WorldWideScience

Sample records for cell movement restriction

  1. Restricted movement of lipid and aqueous dyes through pores formed by influenza hemagglutinin during cell fusion

    OpenAIRE

    1994-01-01

    The fusion of cells by influenza hemagglutinin (HA) is the best characterized example of protein-mediated membrane fusion. In simultaneous measurements of pairs of assays for fusion, we determined the order of detectable events during fusion. Fusion pore formation in HA-triggered cell-cell fusion was first detected by changes in cell membrane capacitance, next by a flux of fluorescent lipid, and finally by flux of aqueous fluorescent dye. Fusion pore conductance increased by small steps. A re...

  2. Restrictions on the transnational movement of uranium

    International Nuclear Information System (INIS)

    This paper analyses the United States policy on uranium imports. Recently, the US has moved closer to placing legislative restrictions on enrichment by DOE of foreign-origin uranium and has imposed a ban on the import of South African uranium ore and uranium oxide. American uranium producers have also sought relief in the courts against competition from abroad. The impetus for these events comes from a glut of uranium on world markets coupled with the existence of uranium mines outside the US with significant cost advantages over US producers. The remedies sought by the latter, if adopted, hold the potential for broad disruption of significant commercial interests in international trade in nuclear materials and could adversely affect US nonproliferation objectives (NEA)

  3. Does reduced movement restrictions and use of assistive devices affect rehabilitation outcome after total hip replacement?

    DEFF Research Database (Denmark)

    Mikkelsen, Lone Ramer; Petersen, Annemette Krintel; Søballe, Kjeld;

    2014-01-01

    . DESIGN: Non-randomized, controlled study. SETTING: Inpatient. POPULATION: 365 consecutively included THR patients. METHODS: Patients included the 3 initial month of the study underwent rehabilitation with restrictions in hip movement and a standard package of assistive devices (restricted group). This...... IMPACT: It is possible to reduce movement restrictions and use of assistive devices considerably. More research on safety issues is needed to elucidate the effect of unrestricted rehabilitation on hip dislocation....

  4. 7 CFR 360.300 - General prohibitions and restrictions on the movement of noxious weeds; permits.

    Science.gov (United States)

    2010-01-01

    ... of noxious weeds; permits. 360.300 Section 360.300 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 General prohibitions and restrictions on the movement of noxious weeds; permits. (a)...

  5. The "occlusis" model of cell fate restriction.

    Science.gov (United States)

    Lahn, Bruce T

    2011-01-01

    A simple model, termed "occlusis", is presented here to account for both cell fate restriction during somatic development and reestablishment of pluripotency during reproduction. The model makes three assertions: (1) A gene's transcriptional potential can assume one of two states: the "competent" state, wherein the gene is responsive to, and can be activated by, trans-acting factors in the cellular milieu, and the "occluded" state, wherein the gene is blocked by cis-acting, chromatin-based mechanisms from responding to trans-acting factors such that it remains silent irrespective of whether transcriptional activators are present in the milieu. (2) As differentiation proceeds in somatic lineages, lineage-inappropriate genes shift progressively and irreversibly from competent to occluded state, thereby leading to the restriction of cell fate. (3) During reproduction, global deocclusion takes place in the germline and/or early zygotic cells to reset the genome to the competent state in order to facilitate a new round of organismal development. PMID:20954221

  6. Cell-to-cell movement of mitochondria in plants

    OpenAIRE

    Gurdon, Csanad; Svab, Zora; Feng, Yaping; Kumar, Dibyendu; Maliga, Pal

    2016-01-01

    We report cell-to-cell movement of mitochondria through a graft junction of two tobacco species, Nicotiana tabacum and Nicotiana sylvestris. The flowers of the N. tabacum line we used are male sterile due to a sterility-causing mitochondrial genome, whereas the N. sylvestris flowers are fertile. Grafting created an opportunity for organelle movement during the healing process when cell-to-cell connections at the graft junction were restored. We recognized N. sylvestris mitochondrial DNA trans...

  7. Restriction of porcine parvovirus replication in nonpermissive cells.

    OpenAIRE

    Oraveerakul, K; Choi, C S; Molitor, T W

    1992-01-01

    Swine testicle (ST) cells and Madin-Darby canine kidney (MDCK) cells differ in their ability to support replication of porcine parvovirus (PPV). Viral replication events in ST cells, a permissive cell type, and MDCK cells, a nonpermissive cell type, were compared in an attempt to elucidate putative mechanisms of restrictive virus replication. Radiolabeled PPV bound to the cell surface of both cell types equally well and the binding was shown to be PPV specific, indicating that the restriction...

  8. Tetherin restricts productive HIV-1 cell-to-cell transmission.

    Directory of Open Access Journals (Sweden)

    Nicoletta Casartelli

    Full Text Available The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24 impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or DeltaVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DeltaVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.

  9. Cell-to-cell movement of mitochondria in plants.

    Science.gov (United States)

    Gurdon, Csanad; Svab, Zora; Feng, Yaping; Kumar, Dibyendu; Maliga, Pal

    2016-03-22

    We report cell-to-cell movement of mitochondria through a graft junction. Mitochondrial movement was discovered in an experiment designed to select for chloroplast transfer fromNicotiana sylvestrisintoNicotiana tabacumcells. The alloplasmicN. tabacumline we used carriesNicotiana undulatacytoplasmic genomes, and its flowers are male sterile due to the foreign mitochondrial genome. Thus, rare mitochondrial DNA transfer fromN. sylvestristoN. tabacumcould be recognized by restoration of fertile flower anatomy. Analyses of the mitochondrial genomes revealed extensive recombination, tentatively linking male sterility toorf293, a mitochondrial gene causing homeotic conversion of anthers into petals. Demonstrating cell-to-cell movement of mitochondria reconstructs the evolutionary process of horizontal mitochondrial DNA transfer and enables modification of the mitochondrial genome by DNA transmitted from a sexually incompatible species. Conversion of anthers into petals is a visual marker that can be useful for mitochondrial transformation. PMID:26951647

  10. 7 CFR 301.32 - Restrictions on interstate movement of regulated articles.

    Science.gov (United States)

    2010-01-01

    ... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES Fruit Flies... other requirements for the interstate movement of any of the fruit flies regulated under this...

  11. From mace to restricted movement :feminist social control theory and college women's fear of rape

    OpenAIRE

    Jones, Kathleen A.

    1995-01-01

    This research utilizes feminist social control theory to explore college women's fear of crime, specifically rape. Elements within this analysis include: comparisons of males and females on their relative fear of crime in both stranger and acquaintance situations, an assessment of behavioral/social self-restrictions, and an examination of the relative impact of previous victimization on women's fear. Data are derived from a self-administered questionnaire from a non-probability...

  12. Cucumovirus- and bromovirus-encoded movement functions potentiate cell-to-cell movement of tobamo- and potexviruses

    International Nuclear Information System (INIS)

    Cucumber mosaic virus (CMV, a cucumovirus) and Brome mosaic virus (BMV, a bromovirus) require the coat protein (CP) in addition to the 3a movement protein (MP) for cell-to-cell movement, while Cowpea chlorotic mottle virus (CCMV, a bromovirus) does not. Using bombardment-mediated transcomplementation assays, we investigated whether the movement functions encoded by these viruses potentiate cell-to-cell movement of movement-defective Tomato mosaic virus (ToMV, a tobamovirus) and Potato virus X (PVX, a potexvirus) mutants in Nicotiana benthamiana. Coexpression of CMV 3a and CP, but neither protein alone, complemented the defective movement of ToMV and PVX. A C-terminal deletion in CMV 3a (3aΔC33) abolished the requirement of CP in transporting the ToMV genome. The action of 3aΔC33 was inhibited by coexpression of wild-type 3a. These findings were confirmed in tobacco with ToMV-CMV chimeric viruses. Either BMV 3a or CCMV 3a alone efficiently complemented the movement-defective phenotype of the ToMV mutant. Therefore, every 3a protein examined intrinsically possesses the activity required to act as MP. In transcomplementation of the PVX mutant, the activities of BMV 3a, CCMV 3a, and CMV 3aΔC33 were very low. The activities of the bromovirus 3a proteins were enhanced by coexpression of the cognate CP but the activity of CMV 3aΔC33 was not. Based on these results, possible roles of cucumo- and bromovirus CPs in cell-to-cell movement are discussed

  13. Cucumovirus- and bromovirus-encoded movement functions potentiate cell-to-cell movement of tobamo- and potexviruses.

    Science.gov (United States)

    Tamai, Atsushi; Kubota, Kenji; Nagano, Hideaki; Yoshii, Motoyasu; Ishikawa, Masayuki; Mise, Kazuyuki; Meshi, Tetsuo

    2003-10-10

    Cucumber mosaic virus (CMV, a cucumovirus) and Brome mosaic virus (BMV, a bromovirus) require the coat protein (CP) in addition to the 3a movement protein (MP) for cell-to-cell movement, while Cowpea chlorotic mottle virus (CCMV, a bromovirus) does not. Using bombardment-mediated transcomplementation assays, we investigated whether the movement functions encoded by these viruses potentiate cell-to-cell movement of movement-defective Tomato mosaic virus (ToMV, a tobamovirus) and Potato virus X (PVX, a potexvirus) mutants in Nicotiana benthamiana. Coexpression of CMV 3a and CP, but neither protein alone, complemented the defective movement of ToMV and PVX. A C-terminal deletion in CMV 3a (3a Delta C33) abolished the requirement of CP in transporting the ToMV genome. The action of 3a Delta C33 was inhibited by coexpression of wild-type 3a. These findings were confirmed in tobacco with ToMV-CMV chimeric viruses. Either BMV 3a or CCMV 3a alone efficiently complemented the movement-defective phenotype of the ToMV mutant. Therefore, every 3a protein examined intrinsically possesses the activity required to act as MP. In transcomplementation of the PVX mutant, the activities of BMV 3a, CCMV 3a, and CMV 3a Delta C33 were very low. The activities of the bromovirus 3a proteins were enhanced by coexpression of the cognate CP but the activity of CMV 3a Delta C33 was not. Based on these results, possible roles of cucumo- and bromovirus CPs in cell-to-cell movement are discussed. PMID:14592759

  14. The cell biology of Tobacco mosaic virus replication and movement

    OpenAIRE

    Liu, Chengke; Richard S Nelson

    2013-01-01

    Successful systemic infection of a plant by Tobacco mosaic virus (TMV) requires three processes that repeat over time: initial establishment and accumulation in invaded cells, intercellular movement, and systemic transport. Accumulation and intercellular movement of TMV necessarily involves intracellular transport by complexes containing virus and host proteins and virus RNA during a dynamic process that can be visualized. Multiple membranes appear to assist TMV accumulation, while membranes,...

  15. Rights and Restrictions of EU Citizens within the Freedom of Movement of Persons

    Directory of Open Access Journals (Sweden)

    Diana Duca

    2014-05-01

    Full Text Available This Paper aims at presenting the risks and advantages of being a citizen of the European Union Member State/s, with respect to the Freedom of Movement of Persons, with focus on the Principle of Equality and Anti- Discrimination, as enshrined by the Treaties and other incident legislative acts, at first, and then as applied by the European Court of Justice via its established case law. Moreover, the two indicated Principles are quintessential when it comes to the rights pertaining to EU citizens, and therefore other Freedoms are interpreted in the light of Equality and Anti- Discrimination, e.g. Services, Capital etc. Regardless if one is a worker, a student or just someone who wishes to exercise his/her rights as an EU citizen in other capacities, it is highly desirable to understand the rationale behind those rights/freedoms.

  16. Dietary restriction, cell proliferation and carcinogenesis: a preliminary study

    International Nuclear Information System (INIS)

    Four groups of female Swiss Webster mice were given either laboratory chow or a purified (semi-synthetic) diet (AIN-76A) either ad libitum or at 75% of the ad libitum rate for about 30 days. Three tissues, the crypt cells of the jejunum, the dermis and the basal epithelial cells of the esophagus were investigated using [3H]thymidine labelling and by counting mitoses; four other tissues, the alveolar cells of the mammary gland, the crypt cells of the duodenum and colo-rectum, and the transitional cells of the urinary bladder were examined using [3H]thymidine labelling only. In each case dietary restriction led to a reduction of cellular proliferation assessed by these indices. The potential of the approach for the study of the effects of dietary modification on the introduction of cancer is discussed. (author). 22 refs

  17. Restricted movements and mangrove dependency of the nervous shark Carcharhinus cautus in nearshore coastal waters.

    Science.gov (United States)

    Escalle, L; Speed, C W; Meekan, M G; White, W T; Babcock, R C; Pillans, R D; Huveneers, C

    2015-08-01

    This study used a network of acoustic receivers deployed around a no-take zone in Mangrove Bay, within the Ningaloo Reef Marine Park in Western Australia, to study residency and habitat preference of a small coastal shark, the nervous shark Carcharhinus cautus. Twelve C. cautus were tagged with acoustic tags and monitored for up to 579 days. Based on individuals detected within the receiver array for at least 2 months, C. cautus had small core (50% kernel utilization distribution, KUD) and home ranges (95% KUD) of 0.66 and 3.64 km2, respectively, and showed a strong habitat preference for mangroves, which are only found in the no-take zone. This resulted in C. cautus spending most of their detected time within the no-take zone boundaries (mean = 81.5%), showing that such a protected area could be beneficial to protect this species from extensive fishing pressure and local depletion, where required. Not all C. cautus remained within the acoustic array, however, suggesting that individual variations occur and that not all individuals would benefit from such protection. This study provides important information about the habitat, residency and movements of C. cautus that can be used for management and conservation. The strong affinity and residency of C. cautus within a mangrove-fringing coastline, emphasizes the importance of mangrove habitat to the species and suggests that such preferences can be used to design appropriate no-take zones for this species or others with similar habitat preferences. PMID:26179676

  18. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    Energy Technology Data Exchange (ETDEWEB)

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

  19. Cortactin mediated morphogenic cell movements during zebrafish (Danio rerio) gastrulation

    Institute of Scientific and Technical Information of China (English)

    YU Dan; ZHANG Peijun; ZHAN Xi

    2005-01-01

    Cell migration is essential to direct embryonic cells to specific sites at which their developmental fates are ultimately determined. However, the mechanism by which cell motility is regulated in embryonic development is largely unknown. Cortactin, a filamentous actin binding protein, is an activator of Arp2/3 complex in the nucleation of actin cytoskeleton at the cell leading edge and acts directly on the machinery of cell motility. To determine whether cortactin and Arp2/3 mediated actin assembly plays a role in the morphogenic cell movements during the early development of zebrafish, we initiated a study of cortactin expression in zebrafish embryos at gastrulating stages when massive cell migrations occur. Western blot analysis using a cortactin specific monoclonal antibody demonstrated that cortactin protein is abundantly present in embryos at the most early developmental stages. Immunostaining of whole-mounted embryo showed that cortactin immunoreactivity was associated with the embryonic shield, predominantly at the dorsal side of the embryos during gastrulation. In addition, cortactin was detected in the convergent cells of the epiblast and hypoblast, and later in the central nervous system. Immunofluorescent staining with cortactin and Arp3 antibodies also revealed that cortactin and Arp2/3 complex colocalized at the periphery and many patches associated with the cell-to-cell junction in motile embryonic cells. Therefore, our data suggest that cortactin and Arp2/3 mediated actin polymerization is implicated in the cell movement during gastrulation and perhaps the development of the central neural system as well.

  20. The cell biology of Tobacco mosaic virus replication and movement

    Directory of Open Access Journals (Sweden)

    Chengke eLiu

    2013-02-01

    Full Text Available Successful systemic infection of a plant by Tobacco mosaic virus (TMV requires three processes that repeat over time: initial establishment and accumulation in invaded cells, intercellular movement and systemic transport. Accumulation and intercellular movement of TMV necessarily involves intracellular transport by complexes containing virus and host proteins and virus RNA during a dynamic process that can be visualized. Multiple membranes appear to assist TMV accumulation, while membranes, microfilaments and microtubules appear to assist TMV movement. Here we review cell biological studies that describe TMV-membrane, -cytoskeleton and -other host protein interactions which influence virus accumulation and movement in leaves and callus tissue. The importance of understanding the developmental phase of the infection in relationship to the observed virus-membrane or -host protein interaction is emphasized. Utilizing the latest observations of TMV-membrane and -host protein interactions within our evolving understanding of the infection ontogeny, a model for TMV accumulation and intracellular spread in a cell biological context is provided.

  1. Exosomes released from breast cancer carcinomas stimulate cell movement.

    Directory of Open Access Journals (Sweden)

    Dinari A Harris

    Full Text Available For metastasis to occur cells must communicate with to their local environment to initiate growth and invasion. Exosomes have emerged as an important mediator of cell-to-cell signalling through the transfer of molecules such as mRNAs, microRNAs, and proteins between cells. Exosomes have been proposed to act as regulators of cancer progression. Here, we study the effect of exosomes on cell migration, an important step in metastasis. We performed cell migration assays, endocytosis assays, and exosome proteomic profiling on exosomes released from three breast cancer cell lines that model progressive stages of metastasis. Results from these experiments suggest: (1 exosomes promote cell migration and (2 the signal is stronger from exosomes isolated from cells with higher metastatic potentials; (3 exosomes are endocytosed at the same rate regardless of the cell type; (4 exosomes released from cells show differential enrichment of proteins with unique protein signatures of both identity and abundance. We conclude that breast cancer cells of increasing metastatic potential secrete exosomes with distinct protein signatures that proportionally increase cell movement and suggest that released exosomes could play an active role in metastasis.

