific nuclear protein. The proportions of PV-, CR-, and SS-positive cells among GFP+ cells were 35.5%, 15.7%, and 17.1%, respectively; around 15% of GFP+ cells were identified as pyramidal neurons. Those electrophysiologically and histological identified GFP+ hNPCs were shown to fire action potentials with the appropriate firing patterns for different classes of neurons and to display spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs. The amplitude, frequency and kinetic properties of sEPSCs and sIPSCs in different types of hNPCs were comparable to host cells of the same type. In conclusion, GFP+ hNPCs produce neurons that are competent to integrate functionally into host neocortical neuronal networks. This provides promising data on the potential for hNPCs to serve as therapeutic agents in neurological diseases with abnormal neuronal circuitry such as epilepsy.

  14. Suppressor cell function is preserved in pemphigus and pemphigoid

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    King, A.J.; Schwartz, S.A.; Lopatin, D.; Voorhees, J.J.; Diaz, L.A.

    1982-09-01

    Human peripheral blood lymphocytes (PBL) are activated to become suppressor T cells (S-T-C) by incubation with Concanavalin-A (Con-A). This has become the standard method for evaluation of suppressor function in patients. S-T-C function has been found to be impaired in several autoimmune diseases, including systemic lupus erythematosus (SLE). Using this assay, we have investigated suppressor-cell function in 2 autoimmune disorders, bullous pemphigoid (BP) and pemphigus vulgaris (PV), studying 6 patients from each group. Three patients with active SLE (positive controls), and 11 normal donors (negative controls) were also included. None of these patients had received systemic therapy with the exception of 2 patients with PV who were treated with gold in the past. PBL from these patients were incubated with and without 40 micrograms/ml Con-A for 72 hr to generate suppressor cells. Both groups of PBL were then irradiated wih 1500 r cobalt. Co-cultures were set up in sextuplicate using normal PBL as responders. Responder PBL were stimulated with 0.5, 1.0, and 2.0 micrograms/ml of phytohemagglutin (PHA) and 5.0, 10.0, and 20.0 micrograms/ml of Con-A. Cultures were pulsed on day 3 with /sup 3/H-thymidine and harvested on day 4. Data were analyzed using Student's t-test. S-T-C function was found to be significantly impaired in SLE vs normal (p . 0.0316). No statistically significant difference was seen in BP (p . 0.5883) and PV (p . 0.0921) as compared with normals. A defect in suppressor cell function may still be present in patients with PV and BP for the defect may be antigen-specific and therefore remain undetected by the Con-A suppressor assay.

  15. Neurogenic and non neurogenic functions of endogenous neural stem cells.

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    Erica eButti

    2014-04-01

    Full Text Available Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ of the lateral ventricles and in the subgranular zone (SGZ of the dentate gyrus (DG in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic markers. The precise tracing of neural stem/progenitor cells (NPCs was therefore, not properly feasible. After the (partial identification of those markers, it was the lack of specific tools that hindered a proper experimental elimination and tracing of those cells to demonstrate their terminal fate and commitment. Nowadays, irradia-tion, cytotoxic drugs as well as genetic tracing/ablation procedures have moved the field forward and increased our understanding of neurogenesis processes in both physiological and pathological conditions. Newly formed NPC progeny from the SVZ can replace granule cells in the olfactory bulbs of rodents, thus contributing to orchestrate sophisticated odour behaviour. SGZ-derived new granule cells, instead, integrate within the DG where they play an essential role in memory functions. Furthermore, converging evidence claim that endogenous NPCs not only exert neurogenic functions, but might also have non-neurogenic homeostatic functions by the release of different types of neuroprotective molecules. Remarkably, these non-neurogenic homeostatic functions seem to be necessary, both in healthy and diseased conditions, for example for preventing or limiting tissue damage. In this review, we will discuss the neurogenic and the non-neurogenic functions of adult NPCs both in physiological and pathological conditions.

  16. Functional bitter taste receptors are expressed in brain cells.

    Science.gov (United States)

    Singh, Nisha; Vrontakis, Maria; Parkinson, Fiona; Chelikani, Prashen

    2011-03-04

    Humans are capable of sensing five basic tastes which are sweet, sour, salt, umami and bitter. Of these, bitter taste perception provides protection against ingestion of potentially toxic substances. Bitter taste is sensed by bitter taste receptors (T2Rs) that belong to the G-protein coupled receptors (GPCRs) superfamily. Humans have 25 T2Rs that are expressed in the oral cavity, gastrointestinal (GI) neuroendocrine cells and airway cells. Electrophysiological studies of the brain neurons show that the neurons are able to respond to different tastants. However, the presence of bitter taste receptors in brain cells has not been elucidated. In this report using RT-PCR, and immunohistochemistry analysis we show that T2Rs are expressed in multiple regions of the rat brain. RT-PCR analysis revealed the presence of T2R4, T2R107 and T2R38 transcripts in the brain stem, cerebellum, cortex and nucleus accumbens. The bitter receptor T2R4 was selected for further analysis at the transcript level by quantitative real time PCR and at the protein level by immunohistochemistry. To elucidate if the T2R4 expressed in these cells is functional, assays involving G-protein mediated calcium signaling were carried out. The functional assays showed an increase in intracellular calcium levels after the application of exogenous ligands for T2R4, denatonium benzoate and quinine to these cultured cells, suggesting that endogenous T2R4 expressed in these cells is functional. We discuss our results in terms of the physiological relevance of bitter receptor expression in the brain.

  17. Transcriptional profiles of mating-responsive genes from testes and male accessory glands of the Mediterranean fruit fly, Ceratitis capitata.

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    Francesca Scolari

    Full Text Available BACKGROUND: Insect seminal fluid is a complex mixture of proteins, carbohydrates and lipids, produced in the male reproductive tract. This seminal fluid is transferred together with the spermatozoa during mating and induces post-mating changes in the female. Molecular characterization of seminal fluid proteins in the Mediterranean fruit fly, Ceratitis capitata, is limited, although studies suggest that some of these proteins are biologically active. METHODOLOGY/PRINCIPAL FINDINGS: We report on the functional annotation of 5914 high quality expressed sequence tags (ESTs from the testes and male accessory glands, to identify transcripts encoding putative secreted peptides that might elicit post-mating responses in females. The ESTs were assembled into 3344 contigs, of which over 33% produced no hits against the nr database, and thus may represent novel or rapidly evolving sequences. Extraction of the coding sequences resulted in a total of 3371 putative peptides. The annotated dataset is available as a hyperlinked spreadsheet. Four hundred peptides were identified with putative secretory activity, including odorant binding proteins, protease inhibitor domain-containing peptides, antigen 5 proteins, mucins, and immunity-related sequences. Quantitative RT-PCR-based analyses of a subset of putative secretory protein-encoding transcripts from accessory glands indicated changes in their abundance after one or more copulations when compared to virgin males of the same age. These changes in abundance, particularly evident after the third mating, may be related to the requirement to replenish proteins to be transferred to the female. CONCLUSIONS/SIGNIFICANCE: We have developed the first large-scale dataset for novel studies on functions and processes associated with the reproductive biology of Ceratitis capitata. The identified genes may help study genome evolution, in light of the high adaptive potential of the medfly. In addition, studies of male

  18. Transcriptional profiles of mating-responsive genes from testes and male accessory glands of the Mediterranean fruit fly, Ceratitis capitata.

    Science.gov (United States)

    Scolari, Francesca; Gomulski, Ludvik M; Ribeiro, José M C; Siciliano, Paolo; Meraldi, Alice; Falchetto, Marco; Bonomi, Angelica; Manni, Mosè; Gabrieli, Paolo; Malovini, Alberto; Bellazzi, Riccardo; Aksoy, Serap; Gasperi, Giuliano; Malacrida, Anna R

    2012-01-01

    Insect seminal fluid is a complex mixture of proteins, carbohydrates and lipids, produced in the male reproductive tract. This seminal fluid is transferred together with the spermatozoa during mating and induces post-mating changes in the female. Molecular characterization of seminal fluid proteins in the Mediterranean fruit fly, Ceratitis capitata, is limited, although studies suggest that some of these proteins are biologically active. We report on the functional annotation of 5914 high quality expressed sequence tags (ESTs) from the testes and male accessory glands, to identify transcripts encoding putative secreted peptides that might elicit post-mating responses in females. The ESTs were assembled into 3344 contigs, of which over 33% produced no hits against the nr database, and thus may represent novel or rapidly evolving sequences. Extraction of the coding sequences resulted in a total of 3371 putative peptides. The annotated dataset is available as a hyperlinked spreadsheet. Four hundred peptides were identified with putative secretory activity, including odorant binding proteins, protease inhibitor domain-containing peptides, antigen 5 proteins, mucins, and immunity-related sequences. Quantitative RT-PCR-based analyses of a subset of putative secretory protein-encoding transcripts from accessory glands indicated changes in their abundance after one or more copulations when compared to virgin males of the same age. These changes in abundance, particularly evident after the third mating, may be related to the requirement to replenish proteins to be transferred to the female. We have developed the first large-scale dataset for novel studies on functions and processes associated with the reproductive biology of Ceratitis capitata. The identified genes may help study genome evolution, in light of the high adaptive potential of the medfly. In addition, studies of male recovery dynamics in terms of accessory gland gene expression profiles and correlated remating

  19. Metabostemness: Metaboloepigenetic reprogramming of cancer stem-cell functions

    Science.gov (United States)

    Menendez, Javier A.; Corominas-Faja, Bruna; Cuyàs, Elisabet; Alarcón, Tomás

    2014-01-01

    Cancer researchers are currently embarking on one of their field's biggest challenges, namely the understanding of how cellular metabolism or certain classes of elite metabolites (e.g., oncometabolites) can directly influence chromatin structure and the functioning of epi-transcriptional circuits to causally drive tumour formation. We here propose that refining the inherent cell attractor nature of nuclear reprogramming phenomena by adding the under-appreciated capacity of metabolism to naturally reshape the Waddingtonian landscape's topography provides a new integrative metabolo-epigenetic model of the cancer stem cell (CSC) theory. PMID:25621295

  20. Development of Functional Microfold (M Cells from Intestinal Stem Cells in Primary Human Enteroids.

    Directory of Open Access Journals (Sweden)

    Joshua D Rouch

    Full Text Available Intestinal microfold (M cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs, and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2 in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an

  1. Medroxyprogesterone acetate impairs human dendritic cell activation and function.

    Science.gov (United States)