  2. Epitopes associated with MHC restriction site of T cells. III. I-J epitope on MHC-restricted T helper cells

    International Nuclear Information System (INIS)

    I-J epitopes were found to be associated with the functional site of the class II MHC-restricted helper T (Th) cells: Virtually all of the H-2k-restricted Th cell function of H-2kxbF1 T cells was inhibited by the anti-I-Jk mAb, leaving the H-2b-restricted function unaffected. The I-Jk epitope was inducible in Th cells of different genotype origin according to the environmental class II antigens present in the early ontogeny of T cells. Although above results suggested that I-J is the structure reflecting the inducible MHC restriction specificity, further studies revealed some interesting controversies: First, the I-J phenotype did not always correlate with the class II restriction specificity, e.g., I-Ab-restricted Th from 5R was I-Jk-positive, whereas I-Ak-restricted Th of 4R was not. Second, there was no trans expression of parental I-J phenotypes and restriction specificities in F1 Th, e.g., the I-J phenotype was detected only on I-Ab-restricted Th of (4R X 5R)F1, whereas it was absent on I-Ak-restricted Th. This strict linkage between the restriction specificity and I-J phenotype was also found on Th cells developed in bone marrow chimera constructed with intra-H-2-recombinant mice. The expression of I-Jk was always associated with the restriction specificity of the relevant host. Thus, the restriction specificity of Th cells followed the host type, and the I-J expression on Th was exactly the same as that expressed by the host haplotype. These results indicate that I-J is an isomorphic structure adaptively expressed on Th cells that is involved in the unidirectional regulatory cell interactions, and that the polymorphism cannot be explained merely by the restriction specificity of the conventional T cell receptor heterodimer

  3. Contrasting levels of heavy metals in the feathers of urban pigeons from close habitats suggest limited movements at a restricted scale

    International Nuclear Information System (INIS)

    Despite restrictions in emissions, heavy metals may remain a major environmental issue due to their numerous sources and their persistence. Here, we assessed current levels of 4 metals (Copper, Cadmium, Lead, Zinc) in the feathers of 91 feral pigeons (Columba livia) from 7 sites in the urbanized region of Paris. Elements were detected in all pigeons, indicating that metals persist in urbanized areas. The ratio between metal concentrations in the feathers vs. in the environment calculated using data from other studies was 2–90 times higher for cadmium than for other metals, underlying its ecological importance. Concentrations in the feathers depended on locality, suggesting that pigeons remain in local habitats at this restricted scale, as expected from previous observations. Overall, our study suggests that urban feral pigeons may represent a good model system for metal biomonitoring. Highlights: ► We measured the concentrations of 4 heavy metals in pigeon feathers through Paris. ► Cadmium, Copper, Lead and Zinc were present in pigeons from all 7 sites. ► Metals thus still persist in the city though their emissions have been reduced. ► Metal concentrations in the feathers depended on the local origin of the pigeons. ► These differences suggest limited pigeon movements at a very restricted scale. - Concentrations of metals in the feathers of Parisian feral pigeons (Columba livia) strongly differ at a restricted spatial scale, suggesting limited movements in urban areas.

  4. The Arabidopsis synaptotagmin SYTA regulates the cell-to-cell movement of diverse plant viruses

    Directory of Open Access Journals (Sweden)

    Asako eUchiyama

    2014-11-01

    Full Text Available Synaptotagmins are a large gene family in animals that have been extensively characterized due to their role as calcium sensors to regulate synaptic vesicle exocytosis and endocytosis in neurons, and dense core vesicle exocytosis for hormone secretion from neuroendocrine cells. Thought to be exclusive to animals, synaptotagmins have recently been characterized in Arabidopsis thaliana, in which they comprise a five gene family. Using infectivity and leaf-based functional assays, we have shown that Arabidopsis SYTA regulates endocytosis and marks an endosomal vesicle recycling pathway to regulate movement protein-mediated trafficking of the Begomovirus Cabbage leaf curl virus (CaLCuV and the Tobamovirus Tobacco mosaic virus (TMV through plasmodesmata (Lewis and Lazarowitz, 2010. To determine whether SYTA has a central role in regulating the cell-to-cell trafficking of a wider range of diverse plant viruses, we extended our studies here to examine the role of SYTA in the cell-to-cell movement of additional plant viruses that employ different modes of movement, namely the Potyvirus Turnip mosaic virus (TuMV, the Caulimovirus Cauliflower mosaic virus (CaMV and the Tobamovirus Turnip vein clearing virus (TVCV, which in contrast to TMV does efficiently infect Arabidopsis. We found that both TuMV and TVCV systemic infection, and the cell-to-cell trafficking of the their movement proteins, were delayed in the Arabidopsis Col-0 syta-1 knockdown mutant. In contrast, CaMV systemic infection was not inhibited in syta-1. Our studies show that SYTA is a key regulator of plant virus intercellular movement, being necessary for the ability of diverse cell-to-cell movement proteins encoded by Begomoviruses (CaLCuV MP, Tobamoviruses (TVCV and TMV 30K protein and Potyviruses (TuMV P3N-PIPO to alter PD and thereby mediate virus cell-to-cell spread.

  5. Translocation of Magnaporthe oryzae effectors into rice cells and their subsequent cell-to-cell movement.

    Science.gov (United States)

    Khang, Chang Hyun; Berruyer, Romain; Giraldo, Martha C; Kankanala, Prasanna; Park, Sook-Young; Czymmek, Kirk; Kang, Seogchan; Valent, Barbara

    2010-04-01

    Knowledge remains limited about how fungal pathogens that colonize living plant cells translocate effector proteins inside host cells to regulate cellular processes and neutralize defense responses. To cause the globally important rice blast disease, specialized invasive hyphae (IH) invade successive living rice (Oryza sativa) cells while enclosed in host-derived extrainvasive hyphal membrane. Using live-cell imaging, we identified a highly localized structure, the biotrophic interfacial complex (BIC), which accumulates fluorescently labeled effectors secreted by IH. In each newly entered rice cell, effectors were first secreted into BICs at the tips of the initially filamentous hyphae in the cell. These tip BICs were left behind beside the first-differentiated bulbous IH cells as the fungus continued to colonize the host cell. Fluorescence recovery after photobleaching experiments showed that the effector protein PWL2 (for prevents pathogenicity toward weeping lovegrass [Eragrostis curvula]) continued to accumulate in BICs after IH were growing elsewhere. PWL2 and BAS1 (for biotrophy-associated secreted protein 1), BIC-localized secreted proteins, were translocated into the rice cytoplasm. By contrast, BAS4, which uniformly outlines the IH, was not translocated into the host cytoplasm. Fluorescent PWL2 and BAS1 proteins that reached the rice cytoplasm moved into uninvaded neighbors, presumably preparing host cells before invasion. We report robust assays for elucidating the molecular mechanisms that underpin effector secretion into BICs, translocation to the rice cytoplasm, and cell-to-cell movement in rice. PMID:20435900

  6. SAMHD1: a new insight into HIV-1 restriction in myeloid cells

    OpenAIRE

    Wu Li; St Gelais Corine

    2011-01-01

    Abstract Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of a putative restriction factor. Two recent studies discovered the cellular protein SAMHD1 to be this restriction factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid-cell-specific HIV-1 ...

  7. Is nectar reabsorption restricted by the stalk cells of floral and extrafloral nectary trichomes?

    Science.gov (United States)

    Cardoso-Gustavson, P; Davis, A R

    2015-01-01

    Reabsorption is a phase of nectar dynamics that occurs concurrently with secretion; it has been described in floral nectaries that exude nectar through stomata or unicellular trichomes, but has not yet been recorded in extrafloral glands. Apparently, nectar reabsorption does not occur in multicellular secretory trichomes (MST) due to the presence of lipophilic impregnations - which resemble Casparian strips - in the anticlinal walls of the stalk cells. It has been assumed that these impregnations restrict solute movement within MST to occur unidirectionally and exclusively by the symplast, thereby preventing nectar reflux toward the underlying nectary tissues. We hypothesised that reabsorption is absent in nectaries possessing MST. The fluorochrome lucifer yellow (LYCH) was applied to standing nectar of two floral and extrafloral glands of distantly related species, and then emission spectra from nectary sections were systematically analysed using confocal microscopy. Passive uptake of LYCH via the stalk cells to the nectary tissues occurred in all MST examined. Moreover, we present evidence of nectar reabsorption in extrafloral nectaries, demonstrating that LYCH passed the stalk cells of MST, although it did not reach the deepest nectary tissues. Identical (control) experiments performed with neutral red (NR) demonstrated no uptake of this stain by actively secreting MST, whereas diffusion of NR did occur in plasmolysed MST of floral nectaries at the post-secretory phase, indicating that nectar reabsorption by MST is governed by stalk cell physiology. Interestingly, non-secretory trichomes failed to reabsorb nectar. The role of various nectary components is discussed in relation to the control of nectar reabsorption by secretory trichomes. PMID:24987788

  8. Border Cell Migration: A Model System for Live Imaging and Genetic Analysis of Collective Cell Movement

    OpenAIRE

    M Prasad; Wang, X; He, L.; Cai, D.; Montell, DJ

    2015-01-01

    © 2015, Springer Science+Business Media New York. Border cell migration in the Drosophila ovary has emerged as a genetically tractable model for studying collective cell movement. Over many years border cell migration was exclusively studied in fixed samples due to the inability to culture stage 9 egg chambers in vitro. Although culturing late-stage egg chambers was long feasible, stage 9 egg chambers survived only briefl y outside the female body. We identifi ed culture conditions that suppo...

  9. Transfer of experimental allergic encephalomyelitis to bone marrow chimeras. Endothelial cells are not a restricting element

    International Nuclear Information System (INIS)

    The adoptive transfer of clinical and histopathologic signs of experimental allergic encephalomyelitis (EAE) requires MHC compatibility between cell donor and cell recipient. The results of adoptive transfer studies using F1 to parent bone marrow chimeras as recipients of parental-derived BP-sensitive spleen cells indicate that this restriction is not expressed at the level of the endothelial cell but is confined to the cells of bone marrow derivation. Furthermore, these results indicate that the development of EAE is not dependent on the activity of MHC-restricted cytotoxic cells

  10. CALORIE RESTRICTION ENHANCES T CELL MEDIATED IMMUNE RESPONSE IN OVERWEIGHT MEN AND WOMEN

    Science.gov (United States)

    It is well known that dietary energy restriction prolongs lifespan and enhances immune responsiveness in a wide range of laboratory animals. However, information on the applicability of these results to humans is limited. In this study we examined the effects of calorie restriction on T cell mediate...

  11. Effect of Cell Adhesion Molecule 1 Expression on Intracellular Granule Movement in Pancreatic α Cells.

    Science.gov (United States)

    Yokawa, Satoru; Furuno, Tadahide; Suzuki, Takahiro; Inoh, Yoshikazu; Suzuki, Ryo; Hirashima, Naohide

    2016-09-01

    Although glucagon secreted from pancreatic α cells plays a role in increasing glucose concentrations in serum, the mechanism regulating glucagon secretion from α cells remains unclear. Cell adhesion molecule 1 (CADM1), identified as an adhesion molecule in α cells, has been reported not only to communicate among α cells and between nerve fibers, but also to prevent excessive glucagon secretion from α cells. Here, we investigated the effect of CADM1 expression on the movement of intracellular secretory granules in α cells because the granule transport is an important step in secretion. Spinning disk microscopic analysis showed that granules moved at a mean velocity of 0.236 ± 0.010 μm/s in the mouse α cell line αTC6 that expressed CADM1 endogenously. The mean velocity was significantly decreased in CADM1-knockdown (KD) cells (mean velocity: 0.190 ± 0.016 μm/s). The velocity of granule movement decreased greatly in αTC6 cells treated with the microtubule-depolymerizing reagent nocodazole, but not in αTC6 cells treated with the actin-depolymerizing reagent cytochalasin D. No difference in the mean velocity was observed between αTC6 and CADM1-KD cells treated with nocodazole. These results suggest that intracellular granules in pancreatic α cells move along the microtubule network, and that CADM1 influences their velocity. PMID:27262873

  12. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement

    International Nuclear Information System (INIS)

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed

  13. The Cell Adhesion-associated Protein Git2 Regulates Morphogenetic Movements during Zebrafish Embryonic Development

    OpenAIRE

    Yu, Jianxin A.; Foley, Fiona C.; Amack, Jeffrey D.; Christopher E Turner

    2010-01-01

    Signaling through cell adhesion complexes plays a critical role in coordinating cytoskeletal remodeling necessary for efficient cell migration. During embryonic development, normal morphogenesis depends on a series of concerted cell movements; but the roles of cell adhesion signaling during these movements are poorly understood. The transparent zebrafish embryo provides an excellent system to study cell migration during development. Here, we have identified zebrafish git2a and git2b, two new ...

  14. Does reduced movement restrictions and use of assistive devices affect rehabilitation outcome after total hip replacement? A non-randomized, controlled study in 365 patients with six week follow up

    DEFF Research Database (Denmark)

    Mikkelsen, Lone Ramer; Petersen, Annemette Krintel; Søballe, Kjeld;

    standard package of assistive devices (restricted group, RG). This group was compared to patients included into the study the following 3 months with a less restricted hip movement regime and use of assistive devices according to individual needs (unrestricted group, UG). Questionnaires on function...

  15. A multidirectional non-cell autonomous control and a genetic interaction restricting tobacco etch virus susceptibility in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Suresh Gopalan

    Full Text Available BACKGROUND: Viruses constitute a major class of pathogens that infect a variety of hosts. Understanding the intricacies of signaling during host-virus interactions should aid in designing disease prevention strategies and in understanding mechanistic aspects of host and pathogen signaling machinery. METHODOLOGY/PRINCIPAL FINDINGS: An Arabidopsis mutant, B149, impaired in susceptibility to Tobacco etch virus (TEV, a positive strand RNA virus of picoRNA family, was identified using a high-throughput genetic screen and a counterselection scheme. The defects include initiation of infection foci, rate of cell-to-cell movement and long distance movement. CONCLUSIONS/SIGNIFICANCE: The defect in infectivity is conferred by a recessive locus. Molecular genetic analysis and complementation analysis with three alleles of a previously published mutant lsp1 (loss of susceptibility to potyviruses indicate a genetic interaction conferring haploinsufficiency between the B149 locus and certain alleles of lsp1 resulting in impaired host susceptibility. The pattern of restriction of TEV foci on leaves at or near the boundaries of certain cell types and leaf boundaries suggest dysregulation of a multidirectional non-cell autonomous regulatory mechanism. Understanding the nature of this multidirectional signal and the molecular genetic mechanism conferring it should potentially reveal a novel arsenal in the cellular machinery.

  16. Restriction of Human Polyomavirus BK Virus DNA Replication in Murine Cells and Extracts

    OpenAIRE

    Mahon, C.; Liang, B.; Tikhanovich, I.; et al

    2009-01-01

    BK virus (BKV) causes persistent and asymptomatic infections in most humans and is the etiologic agent of polyomavirus-associated nephropathy (PVAN) and other pathologies. Unfortunately, there are no animal models with which to study activation of BKV replication in the human kidney and the accompanying PVAN. Here we report studies of the restriction of BKV replication in murine cells and extracts and the cause(s) of this restriction. Upon infection of murine cells, BKV expressed large T anti...

  17. Lsd1 restricts the number of germline stem cells by regulating multiple targets in escort cells.

    Directory of Open Access Journals (Sweden)

    Susan Eliazer

    2014-03-01

    Full Text Available Specialized microenvironments called niches regulate tissue homeostasis by controlling the balance between stem cell self-renewal and the differentiation of stem cell daughters. However the mechanisms that govern the formation, size and signaling of in vivo niches remain poorly understood. Loss of the highly conserved histone demethylase Lsd1 in Drosophila escort cells results in increased BMP signaling outside the cap cell niche and an expanded germline stem cell (GSC phenotype. Here we present evidence that loss of Lsd1 also results in gradual changes in escort cell morphology and their eventual death. To better characterize the function of Lsd1 in different cell populations within the ovary, we performed Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq. This analysis shows that Lsd1 associates with a surprisingly limited number of sites in escort cells and fewer, and often, different sites in cap cells. These findings indicate that Lsd1 exhibits highly selective binding that depends greatly on specific cellular contexts. Lsd1 does not directly target the dpp locus in escort cells. Instead, Lsd1 regulates engrailed expression and disruption of engrailed and its putative downstream target hedgehog suppress the Lsd1 mutant phenotype. Interestingly, over-expression of engrailed, but not hedgehog, results in an expansion of GSC cells, marked by the expansion of BMP signaling. Knockdown of other potential direct Lsd1 target genes, not obviously linked to BMP signaling, also partially suppresses the Lsd1 mutant phenotype. These results suggest that Lsd1 restricts the number of GSC-like cells by regulating a diverse group of genes and provide further evidence that escort cell function must be carefully controlled during development and adulthood to ensure proper germline differentiation.

  18. Restriction of Rift Valley Fever Virus Virulence in Mosquito Cells

    Directory of Open Access Journals (Sweden)

    Sonja R. Gerrard

    2010-02-01

    Full Text Available Arboviruses are maintained in a natural cycle that requires blood-sucking arthropod and vertebrate hosts. Arboviruses are believed to persistently infect their arthropod host without overt pathology and cause acute infection with viremia in their vertebrate host. We have focused on elucidating how a specific arbovirus, Rift Valley fever (RVF virus, causes cytopathic effect in cells derived from vertebrates and non-cytopathic infection in cells derived from arthropods. We demonstrate that the vertebrate virulence factor, NSs, is functional in arthropod cells but is expressed at significantly lower levels in infected arthropod versus infected vertebrate cells.

  19. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai;

    2015-01-01

    titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean...... trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials....... TRIAL SELECTION: Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size. DATA EXTRACTION: Two authors independently screened...

  20. Studies on the mechanism of the self restriction of T cell responses in radiation chimeras

    International Nuclear Information System (INIS)

    Recent experiments with murine radiation chimeras have shown that F1 T cells that mature in an H-2 homozygous thymus, as is the case in [F1 → Parent 1] chimeras, are restricted to recognizing foreign antigen in the context of Parent 1 H-2 antigens. Conflicting results on the stringency of self H-2 restriction of T cells from normal mice have suggested that the thymic restriction in chimeras may be due to active suppression of parent 2-restricted T cell clones. We have therefore conducted 3 sets of experiments to test for suppression of maturing T cells that could mediate thymic tutoring of H-2-restriction specificity in chimeras. In 2 sets of experiments, we found no evidence that suppressor cells could be exported from 1 thymus and act either intrathymically on thymocytes in a 2nd thymus or extrathymically on recent thymic emigrants. We believe current data support a role for the thymus in positive as well as negative selection of maturing thymocytes on the basis of self recognition, in the absence of any suppression. Our results do not support the concept that suppression is responsible for the difference in the degree of self preference in the T cells of chimeric mice relative to cell populations obtained from neonatally tolerant mice or from normal mice after acute negative selection

  1. Endothelial progenitor cells display clonal restriction in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dai Kezhi

    2006-06-01

    Full Text Available Abstract Background In multiple myeloma (MM, increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI patterns in female patients by a human androgen receptor assay (HUMARA. In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. Methods A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH. Results In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele in 64% (n = 7. In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele. In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5 of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status

  2. Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Wilfried Posch

    2015-06-01

    Full Text Available DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.

  3. Single Cell Analysis to locate the Restriction Point with respect to E2F Expression

    Science.gov (United States)

    Pimienta, R.; Johnson, A.

    2011-12-01

    The restriction point is a G1-phase checkpoint that regulates passage through the cell cycle and is misregulated in all known types of cancer. The Rb-E2F switch is thought to be one of the most relevant molecular mechanisms which regulate the restriction point in mammalian cells. However, recent experiments have brought the timing of the restriction point into question. In previous studies, cells were analyzed as populations and this prevented an accurate determination of the restriction point. By creating and analyzing an E2F-GFP reporter in single cells, we can pinpoint the timing of E2F activation and determine whether it coincides with the restriction point. Using calcium phosphate and Fugene,we transfected human embryonic kidney (293T) cells with a CMV-GFP plasmid and an E2F-GFP reporter. Based on our results, it appears that calcium phosphate is more effective than Fugene at transfecting mammalian cells. The calcium phosphate transfection had 9.59% more fluorescent cells than Fugene. However, this result only occurred with the CMV-GFP plasmid and not the E2F-GFP reporter, which was not properly expressed in human embryonic kidney (293T) cells. We will continue troubleshooting to fix this reporter as we proceed with our research. Once the reporter is properly cloned, we will transfect it into retinal pigmented epithelial (RPE1-hTERT) cells using the calcium phosphate method. RPE1-hTERT cells are an immortalized with telomerase and are more close to normal cells than tumor-derived cell lines. Through this research we will better comprehend commitment to the mammalian cell cycle.

  4. Extrachromosomal recombination substrates recapitulate beyond 12/23 restricted VDJ recombination in nonlymphoid cells.

    Science.gov (United States)

    Jung, David; Bassing, Craig H; Fugmann, Sebastian D; Cheng, Hwei-Ling; Schatz, David G; Alt, Frederick W

    2003-01-01

    V(D)J recombination occurs efficiently only between gene segments flanked by recombination signals (RSs) containing 12 and 23 base pair spacers (the 12/23 rule). A further limitation "beyond the 12/23 rule" (B12/23) exists at the TCRbeta locus and ensures Dbeta usage. Herein, we show that extrachromosomal V(D)J recombination substrates recapitulate B12/23 restriction in nonlymphoid cells. We further demonstrate that the Vbeta coding flank, the 12-RS heptamer/nonamer, and the 23-RS spacer each can significantly influence B12/23 restriction. Finally, purified core RAG1 and RAG2 proteins (together with HMG2) also reproduce B12/23 restriction in a cell-free system. Our findings indicate that B12/23 restriction of V(D)J recombination is cemented at the level of interactions between the RAG proteins and TCRbeta RS sequences. PMID:12530976

  5. Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery.

    Science.gov (United States)

    Lee, Soo Young; Gertler, Frank B; Goldberg, Marcia B

    2015-11-01

    Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells. PMID:26358985

  6. The Potato virus X TGBp3 protein associates with the ER network for virus cell-to-cell movement

    Science.gov (United States)

    Krishnamurthy, Konduru; Heppler, Marty; Mitra, Ruchira; Blancaflor, Elison; Payton, Mark; Nelson, Richard S.; Verchot-Lubicz, Jeanmarie

    2003-01-01

    Potato virus X (PVX) TGBp3 is required for virus cell-to-cell movement. Cell-to-cell movement of TGBp3 was studied using biolistic bombardment of plasmids expressing GFP:TGBp3. TGBp3 moves between cells in Nicotiana benthamiana, but requires TGBp1 to move in N. tabacum leaves. In tobacco leaves GFP:TGBp3 accumulated in a pattern resembling the endoplasmic reticulum (ER). To determine if the ER network is important for GFP:TGBp3 and for PVX cell-to-cell movement, a single mutation inhibiting membrane binding of TGBp3 was introduced into GFP:TGBp3 and into PVX. This mutation disrupted movement of GFP:TGBp3 and PVX. Brefeldin A, which disrupts the ER network, also inhibited GFP:TGBp3 movement in both Nicotiana species. Two deletion mutations, that do not affect membrane binding, hindered GFP:TGBp3 and PVX cell-to-cell movement. Plasmids expressing GFP:TGBp2 and GFP:TGBp3 were bombarded to several other PVX hosts and neither protein moved between adjacent cells. In most hosts, TGBp2 or TGBp3 cannot move cell-to-cell.

  7. Downregulation of the NbNACa1 gene encoding a movement-protein-interacting protein reduces cell-to-cell movement of Brome mosaic virus in Nicotiana benthamiana.

    Science.gov (United States)

    Kaido, Masanori; Inoue, Yosuke; Takeda, Yoshika; Sugiyama, Kazuhiko; Takeda, Atsushi; Mori, Masashi; Tamai, Atsushi; Meshi, Tetsuo; Okuno, Tetsuro; Mise, Kazuyuki

    2007-06-01

    The 3a movement protein (MP) plays a central role in the movement of the RNA plant virus, Brome mosaic virus (BMV). To identify host factor genes involved in viral movement, a cDNA library of Nicotiana benthamiana, a systemic host for BMV, was screened with far-Western blotting using a recombinant BMV MP as probe. One positive clone encoded a protein with sequence similarity to the alpha chain of nascent-polypeptide-associated complex from various organisms, which is proposed to contribute to the fidelity of translocation of newly synthesized proteins. The orthologous gene from N. benthamiana was designated NbNACa1. The binding of NbNACa1 to BMV MP was confirmed in vivo with an agroinfiltration-immunoprecipitation assay. To investigate the involvement of NbNACa1 in BMV multiplication, NbNACa1-silenced (GSNAC) transgenic N. benthamiana plants were produced. Downregulation of NbNACa1 expression reduced virus accumulation in inoculated leaves but not in protoplasts. A microprojectile bombardment assay to monitor BMV-MP-assisted viral movement demonstrated reduced virus spread in GSNAC plants. The localization to the cell wall of BMV MP fused to green fluorescent protein was delayed in GSNAC plants. From these results, we propose that NbNACa1 is involved in BMV cell-to-cell movement through the regulation of BMV MP localization to the plasmodesmata. PMID:17555275

  8. Polyclonal B-cell response to stimulation with Escherichia coli lipopolysaccharide in dietary protein restriction.

    OpenAIRE

    Malavé, I; Pocino, M

    1982-01-01

    The polyclonal B-cell response to Escherichia coli lipopolysaccharide was studied in C57BL/6 mice maintained after weaning on either a moderate protein-restricted diet with 8% casein or a normal diet. After in vitro or in vivo stimulation with the endotoxin, autoreactive and anti-hapten antibody-producing cells were quantitated by direct plaque assay, using bromelain-treated mouse erythrocytes and trinitrophenylated sheep erythrocytes as targets. Larger numbers of plaque-forming cells were ge...

  9. Toddler: An Embryonic Signal That Promotes Cell Movement via Apelin Receptors

    OpenAIRE

    Pauli, Andrea; Norris, Megan L.; Valen, Eivind; Chew, Guo-Liang; Gagnon, James A.; Zimmerman, Steven; Mitchell, Andrew; Ma, Jiao; Dubrulle, Julien; Reyon, Deepak; Tsai, Shengdar Q.; Joung, J. Keith; Saghatelian, Alan; Schier, Alexander F.

    2014-01-01

    It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neithe...

  10. Passage-restricted differentiation potential of mesenchymal stem cells into cardiomyocyte-like cells

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) have limited ability to differentiate into cardiomyocytes and the factors affect this process are not fully understood. In this study, we investigated the passage (P)-related transdifferentiation potential of MSCs into cardiomyocyte-like cells and its relationship to the proliferation ability. After 5-azacytidine treatment, only P4 but not P1 and P8 rat bone marrow MSCs (rMSCs) showed formation of myotube and expressed cardiomyocyte-associated markers. The growth property analysis showed P4 rMSCs had a growth-arrest appearance, while P1 and P8 rMSCs displayed an exponential growth pattern. When the rapid proliferation of P1 and P8 rMSCs was inhibited by 5-bromo-2-deoxyuridine, a mitosis inhibitor, only P1, not P8 rMSCs, differentiated into cardiomyocyte-like cells after 5-azacytidine treatment. These results demonstrate that the differentiation ability of rMSCs into cardiomyocytes is in proliferation ability-dependent and passage-restricted patterns. These findings reveal a novel regulation on the transdifferentiation of MSCs and provide useful information for exploiting the clinical therapeutic potential of MSCs

  11. Exosomes Released from Breast Cancer Carcinomas Stimulate Cell Movement

    OpenAIRE

    Dinari A Harris; Patel, Sajni H.; Gucek, Marjan; Hendrix, An; Westbroek, Wendy; Taraska, Justin W.

    2015-01-01

    For metastasis to occur cells must communicate with to their local environment to initiate growth and invasion. Exosomes have emerged as an important mediator of cell-to-cell signalling through the transfer of molecules such as mRNAs, microRNAs, and proteins between cells. Exosomes have been proposed to act as regulators of cancer progression. Here, we study the effect of exosomes on cell migration, an important step in metastasis. We performed cell migration assays, endocytosis assays, and e...

  12. Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism.

    Science.gov (United States)

    Dodson, Paul D; Dreyer, Jakob K; Jennings, Katie A; Syed, Emilie C J; Wade-Martins, Richard; Cragg, Stephanie J; Bolam, J Paul; Magill, Peter J

    2016-04-12

    Midbrain dopaminergic neurons are essential for appropriate voluntary movement, as epitomized by the cardinal motor impairments arising in Parkinson's disease. Understanding the basis of such motor control requires understanding how the firing of different types of dopaminergic neuron relates to movement and how this activity is deciphered in target structures such as the striatum. By recording and labeling individual neurons in behaving mice, we show that the representation of brief spontaneous movements in the firing of identified midbrain dopaminergic neurons is cell-type selective. Most dopaminergic neurons in the substantia nigra pars compacta (SNc), but not in ventral tegmental area or substantia nigra pars lateralis, consistently represented the onset of spontaneous movements with a pause in their firing. Computational modeling revealed that the movement-related firing of these dopaminergic neurons can manifest as rapid and robust fluctuations in striatal dopamine concentration and receptor activity. The exact nature of the movement-related signaling in the striatum depended on the type of dopaminergic neuron providing inputs, the striatal region innervated, and the type of dopamine receptor expressed by striatal neurons. Importantly, in aged mice harboring a genetic burden relevant for human Parkinson's disease, the precise movement-related firing of SNc dopaminergic neurons and the resultant striatal dopamine signaling were lost. These data show that distinct dopaminergic cell types differentially encode spontaneous movement and elucidate how dysregulation of their firing in early Parkinsonism can impair their effector circuits. PMID:27001837

  13. Simultaneous Measurement of Growth and Movement of Cells Exploiting On-Chip Single-Cell Cultivation Assay

    Science.gov (United States)

    Umehara, Senkei; Hattori, Akihiro; Wakamoto, Yuichi; Yasuda, Kenji

    2004-03-01

    We have developed an on-chip single-cell microcultivation assay as a means of simultaneously observing the growth and movement of single bacterial cells during long-term cultivation. This assay enables the direct observation of single cells captured in microchambers fabricated on thin glass slides and having semipermeable membrane lids, in which the cells can swim within the space without escape for the long periods. Using this system, the relationship between the cell cycle and the tendency of movement was observed and it was found that the mean free path length did not change during the cell cycle, and that the growth and the swimming were not synchronized. The result indicates that the ability of movement of the cells was independent of the cell cycle.

  14. Interplay of Notch and FGF signaling restricts cell fate and MAPK activation in the Drosophila trachea.

    Science.gov (United States)

    Ikeya, T; Hayashi, S

    1999-10-01

    The patterned branching in the Drosophila tracheal system is triggered by the FGF-like ligand Branchless that activates a receptor tyrosine kinase Breathless and the MAP kinase pathway. A single fusion cell at the tip of each fusion branch expresses the zinc-finger gene escargot, leads branch migration in a stereotypical pattern and contacts with another fusion cell to mediate fusion of the branches. A high level of MAP kinase activation is also limited to the tip of the branches. Restriction of such cell specialization events to the tip is essential for tracheal tubulogenesis. Here we show that Notch signaling plays crucial roles in the singling out process of the fusion cell. We found that Notch is activated in tracheal cells by Branchless signaling through stimulation of &Dgr; expression at the tip of tracheal branches and that activated Notch represses the fate of the fusion cell. In addition, Notch is required to restrict activation of MAP kinase to the tip of the branches, in part through the negative regulation of Branchless expression. Notch-mediated lateral inhibition in sending and receiving cells is thus essential to restrict the inductive influence of Branchless on the tracheal tubulogenesis. PMID:10498681

  15. Impact of HLA class I restricted T cells on HIV-1 disease progression

    NARCIS (Netherlands)

    Schellens, I.M.M.

    2009-01-01

    This thesis focuses on the impact of HLA class I restricted T cells on HIV-1 disease progression. It is generally accepted that cytotoxic T lymphocytes (CTL) play an important role in controlling HIV replication. In line with this, it has been well established that HLA class I alleles influence the

  16. In vivo monitoring of mRNA movement in Drosophila body wall muscle cells reveals the presence of myofiber domains.

    Directory of Open Access Journals (Sweden)

    Alice M C van Gemert

    Full Text Available BACKGROUND: In skeletal muscle each muscle cell, commonly called myofiber, is actually a large syncytium containing numerous nuclei. Experiments in fixed myofibers show that mRNAs remain localized around the nuclei in which they are produced. METHODOLOGY/PRINCIPAL FINDINGS: In this study we generated transgenic flies that allowed us to investigate the movement of mRNAs in body wall myofibers of living Drosophila embryos. We determined the dynamic properties of GFP-tagged mRNAs using in vivo confocal imaging and photobleaching techniques and found that the GFP-tagged mRNAs are not free to move throughout myofibers. The restricted movement indicated that body wall myofibers consist of three domains. The exchange of mRNAs between the domains is relatively slow, but the GFP-tagged mRNAs move rapidly within these domains. One domain is located at the centre of the cell and is surrounded by nuclei while the other two domains are located at either end of the fiber. To move between these domains mRNAs have to travel past centrally located nuclei. CONCLUSIONS/SIGNIFICANCE: These data suggest that the domains made visible in our experiments result from prolonged interactions with as yet undefined structures close to the nuclei that prevent GFP-tagged mRNAs from rapidly moving between the domains. This could be of significant importance for the treatment of myopathies using regenerative cell-based therapies.

  17. Two mechanisms that account for major histocompatibility complex restriction of T cells

    OpenAIRE

    Kranz, David M.

    2009-01-01

    In recent studies, two distinct mechanisms have been proposed to account for major histocompatibility complex (MHC) restriction of T-cell activity: (a) evolution-driven interactions between T-cell receptor (TCR) variable regions and MHC, and (b) a requirement for CD4 or CD8 binding to MHC to initiate signalling through the TCR complex. Both mechanisms are likely to be essential, but for different reasons.

  18. Delineation of Several DR-Restricted Tetanus Toxin T Cell Epitopes

    OpenAIRE

    Demotz, Stephane; Lanzavecchia, Antonio; Eisel, Ulrich; Niemann, Heiner; Widmann, Christian; Corradin, Giampietro

    1989-01-01

    We have characterized five human T cell clones specific for tetanus toxin. The combination of different techniques allowed us to precisely map two T cell epitopes within fragments 830-843 and 1273-1284 of tetanus toxin, as formally demonstrated by the use of corresponding synthetic peptides. The three other T cell clones were specific for regions 2-602, 604-742, and 865-1315 of tetanus toxin, respectively. The five T cell clones were shown to be restricted to HLA-DR Ag. Furthermore, the allel...

  19. The Immunology of CD1- and MR1-Restricted T Cells.

    Science.gov (United States)

    Mori, Lucia; Lepore, Marco; De Libero, Gennaro

    2016-05-20

    CD1- and MHC-related molecule-1 (MR1)-restricted T lymphocytes recognize nonpeptidic antigens, such as lipids and small metabolites, and account for a major fraction of circulating and tissue-resident T cells. They represent a readily activated, long-lasting population of effector cells and contribute to the early phases of immune response, orchestrating the function of other cells. This review addresses the main aspects of their immunological functions, including antigen and T cell receptor repertoires, mechanisms of nonpeptidic antigen presentation, and the current evidence for their participation in human and experimental diseases. PMID:26927205

  20. Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

    OpenAIRE

    Szu-Chieh Mei; Charles Brenner

    2015-01-01

    In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we develop...

  1. Lineage-restricted expression of homeobox-containing genes in human hematopoietic cell lines

    International Nuclear Information System (INIS)

    The authors investigated the role of homeobox-containing genes in human hematopoiesis because homeobox genes (i) control cell fate in the Drosophila embryo, (ii) are expressed in specific patterns in human embryos, and (iii) appear to function as transcription factors that control cell phenotype in other mammalian organs. Using four homeobox probes from the HOX2 locus and a previously undescribed homeobox cDNA (PL1), they screened mRNAs from 18 human leukemic cell lines representing erythroid, myeloid, and T- and B-cell lineages. Complex patterns of lineage-restricted expression are observed. No single homeobox gene is expressed in all types of hematopoietic cells, but each cell type exhibits homeobox gene expression. They have demonstrated (i) lineage-restricted expression of five homeobox genes in erythroid and monocytic cell lines; (ii) expression of additional homeobox genes in other cell lineages (HL-60 and lymphoid cells); (iii) expression of one homeobox gene in normal marrow cells; and (iv) modulation of expression during differentiation. These data suggest that these genes play a role in human hematopoietic development and lineage commitment

  2. APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells

    International Nuclear Information System (INIS)

    Cellular APOBEC3G (A3G) protein is packaged into human immunodeficiency virus type 1 (HIV-1) virions in producer cells yet restricts viral replication in target cells. To characterize this restriction in target cells, the effect of A3G on generating various HIV-1 cDNA products was measured by quantitative real-time PCR. A3G decreased cDNA products from Vif-deficient HIV-1, with minor effects on early reverse transcripts and larger declines in late reverse transcripts. However, the greatest decline was typically observed in nuclear 2-LTR circles. Moreover, the magnitude of these declines varied with A3G dose. Adding integration inhibitor did not stop the A3G-mediated loss in 2-LTR circles. Moreover, obstructing HIV-1 nuclear entry using vesicular stomatitis virus matrix protein did not stop the A3G-mediated decline in late reverse transcripts. Collectively, these data suggest that A3G has important restriction activity in the cytoplasm and progressively diminishes viral cytoplasmic and nuclear cDNA forms with increasing magnitude during restriction

  3. Cell-Specific Expression of Connexins and Evidence of Restricted Gap Junctional Coupling between Glial Cells and between Neurons

    OpenAIRE

    Rash, John E.; Yasumura, Thomas; Dudek, F. Edward; NAGY, JAMES I.