    Quispe Calla, N E; Ghonime, M G; Cherpes, T L; Vicetti Miguel, R D

    2015-05-01

    Does medroxyprogesterone acetate (MPA) impair human dendritic cell (DC) activation and function? In vitro MPA treatment suppressed expression of CD40 and CD80 by human primary DCs responding to Toll-like receptor 3 (TLR3) agonist stimulation (i.e. DC activation). Moreover, this MPA-mediated decrease in CD40 expression impaired DC capacity to stimulate T cell proliferation (i.e. DC function). MPA is the active molecule in Depo-Provera(®) (DMPA), a commonly used injectable hormonal contraceptive (HC). Although DMPA treatment of mice prior to viral mucosal tissue infection impaired the capacity of DCs to up-regulate CD40 and CD80 and prime virus-specific T cell proliferation, neither DC activation marker expression nor the ability of DCs to promote T cell proliferation were affected by in vitro progesterone treatment of human DCs generated from peripheral blood monocytes. This cross-sectional study examined MPA-mediated effects on the activation and function of human primary untouched peripheral blood DCs. Human DCs isolated from peripheral blood mononuclear cells by negative immunomagnetic selection were incubated for 24 h with various concentrations of MPA. After an additional 24 h incubation with the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C), flow cytometry was used to evaluate DC phenotype (i.e. expression of CD40, CD80, CD86, and HLA-DR). In separate experiments, primary untouched human DCs were sequentially MPA-treated, poly I:C-activated, and incubated for 7 days with fluorescently labeled naïve allogeneic T cells. Flow cytometry was then used to quantify allogeneic T cell proliferation. Several pharmacologically relevant concentrations of MPA dramatically reduced CD40 and CD80 expression in human primary DCs responding to the immunostimulant poly I:C. In addition, MPA-treated DCs displayed a reduced capacity to promote allogeneic CD4(+) and CD8(+) T cell proliferation. In other DC: T cell co-cultures, the addition of antibody blocking the CD40

  2. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jinghua [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Zhang, Jianyun [Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Li, Feixue [Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Liu, Jing, E-mail: jliue@zju.edu.cn [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-05-05

    Highlights: • Tebuconazole (TEB) inhibited the proliferation of human placental trophoblasts. • TEB changed cell cycle distribution of G1 and G2 phases of trophoblasts. • TEB induced apoptosis of trophoblasts via mitochondrial pathway. • TEB decreased the invasive and migratory capacities of trophoblasts. • TEB altered the mRNA levels of key regulatory genes in trophoblasts - Abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  3. A transfer function approach to measuring cell inheritance

    Directory of Open Access Journals (Sweden)

    Errington Rachel J

    2011-02-01

    Full Text Available Abstract Background The inheritance of cellular material between parent and daughter cells during mitosis is highly influential in defining the properties of the cell and therefore the population lineage. This is of particular relevance when studying cell population evolution to assess the impact of a disease or the perturbation due to a drug treatment. The usual technique to investigate inheritance is to use time-lapse microscopy with an appropriate biological marker, however, this is time consuming and the number of inheritance events captured are too low to be statistically meaningful. Results Here we demonstrate the use of a high throughput fluorescence measurement technique e.g. flow cytometry, to measure the fluorescence from quantum dot markers which can be used to target particular cellular sites. By relating, the fluorescence intensity measured between two time intervals to a transfer function we are able to deconvolve the inheritance of cellular material during mitosis. To demonstrate our methodology we use CdTe/ZnS quantum dots to measure the ratio of endosomes inherited by the two daughter cells during mitosis in the U2-OS, human osteoscarcoma cell line. The ratio determined is in excellent agreement with results obtained previously using a more complex and computational intensive bespoke stochastic model. Conclusions The use of a transfer function approach allows us to utilise high throughput measurement of large cell populations to derive statistically relevant measurements of the inheritance of cellular material. This approach can be used to measure the inheritance of organelles, proteins etc. and also particles introduced to cells for drug delivery.

  4. Mast cells express novel functional IL-15 receptor alpha isoforms.

    Science.gov (United States)

    Bulanova, Elena; Budagian, Vadim; Orinska, Zane; Krause, Hans; Paus, Ralf; Bulfone-Paus, Silvia

    2003-05-15

    Mast cells previously have been reported to be regulated by IL-15 and to express a distinct IL-15R, termed IL-15RX. To further examine IL-15 binding and signaling in mast cells, we have studied the nature of the IL-15R and some of its biological activities in these cells. In this study, we report the existence of three novel isoforms of the IL-15R alpha chain in murine bone marrow-derived mast cells as a result of an alternative exon-splicing mechanism within the IL-15R alpha gene. These correspond to new mRNA transcripts lacking exon 4; exons 3 and 4; or exons 3, 4, and 5 (IL-15R alpha Delta 4, IL-15R alpha Delta 3,4, IL-15R alpha Delta 3,4,5). After transient transfection in COS-7 cells, all IL-15R alpha isoforms associate with the Golgi apparatus, the endoplasmic reticulum, the perinuclear space, and the cell membrane. Analysis of glycosylation pattern demonstrates the usage of a single N-glycosylation site, while no O-glycosylation is observed. Importantly, IL-15 binds with high affinity to, and promotes the survival of, murine BA/F3 cells stably transfected with the IL-15R alpha isoforms. Furthermore, we report that signaling mediated by IL-15 binding to the newly identified IL-15R alpha isoforms involves the phosphorylation of STAT3, STAT5, STAT6, Janus kinase 2, and Syk kinase. Taken together, our data indicate that murine mast cells express novel, fully functional IL-15R alpha isoforms, which can explain the selective regulatory effects of IL-15 on these cells.

  5. Deducing protein function by forensic integrative cell biology.

    Directory of Open Access Journals (Sweden)

    William C Earnshaw

    2013-12-01

    Full Text Available Our ability to sequence genomes has provided us with near-complete lists of the proteins that compose cells, tissues, and organisms, but this is only the beginning of the process to discover the functions of cellular components. In the future, it's going to be crucial to develop computational analyses that can predict the biological functions of uncharacterised proteins. At the same time, we must not forget those fundamental experimental skills needed to confirm the predictions or send the analysts back to the drawing board to devise new ones.

  6. Muscle glycogen and cell function - Location, location, location

    DEFF Research Database (Denmark)

    Ørtenblad, N; Nielsen, Joachim

    2015-01-01

    , and immobilization. Furthermore, these defined pools may serve specific functions in the cell. Specifically, reduced levels of these pools of glycogen are associated with reduced SR Ca(2+) release, muscle relaxation rate, and membrane excitability. Collectively, the available literature strongly demonstrates...... that the subcellular localization of glycogen has to be considered to fully understand the role of glycogen metabolism and signaling in skeletal muscle function. Here, we propose that the effect of low muscle glycogen on excitation-contraction coupling may serve as a built-in mechanism, which links the energetic state...

  7. Deducing protein function by forensic integrative cell biology.

    Science.gov (United States)

    Earnshaw, William C

    2013-12-01

    Our ability to sequence genomes has provided us with near-complete lists of the proteins that compose cells, tissues, and organisms, but this is only the beginning of the process to discover the functions of cellular components. In the future, it's going to be crucial to develop computational analyses that can predict the biological functions of uncharacterised proteins. At the same time, we must not forget those fundamental experimental skills needed to confirm the predictions or send the analysts back to the drawing board to devise new ones.

  8. Engineered microtopographies and surface chemistries direct cell attachment and function

    Science.gov (United States)

    Magin, Chelsea Marie

    Harrison, in 1914, first recognized that cells respond to physicochemical cues such as substratum topography when he observed that fibroblasts elongated while cultured on spider silk. Recently, techniques developed in the micro-electronics industry have been used to create molds for producing microscaled topographies with various shapes and spatial arrangements. Although these patterning techniques are well-established, very little is known about the mechanisms underlying cell sensing and response to microtopographies. In this work cellular micro-environments with varying surface topographies and chemistries were evaluated with marine organisms and mammalian cells to investigate cellular sensing and response. Biofouling---the accumulation of micro-organisms, plants, and animals on submerged surfaces---is an environmental and economic concern. Engineered topographies, replicated in polydimethylsiloxane elastomer (PDMSe) and functionalized poly(ethylene glycol)-dimethacrylate (PEGDMA) hydrogels, were evaluated for inhibition of marine fouling organism attachment. Microtopographies replicated in PDMSe inhibited attachment of the marine bacterium, Cobetia marina up to 99% versus smooth. The average normalized attachment densities of cells of C. marina and zoospores of the green algae Ulva on PDMSe topographies scaled inversely with the Engineered Roughness Index (ERIII), a representation of surface energy. Attachment densities of Ulva from four assays and C. marina from two growth phases to PDMSe surfaces scaled inversely with one equation: ERI II multiplied by the Reynolds number of the organism (Re) (R 2 = 0.77). The same microtopographies created in PDMSe reduced the initial attachment density and attachment strength of cells of the diatoms Navicula incerta and Seminavis robusta compared to smooth PDMSe. The average normalized attachment density of Navicula after exposure to shear stress (48 Pa) was correlated with the contact area between the diatom and a

  9. Accessory subunit NUYM (NDUFS4) is required for stability of the electron input module and activity of mitochondrial complex I.

    Science.gov (United States)

    Kahlhöfer, Flora; Kmita, Katarzyna; Wittig, Ilka; Zwicker, Klaus; Zickermann, Volker

    2017-02-01

    Mitochondrial complex I is an intricate 1MDa membrane protein complex with a central role in aerobic energy metabolism. The minimal form of complex I consists of fourteen central subunits that are conserved from bacteria to man. In addition, eukaryotic complex I comprises some 30 accessory subunits of largely unknown function. The gene for the accessory NDUFS4 subunit of human complex I is a hot spot for fatal pathogenic mutations in humans. We have deleted the gene for the orthologous NUYM subunit in the aerobic yeast Yarrowia lipolytica, an established model system to study eukaryotic complex I and complex I linked diseases. We observed assembly of complex I which lacked only subunit NUYM and retained weak interaction with assembly factor N7BML (human NDUFAF2). Absence of NUYM caused distortion of iron sulfur clusters of the electron input domain leading to decreased complex I activity and increased release of reactive oxygen species. We conclude that NUYM has an important stabilizing function for the electron input module of complex I and is essential for proper complex I function.