    2001-01-01

    The transmembrane connexin proteins of gap junctions link extracellularly to form channels for cell-to-cell exchange of ions and small molecules. Two primary hypotheses of gap junction coupling in the CNS are the following: (1) generalized coupling occurs between neurons and glia, with some connexins expressed in both neurons and glia, and (2) intercellular junctional coupling is restricted to specific coupling partners, with different connexins expressed in each cell type. There is consensus...

  4. CD1d-restricted peripheral T cell lymphoma in mice and humans.

    Science.gov (United States)

    Bachy, Emmanuel; Urb, Mirjam; Chandra, Shilpi; Robinot, Rémy; Bricard, Gabriel; de Bernard, Simon; Traverse-Glehen, Alexandra; Gazzo, Sophie; Blond, Olivier; Khurana, Archana; Baseggio, Lucile; Heavican, Tayla; Ffrench, Martine; Crispatzu, Giuliano; Mondière, Paul; Schrader, Alexandra; Taillardet, Morgan; Thaunat, Olivier; Martin, Nadine; Dalle, Stéphane; Le Garff-Tavernier, Magali; Salles, Gilles; Lachuer, Joel; Hermine, Olivier; Asnafi, Vahid; Roussel, Mikael; Lamy, Thierry; Herling, Marco; Iqbal, Javeed; Buffat, Laurent; Marche, Patrice N; Gaulard, Philippe; Kronenberg, Mitchell; Defrance, Thierry; Genestier, Laurent

    2016-05-01

    Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans. PMID:27069116

  5. Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells

    International Nuclear Information System (INIS)

    The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors

  6. Structural and biomechanical basis of mitochondrial movement in eukaryotic cells

    OpenAIRE

    Wu M; Kalyanasundaram A; Zhu J

    2013-01-01

    Min Wu,1 Aruna Kalyanasundaram,2 Jie Zhu1 1Laboratory of Biomechanics and Engineering, Institute of Biophysics, College of Science, Northwest A&F University, Yangling, Shaanxi, People's Republic of China; 2College of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA Abstract: Mitochondria serve as energy-producing organelles in eukaryotic cells. In addition to providing the energy supply for cells, the mitochondria are also involved in other processes, such as...

  7. Cells in the monkey ponto-medullary reticular formation modulate their activity with slow finger movements.

    Science.gov (United States)

    Soteropoulos, Demetris S; Williams, Elizabeth R; Baker, Stuart N

    2012-08-15

    Recent work has shown that the primate reticulospinal tract can influence spinal interneurons and motoneurons involved in control of the hand. However, demonstrating connectivity does not reveal whether reticular outputs are modulated during the control of different types of hand movement. Here, we investigated how single unit discharge in the pontomedullary reticular formation (PMRF) modulated during performance of a slow finger movement task in macaque monkeys. Two animals performed an index finger flexion–extension task to track a target presented on a computer screen; single units were recorded both from ipsilateral PMRF (115 cells) and contralateral primary motor cortex (M1, 210 cells). Cells in both areas modulated their activity with the task (M1: 87%, PMRF: 86%). Some cells (18/115 in PMRF; 96/210 in M1) received sensory input from the hand, showing a short-latency modulation in their discharge following a rapid passive extension movement of the index finger. Effects in ipsilateral electromyogram to trains of stimuli were recorded at 45 sites in the PMRF. These responses involved muscles controlling the digits in 13/45 sites (including intrinsic hand muscles, 5/45 sites). We conclude that PMRF may contribute to the control of fine finger movements, in addition to its established role in control of more proximal limb and trunk movements. This finding may be especially important in understanding functional recovery after brain lesions such as stroke. PMID:22641776

  8. Functionalized iron oxide nanoparticles for controlling the movement of immune cells

    Science.gov (United States)

    White, Ethan E.; Pai, Alex; Weng, Yiming; Suresh, Anil K.; van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

    2015-04-01

    Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were

  9. Cell Docking, Movement and Cell-Cell Interactions of Heterogeneous Cell Suspensions in a Cell Manipulation Microdevice

    OpenAIRE

    Long-Sun Huang; Yu-Hung Wang; Yu-Wei Chung; Fei-Lung Lai; Shiaw-Min Hwang

    2011-01-01

    This study demonstrates a novel cell manipulation microdevice for cell docking, culturing, cell-cell contact and interaction by microfluidic manipulation of heterogeneous cell suspensions. Heterogeneous cell suspensions include disparate blood cells of natural killer cells and leukemia cancer cells for immune cell transplantation therapy. However, NK cell alloreactivity from different healthy donors present various recovery response levels. Little is still known about the interactions and cyt...

  10. Demonstration of a Novel HIV-1 Restriction Phenotype from a Human T Cell Line

    OpenAIRE

    Han, Yanxing; Xiaojun WANG; Dang, Ying; Zheng, Yong-Hui

    2008-01-01

    Background Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5α, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized b...

  11. Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling

    Directory of Open Access Journals (Sweden)

    Kei Sugihara

    2015-12-01

    Full Text Available Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.

  12. Why drivers use cell phones and support legislation to restrict this practice.

    Science.gov (United States)

    Sanbonmatsu, David M; Strayer, David L; Behrends, Arwen A; Ward, Nathan; Watson, Jason M

    2016-07-01

    The use of cell phones while driving is ubiquitous, particularly in countries where the practice is legal. However, surveys indicate that most drivers favor legislation to limit the use of mobile devices during the operation of a vehicle. A study was conducted to understand this inconsistency between what drivers do and what they advocate for others. Participants completed a survey about their driving attitudes, abilities, and behaviors. Following previous research, drivers reported using cell phones for benefits such as getting work done. The hypocrisy of using cell phones while advocating restrictions appears to stem from differences in the perceived safety risks of self vs. others' use of cell phones. Many if not most drivers believe they can drive safely while using mobile devices. However, they lack confidence in others' ability to drive safely while distracted and believe that others' use of cell phones is dangerous. The threat to public safety of others' usage of mobile devices was one of the strongest independent predictors of support for legislation to restrict cell phone use. PMID:27035396

  13. Restriction of intestinal stem cell expansion and the regenerative response by YAP.

    Science.gov (United States)

    Barry, Evan R; Morikawa, Teppei; Butler, Brian L; Shrestha, Kriti; de la Rosa, Rosemarie; Yan, Kelley S; Fuchs, Charles S; Magness, Scott T; Smits, Ron; Ogino, Shuji; Kuo, Calvin J; Camargo, Fernando D

    2013-01-01

    A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate in mice and humans that yes-associated protein 1 (YAP; also known as YAP1)--a protein known for its powerful growth-inducing and oncogenic properties--has an unexpected growth-suppressive function, restricting Wnt signals during intestinal regeneration. Transgenic expression of YAP reduces Wnt target gene expression and results in the rapid loss of intestinal crypts. In addition, loss of YAP results in Wnt hypersensitivity during regeneration, leading to hyperplasia, expansion of intestinal stem cells and niche cells, and formation of ectopic crypts and microadenomas. We find that cytoplasmic YAP restricts elevated Wnt signalling independently of the AXIN-APC-GSK-3β complex partly by limiting the activity of dishevelled (DVL). DVL signals in the nucleus of intestinal stem cells, and its forced expression leads to enhanced Wnt signalling in crypts. YAP dampens Wnt signals by restricting DVL nuclear translocation during regenerative growth. Finally, we provide evidence that YAP is silenced in a subset of highly aggressive and undifferentiated human colorectal carcinomas, and that its expression can restrict the growth of colorectal carcinoma xenografts. Collectively, our work describes a novel mechanistic paradigm for how proliferative signals are counterbalanced in regenerating tissues. Additionally, our findings have important implications for the targeting of YAP in human malignancies. PMID:23178811

  14. Focus on People and the Science Will Follow: Motivating Forces for Professional Movement in Stem Cell Research.

    Science.gov (United States)

    Jacob, K J; Longstaff, H; Scott, C T; Illes, J

    2015-08-01

    The migration of researchers across geographic borders, or "brain drain" as it is commonly called, remains an important issue for governments around the world as loss or gain of highly qualified personnel in research can have substantial social, economic and political consequences. In the present study we seek to examine the forces that drive international professional migration of stem cell (SC) researchers, for which variation of SC policy in different jurisdictions has previously been implicated as a driving force. Structured interviews were carried out with a purposive sample of SC researchers in the professoriate who had made international moves after postdoctoral work between the years 2001-2014, or were actively anticipating a future move. Participants were asked to rank motivators of international movement on a 5-point Likert scale and prompted to elaborate on their answers. The results suggest that career considerations, availability of research funding, and personal considerations are of high importance to the participants when considering an international move, while the permissiveness or restrictiveness SC research policy is of comparably lower importance. Participants also expressed that international movements are beneficial to scientific careers overall. The findings have important implications for policy and strategies to attract and retain members of the SC research community. PMID:26022505

  15. Restriction specificity of virus-specific cytotoxic T cells from thymectomised irradiated bone marrow chimeras reconstituted with thymus grafts

    International Nuclear Information System (INIS)

    Adult-thymectomised lethally irradiated mice A that were reconstituted with T-cell-depleted bone marrow cells of (A X B)F1 origin plus fetal thymus grafts of (B X C)F1 origin generated virus-specific T cells restricted to B alone; adult-thymectomised and lethally irradiated (A X B)F1 mice that were reconstituted with T-cell depleted bone marrow cells of (A X B)F1 origin plus fetal thymus grafts of A and of B origin generated virus-specific T cells restricted to A or to B. These results do not reveal obvious suppressive influences of host or stem-cell origin that might have explained results obtained with various irradiated bone marrow or thymus chimeras, they indicate that the thymus' influence on maturing T cells is one of the limiting steps in the selection of T cells' restriction specificities. (Auth.)

  16. Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting

    Directory of Open Access Journals (Sweden)

    Ajioka Itsuki

    2007-09-01

    Full Text Available Abstract Background Development of multicellular organisms proceeds from a single fertilized egg as the combined effect of countless numbers of cellular interactions among highly dynamic cells. Since at least a reminiscent pattern of morphogenesis can be recapitulated in a reproducible manner in reaggregation cultures of dissociated embryonic cells, which is known as cell sorting, the cells themselves must possess some autonomous cell behaviors that assure specific and reproducible self-organization. Understanding of this self-organized dynamics of heterogeneous cell population seems to require some novel approaches so that the approaches bridge a gap between molecular events and morphogenesis in developmental and cell biology. A conceptual cell model in a computer may answer that purpose. We constructed a dynamical cell model based on autonomous cell behaviors, including cell shape, growth, division, adhesion, transformation, and motility as well as cell-cell signaling. The model gives some insights about what cellular behaviors make an appropriate global pattern of the cell population. Results We applied the model to "inside and outside" pattern of cell-sorting, in which two different embryonic cell types within a randomly mixed aggregate are sorted so that one cell type tends to gather in the central region of the aggregate and the other cell type surrounds the first cell type. Our model can modify the above cell behaviors by varying parameters related to them. We explored various parameter sets with which the "inside and outside" pattern could be achieved. The simulation results suggested that direction of cell movement responding to its neighborhood and the cell's mobility are important for this specific rearrangement. Conclusion We constructed an in silico cell model that mimics autonomous cell behaviors and applied it to cell sorting, which is a simple and appropriate phenomenon exhibiting self-organization of cell population. The model

  17. Over-expression of putative transcriptional coactivator KELP interferes with Tomato mosaic virus cell-to-cell movement.

    Science.gov (United States)

    Sasaki, Nobumitsu; Ogata, Takuya; Deguchi, Masakazu; Nagai, Shoko; Tamai, Atsushi; Meshi, Tetsuo; Kawakami, Shigeki; Watanabe, Yuichiro; Matsushita, Yasuhiko; Nyunoya, Hiroshi

    2009-03-01

    Tomato mosaic virus (ToMV) encodes a movement protein (MP) that is necessary for virus cell-to-cell movement. We have demonstrated previously that KELP, a putative transcriptional coactivator of Arabidopsis thaliana, and its orthologue from Brassica campestris can bind to ToMV MP in vitro. In this study, we examined the effects of the transient over-expression of KELP on ToMV infection and the intracellular localization of MP in Nicotiana benthamiana, an experimental host of the virus. In co-bombardment experiments, the over-expression of KELP inhibited virus cell-to-cell movement. The N-terminal half of KELP (KELPdC), which had been shown to bind to MP, was sufficient for inhibition. Furthermore, the over-expression of KELP and KELPdC, both of which were co-localized with ToMV MP, led to a reduction in the plasmodesmal association of MP. In the absence of MP expression, KELP was localized in the nucleus and the cytoplasm by the localization signal in its N-terminal half. It was also shown that ToMV amplified normally in protoplasts prepared from leaf tissue that expressed KELP transiently. These results indicate that over-expressed KELP interacts with MP in vivo and exerts an inhibitory effect on MP function for virus cell-to-cell movement, but not on virus amplification in individual cells. PMID:19236566

  18. Evaluation of the Usefulness of Restricted Respiratory Period at the Time of Radiotherapy for Non-Small Cell Lung Cancer Patient

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Yeon; Ahn, Jong Ho; Kim, Yung Il; Kim, Jin Man; Choi, Byung Ki; Pyo, Hong Ryul; Song, Ki Won [Dept. of Radiation Oncology, Samsung Medical Center, Seoul (Korea, Republic of); Suh, Jung Min [Dept. of Radiological Science, Daewon University Colloge, Jecheon (Korea, Republic of)

    2012-09-15

    It is essential to minimize the movement of tumor due to respiratory movement at the time of respiration controlled radiotherapy of non-small cell lung cancer patient. Accordingly, this Study aims to evaluate the usefulness of restricted respiratory period by comparing and analyzing the treatment plans that apply free and restricted respiration period respectively. After having conducted training on 9 non-small cell lung cancer patients (tumor n=10) from April to December 2011 by using 'signal monitored-breathing (guided- breathing)' method for the 'free respiratory period' measured on the basis of the regular respiratory period of the patents and 'restricted respiratory period' that was intentionally reduced, total of 10 CT images for each of the respiration phases were acquired by carrying out 4D CT for treatment planning purpose by using RPM and 4-dimensional computed tomography simulator. Visual gross tumor volume (GTV) and internal target volume (ITV) that each of the observer 1 and observer 2 has set were measured and compared on the CT image of each respiratory interval. Moreover, the amplitude of movement of tumor was measured by measuring the center of mass (COM) at the phase of 0% which is the end-inspiration (EI) and at the phase of 50% which is the end-exhalation (EE). In addition, both observers established treatment plan that applied the 2 respiratory periods, and mean dose to normal lung (MDTNL) was compared and analyzed through dose-volume histogram (DVH). Moreover, normal tissue complication probability (NTCP) of the normal lung volume was compared by using dose-volume histogram analysis program (DVH analyzer v.1) and statistical analysis was performed in order to carry out quantitative evaluation of the measured data. As the result of the analysis of the treatment plan that applied the 'restricted respiratory period' of the observer 1 and observer 2, there was reduction rate of 38.75% in the 3-dimensional

  19. Radioprotective effect of calorie restriction in Hela cells and SD rats

    International Nuclear Information System (INIS)

    Objective: To explore the effect of low calorie metabolism on the survival of HeLa cells exposed to X-rays, and the influence of starvation on the antioxidative factors in the blood of rats after irradiation. Methods: MTT method was used to evaluate the impact of different concentration glucose on the proliferation of HeLa cells. Colony formation assay was employed to detect the influence of glucose (1, 5, 10 and 25 mmol/L) on radiosensitivity of HeLa cells. Flow cytometry assay was used to analyze distribution of cell cycle and apoptosis. 60 male SD rats were randomly divided into 6 groups with 10 rats each. Rats in every two groups were fed ad libitum, fasted for 24 h and fasted for 48 h, respectively. Rats in one group of each approach were respectively exposed to whole-body X-rays at 11 Gy. At 2 h after irradiation,all of rats were sacrificed and their venous blood was collected. Elisa kits were used to detect superoxide dismutase (SOD) and total antioxidant capacity (T-AOC). Results: An increased viability was observed in HeLa cells treated with the glucose at low concentration (<25 mmol/L), while HeLa cell growth was inhibited by glucose at doses of >25 mmol/L. Relevant to cells treated with 1 mmoL/L glucose, SERs (sensitive enhancement ratio) in cells exposed to 5, 10 and 25 mmol/L glucose were 1.07, 1.10 and 1.23,respectively. A reduction of G2/M and S arrests and apoptosis caused by 6 Gy X-ray irradiation were observed [(49.68 ±1.88)% and (35.54±1.45)% at G2/M phase, (16.88 ±1.22)% and (10.23 ±1.65)% at S phase, t=10.42, 5.61, P<0.05] and in the cells treated with 1 mmol/L glucose compared with cells treated with 25 mmol/L glucose [(25.50 ± 0.95)% and (7.56 ± 1.07)%, t=21.72, P<0.05].Without irradiation, calorie restriction exhibited a negligible influence on SOD and T-AOC in rats. However, after 11 Gy irradiation, compared with rats fed ad libitum, the levels of SOD and T-AOC were significantly increased in rats with calorie restriction (t=40.32, 42

  20. Expression of hermes gene is restricted to the ganglion cells in the retina.

    Science.gov (United States)

    Piri, Natik; Kwong, Jacky M K; Song, Min; Caprioli, Joseph

    2006-09-11

    The RNA binding protein with multiple splicing 2, or hermes, is a member of the RRM (RNA recognition motif) family of RNA-binding proteins. In this study, we show that the hermes gene is expressed in the rat retina, and its expression is restricted to the ganglion cell layer. Double in situ hybridization with riboprobes corresponding to the hermes gene and Thy-1, the RGC marker in the retina, showed that the majority of the Thy-1 positive cells in the ganglion cell layer were also hermes positive. This was also shown by co-localization of the hermes in situ hybridization signals with the retrogradely labeled RGCs. Our observations suggest that hermes is expressed in the majority, if not all, of RGCs and is not restricted to only certain RGC types. Hermes in situ hybridization signals were not detected in the retinal sections of optic nerve transected animals, which are characterized by rapid and specific RGC degeneration. The dramatic reduction of the hermes mRNA level in axotomized retinas was also observed by semi-quantitative RT-PCR. The specific expression of hermes in retinal ganglion cells qualifies this gene as a potential RGC marker in the retina. Outside the retina, hermes is expressed in the heart, liver, and kidney, and to a lesser degree in the cerebellum, cortex, lung, and small intestine. PMID:16870336

  1. Calibração binocular com gabaritos 1D sem restrição demovimentos Binocular calibration with 1D parttern without movements restriction

    Directory of Open Access Journals (Sweden)

    José Alexandre de França

    2011-06-01

    Full Text Available Na visão computacional, a calibração de câmeras é um processo necessário quando deseja-se recuperar informações como, por exemplo, ângulos e distâncias. O presente trabalho trata do problema de calibração de câmeras com gabaritos de uma única dimensão. Atualmente, tal problema só tem solução se forem impostas restrições ao movimento do gabarito ou se alguns parâmetros das câmeras já sejam previamente conhecidos. Contudo, demonstra-se que uma abordagem diferente pode ser aplicada se, ao invés de uma única câmera, um conjunto binocular for considerado. Nesse caso, a calibração é possível com um gabarito 1D que realiza um deslocamento desconhecido e sem restrições, mesmo sem nenhuma informação prévia a respeito das câmeras. Tal método baseia-se na estimação de uma transformação que, após a estimação da matriz fundamental do sistema, permite atualizar uma calibração projetiva para uma calibração euclidiana. Experimentos em imagens reais e sintéticas validam o novo método e mostram que a sua exatidão é comparável a de outros métodos clássicos de calibração, já bem conhecidos na literatura.In computer vision, the camera calibration is a process needed when the recovery of some information, such as angles and distances, is desired. The present work deals with the problem of camera calibration using one-dimensional patterns. Nowadays, this problem only has a solution if some restrictions to the pattern's movement are imposed or if some angles of the cameras are known in advance. However, a different approach can be applied if, instead of only one camera, a stereo system is considered. In that case, the calibration is possible with a one-dimensional pattern that executes an unknown and unrestricted movement, even without any previous information concerning the cameras. Such method is based on the estimation of a transform which, after the estimation of the system's fundamental matrix, allows

  2. Spatial structure arising from neighbour-dependent bias in collective cell movement.

    Science.gov (United States)

    Binny, Rachelle N; Haridas, Parvathi; James, Alex; Law, Richard; Simpson, Matthew J; Plank, Michael J

    2016-01-01

    Mathematical models of collective cell movement often neglect the effects of spatial structure, such as clustering, on the population dynamics. Typically, they assume that individuals interact with one another in proportion to their average density (the mean-field assumption) which means that cell-cell interactions occurring over short spatial ranges are not accounted for. However, in vitro cell culture studies have shown that spatial correlations can play an important role in determining collective behaviour. Here, we take a combined experimental and modelling approach to explore how individual-level interactions give rise to spatial structure in a moving cell population. Using imaging data from in vitro experiments, we quantify the extent of spatial structure in a population of 3T3 fibroblast cells. To understand how this spatial structure arises, we develop a lattice-free individual-based model (IBM) and simulate cell movement in two spatial dimensions. Our model allows an individual's direction of movement to be affected by interactions with other cells in its neighbourhood, providing insights into how directional bias generates spatial structure. We consider how this behaviour scales up to the population level by using the IBM to derive a continuum description in terms of the dynamics of spatial moments. In particular, we account for spatial correlations between cells by considering dynamics of the second spatial moment (the average density of pairs of cells). Our numerical results suggest that the moment dynamics description can provide a good approximation to averaged simulation results from the underlying IBM. Using our in vitro data, we estimate parameters for the model and show that it can generate similar spatial structure to that observed in a 3T3 fibroblast cell population. PMID:26893970

  3. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    International Nuclear Information System (INIS)

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells

  4. Ebola virus mediated infectivity is restricted in canine and feline cells.

    Science.gov (United States)

    Han, Ziying; Bart, Stephen M; Ruthel, Gordon; Vande Burgt, Nathan H; Haines, Kathleen M; Volk, Susan W; Vite, Charles H; Freedman, Bruce D; Bates, Paul; Harty, Ronald N

    2016-01-15

    Ebolaviruses and marburgviruses belong to the Filoviridae family and often cause severe, fatal hemorrhagic fever in humans and non-human primates. The magnitude of the 2014 outbreak in West Africa and the unprecedented emergence of Ebola virus disease (EVD) in the United States underscore the urgency to better understand the dynamics of Ebola virus infection, transmission and spread. To date, the susceptibility and possible role of domestic animals and pets in the transmission cycle and spread of EVD remains unclear. We utilized infectious VSV recombinants and lentivirus pseudotypes expressing the EBOV surface glycoprotein (GP) to assess the permissiveness of canine and feline cells to EBOV GP-mediated entry. We observed a general restriction in EBOV-mediated infection of primary canine and feline cells. To address the entry mechanism, we used cells deficient in NPC1, a host protein implicated in EBOV entry, and a pharmacological blockade of cholesterol transport, to show that an NPC1-dependent mechanism of EBOV entry is conserved in canine and feline cells. These data demonstrate that cells of canine and feline origin are susceptible to EBOV GP mediated infection; however, infectivity of these cells is reduced significantly compared to controls. Moreover, these data provide new insights into the mechanism of EBOV GP mediated entry into cells of canine and feline origin. PMID:26711035

  5. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression

    OpenAIRE

    Li, Yuanyuan; Liang LIU; Tollefsbol, Trygve O.

    2010-01-01

    Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-3...

  6. Lsd1 Restricts the Number of Germline Stem Cells by Regulating Multiple Targets in Escort Cells

    OpenAIRE

    Eliazer, Susan; Palacios, Victor; Wang, Zhaohui; Kollipara, Rahul K.; Kittler, Ralf; Buszczak, Michael

    2014-01-01

    Specialized microenvironments called niches regulate tissue homeostasis by controlling the balance between stem cell self-renewal and the differentiation of stem cell daughters. However the mechanisms that govern the formation, size and signaling of in vivo niches remain poorly understood. Loss of the highly conserved histone demethylase Lsd1 in Drosophila escort cells results in increased BMP signaling outside the cap cell niche and an expanded germline stem cell (GSC) phenotype. Here we pre...

  7. Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Paul Riccio

    2016-02-01

    Full Text Available Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM, combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret-/- or Etv4-/- sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret

  8. Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration

    Directory of Open Access Journals (Sweden)

    Goffinet Christine

    2008-07-01

    Full Text Available Abstract Background The development of an immunocompetent, genetically modified mouse model to study HIV-1 pathogenesis and to test antiviral strategies has been hampered by the fact that cells from native mice do not or only inefficiently support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse T-cell lines fail to express viral proteins, but the underlying replication barrier has thus far not been unambiguously identified. Here, we performed a kinetic and quantitative assessment of consecutive steps in the early phase of the HIV-1 replication cycle in T-cells from mice and humans. Results Both T-cell lines and primary T-cells from mice harbor a severe post-entry defect that is independent of potential species-specTR transactivation. Reverse transcription occurred efficiently following VSV-G-mediated entry of virions into mouse T-cells, and abundant levels of 2-LTR circles indicated successful nuclear import of the pre-integration complex. To probe the next step in the retroviral replication cycle, i.e. the integration of HIV-1 into the host cell genome, we established and validated a nested real-time PCR to specifically quantify HIV-1 integrants exploiting highly repetitive mouse B1 elements. Importantly, we demonstrate that the frequency of integrant formation is diminished 18- to > 305-fold in mouse T-cell lines compared to a human counterpart, resulting in a largely abortive infection. Moreover, differences in transgene expression from residual vector integrants, the transcription off which is cyclin T1-independent, provided evidence for an additional, peri-integrational deficit in certain mouse T-cell lines. Conclusion In contrast to earlier reports, we find that mouse T-cells efficiently support early replication steps up to and including nuclear import, but restrict HIV-1 at the level of chromosomal integration.

  9. Performance comparison of CPCs with and without exit angle restriction for concentrating radiation on solar cells

    International Nuclear Information System (INIS)

    Highlights: • CPCs with and without exit angle restriction based PV modules were fabricated and tested. • Performance of both CPVs was investigated and compared. • Results showed that CPV-65 performed slightly but insignificantly better as compared to CPV-90. - Abstract: To perform this comparison, the compound parabolic concentrator with a restricted exit angle of 65° (CPC-65) and the one without exit angle restriction (CPC-90) were fabricated and tested for concentrating radiation on multi-crystalline solar cells. Both CPC-65 and CPC-90 are identical in the acceptance half-angle (20°) and geometrical concentration factor (2×). Theoretical calculations showed that CPC-90 based PV system (CPV-90) annually concentrated about 3–5% more radiation on solar cells as compared to CPC-65 based PV system (CPV-65). For CPV-65, all radiation would arrive on the solar cells at the incidence angle less than 65°, but for CPV-90, about 8–10% of annual collectible radiation would arrive on solar cells at the incidence angle larger than 65°. Measurements at outdoor conditions showed that the CPV-65 performed slightly better than CPV-90 in terms of short-circuit current and power output as the projection incidence angle of solar rays on the cross-section of CPC-troughs (θp) less than the acceptance half-angle, otherwise the CPV-90 did better. Compared to CPV-90, the power output at maximum power points from CPV-65 were slightly higher, and increases of 2.1%, 5.4% and 8.17% were measured for θp = 0°, 10° and 16°, respectively. Analysis indicated that effect of solar flux distribution over solar cells on power output of both CPVs was almost identical and insignificant, and the CPV-65 performed slightly but insignificantly better than the CPV-90 in terms of annual power output except in areas with poor solar resources where the annual power output from both systems was almost identical

  10. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    Science.gov (United States)

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.

  11. Can spontaneous cell movements be modelled as Lévy walks?

    Science.gov (United States)

    Reynolds, A. M.

    2010-01-01

    Spontaneous cell movement is a random motion that takes place in the absence of external guiding stimuli. The spontaneous movements of HaCaT and NHDF cells (cells of the epidermis) are well represented as continuous Markovian processes driven by multiplicative noise [D. Selmeczi, S. Mosler, P.H. Hagedorn, N.B. Larsen, H. Flyvbjerg, Biophysical Journal 89 (2005) 912]. Model components are, however, ad hoc as they are inspired by fits to experimental data. As a consequence, model agreement with experimental data does not add much to our understanding of spontaneous movements of these cells beyond demonstrating that they can be modelled phenomenologically. Here it is noted that a slight re-parameterization and re-interpretation of the driving noise leads to the model of Lubashevsky et al. (2009) [I. Lubashevsky, R. Friedrich, A. Heuer, Physical Review E 79 (2009) 011110] that realises Lévy walks as Markovian stochastic processes. This brings forth new biological insight as Lévy walks are advantageous when searching in the absence of external stimuli and without knowledge of the target distribution, as may be the case with cells of the epidermis that form new tissue by locating and then attaching on to one another. The Hänggi-Klimontovich interpretation of the driving noise in the model of Lubashevsky et al. (2009) and Cauchy distributions of predicted velocities do, however, appear problematic, even unphysical. Here it is shown that these are perceived rather than actual difficulties. Intermittent stop-start motions of the kind displayed by some cells and protozoan are found to underlie the formulation of the model of Lubashevsky et al. (2009) and the velocities of starved Dictyostelium discoideum (a unicellular organism) are found to be Cauchy distributed to a good approximation. It is therefore suggested that the model of Lubashevsky et al. (2009) can describe the spontaneous movements of some cells, and that some cells have spontaneous movement patterns that can

  12. A novel lineage restricted, pericyte-like cell line isolated from human embryonic stem cells.

    Science.gov (United States)

    Greenwood-Goodwin, Midori; Yang, Jiwei; Hassanipour, Mohammad; Larocca, David

    2016-01-01

    Pericytes (PCs) are endothelium-associated cells that play an important role in normal vascular function and maintenance. We developed a method comparable to GMP quality protocols for deriving self-renewing perivascular progenitors from the human embryonic stem cell (hESC), line ESI-017. We identified a highly scalable, perivascular progenitor cell line that we termed PC-A, which expressed surface markers common to mesenchymal stromal cells. PC-A cells were not osteogenic or adipogenic under standard differentiation conditions and showed minimal angiogenic support function in vitro. PC-A cells were capable of further differentiation to perivascular progenitors with limited differentiation capacity, having osteogenic potential (PC-O) or angiogenic support function (PC-M), while lacking adipogenic potential. Importantly, PC-M cells expressed surface markers associated with pericytes. Moreover, PC-M cells had pericyte-like functionality being capable of co-localizing with human umbilical vein endothelial cells (HUVECs) and enhancing tube stability up to 6 days in vitro. We have thus identified a self-renewing perivascular progenitor cell line that lacks osteogenic, adipogenic and angiogenic potential but is capable of differentiation toward progenitor cell lines with either osteogenic potential or pericyte-like angiogenic function. The hESC-derived perivascular progenitors described here have potential applications in vascular research, drug development and cell therapy. PMID:27109637

  13. Escargot Restricts Niche Cell to Stem Cell Conversion in the Drosophila Testis

    Directory of Open Access Journals (Sweden)

    Justin Voog

    2014-05-01

    Full Text Available Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behavior. Somatic hub cells in the Drosophila testis regulate the behavior of cyst stem cells (CySCs and germline stem cells (GSCs and are a primary component of the testis stem cell niche. The shutoff (shof mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg. Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the corepressor C-terminal binding protein (CtBP, which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo.

  14. Escargot restricts niche cell to stem cell conversion in the Drosophila testis.

    Science.gov (United States)

    Voog, Justin; Sandall, Sharsti L; Hime, Gary R; Resende, Luís Pedro F; Loza-Coll, Mariano; Aslanian, Aaron; Yates, John R; Hunter, Tony; Fuller, Margaret T; Jones, D Leanne

    2014-05-01

    Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behavior. Somatic hub cells in the Drosophila testis regulate the behavior of cyst stem cells (CySCs) and germline stem cells (GSCs) and are a primary component of the testis stem cell niche. The shutoff (shof) mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg). Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the corepressor C-terminal binding protein (CtBP), which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo. PMID:24794442

  15. Generation of MHC class I-restricted cytotoxic T cell lines and clones against colonic epithelial cells from ulcerative colitis.

    Science.gov (United States)

    Yonamine, Y; Watanabe, M; Kinjo, F; Hibi, T

    1999-01-01

    We established CTL lines and clones against colonic epithelial cells from PBLs of patients with ulcerative colitis by continuous stimulation with HLA-A locus-matched colonic epithelial cell lines. We developed a nonradioactive europium release cytotoxicity assay to detect CTLs. PBLs from 3 of 12 patients but not from any of 14 normal controls who shared at least one haplotype of HLA-A locus with two colonic epithelial cell lines, CW2 and ACM, showed increased cytotoxicity against these lines. Three CTL lines established from the PBLs of patients showed increased cytotoxicity against HLA-A locus-matched CW2 or ACM but not against matched lung or esophagus cell lines. The phenotypes of CTL lines were alpha beta-TCR+ CD3+ CD8+ CD16-. The CTL line MS showed increased cytotoxicity against freshly isolated colonic epithelial cells but not against cells with a different HLA-A locus. Two CTL clones were generated from MS and clone 3-2, expressing CD3+ CD8+ CD4- CD56-, showed high MHC class I-restricted cytotoxicity against the colonic epithelial cells. These results indicated that CTLs against colonic epithelial cells may contribute to epithelial cell damage in ulcerative colitis. PMID:10080107

  16. Tubule-guided cell-to-cell movement of a plant virus requires class XI myosin motors.

    Directory of Open Access Journals (Sweden)

    Khalid Amari

    2011-10-01

    Full Text Available Cell-to-cell movement of plant viruses occurs via plasmodesmata (PD, organelles that evolved to facilitate intercellular communications. Viral movement proteins (MP modify PD to allow passage of the virus particles or nucleoproteins. This passage occurs via several distinct mechanisms one of which is MP-dependent formation of the tubules that traverse PD and provide a conduit for virion translocation. The MP of tubule-forming viruses including Grapevine fanleaf virus (GFLV recruit the plant PD receptors called Plasmodesmata Located Proteins (PDLP to mediate tubule assembly and virus movement. Here we show that PDLP1 is transported to PD through a specific route within the secretory pathway in a myosin-dependent manner. This transport relies primarily on the class XI myosins XI-K and XI-2. Inactivation of these myosins using dominant negative inhibition results in mislocalization of PDLP and MP and suppression of GFLV movement. We also found that the proper targeting of specific markers of the Golgi apparatus, the plasma membrane, PD, lipid raft subdomains within the plasma membrane, and the tonoplast was not affected by myosin XI-K inhibition. However, the normal tonoplast dynamics required myosin XI-K activity. These results reveal a new pathway of the myosin-dependent protein trafficking to PD that is hijacked by GFLV to promote tubule-guided transport of this virus between plant cells.