  10. Relating structure and function of inner hair cell ribbon synapses.

    Science.gov (United States)

    Wichmann, C; Moser, T

    2015-07-01

    In the mammalian cochlea, sound is encoded at synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to hundreds of Hz to encode acoustic stimuli with submillisecond precision. Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands. However, we are only beginning to understand key features such as stimulus-secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of endocytosis and vesicle reformation, as well as replenishment of the readily releasable pool. Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses. Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

  11. Functional Assessment of Pharmacological Telomerase Activators in Human T Cells

    Directory of Open Access Journals (Sweden)

    Rita B. Effros

    2013-01-01

    Full Text Available Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.

  12. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia.

    Science.gov (United States)

    Geyh, S; Rodríguez-Paredes, M; Jäger, P; Khandanpour, C; Cadeddu, R-P; Gutekunst, J; Wilk, C M; Fenk, R; Zilkens, C; Hermsen, D; Germing, U; Kobbe, G; Lyko, F; Haas, R; Schroeder, T

    2016-03-01

    Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.

  13. Functional Materials for Dye-sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    S.V. Raksha

    2015-12-01

    Full Text Available A review on the analysis of characteristics of dye-sensitized solar cells (DSSC is provided. DSSC design, materials that are used for the manufacture of functional layers and the characteristics of elements depending on their properties are analyzed. The basic disadvantages DSSC, the factors leading to their appearance, as well as solutions to eliminate or reduce the impact of these factors are revealed.

  14. ARPE-19 cell growth and cell functions in euglycemic culture media.

    Science.gov (United States)

    Heimsath, Ernest G; Unda, Richard; Vidro, Eileen; Muniz, Albert; Villazana-Espinoza, Elia T; Tsin, Andrew

    2006-12-01

    Human retinal pigmented epithelial cells (ARPE-19) grown in euglycemic media (5.5 mM) had lower cell number, significantly different cell morphology, and lower levels of vascular endothelial growth factor (VEGF) in the culture media than those grown in hyperglycemic media (18 mM) customarily used for culturing ARPE-19 cells. Although it has been shown that within a 24-hour period, all-trans retinoic acid significantly reduces VEGF secretion by retinal pigmented epithelial cells (grown in 18 mM glucose), such an inhibitory effect was not observed in cells grown in 5.5 mM glucose. Our results suggest that ARPE-19 cells grown in euglycemic media exhibit distinctly different cell growth, cell differentiation, and cell functions in comparison to cells grown in hyperglycemic media. Because euglycemic conditions provide a physiological glucose environment, this glucose concentration must be included in all future investigations of the mechanism of diabetic retinopathy when studying VEGF secretion by ARPE-19 cells.

  15. Ethanol inhibits human bone cell proliferation and function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Friday, K.E.; Howard, G.A. (University of Washington, Seattle (USA))

    1991-06-01

    The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantly reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.

  16. Krebs cycle rewired for macrophage and dendritic cell effector functions.

    Science.gov (United States)

    Ryan, Dylan Gerard; O'Neill, Luke A J

    2017-07-07

    The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate. Interestingly, a new role for Krebs cycle intermediates as signalling molecules and immunomodulators that dictate the inflammatory response has begun to emerge. This review will discuss the latest developments in Krebs cycle rewiring and immune cell effector functions, with a particular focus on the regulation of cytokine production. © 2017 Federation of European Biochemical Societies.

  17. A Review of Cell Formation from Perspective of Objective Function

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaoqing; TANG Jiafu

    2006-01-01

    The initial and significant step in the design of a cellular manufacturing system is cell formation (CF). CF problem is proposed in this paper as a decision problem that determines to manufacture specified types of part in a manufacturing plant which machines and their associated parts are grouped together to form cell in a way that a concerned objective is optimized. For describing CF problem clearly, this paper firstly presents a review of cell formation problem from the view points of objective function. The CF problems are classified into three categories, which are cost oriented, flexibility oriented and grouping efficiency oriented CF problems. Then, the paper presents a comprehensive conceptual mathematical formulation describing the general cost problem and a decision variable for comprehensive describing routing flexibility and two trade-off questions in grouping efficiency issues. Finally, based on the review and discussion, the paper proposes five directions for future research in the CF field.

  18. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells.

    Science.gov (United States)

    Li, Tianqing; Lewallen, Michelle; Chen, Shuyi; Yu, Wei; Zhang, Nian; Xie, Ting

    2013-06-01

    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptor-deficient mice, but there is still some concern of tumor formation. In this study, we have successfully cultured Nestin(+)Sox2(+)Pax6(+) multipotent retinal stem cells (RSCs) from the adult mouse retina, which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation. After they have been expanded for over 35 passages in the presence of FGF and EGF, the cultured RSCs still maintain stable proliferation and differentiation potential. Under proper differentiation conditions, they can differentiate into all the major retinal cell types found in the adult retina. More importantly, they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions. Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes, RSC-derived photoreceptor cells integrate into the retina, morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons. When transplanted into eyes of photoreceptor-deficient rd1 mutant mice, a RP model, RSC-derived photoreceptors can partially restore light response, indicating that those RSC-derived photoreceptors are functional. Finally, there is no evidence for tumor formation in the photoreceptor-transplanted eyes. Therefore, this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  19. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells

    Institute of Scientific and Technical Information of China (English)

    Tianqing Li; Michelle Lewallen; Shuyi Chen; Wei Yu; Nian Zhang; Ting Xie

    2013-01-01

    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases,such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptordeficient mice,but there is still some concern of tumor formation.In this study,we have successfully cultured Nestin+Sox2+Pax6+ multipotent retinal stem cells (RSCs) from the adult mouse retina,which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation.After they have been expanded for over 35 passages in the presence of FGF and EGF,the cultured RSCs still maintain stable proliferation and differentiation potential.Under proper differentiation conditions,they can differentiate into all the major retinal cell types found in the adult retina.More importantly,they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions.Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes,RSC-derived photoreceptor cells integrate into the retina,morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons.When transplanted into eyes of photoreceptor-deficient rd1 mutant mice,a RP model,RSC-derived photoreceptors can partially restore light response,indicating that those RSC-derived photoreceptors are functional.Finally,there is no evidence for tumor formation in the photoreceptor-transplanted eyes.Therefore,this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  20. Precursors of executive function in infants with sickle cell anemia.

    Science.gov (United States)

    Hogan, Alexandra M; Telfer, Paul T; Kirkham, Fenella J; de Haan, Michelle

    2013-10-01

    Executive dysfunction occurs in sickle cell anemia, but there are few early data. Infants with sickle cell anemia (n = 14) and controls (n = 14) performed the "A-not-B" and Object Retrieval search tasks, measuring precursors of executive function at 9 and 12 months. Significant group differences were not found. However, for the A-not-B task, 7 of 11 sickle cell anemia infants scored in the lower 2 performance categories at 9 months, but only 1 at 12 months (P = .024); controls obtained scores at 12 months that were statistically comparable to the scores they had already obtained at 9 months. On the Object Retrieval task, 9- and 12-month controls showed comparable scores, whereas infants with sickle cell anemia continued to improve (P = .027); at 9 months, those with lower hemoglobin oxygen saturation passed fewer trials (R s = 0.670, P = .024) and took longer to obtain the toy (R s = -0.664, P = .013). Subtle delays in acquiring developmental skills may underlie abnormal executive function in childhood.

  1. Myeloid dendritic cells: Development, functions, and role in atherosclerotic inflammation.

    Science.gov (United States)

    Chistiakov, Dimitry A; Sobenin, Igor A; Orekhov, Alexander N; Bobryshev, Yuri V

    2015-06-01

    Myeloid dendritic cells (mDCs) comprise a heterogeneous population of professional antigen-presenting cells, which are responsible for capture, processing, and presentation of antigens on their surface to T cells. mDCs serve as a bridge linking adaptive and innate immune responses. To date, the development of DC lineage in bone marrow is better characterized in mice than in humans. DCs and macrophages share the common myeloid progenitor called macrophage-dendritic cell progenitor (MDP) that gives rise to monocytoid lineage and common DC progenitors (CDPs). CDP in turn gives rise to plasmacytoid DCs and predendritic cells (pre-mDCs) that are common precursor of myeloid CD11b+ and CD8α(+) DCs. The development and commitment of mDCs is regulated by several transcription and hematopoietic growth factors of which CCr7, Zbtb46, and Flt3 represent 'core' genes responsible for development and functional and phenotypic maintenance of mDCs. mDCs were shown to be involved in the pathogenesis of many autoimmune and inflammatory diseases including atherosclerosis. In atherogenesis, different subsets of mDCs could possess both proatherogenic (e.g. proinflammatory) and atheroprotective (e.g. anti-inflammatory and tolerogenic) activities. The proinflammatory role of mDCs is consisted in production of inflammatory molecules and priming proinflammatory subsets of effector T cells. In contrast, tolerogenic mDCs fight against inflammation through arrest of activity of proinflammatory T cells and macrophages and induction of immunosuppressive regulatory T cells. Microenvironmental conditions trigger differentiation of mDCs to acquire proinflammatory or regulatory properties.

  2. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    Directory of Open Access Journals (Sweden)

    Wenke YUE

    2011-06-01

    Full Text Available Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained. Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed. Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse. Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance. Doubling time of adherent cells and sphere cells are (56.05±1.95 h and (33.00±1.44 h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells. Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations. Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells. These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.

  3. Identification and functional characterization of cardiac pacemaker cells in zebrafish.

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    Federico Tessadori

    Full Text Available In the mammalian heart a conduction system of nodes and conducting cells generates and transduces the electrical signals evoking myocardial contractions. Specialized pacemaker cells initiating and controlling cardiac contraction rhythmicity are localized in an anatomically identifiable structure of myocardial origin, the sinus node. We previously showed that in mammalian embryos sinus node cells originate from cardiac progenitors expressing the transcription factors T-box transcription factor 3 (Tbx3 and Islet-1 (Isl1. Although cardiac development and function are strikingly conserved amongst animal classes, in lower vertebrates neither structural nor molecular distinguishable components of a conduction system have been identified, questioning its evolutionary origin. Here we show that zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1 display heart rate defects related to pacemaker dysfunction. Moreover, 3D reconstructions of gene expression patterns in the embryonic and adult zebrafish heart led us to uncover a previously unidentified, Isl1-positive and Tbx2b-positive region in the myocardium at the junction of the sinus venosus and atrium. Through their long interconnecting cellular protrusions the identified Isl1-positive cells form a ring-shaped structure. In vivo labeling of the Isl1-positive cells by transgenic technology allowed their isolation and electrophysiological characterization, revealing their unique pacemaker activity. In conclusion we demonstrate that Isl1-expressing cells, organized as a ring-shaped structure around the venous pole, hold the pacemaker function in the adult zebrafish heart. We have thereby identified an evolutionary conserved, structural and molecular distinguishable component of the cardiac conduction system in a lower vertebrate.

  4. Contextualizing Hepatocyte Functionality of Cryopreserved HepaRG Cell Cultures.

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    Jackson, Jonathan P; Li, Linhou; Chamberlain, Erica D; Wang, Hongbing; Ferguson, Stephen S

    2016-09-01

    Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (∼28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format of HepaRG cells (termed here "cryo-HepaRG") has emerged as a new model that improves global availability and experimental flexibility; however, it is largely unknown whether HepaRG cells in this format fully retain their hepatic characteristics. Therefore, we systematically investigated the hepatocyte functionality of cryo-HepaRG cultures in context with the range of interindividual variation observed with PHH in both sandwich-culture and suspension formats. These evaluations uncovered a novel adaptation period for the cryo-HepaRG format and demonstrated the impact of extracellular matrix on cryo-HepaRG functionality. Pharmacologically important drug-metabolizing alleles were genotyped in HepaRG cells and poor metabolizer alleles for CYP2D6, CYP2C9, and CYP3A5 were identified and consistent with higher frequency alleles found in individuals of Caucasian decent. We observed liver enzyme inducibility with aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor activators comparable to that of sandwich-cultured PHH. Finally, we show for the first time that cryo-HepaRG supports proper CAR cytosolic sequestration and translocation to hepatocyte nuclei in response to phenobarbital treatment. Taken together, these data reveal important considerations for the use of this cell model and demonstrate that cryo-HepaRG are suitable for metabolism and toxicology screening.

  5. Effect of fluoroquinolones on mitochondrial function in pancreatic beta cells.

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    Ghaly, Hany; Jörns, Anne; Rustenbeck, Ingo

    2014-02-14

    Hyper- and hypoglycaemias are known side effects of fluoroquinolone antibiotics, resulting in a number of fatalities. Fluoroquinolone-induced hypoglycaemias are due to stimulated insulin release by the inhibition of the KATP channel activity of the beta cell. Recently, it was found that fluoroquinolones were much less effective on metabolically intact beta cells than on open cell preparations. Thus the intracellular effects of gatifloxacin, moxifloxacin and ciprofloxacin were investigated by measuring NAD(P)H- and FAD-autofluorescence, the mitochondrial membrane potential, and the adenine nucleotide content of isolated pancreatic islets and beta cells. 100 μM of moxifloxacin abolished the NAD(P)H increase elicited by 20mM glucose, while gatifloxacin diminished it and ciprofloxacin had no significant effect. This pattern was also seen with islets from SUR1 Ko mice, which have no functional KATP channels. Moxifloxacin also diminished the glucose-induced decrease of FAD-fluorescence, which reflects the intramitochondrial production of reducing equivalents. Moxifloxacin, but not ciprofloxacin or gatifloxacin significantly reduced the effect of 20mM glucose on the ATP/ADP ratio. The mitochondrial hyperpolarization caused by 20mM glucose was partially antagonized by moxifloxacin, but not by ciprofloxacin or gatifloxacin. Ultrastructural analyses after 20 h tissue culture showed that all three compounds (at 10 and 100 μM) diminished the number of insulin secretory granules and that gatifloxacin and ciprofloxacin, but not moxifloxacin induced fission/fusion configurations of the beta cell mitochondria. In conclusion, fluoroquinolones affect the function of the mitochondria in pancreatic beta cells which may diminish the insulinotropic effect of KATP channel closure and contribute to the hyperglycaemic episodes.

  6. Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection.

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    Kristin L Boswell

    2014-01-01

    Full Text Available The interaction between follicular T helper cells (TFH and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination. Recent studies described a functional equivalent of these cells among circulating CD4 T cells, referred to as peripheral TFH cells. Here, we characterize the phenotype and in vitro B cell helper activity of peripheral TFH populations, as well as the effect of HIV infection on these populations. In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7(highCXCR5(highCCR6(highPD-1(high CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. This population is significantly decreased in treatment-naïve, HIV-infected individuals and can be recovered after anti-retroviral therapy. We found impaired immunoglobulin production in co-cultures from HIV-infected individuals and found no correlation between the frequency of peripheral TFH cells and memory B cells, or with neutralization activity in untreated HIV infection in our cohort. Furthermore, we found that within the peripheral TFH population, the expression level of TFH-associated genes more closely resembles a memory, non-TFH population, as opposed to a TFH population. Overall, our data identify a heterogeneous population of circulating CD4 T cells that provides in vitro help to B cells, and challenges the origin of these cells as memory TFH cells.

  7. Peroneal spastic flatfoot in adolescents with accessory talar facet impingement: a preliminary report.

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    Niki, Hisateru; Aoki, Haruhito; Hirano, Takaaki; Akiyama, Yui; Fujiya, Hiroto

    2015-07-01

    This study analyzed imaging, arthroscopic findings, and treatment responses for peroneal spastic flatfoot (PSFF) caused by talocalcaneal impingement at the accessory anterolateral talar facet (AALTF) (accessory talar facet impingement) in 13 adolescents without histories of trauma and tarsal coalition. The AALTF was determined with computed tomography and MRI. Focal abutting bone marrow edema (FABME) on MRI around the AALTF was confirmed. In seven patients who underwent AALTF resection, subtalar arthroscopy was performed. All experienced alleviation PSFF after treatment; reduction in FABME was observed. AALTF resection alone is beneficial for PSFF caused by accessory talar facet impingement when peroneal spasms are restored by an injection of local anesthesia.

  8. Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming human beta cell function

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    Rodriguez-Diaz, Rayner; Dando, Robin; Jacques-Silva, M. Caroline; Fachado, Alberto; Molina, Judith; Abdulreda, Midhat; Ricordi, Camillo; Roper, Stephen D.; Berggren, Per-Olof; Caicedo, Alejandro

    2011-01-01

    Acetylcholine is a neurotransmitter that plays a major role in the function of the insulin secreting pancreatic beta cell1,2. Parasympathetic innervation of the endocrine pancreas, the islets of Langerhans, has been shown to provide cholinergic input to the beta cell in several species1,3,4, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of the human islet provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. We anticipate these results to revise models about neural input and cholinergic signaling in the endocrine pancreas. Cholinergic signaling within the islet represents a potential therapeutic target in diabetes5, highlighting the relevance of this advance to future drug development. PMID:21685896

  9. Characterization of mitochondrial function in cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function.

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    Atlante, Anna; Favia, Maria; Bobba, Antonella; Guerra, Lorenzo; Casavola, Valeria; Reshkin, Stephan Joel

    2016-06-01

    Evidence supporting the occurrence of oxidative stress in Cystic Fibrosis (CF) is well established and the literature suggests that oxidative stress is inseparably linked to mitochondrial dysfunction. Here, we have characterized mitochondrial function, in particular as it regards the steps of oxidative phosphorylation and ROS production, in airway cells either homozygous for the F508del-CFTR allele or stably expressing wt-CFTR. We find that oxygen consumption, ΔΨ generation, adenine nucleotide translocator-dependent ADP/ATP exchange and both mitochondrial Complex I and IV activities are impaired in CF cells, while both mitochondrial ROS production and membrane lipid peroxidation increase. Importantly, treatment of CF cells with the small molecules VX-809 and 4,6,4'-trimethylangelicin, which act as "correctors" for F508del CFTR by rescuing the F508del CFTR-dependent chloride secretion, while having no effect per sè on mitochondrial function in wt-CFTR cells, significantly improved all the above mitochondrial parameters towards values found in the airway cells expressing wt-CFTR. This novel study on mitochondrial bioenergetics provides a springboard for future research to further understand the molecular mechanisms responsible for the involvement of mitochondria in CF and identify the proteins primarily responsible for the F508del-CFTR-dependent mitochondrial impairment and thus reveal potential novel targets for CF therapy.

  10. Mast-Cell-Derived TNF Amplifies CD8+ Dendritic Cell Functionality and CD8+ T Cell Priming

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    Jan Dudeck

    2015-10-01

    Full Text Available Mast cells are critical promoters of adaptive immunity in the contact hypersensitivity model, but the mechanism of allergen sensitization is poorly understood. Using Mcpt5-CreTNFFL/FL mice, we show here that the absence of TNF exclusively in mast cells impaired the expansion of CD8+ T cells upon sensitization and the T-cell-driven adaptive immune response to elicitation. T cells primed in the absence of mast cell TNF exhibited a diminished efficiency to transfer sensitization to naive recipients. Specifically, mast cell TNF promotes CD8+ dendritic cell (DC maturation and migration to draining lymph nodes. The peripherally released mast cell TNF further critically boosts the CD8+ T-cell-priming efficiency of CD8+ DCs, thereby linking mast cell effects on T cells to DC modulation. Collectively, our findings identify the distinct potential of mast cell TNF to amplify CD8+ DC functionality and CD8+ T-cell-dominated adaptive immunity, which may be of great importance for immunotherapy and vaccination approaches.

  11. Neurospheres from rat adipose-derived stem cells could be induced into functional Schwann cell-like cells in vitro

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    Shan Yanchang

    2008-02-01

    Full Text Available Abstract Background Schwann cells (SC which are myelin-forming cells in peripheral nervous system are very useful for the treatment of diseases of peripheral nervous system and central nervous system. However, it is difficult to obtain sufficient large number of SC for clinical use, so alternative cell systems are desired. Results Using a procedure similar to the one used for propagation of neural stem cells, we could induce rat adipose-derived stem cells (ADSC into floating neurospheres. In addition to being able to differentiate into neuronal- and glial-like cells, neurospheres could be induced to differentiate into SC-like cells. SC-like cells were bi- or tri-polar in shape and immunopositive for nestin and SC markers p75, GFAP and S-100, identical to genuine SC. We also found that SC-like cells could induce the differentiation of SH-SY5Y neuroblastoma cells efficiently, perhaps through secretion of soluble substances. We showed further that SC-like cells could form myelin structures with PC12 cell neurites in vitro. Conclusion These findings indicated that ADSC could differentiate into SC-like cells in terms of morphology, phenotype and functional capacities. SC-like cells induced from ADSC may be useful for the treatment of neurological diseases.