  17. The potato virus X TGBp2 protein association with the endoplasmic reticulum plays a role in but is not sufficient for viral cell-to-cell movement

    Science.gov (United States)

    Mitra, Ruchira; Krishnamurthy, Konduru; Blancaflor, Elison; Payton, Mark; Nelson, Richard S.; Verchot-Lubicz, Jeanmarie

    2003-01-01

    Potato virus X (PVX) TGBp1, TGBp2, TGBp3, and coat protein are required for virus cell-to-cell movement. Plasmids expressing GFP fused to TGBp2 were bombarded to leaf epidermal cells and GFP:TGBp2 moved cell to cell in Nicotiana benthamiana leaves but not in Nicotiana tabacum leaves. GFP:TGBp2 movement was observed in TGBp1-transgenic N. tabacum, indicating that TGBp2 requires TGBp1 to promote its movement in N. tabacum. In this study, GFP:TGBp2 was detected in a polygonal pattern that resembles the endoplasmic reticulum (ER) network. Amino acid sequence analysis revealed TGBp2 has two putative transmembrane domains. Two mutations separately introduced into the coding sequences encompassing the putative transmembrane domains within the GFP:TGBp2 plasmids and PVX genome, disrupted membrane binding of GFP:TGBp2, inhibited GFP:TGBp2 movement in N. benthamiana and TGBp1-expressing N. tabacum, and inhibited PVX movement. A third mutation, lying outside the transmembrane domains, had no effect on GFP:TGBp2 ER association or movement in N. benthamiana but inhibited GFP:TGBp2 movement in TGBp1-expressing N. tabacum and PVX movement in either Nicotiana species. Thus, ER association of TGBp2 may be required but not be sufficient for virus movement. TGBp2 likely provides an activity for PVX movement beyond ER association.

  18. Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

    Science.gov (United States)

    Philippe, Claude; Vargas-Landin, Dulce B; Doucet, Aurélien J; van Essen, Dominic; Vera-Otarola, Jorge; Kuciak, Monika; Corbin, Antoine; Nigumann, Pilvi; Cristofari, Gaël

    2016-01-01

    LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants. DOI: http://dx.doi.org/10.7554/eLife.13926.001 PMID:27016617

  19. Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

    International Nuclear Information System (INIS)

    The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

  20. Cbl enforces Vav1 dependence and a restricted pathway of T cell development.

    Directory of Open Access Journals (Sweden)

    Jeffrey Chiang

    Full Text Available Extensive studies of pre-TCR- and TCR-dependent signaling have led to characterization of a pathway deemed essential for efficient T cell development, and comprised of a cascade of sequential events involving phosphorylation of Lck and ZAP-70, followed by phosphorylation of LAT and SLP-76, and subsequent additional downstream events. Of interest, however, reports from our lab as well as others have indicated that the requirements for ZAP-70, LAT, and SLP-76 are partially reversed by inactivation of c-Cbl (Cbl, an E3 ubiquitin ligase that targets multiple molecules for ubiquitination and degradation. Analysis of signaling events in these Cbl knockout models, including the recently reported analysis of SLP-76 transgenes defective in interaction with Vav1, suggested that activation of Vav1 might be a critical event in alternative pathways of T cell development. To extend the analysis of signaling requirements for thymic development, we have therefore assessed the effect of Cbl inactivation on the T cell developmental defects that occur in Vav1-deficient mice. The defects in Vav1-deficient thymic development, including a marked defect in DN3-DN4 transition, were completely reversed by Cbl inactivation, accompanied by enhanced phosphorylation of PLC-γ1 and ERKs in response to pre-TCR/TCR cross-linking of Vav1⁻/⁻Cbl⁻/⁻ DP thymocytes. Taken together, these results suggest a substantially modified paradigm for pre-TCR/TCR signaling and T cell development. The observed consensus pathways of T cell development, including requirements for ZAP-70, LAT, SLP-76, and Vav1, appear to reflect the restriction by Cbl of an otherwise much broader set of molecular pathways capable of mediating T cell development.

  1. Carbonic anhydrases are upstream regulators of CO2-controlled stomatal movements in guard cells

    KAUST Repository

    Hu, Honghong

    2009-12-13

    The continuing rise in atmospheric CO2 causes stomatal pores in leaves to close and thus globally affects CO2 influx into plants, water use efficiency and leaf heat stress. However, the CO2-binding proteins that control this response remain unknown. Moreover, which cell type responds to CO2, mesophyll or guard cells, and whether photosynthesis mediates this response are matters of debate. We demonstrate that Arabidopsis thaliana double-mutant plants in the beta-carbonic anhydrases betaCA1 and betaCA4 show impaired CO2-regulation of stomatal movements and increased stomatal density, but retain functional abscisic-acid and blue-light responses. betaCA-mediated CO2-triggered stomatal movements are not, in first-order, linked to whole leaf photosynthesis and can function in guard cells. Furthermore, guard cell betaca-overexpressing plants exhibit instantaneous enhanced water use efficiency. Guard cell expression of mammalian alphaCAII complements the reduced sensitivity of ca1 ca4 plants, showing that carbonic anhydrase-mediated catalysis is an important mechanism for betaCA-mediated CO2-induced stomatal closure and patch clamp analyses indicate that CO2/HCO3- transfers the signal to anion channel regulation. These findings, together with ht1-2 (ref. 9) epistasis analysis demonstrate that carbonic anhydrases function early in the CO2 signalling pathway, which controls gas-exchange between plants and the atmosphere.

  2. Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells

    OpenAIRE

    Fernando, R. N.; Eleuteri, B.; Abdelhady, S.; Nussenzweig, A; Andang, M; Ernfors, P.

    2011-01-01

    Adult neural stem cell proliferation is dynamic and has the potential for massive self-renewal yet undergoes limited cell division in vivo. Here, we report an epigenetic mechanism regulating proliferation and self-renewal. The recruitment of the PI3K-related kinase signaling pathway and histone H2AX phosphorylation following GABAA receptor activation limits subventricular zone proliferation. As a result, NSC self-renewal and niche size is dynamic and can be directly modulated in both directio...

  3. Guard cell hydrogen peroxide and nitric oxide mediate elevated CO2 -induced stomatal movement in tomato.

    Science.gov (United States)

    Shi, Kai; Li, Xin; Zhang, Huan; Zhang, Guanqun; Liu, Yaru; Zhou, Yanhong; Xia, Xiaojian; Chen, Zhixiang; Yu, Jingquan

    2015-10-01

    Climate change as a consequence of increasing atmospheric CO2 influences plant photosynthesis and transpiration. Although the involvement of stomata in plant responses to elevated CO2 has been well established, the underlying mechanism of elevated CO2 -induced stomatal movement remains largely unknown. We used diverse techniques, including laser scanning confocal microscopy, transmission electron microscopy, biochemical methodologies and gene silencing to investigate the signaling pathway for elevated CO2 -induced stomatal movement in tomato (Solanum lycopersicum). Elevated CO2 -induced stomatal closure was dependent on the production of RESPIRATORY BURST OXIDASE 1 (RBOH1)-mediated hydrogen peroxide (H2 O2 ) and NITRATE REDUCTASE (NR)-mediated nitric oxide (NO) in guard cells in an abscisic acid (ABA)-independent manner. Silencing of OPEN STOMATA 1 (OST1) compromised the elevated CO2 -induced accumulation of H2 O2 and NO, upregulation of SLOW ANION CHANNEL ASSOCIATED 1 (SLAC1) gene expression and reduction of stomatal aperture, whereas silencing of RBOH1 or NR had no effects on the expression of OST1. Our results demonstrate that as critical signaling molecules, RBOH1-dependent H2 O2 and NR-dependent NO act downstream of OST1 that regulate SLAC1 expression and elevated CO2 -induced stomatal movement. This information is crucial to deepen the understanding of CO2 signaling pathway in guard cells. PMID:26308648

  4. Analyses of movement and contact of two nucleated cells using a gas-driven micropipette aspiration technique.

    Science.gov (United States)

    Yang, Hao; Tong, Chunfang; Fu, Changliang; Xu, Yanhong; Liu, Xiaofeng; Chen, Qin; Zhang, Yan; Lü, Shouqin; Li, Ning; Long, Mian

    2016-01-01

    Adhesion between two nucleated cells undergoes specific significances in immune responses and tumor metastasis since cellular adhesive molecules usually express on two apposed cell membranes. However, quantification of the interactions between two nucleated cells is still challenging in microvasculature. Here distinct cell systems were used, including three types of human cells (Jurkat cell or PMN vs. MDA-MB-231 cell) and two kinds of murine native cells (PMN vs. liver sinusoidal endothelial cell). Cell movement, compression to, and relaxation from the counterpart cell were quantified using an in-house developed gas-driven micropipette aspiration technique (GDMAT). This assay is robust to quantify this process since cell movement and contact inside a pipette are independent of the repeated test cycles. Measured approaching or retraction velocity follows well a normal distribution, which is independent on the cycle period. Contact area or duration also fits a Gaussian distribution and moreover contact duration is linearly correlated with the cycle period. Cell movement is positively related to gas flux but negatively associated to medium viscosity. Cell adhesion tends to reach an equilibrium state with increase of cycle period or contact duration. These results further the understanding in the dynamics of cell movement and contact in microvasculature. PMID:26631492

  5. Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted

    Science.gov (United States)

    Farrell, E. R.; Keshishian, H.

    1999-01-01

    In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.

  6. Cytotoxic effect of lapatinib is restricted to human papillomavirus-positive head and neck squamous cell carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Fumagalli I

    2015-02-01

    Full Text Available Ingrid Fumagalli,1,2 Delphine Dugue,1 Jean Emmanuel Bibault,1,2 Céline Clémenson,1 Marie Catherine Vozenin,1 Michele Mondini,1,* Eric Deutsch1,3,*1Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France; 2Radiation Therapy Department, Oscar Lambret Comprehensive Cancer Center, Lille, France; 3Department of Radiation Oncology, Gustave Roussy, University Paris XI, Villejuif, France*These authors share senior authorshipBackground: Lapatinib is a dual epidermal growth factor receptor (EGFR and HER2 inhibitor. Overexpression of these receptors is frequently observed in head and neck squamous cell carcinoma (HNSCC. As growing proportion of HNSCC is characterized by human papillomavirus (HPV infection, we aimed at evaluating the efficacy of lapatinib as function of HPV status in HNSCC cell lines.Methods: Two HPV-positive and two HPV-negative HNSCC cell lines were used. Proliferation, cell cycle, and Annexin V assays were performed to test their sensitivity to lapatinib. Combination of lapatinib and ionizing radiation was evaluated with clonogenic survival assays. Akt, EGFR and HER2, and E6/E7 expression and activation were analyzed by immunoblotting and quantitative reverse transcription polymerase chain reaction.Results: Lapatinib reduced E6 and E7 expression and Akt phosphorylation, inhibited cell proliferation and induced cell death in HPV-positive cell lines. An additive effect of lapatinib with radiation was observed in these cells. Lapatinib had no effect on HPV-negative cells.Conclusion: Lapatinib efficacy restricted to the HPV-positive cells suggests that HPV status could be a potential marker for enhanced response to lapatinib in HNSCC.Keywords: HPV, lapatinib, ionizing radiation, EGFR, HER2, tyrosine kinase inhibitor

  7. Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Asano, Y.; Tada, T.

    1987-01-01

    We described in this paper systematic alterations in the expression of unique I region controlled epitopes on helper T cells (Th) in chimeras according to the changes in their H-2 restriction specificity. Taking advantage of the reactivity of monoclonal antibodies (anti-Iat) putatively specific for the epitopes indirectly controlled by I region and expressed in association with the Iak restriction site of Th, we examined the alterations of these epitopes on Th cells from various bone marrow chimeras. Iatk epitopes were physiologically expressed on Iak-restricted but not on Iab-restricted Th cells in (H-2k X H-2b)F1 mice. In the chimeric condition, the H-2k-restricted Th of B6----F1 chimera acquired the expression of Iatk even though B6 Th is unable to express Iatk when developed under the physiologic condition. Iatk are also found on Th of fully allogeneic chimera of B6----C3H, whereas Th cells of C3H----B6 completely lost the Iatk expression. These results indicate that Iat epitopes originally defined as unique I region-controlled determinants selectively expressed on T cells are not encoded by the I region genes but are associated with the T cell receptor that sees the self Ia. The epitopes undergo the adaptive alterations according to the acquisition of a new MHC restriction. This is the first example to demonstrate the epitope associated with T cell receptor which undergo the systematic adaptive differentiation.

  8. Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    We described in this paper systematic alterations in the expression of unique I region controlled epitopes on helper T cells (Th) in chimeras according to the changes in their H-2 restriction specificity. Taking advantage of the reactivity of monoclonal antibodies (anti-Iat) putatively specific for the epitopes indirectly controlled by I region and expressed in association with the Iak restriction site of Th, we examined the alterations of these epitopes on Th cells from various bone marrow chimeras. Iatk epitopes were physiologically expressed on Iak-restricted but not on Iab-restricted Th cells in (H-2k X H-2b)F1 mice. In the chimeric condition, the H-2k-restricted Th of B6----F1 chimera acquired the expression of Iatk even though B6 Th is unable to express Iatk when developed under the physiologic condition. Iatk are also found on Th of fully allogeneic chimera of B6----C3H, whereas Th cells of C3H----B6 completely lost the Iatk expression. These results indicate that Iat epitopes originally defined as unique I region-controlled determinants selectively expressed on T cells are not encoded by the I region genes but are associated with the T cell receptor that sees the self Ia. The epitopes undergo the adaptive alterations according to the acquisition of a new MHC restriction. This is the first example to demonstrate the epitope associated with T cell receptor which undergo the systematic adaptive differentiation

  9. The role of Ia molecules in the activation of T lymphocytes. III. Antigen-specific, Ia-restricted, interleukin 2-producing T cell hybridomas with detectable affinity for the restricting I-A molecule

    OpenAIRE

    1983-01-01

    Antigen-specific I region-restricted, interleukin 2-producing T cell hybridomas were produced by fusing GAT-specific T cell blasts with BW5147. Two antigen-specific phenotypes were identified, one autoreactive and one nonautoreactive. All of the antigen-specific and autoreactive clones were H-2 restricted, mapping to the IA subregion by genetic analysis and monoclonal antibody inhibition. Both the antigen- specific and autoreactive stimulation are the property of a single cell and required no...

  10. The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells.

    Science.gov (United States)

    Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M; Vives-Pi, Marta; Esté, José A; Ballana, Ester

    2016-08-01

    Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

  11. Interdisciplinary Evaluation of Broadly-Reactive HLA Class II Restricted Epitopes Eliciting HIV-Specific CD4+T Cell Responses

    DEFF Research Database (Denmark)

    Buggert, M.; Norström, M.; Lundegaard, Claus; Lund, Ole; Nielsen, Morten; Karlsson, A. C.

    2011-01-01

    Background: CD4+ T cells orchestrate immune protection by ‘‘helping’’ other cells of our immune system to clear viral infections. It is well known that the preferential infection and depletion of CD4+ T cells contributes to hampered systemic T cell help following HIV infection. However, the...... functional and immunodominant discrepancies of CD4+ T cell responses targeting promiscuous MHC II restricted HIV epitopes remains poorly defined. Thus, utilization of interdisciplinary approaches might aid revealing broadly- reactive peptides eliciting CD4 + T cell responses. Methods: We utilized the novel...... bioinformatic prediction program NetMHCIIpan to select 64 optimized MHC II restricted epitopes located in the HIV Gag, Pol, Env, Nef and Tat regions. The epitopes were selected to cover the global diversity of the virus (multiple subtypes) and the human immune system(diverse MHC II types). Optimized...

  12. Condensin II subunit dCAP-D3 restricts retrotransposon mobilization in Drosophila somatic cells.

    Directory of Open Access Journals (Sweden)

    Andrew T Schuster

    2013-10-01

    Full Text Available Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1 higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2 increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin

  13. Selective host range restriction of goat cells for recombinant murine leukemia virus and feline leukemia virus type A.

    OpenAIRE

    Fischinger, P J; Thiel, H J; Blevins, C S; Dunlop, N M

    1981-01-01

    We isolated a strain of normal goat fibroblasts which was uniquely selective in that it allowed the replication of xenotropic murine leukemia virus but not polytropic recombinant murine leukemia virus. In addition, feline leukemia virus type A replication was severely diminished in these goat cells, whereas feline leukemia virus type B and feline endogenous RD114-CCC viruses replicated efficiently. No other known cells exhibit this pattern of virus growth restriction. These goat cells allow t...

  14. AltMV TGB1 nucleolar localization requires homologous interaction and correlates with cell wall localization associated with cell-to-cell movement

    Science.gov (United States)

    The Potexvirus Alternanthera mosaic virus has multifunctional triple gene block (TGB) proteins, among which our studies have focused on the properties of the TGB1 protein. The TGB1 of AltMV has functions including RNA binding, RNA silencing suppression, and cell-to-cell movement, and is known to for...

  15. A biophysical analysis of mitochondrial movement: differences between transport in neuronal cell bodies versus processes.

    Science.gov (United States)

    Narayanareddy, Babu Reddy Janakaloti; Vartiainen, Suvi; Hariri, Neema; O'Dowd, Diane K; Gross, Steven P

    2014-07-01

    There is an increasing interest in factors that can impede cargo transport by molecular motors inside the cell. Although potentially relevant (Yi JY, Ori-McKenney KM, McKenney RJ, Vershinin M, Gross SP, Vallee RB. High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport. J Cell Biol 2011;195:193-201), the importance of cargo size and subcellular location has received relatively little attention. Here we address these questions taking advantage of the fact that mitochondria - a common cargo - in Drosophila neurons exhibit a wide distribution of sizes. In addition, the mitochondria can be genetically marked with green fluorescent protein (GFP) making it possible to visualize and compare their movement in the cell bodies and in the processes of living cells. Using total internal reflection microscopy coupled with particle tracking and analysis, we quantified the transport properties of GFP-positive mitochondria as a function of their size and location. In neuronal cell bodies, we find little evidence for significant opposition to motion, consistent with a previous study on lipid droplets (Shubeita GT, Tran SL, Xu J, Vershinin M, Cermelli S, Cotton SL, Welte MA, Gross SP. Consequences of motor copy number on the intracellular transport of kinesin-1-driven lipid droplets. Cell 2008;135:1098-1107). However, in the processes, we observe an inverse relationship between the mitochondrial size and velocity and the run distances. This can be ameliorated via hypotonic treatment to increase process size, suggesting that motor-mediated movement is impeded in this more-confined environment. Interestingly, we also observe local mitochondrial accumulations in processes but not in cell bodies. Such accumulations do not completely block the transport but do increase the probability of mitochondria-mitochondria interactions. They are thus particularly interesting in relation to mitochondrial exchange of elements

  16. T cell determinants of myelin basic protein include a unique encephalitogenic I-E-restricted epitope for Lewis rats

    OpenAIRE

    1989-01-01

    The major encephalitogenic epitope for Lewis rats is the 72-89 sequence of guinea pig basic protein (GP-BP) or rat basic protein (Rt-BP). T cells responsive to this epitope are I-A restricted and preferentially express the V alpha 2:V beta 8 gene combination in their TCR. In this work, we describe for the first time the delayed appearance of T cells specific for additional discrete determinant of BP, the nonencephalitogenic 55-68 sequence of GP-BP restricted by I-A, and the encephalitogenic 8...