  12. Gene function in early mouse embryonic stem cell differentiation

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    Campbell Pearl A

    2007-03-01

    Full Text Available Abstract Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5 undergoing undirected differentiation into embryoid bodies (EBs over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1, our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2 that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of m

  13. Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels.

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    Yu, Yin; Zhang, Yahui; Martin, James A; Ozbolat, Ibrahim T

    2013-09-01

    Organ printing is a novel concept recently introduced in developing artificial three-dimensional organs to bridge the gap between transplantation needs and organ shortage. One of the major challenges is inclusion of blood-vessellike channels between layers to support cell viability, postprinting functionality in terms of nutrient transport, and waste removal. In this research, we developed a novel and effective method to print tubular channels encapsulating cells in alginate to mimic the natural vascular system. An experimental investigation into the influence on cartilage progenitor cell (CPCs) survival, and the function of printing parameters during and after the printing process were presented. CPC functionality was evaluated by checking tissue-specific genetic marker expression and extracellular matrix production. Our results demonstrated the capability of direct fabrication of cell-laden tubular channels by our newly designed coaxial nozzle assembly and revealed that the bioprinting process could induce quantifiable cell death due to changes in dispensing pressure, coaxial nozzle geometry, and biomaterial concentration. Cells were able to recover during incubation, as well as to undergo differentiation with high-level cartilage-associated gene expression. These findings may not only help optimize our system but also can be applied to biomanufacturing of 3D functional cellular tissue engineering constructs for various organ systems.

  14. Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery.

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    Heijink, I H; Brandenburg, S M; Postma, D S; van Oosterhout, A J M

    2012-02-01

    Cigarette smoking, the major cause of chronic obstructive pulmonary disease (COPD), induces aberrant airway epithelial structure and function. The underlying mechanisms are unresolved so far. We studied effects of cigarette smoke extract (CSE) on epithelial barrier function and wound regeneration in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBECs) from COPD patients, nonsmokers and healthy smokers. We demonstrate that CSE rapidly and transiently impairs 16HBE barrier function, largely due to disruption of cell-cell contacts. CSE induced a similar, but stronger and more sustained, defect in PBECs. Application of the specific epidermal growth factor receptor (EGFR) inhibitor AG1478 showed that EGFR activation contributes to the CSE-induced defects in both 16HBE cells and PBECs. Furthermore, our data indicate that the endogenous protease calpain mediates these defects through tight junction protein degradation. CSE also delayed the reconstitution of 16HBE intercellular contacts during wound healing and attenuated PBEC barrier function upon wound regeneration. These findings were comparable between PBECs from smokers, healthy smokers and COPD patients. In conclusion, we demonstrate for the first time that CSE reduces epithelial integrity, probably by EGFR and calpain-dependent disruption of intercellular contacts. This may increase susceptibility to environmental insults, e.g. inhaled pathogens. Thus, EGFR may be a promising target for therapeutic strategies to improve mucosal barrier function in cigarette smoking-related disease.

  15. Identification of Domains within the V-ATPase Accessory Subunit Ac45 Involved in V-ATPase Transport and Ca2+-dependent Exocytosis

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    Jansen, Eric J. R.; van Bakel, Nick. H. M.; Loohuis, Nikkie F. M. Olde; Hafmans, Theo G. M.; Arentsen, Tim; Coenen, Anthon J. M.; Scheenen, Wim J. J. M.; Martens, Gerard J. M.

    2012-01-01

    The vacuolar (H+)-ATPase (V-ATPase) is crucial for maintenance of the acidic microenvironment in intracellular organelles, whereas its membrane-bound V0-sector is involved in Ca2+-dependent membrane fusion. In the secretory pathway, the V-ATPase is regulated by its type I transmembrane and V0-associated accessory subunit Ac45. To execute its function, the intact-Ac45 protein is proteolytically processed to cleaved-Ac45 thereby releasing its N-terminal domain. Here, we searched for the functional domains within Ac45 by analyzing a set of deletion mutants close to the in vivo situation, namely in transgenic Xenopus intermediate pituitary melanotrope cells. Intact-Ac45 was poorly processed and accumulated in the endoplasmic reticulum of the transgenic melanotrope cells. In contrast, cleaved-Ac45 was efficiently transported through the secretory pathway, caused an accumulation of the V-ATPase at the plasma membrane and reduced dopaminergic inhibition of Ca2+-dependent peptide secretion. Surprisingly, removal of the C-tail from intact-Ac45 caused cellular phenotypes also found for cleaved-Ac45, whereas C-tail removal from cleaved-Ac45 still allowed its transport to the plasma membrane, but abolished V-ATPase recruitment into the secretory pathway and left dopaminergic inhibition of the cells unaffected. We conclude that domains located in the N- and C-terminal portions of the Ac45 protein direct its trafficking, V-ATPase recruitment and Ca2+-dependent-regulated exocytosis. PMID:22736765

  16. Identification of domains within the V-ATPase accessory subunit Ac45 involved in V-ATPase transport and Ca2+-dependent exocytosis.

    Science.gov (United States)

    Jansen, Eric J R; van Bakel, Nick H M; Olde Loohuis, Nikkie F M; Hafmans, Theo G M; Arentsen, Tim; Coenen, Anthon J M; Scheenen, Wim J J M; Martens, Gerard J M

    2012-08-10

    The vacuolar (H(+))-ATPase (V-ATPase) is crucial for maintenance of the acidic microenvironment in intracellular organelles, whereas its membrane-bound V(0)-sector is involved in Ca(2+)-dependent membrane fusion. In the secretory pathway, the V-ATPase is regulated by its type I transmembrane and V(0)-associated accessory subunit Ac45. To execute its function, the intact-Ac45 protein is proteolytically processed to cleaved-Ac45 thereby releasing its N-terminal domain. Here, we searched for the functional domains within Ac45 by analyzing a set of deletion mutants close to the in vivo situation, namely in transgenic Xenopus intermediate pituitary melanotrope cells. Intact-Ac45 was poorly processed and accumulated in the endoplasmic reticulum of the transgenic melanotrope cells. In contrast, cleaved-Ac45 was efficiently transported through the secretory pathway, caused an accumulation of the V-ATPase at the plasma membrane and reduced dopaminergic inhibition of Ca(2+)-dependent peptide secretion. Surprisingly, removal of the C-tail from intact-Ac45 caused cellular phenotypes also found for cleaved-Ac45, whereas C-tail removal from cleaved-Ac45 still allowed its transport to the plasma membrane, but abolished V-ATPase recruitment into the secretory pathway and left dopaminergic inhibition of the cells unaffected. We conclude that domains located in the N- and C-terminal portions of the Ac45 protein direct its trafficking, V-ATPase recruitment and Ca(2+)-dependent-regulated exocytosis.

  17. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

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    Yajing Huang

    2016-01-01

    Full Text Available Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

  18. CD103+ Dendritic Cells Control Th17 Cell Function in the Lung

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    Teresa Zelante

    2015-09-01

    Full Text Available Th17 cells express diverse functional programs while retaining their Th17 identity, in some cases exhibiting a stem-cell-like phenotype. Whereas the importance of Th17 cell regulation in autoimmune and infectious diseases is firmly established, the signaling pathways controlling their plasticity are undefined. Using a mouse model of invasive pulmonary aspergillosis, we found that lung CD103+ dendritic cells (DCs would produce IL-2, dependent on NFAT signaling, leading to an optimally protective Th17 response. The absence of IL-2 in DCs caused unrestrained production of IL-23 and fatal hyperinflammation, which was characterized by strong Th17 polarization and the emergence of a Th17 stem-cell-like population. Although several cell types may be affected by deficient IL-2 production in DCs, our findings identify the balance between IL-2 and IL-23 productions by lung DCs as an important regulator of the local inflammatory response to infection.

  19. Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

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    Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

    2016-08-01

    Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

  20. Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells.

    Science.gov (United States)

    Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

    2016-08-01

    Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

  1. Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

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    Bourdieu, Antonin; Avalon, Maryse; Lapostolle, Véronique; Ismail, Sadek; Mombled, Margaux; Debeissat, Christelle; Guérinet, Marianne; Duchez, Pascale; Chevaleyre, Jean; Vlaski-Lafarge, Marija; Villacreces, Arnaud; Praloran, Vincent; Ivanovic, Zoran; Brunet de la Grange, Philippe

    2018-01-01

    Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. © 2017 Wiley Periodicals, Inc.

  2. Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

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    Maria Sophia Mackroth

    2016-11-01

    Full Text Available In acute Plasmodium falciparum (P. falciparum malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.

  3. Functionalization of DNA Nanostructures for Cell Signaling Applications

    Science.gov (United States)

    Pedersen, Ronnie O.

    Transforming growth factor beta (TGF-beta) is an important cytokine responsible for a wide range of different cellular functions including extracellular matrix formation, angiogenesis and epithelial-mesenchymal transition. We have sought to use self-assembling DNA nanostructures to influence TGF-beta signaling. The predictable Watson Crick base pairing allows for designing self-assembling nanoscale structures using oligonucleotides. We have used the method of DNA origami to assemble structures functionalized with multiple peptides that bind TGF-beta receptors outside the ligand binding domain. This allows the nanostructures to cluster TGF-beta receptors and lower the energy barrier of ligand binding thus sensitizing the cells to TGF-beta stimulation. To prove efficacy of our nanostructures we have utilized immunofluorescent staining of Smad2/4 in order to monitor TGF-beta mediated translocation of Smad2/4 to the cell nucleus. We have also utilized Smad2/4 responsive luminescence constructs that allows us to quantify TGF-beta stimulation with and without nanostructures. To functionalize our nanostructures we relied on biotin-streptavidin linkages. This introduces a multivalency that is not necessarily desirable in all designs. Therefore we have investigated alternative means of functionalization. The first approach is based on targeting DNA nanostructure by using zinc finger binding proteins. Efficacy of zinc finger binding proteins was assayed by the use of enzyme-linked immunosorbent (ELISA) assay and atomic force microscopy (AFM). While ELISA indicated a relative specificity of zinc finger proteins for target DNA sequences AFM showed a high degree of non-specific binding and insufficient affinity. The second approach is based on using peptide nucleic acid (PNA) incorporated in the nanostructure through base pairing. PNA is a synthetic DNA analog consisting of a backbone of repeating N-(2-aminoethyl)-glycine units to which purine and pyrimidine bases are linked by

  4. Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.

    Directory of Open Access Journals (Sweden)

    Krzysztof Bryniarski

    Full Text Available Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

  5. Human Amniotic Fluid Cells Form Functional Gap Junctions with Cortical Cells

    Directory of Open Access Journals (Sweden)

    Anna Jezierski

    2012-01-01

    Full Text Available The usage of stem cells is a promising strategy for the repair of damaged tissue in the injured brain. Recently, amniotic fluid (AF cells have received a lot of attention as an alternative source of stem cells for cell-based therapies. However, the success of this approach relies significantly on proper interactions between graft and host tissue. In particular, the reestablishment of functional brain networks requires formation of gap junctions, as a key step to provide sufficient intercellular communication. In this study, we show that AF cells express high levels of CX43 (GJA1 and are able to establish functional gap junctions with cortical cultures. Furthermore, we report an induction of Cx43 expression in astrocytes following injury to the mouse motor cortex and demonstrate for the first time CX43 expression at the interface between implanted AF cells and host brain cells. These findings suggest that CX43-mediated intercellular communication between AF cells and cortical astrocytes may contribute to the reconstruction of damaged tissue by mediating modulatory, homeostatic, and protective factors in the injured brain and hence warrants further investigation.

  6. Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.

    Science.gov (United States)

    Parent, Audrey V; Russ, Holger A; Khan, Imran S; LaFlam, Taylor N; Metzger, Todd C; Anderson, Mark S; Hebrok, Matthias

    2013-08-01

    Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) by precise regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling. The hESC-derived TEPs further mature into functional TECs that support T cell development upon transplantation into thymus-deficient mice. Importantly, the engrafted TEPs produce T cells capable of in vitro proliferation as well as in vivo immune responses. Thus, hESC-derived TEP grafts may have broad applications for enhancing engraftment in cell-based therapies as well as restoring age- and stress-related thymic decline.

  7. Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.

    Science.gov (United States)

    Grover, Amit; Sanjuan-Pla, Alejandra; Thongjuea, Supat; Carrelha, Joana; Giustacchini, Alice; Gambardella, Adriana; Macaulay, Iain; Mancini, Elena; Luis, Tiago C; Mead, Adam; Jacobsen, Sten Eirik W; Nerlov, Claus

    2016-03-24

    Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Here, by analysing HSC transcriptomes and HSC function at the single-cell level, we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets. Depletion of HSC platelet programming through loss of the FOG-1 transcription factor is accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis.

  8. Renal cell carcinoma in functional renal graft: Toward ablative treatments.

    Science.gov (United States)

    Tillou, Xavier; Guleryuz, Kerem; Collon, Sylvie; Doerfler, Arnaud

    2016-01-01

    The occurrence of a kidney transplant tumor is a rare but serious issue with a double risk: the return to dialysis and the development of metastatic cancer. Publications on this topic are mainly case reports. The purpose of this review was to report an exhaustive literature review of functional graft renal cell carcinomas to highlight the impact of tumors on the renal graft outcomes. 201 de novo renal carcinomas in functional renal grafts from 69 publications were included. Incidence was estimated at 0.18%. Graft tumors were mostly asymptomatic (85.9%). Whatever the discovery circumstances of graft tumors, they were mostly documented by graft ultrasounds supplemented by CT-scanning or MR imaging. Nephron sparing surgery (95 patients) was the first treatment performed followed by radiofrequency ablation (38 patients) and cryotherapy (10 patients). The most common tumor graft histology was clear cell carcinoma (46.4%), followed by papillary carcinoma (43.7%). Specific mortality was 2.9% with 6 deaths. Renal graft cell carcinoma is a rare pathology with a low specific death. When possible, conservative treatment should be the first choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. A novel multi-functional cell-based microphysiometer

    Institute of Scientific and Technical Information of China (English)

    XU Ying; XU Gaixia; LIU Qingjun; CAI Hua; LI Yan; LI Rong; WANG Ping

    2006-01-01

    This paper presents a novel multi-functional microphysiometer for simultaneous measurements of several extracellular ion concentrations and action potential measurement in living cells based on MLAPS (multi-light addressable potentiometric sensor). In the microphysiometer, sorts of sensitive membranes are illuminated in parallel with n light sources at working frequencies, and the response amplitudes of each frequency component can be measured on-line by parallel processing algorithm. In the experiments, the relations of the extracellular environmental H+, Na +, K +, Ca2 + under the effects of western medicines (dilantin, phenobarbital sodium) and Chinese drugs (scutellaria, medlar, hemlock parsley) were analyzed, and the effects of several drugs were evaluated. Moreover, the action potential signals of different cell types (cardiac myocytes and neurons) could be measured and analyzed by LAPS. By detecting these parameters, the system can monitor the real-time process of the cell metabolism and action potential, observe the functional responses of different kinds of membrane-bound receptors, and evaluate the activities of drugs.

  10. Generation of functional platelets from canine induced pluripotent stem cells.

    Science.gov (United States)

    Nishimura, Toshiya; Hatoya, Shingo; Kanegi, Ryoji; Sugiura, Kikuya; Wijewardana, Viskam; Kuwamura, Mitsuru; Tanaka, Miyuu; Yamate, Jyoji; Izawa, Takeshi; Takahashi, Masahiro; Kawate, Noritoshi; Tamada, Hiromichi; Imai, Hiroshi; Inaba, Toshio

    2013-07-15

    Thrombocytopenia (TTP) is a blood disease common to canines and human beings. Currently, there is no valid therapy for this disease except blood transfusion. In this study, we report the generation of canine induced pluripotent stem cells (ciPSCs) from canine embryonic fibroblasts, and a novel protocol for creating mature megakaryocytes (MKs) and functional platelets from ciPSCs. The ciPSCs were generated using lentiviral vectors, and differentiated into MKs and platelets on OP9 stromal cells supplemented with growth factors. Our ciPSCs presented in a tightly domed shape and showed expression of a critical pluripotency marker, REX1, and normal karyotype. Additionally, ciPSCs differentiated into cells derived from three germ layers via the formation of an embryoid body. The MKs derived from ciPSCs had hyperploidy and transformed into proplatelets. The proplatelets released platelets early on that expressed specific MK and platelet marker CD41/61. Interestingly, these platelets, when activated with adenosine diphosphate or thrombin, bind to fibrinogen. Moreover, electron microscopy showed that the platelets had the same ultrastructure as peripheral platelets. Thus, we have demonstrated for the first time the generation of ciPSCs that are capable of differentiating into MKs and release functional platelets in vitro. Our system for differentiating ciPSCs into MKs and platelets promises a critical therapy for canine TTP and appears to be extensible in principle to resolve human TTP.

  11. Polyhedral Oligomeric Silsesquioxane Functionalized Carbon Dots for Cell Imaging.

    Science.gov (United States)

    Wang, Wen-Jing; Hai, Xin; Mao, Quan-Xing; Chen, Ming-Li; Wang, Jian-Hua

    2015-08-05

    In the present study, octa-aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt (OA-POSS) functionalized carbon dots (CDs/POSS) are prepared by a one-pot approach with glycerol as carbon source and solvent medium. OA-POSS serves as a passivation agent, and it is obtained via hydrolytic condensation of 3-aminopropyltriethoxysilane (APTES). During the functionalization process, the amino groups on OA-POSS combine with carboxylic groups on the bare CDs via formation of amide bond to construct organic-inorganic hybrid carbon dots. The obtained CDs/POSS are well dispersed in aqueous medium with a diameter of ca. 3.6 nm. It is demonstrated that CDs/POSS provide favorable photoluminescent property with a quantum yield of 24.0%. They also exhibit resistance to photobleaching and excellent photoluminescence stability in the presence of biological sample matrix (characterized by heavy metals and organic molecules), which facilitate cell imaging in biological systems. Both the photoluminescent emission wavelength and the fluorescence intensity depend closely on the excitation wavelength, and thus, it provides a potential for multicolor imaging as demonstrated with HeLa cells and MCF-7 cells.

  12. What happens inside a fuel cell? Developing an experimental functional map of fuel cell performance.

    Science.gov (United States)

    Brett, Daniel J L; Kucernak, Anthony R; Aguiar, Patricia; Atkins, Stephen C; Brandon, Nigel P; Clague, Ralph; Cohen, Lesley F; Hinds, Gareth; Kalyvas, Christos; Offer, Gregory J; Ladewig, Bradley; Maher, Robert; Marquis, Andrew; Shearing, Paul; Vasileiadis, Nikos; Vesovic, Velisa

    2010-09-10

    Fuel cell performance is determined by the complex interplay of mass transport, energy transfer and electrochemical processes. The convolution of these processes leads to spatial heterogeneity in the way that fuel cells perform, particularly due to reactant consumption, water management and the design of fluid-flow plates. It is therefore unlikely that any bulk measurement made on a fuel cell will accurately represent performance at all parts of the cell. The ability to make spatially resolved measurements in a fuel cell provides one of the most useful ways in which to monitor and optimise performance. This Minireview explores a range of in situ techniques being used to study fuel cells and describes the use of novel experimental techniques that the authors have used to develop an 'experimental functional map' of fuel cell performance. These techniques include the mapping of current density, electrochemical impedance, electrolyte conductivity, contact resistance and CO poisoning distribution within working PEFCs, as well as mapping the flow of reactant in gas channels using laser Doppler anemometry (LDA). For the high-temperature solid oxide fuel cell (SOFC), temperature mapping, reference electrode placement and the use of Raman spectroscopy are described along with methods to map the microstructural features of electrodes. The combination of these techniques, applied across a range of fuel cell operating conditions, allows a unique picture of the internal workings of fuel cells to be obtained and have been used to validate both numerical and analytical models.