  17. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

    exclusion and stratification mechanisms. In conclusion the article therefore suggests that future urban research and planning also needs a mobile understanding of spaces in the cities and how different mobility systems play an important role to sustain the exclusiveness that often characterises the private......Privatisation of public spaces in the contemporary city has increased during the last decades but only few studies have approached this field from a mobility perspective. Therefore the article seeks to rectify this by exploring two Australian examples of private spaces in the city; gated...... communities and shopping centres through mobility lenses. The article shows how different mobility systems enable and restrict the public access to private-public spaces, and it points out that proprietary communities create an unequal potential for human movement and access in the city. The main argument in...

  18. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  19. Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras

    International Nuclear Information System (INIS)

    Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells

  20. Calcium concentration and movement in the ventricular cardiac cell during an excitation-contraction cycle.

    OpenAIRE

    Peskoff, A; Langer, G. A.

    1998-01-01

    This paper extends the model for Ca movement in the cardiac ventricular cell from the diadic cleft space to the entire sarcomere. The model predicts the following: 1) Shortly after SR release there is a [Ca] gradient >3 orders of magnitude from cleft center to M-line which, 50 ms after release, is still >30. Outside the cleft, 40 ms after cessation of release, the axial gradient from Z to M-line is >3. 2) At the end of SR release, >50% of the total Ca released is bound to low-affinity inner s...

  1. Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers

    International Nuclear Information System (INIS)

    Evidence is presented that T cells that produce lethal graft-vs.-host disease (GVHD) to minor histocompatibility antigens (minor HA) comprise discrete subgroups of H-2K- and H-2D-restricted T cells; double negative selection of T cells in irradiated H-2 recombinant mice was used to separate these two subgroups. No evidence could be found that I-restricted T cells contributed to GVHD, either as effector cells or helper cells. The (unprimed) precursor cells for GVHD expressed the Thy-1+, Lyt-1+/-2, Ia- phenotype. Studies in which H-2-semiallogeneic bone marrow chimeras were used as hosts for negative selection suggested that presentation of minor HA to T cells during the induction phase is controlled by marrow-derived cells; indirect evidence was obtained that these latter cells can ''process'' minor HA presented on H-2 different cells and thereby render the antigens immunogenic. Studies in which minor HA-different, H-2-compatible chimeras were re-irradiated and then injected with donor-vs.-host T cells suggested that the effector phase of lethal GVHD involves contact of antigen on non-marrow-derived cells

  2. Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

    Science.gov (United States)

    Bronke, Corine; Palmer, Nanette M; Westerlaken, Geertje H A; Toebes, Mireille; van Schijndel, Gijs M W; Purwaha, Veenu; van Meijgaarden, Krista E; Schumacher, Ton N M; van Baarle, Debbie; Tesselaar, Kiki; Geluk, Annemieke

    2005-09-01

    In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.84% of CD4+ T cells by intracellular cytokine staining. In peripheral blood mononuclear cells from M. tuberculosis-exposed, Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated, or CMV-seropositive individuals, we were able to directly detect with both tetramers epitope-specific T cells up to 0.62% and 0.45% of the CD4+ T-cell population reactive to M. tuberculosis and CMV, respectively. After a 6-day culture with peptide p510-522, the frequency of CMV-specific tetramer-binding T cells was expanded up to 9.90% tetramer+ CFSElow (5,6-carboxyfluorescein diacetate succinimidyl ester) cells within the CD4+ T-cell population, further confirming the specificity of the tetrameric molecules. Thus, HLA-DR3/peptide tetrameric molecules can be used to investigate HLA-DR3-restricted antigen-specific CD4+ T cells in clinical disease or after vaccination. PMID:16360834

  3. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene.

    OpenAIRE

    Ho, I C; Vorhees, P; Marin, N; Oakley, B K; Tsai, S F; Orkin, S H; Leiden, J. M.

    1991-01-01

    In addition to its role in the recognition of foreign antigens, the T cell receptor (TCR) alpha gene serves as a model system for studies of developmentally-regulated, lineage-specific gene expression in T cells. TCR alpha gene expression is restricted to cells of the TCR alpha/beta+ lineage, and is controlled by a T cell-specific transcriptional enhancer located 4.5 kb 3' to the C alpha gene segment. The TCR alpha enhancer contains four nuclear protein binding sites called T alpha 1-T alpha ...

  4. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction*

    Institute of Scientific and Technical Information of China (English)

    Jing Liu; Xiaofeng Wang; Ying Liu; Na Yang; Jing Xu; Xiaotun Ren

    2013-01-01

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neo-natal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cel s in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cel apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cel line-derived neuro-trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cel apoptosis through the glial cel line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  5. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

    Directory of Open Access Journals (Sweden)

    Ketty Bacallao

    Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

  6. MicroRNA inhibition fine-tunes and provides robustness to the restriction point switch of the cell cycle

    Science.gov (United States)

    del Rosario, Ricardo C. H.; Damasco, Joseph Ray Clarence G.; Aguda, Baltazar D.

    2016-01-01

    The restriction point marks a switch in G1 from growth factor-dependent to growth factor-independent progression of the cell cycle. The proper regulation of this switch is important for normal cell processes; aberrations could result in a number of diseases such as cancer, neurodegenerative disorders, stroke and myocardial infarction. To further understand the regulation of the restriction point, we extended a mathematical model of the Rb-E2F pathway to include members of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs play an essential role in fine-tuning and providing robustness to the switch. We also demonstrate how microRNA regulation can steer cells in or out of cancer states. PMID:27610602

  7. Dynamics of change of lipid and monoamine metabolisms and the blood coagulation system during experimental atherosclerosis caused by restriction of movement

    Science.gov (United States)

    Gvishiani, G. S.; Kobakhidze, N. G.

    1980-01-01

    Shifts in lipid, catecholamine, and blood coagulation systems following various periods (1, 2, 3, and 4 months) of experimentally induced atherosclerosis were studied. The same indices were studied in the tissues of the myocardium, liver, and brain stem-reticular formation after decapitation of the animals at the end of the experiment. Periodic motion restriction caused an increase in blood beta-lipoproteins in the rabbits at the beginning of the experiment. An increase in general cholesterol content and a decrease in the lecithincholesterol index were established at the end of the experiment. Myocardial beta-lipoprotein and brain stem reticular formation general cholesterol contents were elevated; catecholamine content was increased at the end of the experiment. In the initial months, free adrenaline basically increased, while in later months blood adrenaline decreased and blood noradrenaline increased.

  8. Identification of H-2d Restricted T Cell Epitope of Foot-and-mouth Disease Virus Structural Protein VP1

    Directory of Open Access Journals (Sweden)

    Zhang Zhong-Wang

    2011-09-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is a highly contagious and devastating disease affecting livestock that causes significant financial losses. Therefore, safer and more effective vaccines are required against Foot-and-mouth disease virus(FMDV. The purpose of this study is to screen and identify an H-2d restricted T cell epitope from the virus structural protein VP1, which is present with FMD. We therefore provide a method and basis for studying a specific FMDV T cell epitope. Results A codon-optimized expression method was adopted for effective expression of VP1 protein in colon bacillus. We used foot-and-mouth disease standard positive serum was used for Western blot detection of its immunogenicity. The VP1 protein was used for immunizing BALB/c mice, and spleen lymphocytes were isolated. Then, a common in vitro training stimulus was conducted for potential H-2Dd, H-2Kd and H-2Ld restricted T cell epitope on VP1 proteins that were predicted and synthesized by using a bioinformatics method. The H-2Kd restricted T cell epitope pK1 (AYHKGPFTRL and the H-2Dd restricted T cell epitope pD7 (GFIMDRFVKI were identified using lymphocyte proliferation assays and IFN-γ ELISPOT experiments. Conclusions The results of this study lay foundation for studying the FMDV immune process, vaccine development, among other things. These results also showed that, to identify viral T cell epitopes, the combined application of bioinformatics and molecular biology methods is effective.

  9. A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes

    Indian Academy of Sciences (India)

    Manoj Bhasin; G P S Raghava

    2007-01-01

    In the present study, a systematic attempt has been made to develop an accurate method for predicting MHC class I restricted T cell epitopes for a large number of MHC class I alleles. Initially, a quantitative matrix (QM)-based method was developed for 47 MHC class I alleles having at least 15 binders. A secondary artificial neural network (ANN)-based method was developed for 30 out of 47 MHC alleles having a minimum of 40 binders. Combination of these ANN- and QM-based prediction methods for 30 alleles improved the accuracy of prediction by 6% compared to each individual method. Average accuracy of hybrid method for 30 MHC alleles is 92.8%. This method also allows prediction of binders for 20 additional alleles using QM that has been reported in the literature, thus allowing prediction for 67 MHC class I alleles. The performance of the method was evaluated using jack-knife validation test. The performance of the methods was also evaluated on blind or independent data. Comparison of our method with existing MHC binder prediction methods for alleles studied by both methods shows that our method is superior to other existing methods. This method also identifies proteasomal cleavage sites in antigen sequences by implementing the matrices described earlier. Thus, the method that we discover allows the identification of MHC class I binders (peptides binding with many MHC alleles) having proteasomal cleavage site at C-terminus. The user-friendly result display format (HTML-II) can assist in locating the promiscuous MHC binding regions from antigen sequence. The method is available on the web at www.imtech.res.in/raghava/nhlapred and its mirror site is available at http://bioinformatics.uams.edu/mirror/nhlapred/.

  10. Suppression of local RNA silencing is not sufficient to promote cell-to-cell movement of Turnip crinkle virus in Nicotiana benthamiana

    OpenAIRE

    Shi, Yan; Ryabov, Eugene V.; van Wezel, Rene; Li, Chunyang; Jin, Mingfei; Wang, Wenjing; Fan, Zaifeng; Hong, Yiguo

    2009-01-01

    The biological relationship between suppression of RNA silencing and virus movement poses an intriguing question in virus-plant interactions. Here, we have used a local RNA silencing assay, based on a movement-deficient Turnip crinkle virus TCV/GFPΔCP, to investigate the influence of silencing suppression by three different viral suppressors: the TCV 38K coat protein (CP), the 126K protein of Tobacco mosaic virus (TMV), and P19 of Tomato bushy stunt virus (TBSV) on cell-to-cell movement and l...

  11. Identification of the Immunodominant H-2Kk-Restricted Cytotoxic T-Cell Epitope in the Borna Disease Virus Nucleoprotein

    OpenAIRE

    Schamel, Karin; Staeheli, Peter; Hausmann, Jürgen

    2001-01-01

    Borna disease virus (BDV)-induced immunopathology in mice is most prominent in strains carrying the major histocompatibility complex H-2k allele and is mediated by CD8+ T cells that are directed against the viral nucleoprotein p40. We now identified the highly conserved octamer peptide TELEISSI, located between amino acid residues 129 and 136 of BDV p40, as a potent H-2Kk-restricted cytotoxic T-cell (CTL) epitope. When added to the culture medium of L929 target cells, TELEISSI conferred sensi...

  12. Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B 2705-restricted CD8+ T cells

    DEFF Research Database (Denmark)

    Payne, Rebecca P; Kløverpris, Henrik; Sacha, Jonah B;

    2010-01-01

    The association between HLA-B 2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B 2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8(+) T cells. In order to better define the mechanisms of the HLA-B 2705 immune...... control of HIV, we first characterized the CD8(+) T-cell responses of nine highly active antiretroviral therapy (HAART)-naïve B 2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B 2705-restricted Pol epitope, KRKGGIGGY (KY9), in 8/9 subjects. The magnitude of the KY9 response...... respective CD8(+) T-cell response. By comparing inhibitions of viral replication by CD8(+) T cells specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B 2705-restricted epitopes, we observed a consistent hierarchy of antiviral efficacy (Gag KK10 > Pol KY9 > Vpr VL9). This hierarchy was associated with early...

  13. Kinetics of expression of interleukin 2 receptors on class I and class II restricted murine T cell clones

    International Nuclear Information System (INIS)

    The kinetics of interleukin 2 receptor (IL-2R) expression has been examined on various class I and class II restricted, influenza specific murine T cell clones. Expression and relative levels of IL-2R were examined by Fluorescence Activated Cell Sorter analysis utilizing 3 anti-murine IL-2R monoclonal antibodies. Receptor expression was analyzed by scatchard analysis using radiolabeled recombinant human interleukin 2 to access the number of high and low affinity IL-2R per cell as well as the affinity of binding. The clones tested bound all 3 monoclonal antibodies and were inhibited in an IL-2 dependent proliferation assay by the addition of the antibodies to the culture. There was, however, differing degrees of inhibition ranging up to 99%, depending on the clone and the antibody used. IL-2R expression was detectable as early as 4-6 hours after antigenic stimulation of quiescent cells. After maximal levels of receptors were expressed, which was about 24 hours after stimulation, expression of IL-2R decreased with time on all clones examined (both class I and class II restricted). Differing rates of receptor loss is seen however, with some class II restricted clones retaining relatively high levels of receptors

  14. Selective Rapid Eye Movement Sleep Deprivation Affects Cell Size and Number in Kitten Locus Coeruleus

    Directory of Open Access Journals (Sweden)

    James P Shaffery

    2012-05-01

    Full Text Available Cells in the locus coeruleus (LC constitute the sole source of norepinephrine (NE in the brain, and change their discharge rates according to vigilance state. In addition to its well established role in vigilance, NE affects synaptic plasticity in the postnatal critical period (CP of development. One form of CP synaptic plasticity affected by NE results from monocular occlusion, which leads to physiological and cytoarchitectural alterations in central visual areas. Selective suppression of rapid eye movement sleep (REMS in the CP kitten enhances the central effects of monocular occlusion. The mechanisms responsible for heightened cortical plasticity following REMS deprivation (REMSD remain undetermined. One possible mediator of an increase in plasticity is continuous NE outflow, which presumably persists during extended periods of REMSD. Tyrosine hydroxylase (TH is the rate-limiting enzyme in the synthesis of NE and serves as a marker for NE-producing cells. We selectively suppressed REMS in kittens for one week during the CP. The number and size of LC cells expressing immunoreactivity to tyrosine hydroxylase (TH-ir was assessed in age-matched REMS-deprived (RD-, treatment-control (TXC-, and home cage-reared (HCC animals. Sleep amounts and slow wave activity (SWA were also examined relative to baseline. Time spent in REMS during the study was lower in RD compared to TXC animals, and RD kittens increased SWA delta power in the latter half of the REMSD period. The estimated total number of TH-ir cells in LC was significantly lower in the RD- than in the TXC kittens and numerically lower than in HCC animals. The size of LC cells expressing TH-ir was greatest in the HCC group. They were significantly larger than the cells in the RD kittens. These data are consistent with a possible reduction in NE in forebrain areas, including visual cortex, caused by one week of REMSD.

  15. Structural Requirements for Recognition of the Human Immunodeficiency Virus Type 1 Core during Host Restriction in Owl Monkey Cells

    OpenAIRE

    Forshey, Brett M.; Shi, Jiong; Aiken, Christopher

    2005-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of simian cells is restricted at an early postentry step by host factors whose mechanism of action is unclear. These factors target the viral capsid protein (CA) and attenuate reverse transcription, suggesting that they bind to the HIV-1 core and interfere with its uncoating. To identify the relevant binding determinants in the capsid, we tested the capacity of viruses containing Gag cleavage site mutations and amino acid substitutions in ...

  16. Spatial and Temporal Analysis of Human Movements and Applications for Disaster Response Management Utilizing Cell Phone Usage Data

    Science.gov (United States)

    Yasumiishi, M.; Renschler, C. S.; Bittner, T. E.

    2015-07-01

    As cell phone usage becomes a norm in our daily lives, analysis and application of the data has become part of various research fields. This study focuses on the application of cell phone usage data to disaster response management. Cell phones work as a communication link between emergency responders and victims during and after a major disaster. This study recognizes that there are two kinds of disasters, one with an advance warning, and one without an advance warning. Different movement distance between a day with a blizzard (advanced warning) and a normal weather day was identified. In the scenario of a day with an extreme event without advanced warning (earthquake), factors that alter the phone users' movements were analyzed. Lastly, combining both cases, a conceptual model of human movement factors is proposed. Human movements consist of four factors that are push factors, movement-altering factors, derived attributes and constraint factors. Considering each category of factors in case of emergency, it should be necessary that we prepare different kinds of emergency response plans depending on the characteristics of a disaster.

  17. Preformed purified peptide/major histocompatibility class I complexes are potent stimulators of class I-restricted T cell hybridomas

    DEFF Research Database (Denmark)

    Stryhn, A; Pedersen, L O; Ortiz-Navarrete, V;

    1994-01-01

    A panel of antigen-specific, major histocompatibility complex class I-restricted T cell hybridomas has been generated to examine the capacity of peptide/class I complexes to stimulate T cells at the molecular level. Peptide/class I complexes were generated in detergent solution, purified and...... quantitated. Latex particles were subsequently coated with known amounts of preformed complexes and used to stimulate the T cell hybridomas. Stimulation was specific, i.e. only the appropriate peptide/class I combination were stimulatory, and quite sensitive, i.e. as little as 300 complexes per bead could be...... detected by the T cells. Preformed complexes were about 500,000 times more potent than free peptide in terms of T cell stimulation, demonstrating the physiological relevancy of the biochemically generated complexes. Surprisingly, the majority (including the most sensitive of the hybridomas) had lost CD8...

  18. Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

    OpenAIRE

    Zhao, Mei; Ralat, Maria A.; Da Silva, Vanessa; Garrett, Timothy J; Melnyk, Stephan; James, S. Jill; Gregory, Jesse F.