  13. Single cell cytometry of protein function in RNAi treated cells and in native populations

    Directory of Open Access Journals (Sweden)

    Hill Andrew

    2008-08-01

    Full Text Available Abstract Background High Content Screening has been shown to improve results of RNAi and other perturbations, however significant intra-sample heterogeneity is common and can complicate some analyses. Single cell cytometry can extract important information from subpopulations within these samples. Such approaches are important for immune cells analyzed by flow cytometry, but have not been broadly available for adherent cells that are critical to the study of solid-tumor cancers and other disease models. Results We have directly quantitated the effect of resolving RNAi treatments at the single cell level in experimental systems for both exogenous and endogenous targets. Analyzing the effect of an siRNA that targets GFP at the single cell level permits a stronger measure of the absolute function of the siRNA by gating to eliminate background levels of GFP intensities. Extending these methods to endogenous proteins, we have shown that well-level results of the knockdown of PTEN results in an increase in phospho-S6 levels, but at the single cell level, the correlation reveals the role of other inputs into the pathway. In a third example, reduction of STAT3 levels by siRNA causes an accumulation of cells in the G1 phase of the cell cycle, but does not induce apoptosis or necrosis when compared to control cells that express the same levels of STAT3. In a final example, the effect of reduced p53 levels on increased adriamycin sensitivity for colon carcinoma cells was demonstrated at the whole-well level using siRNA knockdown and in control and untreated cells at the single cell level. Conclusion We find that single cell analysis methods are generally applicable to a wide range of experiments in adherent cells using technology that is becoming increasingly available to most laboratories. It is well-suited to emerging models of signaling dysfunction, such as oncogene addition and oncogenic shock. Single cell cytometry can demonstrate effects on cell

  14. Antagonistic functions of two stardust isoforms in Drosophila photoreceptor cells.

    Science.gov (United States)

    Bulgakova, Natalia A; Rentsch, Michaela; Knust, Elisabeth

    2010-11-15

    Membrane-associated guanylate kinases (MAGUKs) are scaffolding proteins that organize supramolecular protein complexes, thereby partitioning the plasma membrane into spatially and functionally distinct subdomains. Their modular organization is ideally suited to organize protein complexes with cell type- or stage-specific composition, or both. Often more than one MAGUK isoform is expressed by one gene in the same cell, yet very little is known about their individual in vivo functions. Here, we show that two isoforms of Drosophila stardust, Sdt-H (formerly called Sdt-B2) and Sdt-D, which differ in their N terminus, are expressed in adult photoreceptors. Both isoforms associate with Crumbs and PATJ, constituents of the conserved Crumbs-Stardust complex. However, they form distinct complexes, localized at the stalk, a restricted region of the apical plasma membrane. Strikingly, Sdt-H and Sdt-D have antagonistic functions. While Sdt-H overexpression increases stalk membrane length and prevents light-dependent retinal degeneration, Sdt-D overexpression reduces stalk length and enhances light-dependent retinal degeneration. These results suggest that a fine-tuned balance of different Crumbs complexes regulates photoreceptor homeostasis.

  15. Cell-based composite materials with programmed structures and functions

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-03-01

    The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

  16. Characterization of Dendritic Cell and Regulatory T Cell Functions against Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Devin Morris

    2013-01-01

    Full Text Available Glutathione (GSH is a tripeptide that regulates intracellular redox and other vital aspects of cellular functions. GSH plays a major role in enhancing the immune system. Dendritic cells (DCs are potent antigen presenting cells that participate in both innate and acquired immune responses against microbial infections. Regulatory T cells (Tregs play a significant role in immune homeostasis. In this study, we investigated the effects of GSH in enhancing the innate and adaptive immune functions of DCs against Mycobacterium tuberculosis (M. tb infection. We also characterized the functions of the sub-populations of CD4+T cells such as Tregs and non-Tregs in modulating the ability of monocytes to control the intracellular M. tb infection. Our results indicate that GSH by its direct antimycobacterial activity inhibits the growth of intracellular M. tb inside DCs. GSH also increases the expressions of costimulatory molecules such as HLA-DR, CD80 and CD86 on the cell surface of DCs. Furthermore, GSH-enhanced DCs induced a higher level of T-cell proliferation. We also observed that enhancing the levels of GSH in Tregs resulted in downregulation in the levels of IL-10 and TGF-β and reduction in the fold growth of M. tb inside monocytes. Our studies demonstrate novel regulatory mechanisms that favor both innate and adaptive control of M. tb infection.

  17. The Online Marketing Research on the Factors of Competitiveness of Enterprises in the Computer Accessory Market

    Directory of Open Access Journals (Sweden)

    Yashkina Oksana I.

    2017-04-01

    Full Text Available The article is aimed at identifyng the factors of competitiveness of enterprises in the market for computer accessories (on the example of the «ZONA51» store and suggesting certain actions as to creating and strengthening competitive advantages. The main competitors of the enterprise, which offer computer accessories, as well as the basic preferences of consumers in choosing the game-oriented computer accessories, have been explored. The study has found that price and active Internet communications are the main factors in the competitiveness of enterprises in the market for computer accessories. It is also important to use communicative channels such as «word-of-mouth marketing» for specific types of goods. The target audience of the products analyzed is young people, so it is also important to advertise resources near the places of youth gatherings to provide active communications. Further studies should consider the factors of competitiveness of Internet shops with different orientation.

  18. Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

    NARCIS (Netherlands)

    Laman, J.D.; Meurs, M. van; Schellekens, M.M.; Boer, M. de; Melchers, B.; Massacesi, L.; Lassmann, H.; Claassen, E.; Hart, B.A. 't

    1998-01-01

    Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefo

  19. Ultrastructure of the accessory venom gland of the puff-adder and ...

    African Journals Online (AJOL)

    venom duct and accessory glands were perfused while being stimulated electrically. Total protein .... venom produced for indefinite periods; an outlet (or con- trol) system is necessary as in mammalian salivary glands where there exists an ...

  20. 49 CFR 398.5 - Parts and accessories necessary for safe operation.

    Science.gov (United States)

    2010-10-01

    ... REGULATIONS TRANSPORTATION OF MIGRANT WORKERS § 398.5 Parts and accessories necessary for safe operation. (a... worker transported. The seats shall be: Securely attached to the vehicle during the course...

  1. 77 FR 46633 - Parts and Accessories Necessary for Safe Operation: Brakes; Adjustment Limits

    Science.gov (United States)

    2012-08-06

    ... RIN 2126-AB28 Parts and Accessories Necessary for Safe Operation: Brakes; Adjustment Limits AGENCY... Safety Administration (FMCSA) amends the requirements regarding brake readjustment limits in the Federal Motor Carrier Safety Regulations (FMCSRs). This rule amends the readjustment limits, clarifies...

  2. Defective Tbx2-dependent patterning of the atrioventricular canal myocardium causes accessory pathway formation in mice

    NARCIS (Netherlands)

    Aanhaanen, W.T.J.; Boukens, B.J.D.; Sizarov, A.; Wakker, V.; de Gier- de Vries, C.; van Ginneken, A.C.; Moorman, A.F.M.; Coronel, R.; Christoffels, V.M.

    2011-01-01

    Ventricular preexcitation, a feature of Wolff-Parkinson-White syndrome, is caused by accessory myocardial pathways that bypass the annulus fibrosus. This condition increases the risk of atrioventricular tachycardia and, in the presence of atrial fibrillation, sudden death. The developmental

  3. Clinico-embryological perspective of a rare accessory brachial muscle with possible musculocutaneous nerve compression.

    Science.gov (United States)

    Mehta, V; Yadav, Y; Arora, Jyoti; Kumar, H; Suri, R K; Rath, G

    2009-03-01

    Both brachialis and biceps brachii are primary flexors of the arm and elbow from the biomechanical perspective. Numerous reports exist in anatomical literature regarding accessory heads of biceps brachii, although such accessory bellies in relation to brachialis muscle are less frequently elucidated. We report a unilateral case of a rare accessory muscle interposed between the biceps brachii and brachialis, having the musculocutaneous nerve (MCN) entrapped between the two. Furthermore, the muscle divided into two slips, upper slip was attached to biceps brachii and the other gained insertion to the brachial fascia. Innervation to this accessory muscle was derived from MCN. The embryological basis for such supernumerary muscle is discussed. Additionally, the case is considered under surgical and clinical perspective, highlighting the importance of familiarity with such variations. Anatomical variations of the brachial musculature may cause diagnostic perplexities while interpreting MRI or CT scans.

  4. An accessory ossification centre in the calcaneus with talonavicular and second metatarsocuneiform coalitions

    Energy Technology Data Exchange (ETDEWEB)

    Turhan, A.U.; Aydin, H.; Aynaci, O. [KTU Farabi Hospital, Department of Orthopaedic Surgery, Trabzon (Turkey); Dinc, H. [KTU Farabi Hospital, Department of Radiology, Trabzon (Turkey)

    1999-04-01

    We present the case of an 11-year-old girl with an accessory ossification centre of the calcaneus with talonavicular and second metatarsocuneiform coalitions, and bilateral os tibiale externum. (orig.) With 3 figs., 4 refs.

  5. Role of receptor activity modifying protein 1 in function of the calcium sensing receptor in the human TT thyroid carcinoma cell line.

    Directory of Open Access Journals (Sweden)

    Aditya J Desai

    Full Text Available The Calcium Sensing Receptor (CaSR plays a role in calcium homeostasis by sensing minute changes in serum Ca(2+ and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs, specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has

  6. T Cell Functional Disturbances in Patients with Pulmonary Tuberculosis.

    Science.gov (United States)

    Ostanin, Alexander A.; Khonina, Nataliya A.; Norkin, Maxim N.; Leplina, Olga Yu.; Nikonov, Sergey D.; Ogirenko, Anatoly P.; Chernykh, Helen R.

    2000-04-01

    The investigations of 38 patients with pulmonary tuberculosis (PT) revealed combined T cell and monocyte functional disturbances. Indeed, the percentages of CD4(+) and CD8(+) T lymphocytes, proliferative response and IL-2 production, as well as the percentages of HLA DR(+) monocytes and IL-1beta production were significantly decreased in PT patients as compared with normal individuals. Herewith the absolute T lymphocyte number did not undergo the pronounced changes. The decrease of T cell proliferative response was not mediated through immunosuppressive action of monocytes or T lymphocytes since removing of "adherent" cells from patient's peripheral blood mononuclear cells (PBMC) or pretreatment of PBMC with indomethacin and cyclophosphan failed to recover mitogenic reactivity in vitro. The patient's sera also did not significantly influence on PBMC proliferation. The decrease of IL-2 production and the stimulation of T cell proliferative response via TcR-CD3 complex, i.e. through the classic pathway of activation, indicated the anergy of T lymphocyte in tuberculosis patients. Furthermore, T lymphocytes were characterized by enhanced apoptosis. It should be noted, that patient's sera (especially in the patients with an initially high apoptosis) promoted significant anti-apoptotic activity. It is likely that this mechanism may be an explanation, why absolute T lymphopenia is absent during tuberculosis infection. Our findings suggest, that T lymphocyte dysfunctions in patients with PT are caused by impairments of T cell activation process, which lead to predominance of "negative" response (induction anergy, apoptosis) and to a lesser degree connected with direct suppressive mechanisms mediated by monocytes, T lymphocytes or serum factors.

  7. Cell wall structure and function in lactic acid bacteria.

    Science.gov (United States)

    Chapot-Chartier, Marie-Pierre; Kulakauskas, Saulius

    2014-08-29

    The cell wall of Gram-positive bacteria is a complex assemblage of glycopolymers and proteins. It consists of a thick peptidoglycan sacculus that surrounds the cytoplasmic membrane and that is decorated with teichoic acids, polysaccharides, and proteins. It plays a major role in bacterial physiology since it maintains cell shape and integrity during growth and division; in addition, it acts as the interface between the bacterium and its environment. Lactic acid bacteria (LAB) are traditionally and widely used to ferment food, and they are also the subject of more and more research because of their potential health-related benefits. It is now recognized that understanding the composition, structure, and properties of LAB cell walls is a crucial part of developing technological and health applications using these bacteria. In this review, we examine the different components of the Gram-positive cell wall: peptidoglycan, teichoic acids, polysaccharides, and proteins. We present recent findings regarding the structure and function of these complex compounds, results that have emerged thanks to the tandem development of structural analysis and whole genome sequencing. Although general structures and biosynthesis pathways are conserved among Gram-positive bacteria, studies have revealed that LAB cell walls demonstrate unique properties; these studies have yielded some notable, fundamental, and novel findings. Given the potential of this research to contribute to future applied strategies, in our discussion of the role played by cell wall components in LAB physiology, we pay special attention to the mechanisms controlling bacterial autolysis, bacterial sensitivity to bacteriophages and the mechanisms underlying interactions between probiotic bacteria and their hosts.

  8. An Interactive Exercise To Learn Eukaryotic Cell Structure and Organelle Function.

    Science.gov (United States)

    Klionsky, Daniel J.; Tomashek, John J.

    1999-01-01

    Describes a cooperative, interactive problem-solving exercise for studying eukaryotic cell structure and function. Highlights the dynamic aspects of movement through the cell. Contains 15 references. (WRM)

  9. Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Bron Dominique

    2008-04-01

    Full Text Available Abstract Background Neuronal tissue has limited potential to self-renew or repair after neurological diseases. Cellular therapies using stem cells are promising approaches for the treatment of neurological diseases. However, the clinical use of embryonic stem cells or foetal tissues is limited by ethical considerations and other scientific problems. Thus, bone marrow mesenchymal stomal cells (BM-MSC could represent an alternative source of stem cells for cell replacement therapies. Indeed, many studies have demonstrated that MSC can give rise to neuronal cells as well as many tissue-specific cell phenotypes. Methods BM-MSC were differentiated in neuron-like cells under specific induction (NPBM + cAMP + IBMX + NGF + Insulin. By day ten, differentiated cells presented an expression profile of real neurons. Functionality of these differentiated cells was evaluated by calcium influx through glutamate receptor AMPA3. Results Using microarray analysis, we compared gene expression profile of these different samples, before and after neurogenic differentiation. Among the 1943 genes differentially expressed, genes down-regulated are involved in osteogenesis, chondrogenesis, adipogenesis, myogenesis and extracellular matrix component (tuftelin, AGC1, FADS3, tropomyosin, fibronectin, ECM2, HAPLN1, vimentin. Interestingly, genes implicated in neurogenesis are increased. Most of them are involved in the synaptic transmission and long term potentialisation as cortactin, CASK, SYNCRIP, SYNTL4 and STX1. Other genes are involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor (FK506, ARHGAP6, CDKRAP2, PMCH, GFPT2, GRIA3, MCT6, BDNF, PENK, amphiregulin, neurofilament 3, Epha4, synaptotagmin. Using real time RT-PCR, we confirmed the expression of selected neuronal genes: NEGR1, GRIA3 (AMPA3, NEF3, PENK and Epha4. Functionality of these neuron-like cells was demonstrated by Ca2+ influx through glutamate

  10. Exosomes function in cell-cell communication during brain circuit development

    OpenAIRE

    Sharma, Pranav; Schiapparelli, Lucio; Cline, Hollis T.

    2013-01-01

    Exosomes are small extracellular vesicles that mediate intercellular signaling in the brain without requiring direct contact between cells. Although exosomes have been shown to play a role in neurological diseases and in response to nerve trauma, a role for exosome-mediated signaling in brain development and function has not yet been demonstrated. Here we review data building a case for exosome function in the brain.

  11. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Der-Yuan Chen

    2013-01-01

    Full Text Available Dendritic cells (DCs play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM, a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS, proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs. These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

  12. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Science.gov (United States)

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  13. Chemical-functional diversity in cell-penetrating peptides.

    Directory of Open Access Journals (Sweden)

    Sofie Stalmans

    Full Text Available Cell-penetrating peptides (CPPs are a promising tool to overcome cell membrane barriers. They have already been successfully applied as carriers for several problematic cargoes, like e.g. plasmid DNA and (siRNA, opening doors for new therapeutics. Although several hundreds of CPPs are already described in the literature, only a few commercial applications of CPPs are currently available. Cellular uptake studies of these peptides suffer from inconsistencies in used techniques and other experimental conditions, leading to uncertainties about their uptake mechanisms and structural properties. To clarify the structural characteristics influencing the cell-penetrating properties of peptides, the chemical-functional space of peptides, already investigated for cellular uptake, was explored. For 186 peptides, a new cell-penetrating (CP-response was proposed, based upon the scattered quantitative results for cellular influx available in the literature. Principal component analysis (PCA and a quantitative structure-property relationship study (QSPR, using chemo-molecular descriptors and our newly defined CP-response, learned that besides typical well-known properties of CPPs, i.e. positive charge and amphipathicity, the shape, structure complexity and the 3D-pattern of constituting atoms influence the cellular uptake capacity of peptides.

  14. Barrier Functionality of Porcine and Bovine Brain Capillary Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ailar Nakhlband

    2011-09-01

    Full Text Available Introduction: To date, isolated cell based blood-brain barrier (BBB models have been widely used for brain drug delivery and targeting, due to their relatively proper bioelectrical and permeability properties. However, primary cultures of brain capillary endothelial cells (BCECs isolated from different species vary in terms of bioelectrical and permeability properties. Methods: To pursue this, in the current investigation, primary porcine and bovine BCECs (PBCECs and BBCECs, respectively were isolated and used as an in vitro BBB model. The bioelectrical and permeability properties were assessed in BCECs co-cultured with C6 cells with/without hydrocortisone (550 nM. The bioelectrical properties were further validated by means of the permeability coefficients of transcellular and paracellular markers. Results: The primary PBCECs displayed significantly higher trans-endothelial electrical resistance (~900 W.cm2 than BBCECs (~700 W.cm2 - both co-cultured with C6 cells in presence of hydrocortisone. Permeability coefficients of propranolol/diazepam and mannitol/sucrose in PBCECs were ~21 and ~2 (×10-6 cm.sec-1, where these values for BBCECs were ~25 and ~5 (×10-6 cm.sec-1. Conclusion: Upon our bioelectrical and permeability findings, both models display discriminative barrier functionality but porcine BCECs seem to provide a better platform than bovine BCECs for drug screening and brain targeting.

  15. Runx1 Structure and Function in Blood Cell Development.

    Science.gov (United States)

    Bonifer, Constanze; Levantini, Elena; Kouskoff, Valerie; Lacaud, Georges

    2017-01-01

    RUNX transcription factors belong to a highly conserved class of transcriptional regulators which play various roles in the development of the majority of metazoans. In this review we focus on the founding member of the family, RUNX1, and its role in the transcriptional control of blood cell development in mammals. We summarize data showing that RUNX1 functions both as activator and repressor within a chromatin environment, a feature that requires its interaction with multiple other transcription factors and co-factors. Furthermore, we outline how RUNX1 works together with other factors to reshape the epigenetic landscape and the three-dimensional structure of gene loci within the nucleus. Finally, we review how aberrant forms of RUNX1 deregulate blood cell development and cause hematopoietic malignancies.

  16. Effects of diabetic HDL on endothelial cell function.

    Science.gov (United States)

    He, Dan; Pan, Bing; Ren, Hui; Zheng, Lemin

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is accompanied by dysfunctional high-density lipoprotein (HDL) and this is characterized by alterations in its composition and structure compared with HDL from normal subjects (N-HDL). HDL from diabetic subjects (D-HDL) has a diminished endothelial protective capacity including reducted ability to exert antioxidative activity, stimulate endothelial cell (EC) production of nitric oxide (NO) and endothelium-dependent vasomotion, promote endothelial progenitor cell (EPC)-mediated endothelial repair. In addition, D-HDL promotes EC proliferation, migration and adhesion to the matrix. The present review provides an overview of these effects of diabetic HDL on EC function, as well as the possible changes of D-HDL structure and composition which may be responsible for the diminished endothelial protective capacity of D-HDL.

  17. Neuregulin 1 functionalization of organic fibers for Schwann cell guidance

    Science.gov (United States)

    Tonazzini, Ilaria; Moffa, Maria; Pisignano, Dario; Cecchini, Marco

    2017-04-01

    The repair of peripheral nerve lesions is a clinical problem where the functional recovery is often far from being satisfactory, although peripheral nerves generally retain good potential for regeneration. Here, we develop a novel scaffold approach based on bioactive fibers of poly(ε-caprolactone) where nanotopographical guidance and neuregulin 1 (NRG1) cues are combined. We interface them with rat primary Schwann cells (SCs), the peripheral glial cells that drive initial regeneration of injured nerves, and found that the combination of NRG1 with parallel nano-fibrous topographies is effective in improving SC growth up to 72 h, alignment to fiber topography, and bipolar differentiation, opening original perspectives for nerve repair applications.

  18. Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

    Science.gov (United States)

    Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

    2017-10-01

    To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Stem Cells Derived from Tooth Periodontal Ligament Enhance Functional Angiogenesis by Endothelial Cells

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    Yeasmin, Shamima; Ceccarelli, Jacob; Vigen, Marina; Carrion, Bita; Putnam, Andrew J.; Tarle, Susan A.

    2014-01-01

    In regenerative medicine approaches involving cell therapy, selection of the appropriate cell type is important in that the cells must directly (differentiation) or indirectly (trophic effects) participate in the regenerative response. Regardless of the mode of action of the cells, angiogenesis underlies the success of these approaches. Stem