    2012-01-01

    Vitamin B-6 deficiency has been reported to alter n-6 and n-3 fatty acid profiles in plasma and tissue lipids; however, the mechanisms underlying such metabolic changes remain unclear. The objective of this study was to determine the effects of vitamin B-6 restriction on fatty acid profiles and fatty acid synthesis in HepG2 cells. Cells were cultured for 6 wk in media with four different vitamin B-6 concentrations (10, 20, 50, and 2,000 nM added pyridoxal, representing deficient, marginal, ad...

  19. Interspecific variation of intracellular localization and postirradiation movement of Ku70-protein in fibroblastic cells

    International Nuclear Information System (INIS)

    Ku (Ku70 and Ku80) Proteins are known as components of DNA-dependent protein kinase (DNA-PK) and play an important role for DNA repair. We previously reported that more than 70% of Ku proteins were located in cytoplasm of rat cells, the Ku proteins moved into nuclei of normal rat cells after X-irradiation, Ku proteins also moved into nuclei after X-irradiation but were not retained in nucleus of radiosensitive LEC rat cells. While reports have been shown about mechanisms on nuclear localization of Ku proteins, how Ku proteins export from nucleus is poorly understood. Here we show that C-terminal region of Ku70 protein is important for its cytoplasmic localization. When transfected into LEC rat cells, exogenous intact Ku70 (1-609) tagged with enhanced green fluorescent protein (EGFP-Ku70) localized mainly in the cytoplasm, whereas C-terminal-deletion mutant of Ku70 (1-593) tagged with EGFP (EGFP-Ku70D) was mainly localized in the nucleus. After X-irradiation, the endogenous intact EGFP-Ku70 once moved into nucleus, but returned into the cytoplasm. On the other hand, EGFP-Ku70D was retained in nucleus for two hours after X-irradiation. These results suggest that C-terminal region of Ku70 is included in the postirradiation nuclear export. Next, we investigated the intracellular localization of Ku70 proteins and the movement after X-irradiation of fibroblastic cells prepared from some mammalian species. Ku70 proteins were localized in nucleus and the postirradiation-extranuclear transport was not observed in human and African green monkey cells. On the other hand, Ku70 proteins were mainly localized in cytoplasm and moved into nucleus in mouse, Chinese hamster, Golden hamster, cotton rat, squirrel, cat and dog cells. These results may show that alternatively Ku70 protein is localized in the cytoplasm or nucleus depends on species and translocation of cytoplasmic Ku70 into nucleus is a response against low dose irradiation in fibroblasts of rodents, cats and dogs

  20. Interspecific variation of intracellular localization and postirradiation movement of Ku70-protein in fibroblastic cells

    Energy Technology Data Exchange (ETDEWEB)

    Endoh, Daiji; Hayashi, Masanobu [Rakuno Gakuen Univ., School of Veterinary Midicine, Ebetsu, Hokkaido (Japan); Okui, Toyo; Kawase, Shiro [Hokkaido Institute of Public Health, Sapporo, Hokkaido (Japan); Kon, Yasushiro [Hokkaido Univ., Graduate School of Veterinary Medicine, Sapporo, Hokkaido (Japan)

    2003-07-01

    Ku (Ku70 and Ku80) Proteins are known as components of DNA-dependent protein kinase (DNA-PK) and play an important role for DNA repair. We previously reported that more than 70% of Ku proteins were located in cytoplasm of rat cells, the Ku proteins moved into nuclei of normal rat cells after X-irradiation, Ku proteins also moved into nuclei after X-irradiation but were not retained in nucleus of radiosensitive LEC rat cells. While reports have been shown about mechanisms on nuclear localization of Ku proteins, how Ku proteins export from nucleus is poorly understood. Here we show that C-terminal region of Ku70 protein is important for its cytoplasmic localization. When transfected into LEC rat cells, exogenous intact Ku70 (1-609) tagged with enhanced green fluorescent protein (EGFP-Ku70) localized mainly in the cytoplasm, whereas C-terminal-deletion mutant of Ku70 (1-593) tagged with EGFP (EGFP-Ku70D) was mainly localized in the nucleus. After X-irradiation, the endogenous intact EGFP-Ku70 once moved into nucleus, but returned into the cytoplasm. On the other hand, EGFP-Ku70D was retained in nucleus for two hours after X-irradiation. These results suggest that C-terminal region of Ku70 is included in the postirradiation nuclear export. Next, we investigated the intracellular localization of Ku70 proteins and the movement after X-irradiation of fibroblastic cells prepared from some mammalian species. Ku70 proteins were localized in nucleus and the postirradiation-extranuclear transport was not observed in human and African green monkey cells. On the other hand, Ku70 proteins were mainly localized in cytoplasm and moved into nucleus in mouse, Chinese hamster, Golden hamster, cotton rat, squirrel, cat and dog cells. These results may show that alternatively Ku70 protein is localized in the cytoplasm or nucleus depends on species and translocation of cytoplasmic Ku70 into nucleus is a response against low dose irradiation in fibroblasts of rodents, cats and dogs

  1. HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells.

    Science.gov (United States)

    Wang, Zhihao; Hu, Pengchao; Tang, Fang; Xie, Conghua

    2016-05-01

    Sorafenib is a multi-targeted kinase inhibitor and has been the subject of extensive clinical research in advanced non-small cell lung cancer (NSCLC). However, sorafenib fails to improve overall survival of patients with advanced NSCLC. The molecular mechanisms that account for this phenomenon are unclear. Here we show that sorafenib treatment stabilizes epidermal growth factor receptor (EGFR) and activates EGFR pathway. Moreover, this is partly mediated by stabilization of histone deacetylase 6 (HDAC6), which has been shown to regulate EGFR endocytic trafficking and degradation. Overexpression of HDAC6 confers resistance to sorafenib in NSCLC cells. Inhibition of HDAC6 with selective inhibitors synergizes with sorafenib to kill NSCLC cells via inhibition of sorafenib-mediated EGFR pathway activation. Taken together, our findings might partly explain the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. PMID:27090797

  2. Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors

    OpenAIRE

    1993-01-01

    To characterize the T cell receptor (TCR) repertoire expressed by the V delta 1+ gamma/delta T cell population, we have studied the V delta 1-J delta 1 junctional sequences from peripheral blood samples of healthy donors. We show that, surprisingly, this repertoire is restricted in most healthy adults, with a donor-specific and relatively stable pattern, whereas this repertoire remains unrestricted in infants, and is similar to that of thymocytes. These data contrast with the general assumpti...

  3. GABA agonist promoted formation of low affinity GABA receptors on cerebellar granule cells is restricted to early development

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Schousboe, A;

    1988-01-01

    The ability of the GABA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) to promote formation of low affinity GABA receptors on cerebellar granule cells was tested using primary cultures of these neurons. Granule cells were exposed to THIP (150 microM) for 6 hr after......, respectively, 4, 7, 10 and 14 days in culture. It was found that THIP treatment of 4- and 7-day-old cultures led to formation of low affinity GABA receptors, whereas such receptors could not be detected after THIP treatment in the older cultures (10 and 14 days) in spite of the fact that these cultured granule...... cells expressed a high density of high affinity GABA receptors. It is concluded that the ability of THIP to promote formation of low affinity GABA receptors on cerebellar granule cells is restricted to an early developmental period....

  4. Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1994-01-01

    Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate...... the influences of different mycobacterial antigens on non-MHC-restricted cytotoxicity and further to investigate the ways by which various lymphocyte subpopulations contribute to the development of this cytotoxicity. Non-MHC-restricted cytotoxicity was induced following stimulation of mononuclear...... interferon. The CD4+ cells proliferated and expressed interleukin-2 receptors following stimulation with mycobacterial antigens.Depletion studies after antigen stimulation showed that the cytotoxic effector cells were CD16+ CD56+ and CD4-; the CD4+ cells alone did not mediate non-MHC-restricted cytotoxicity...

  5. Lung Injury Combined with Loss of Regulatory T Cells Leads to De Novo Lung-Restricted Autoimmunity.

    Science.gov (United States)

    Chiu, Stephen; Fernandez, Ramiro; Subramanian, Vijay; Sun, Haiying; DeCamp, Malcolm M; Kreisel, Daniel; Perlman, Harris; Budinger, G R Scott; Mohanakumar, Thalachallour; Bharat, Ankit

    2016-07-01

    More than one third of patients with chronic lung disease undergoing lung transplantation have pre-existing Abs against lung-restricted self-Ags, collagen type V (ColV), and k-α1 tubulin (KAT). These Abs can also develop de novo after lung transplantation and mediate allograft rejection. However, the mechanisms leading to lung-restricted autoimmunity remain unknown. Because these self-Ags are normally sequestered, tissue injury is required to expose them to the immune system. We previously showed that respiratory viruses can induce apoptosis in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), the key mediators of self-tolerance. Therefore, we hypothesized that lung-tissue injury can lead to lung-restricted immunity if it occurs in a setting when Tregs are impaired. We found that human lung recipients who suffer respiratory viral infections experienced a decrease in peripheral Tregs. Pre-existing lung allograft injury from donor-directed Abs or gastroesophageal reflux led to new ColV and KAT Abs post respiratory viral infection. Similarly, murine parainfluenza (Sendai) respiratory viral infection caused a decrease in Tregs. Intratracheal instillation of anti-MHC class I Abs, but not isotype control, followed by murine Sendai virus infection led to development of Abs against ColV and KAT, but not collagen type II (ColII), a cartilaginous protein. This was associated with expansion of IFN-γ-producing CD4(+) T cells specific to ColV and KAT, but not ColII. Intratracheal anti-MHC class I Abs or hydrochloric acid in Foxp3-DTR mice induced ColV and KAT, but not ColII, immunity, only if Tregs were depleted using diphtheria toxin. We conclude that tissue injury combined with loss of Tregs can lead to lung-tissue-restricted immunity. PMID:27194786

  6. mTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction.

    Science.gov (United States)

    Igarashi, Masaki; Guarente, Leonard

    2016-07-14

    Longevity-promoting caloric restriction is thought to trigger downregulation of mammalian target of rapamycin complex 1 (mTORC1) signaling and upregulation of SIRT1 activity with associated health benefits. Here, we show that mTORC1 signaling in intestinal stem cells (ISCs) is instead upregulated during calorie restriction (CR). SIRT1 deacetylates S6K1, thereby enhancing its phosphorylation by mTORC1, which leads to an increase in protein synthesis and an increase in ISC number. Paneth cells in the ISC niche secrete cyclic ADP ribose that triggers SIRT1 activity and mTORC1 signaling in neighboring ISCs. Notably, the mTOR inhibitor rapamycin, previously reported to mimic effects of CR, abolishes this expansion of ISCs. We suggest that Paneth cell signaling overrides any direct nutrient sensing in ISCs to sculpt the observed response to CR. Moreover, drugs that modulate pathways important in CR may exert opposing effects on different cell types. PMID:27345368

  7. Restrictive cardiomyopathy

    Science.gov (United States)

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy ... In a case of restrictive cardiomyopathy, the heart muscle is normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does not ...

  8. Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4(+) T cells.

    Science.gov (United States)

    Kok, Yik Lim; Vongrad, Valentina; Shilaih, Mohaned; Di Giallonardo, Francesca; Kuster, Herbert; Kouyos, Roger; Günthard, Huldrych F; Metzner, Karin J

    2016-01-01

    The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4(+) T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4(+) T cells were over-represented in gene hotspots identified in CD4(+) T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4(+) T cells. PMID:27067385

  9. Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4+ T cells

    Science.gov (United States)

    Kok, Yik Lim; Vongrad, Valentina; Shilaih, Mohaned; Di Giallonardo, Francesca; Kuster, Herbert; Kouyos, Roger; Günthard, Huldrych F.; Metzner, Karin J.

    2016-01-01

    The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4+ T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4+ T cells were over-represented in gene hotspots identified in CD4+ T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4+ T cells. PMID:27067385

  10. Methods to recover the narrow Dicke sub-Doppler feature in evacuated wall-coated cells without restrictions on cell size

    Science.gov (United States)

    Robinson, H. G.

    1984-01-01

    The hyperfine resonance observed in evacuated wall-coated cells with dimensions lambda/2 (lambda is the hyperfine resonance wavelength) consists of a narrow Dicke sub-Doppler linewidth feature, the spike, superimposed on a broad pedestal. The hydrogen maser provides a classic example of this lineshape. As cell size is increased, an effect unique to evacuated wall-coated cells occurs. Certain combinations of microwave field distribution and cell size result in a lineshape having a pedestal with a small spike feature or only the broad pedestal with no spike. Such conditions are not appropriate for atomic frequency standard applications. The cause of the evacuated wall-coated cell lineshape is reviewed and methods to recover the narrow spike feature without restrictions on cell size is discussed. One example is a cell with dimensions having equal volumes of exposure to opposite phases of the microwave magnetic field.

  11. Interactions of opsonized immune complexes with whole blood cells: binding to erythrocytes restricts complex uptake by leucocyte populations

    DEFF Research Database (Denmark)

    Nielsen, C H; Svehag, S E; Marquart, H V; Leslie, R G

    1994-01-01

    respect to IC binding, the main contributors being B cells. E initially inhibited and then later enhanced the IC binding to lymphocytes, suggesting that E promote B cell uptake of C3d,g-covered IC via CR2. Our findings, that E can restrict the IC uptake by circulating leucocytes, and that an IC......The binding of opsonized, fluorescein-labelled bovine serum albumin (BSA)/rabbit anti-BSA complexes (IC) to washed human whole blood cells and isolated leucocytes in the presence of autologous serum was investigated by flow cytometry. In the presence of erythrocytes (E), the IC-binding to...... granulocytes (PMN), monocytes and lymphocytes was inhibited by up to 46%, 61% and 48%, respectively, depending on the incubation time and the IC-concentration tested. The E-mediated inhibition of the binding to PMN was found to correlate with the average numbers of CR1 per E during the initial 15 min of...

  12. Interactions of opsonized immune complexes with whole blood cells: binding to erythrocytes restricts complex uptake by leucocyte populations

    DEFF Research Database (Denmark)

    Nielsen, C H; Svehag, S E; Marquart, H V;

    1994-01-01

    The binding of opsonized, fluorescein-labelled bovine serum albumin (BSA)/rabbit anti-BSA complexes (IC) to washed human whole blood cells and isolated leucocytes in the presence of autologous serum was investigated by flow cytometry. In the presence of erythrocytes (E), the IC-binding to...... granulocytes (PMN), monocytes and lymphocytes was inhibited by up to 46%, 61% and 48%, respectively, depending on the incubation time and the IC-concentration tested. The E-mediated inhibition of the binding to PMN was found to correlate with the average numbers of CR1 per E during the initial 15 min of...... respect to IC binding, the main contributors being B cells. E initially inhibited and then later enhanced the IC binding to lymphocytes, suggesting that E promote B cell uptake of C3d,g-covered IC via CR2. Our findings, that E can restrict the IC uptake by circulating leucocytes, and that an IC...

  13. Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Fu

    Full Text Available Progesterone plays a role in breast cancer development and progression but the effects on breast cancer cell movement or invasion have not been fully explored. In this study, we investigate the actions of natural progesterone and of the synthetic progestin medroxyprogesterone acetate (MPA on actin cytoskeleton remodeling and on breast cancer cell movement and invasion. In particular, we characterize the nongenomic signaling cascades implicated in these actions. T47-D breast cancer cells display enhanced horizontal migration and invasion of three-dimensional matrices in the presence of both progestins. Exposure to the hormones triggers a rapid remodeling of the actin cytoskeleton and the formation of membrane ruffles required for cell movement, which are dependent on the rapid phosphorylation of the actin-regulatory protein moesin. The extra-cellular small GTPase RhoA/Rho-associated kinase (ROCK-2 cascade plays central role in progesterone- and MPA-induced moesin activation, cell migration and invasion. In the presence of progesterone, progesterone receptor A (PRA interacts with the G protein G alpha(13, while MPA drives PR to interact with tyrosine kinase c-Src and to activate phosphatidylinositol-3 kinase, leading to the activation of RhoA/ROCK-2. In conclusion, our findings manifest that progesterone and MPA promote breast cancer cell movement via rapid actin cytoskeleton remodeling, which are mediated by moesin activation. These events are triggered by RhoA/ROCK-2 cascade through partially differing pathways by the two compounds. These results provide original mechanistic explanations for the effects of progestins on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.

  14. Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay.

    Science.gov (United States)

    Nicken, Petra; Empl, Michael T; Gerhard, Daniel; Hausmann, Julia; Steinberg, Pablo

    2016-09-01

    High consumption of red meat entails a higher risk of developing colorectal cancer. Methionine, which is more frequently a component of animal proteins, and folic acid are members of the one carbon cycle and as such important players in DNA methylation and cancer development. Therefore, dietary modifications involving altered methionine and folic acid content might inhibit colon cancer development. In the present study, the BALB/c 3T3 cell transformation assay was used to investigate whether methionine and folic acid are able to influence the malignant transformation of mouse fibroblasts after treatment with the known tumour initiator 3-methylcholanthrene. Three different methionine concentrations (representing a -40%, a "normal" and a +40% cell culture medium concentration, respectively) and two different folic acid concentrations (6 and 20 μM) were thereby investigated. Methionine restriction led to a decrease of type III foci, while enhancement of both methionine and folic acid did not significantly increase the cell transformation rate. Interestingly, the focus-lowering effect of methionine was only significant in conjunction with an elevated folic acid concentration. In summary, we conclude that the malignant transformation of mouse fibroblasts is influenced by methionine levels and that methionine restriction could be a possible approach to reduce cancer development. PMID:27427305

  15. Effects of immobilisation and caloric restriction on antioxidant parameters and T-cell apoptosis in healthy young men

    Science.gov (United States)

    Ellinger, S.; Arendt, B. M.; Boese, A.; Juschus, M.; Schaefer, S.; Stoffel-Wagner, B.; Goerlich, R.

    Background: Astronauts are exposed to oxidative stress due to radiation and microgravity, which might impair immune functions. Effects of hypocaloric nutrition as often observed in astronauts on oxidative stress and immune functions are not clear. We investigated, if microgravity, simulated by 6 Head-down tilt (HDT) and caloric restriction (-25%, fat reduced) with adequate supply of micronutrients affect DNA-damage in peripheral leukocytes, antioxidant parameters in plasma, and T-cell apoptosis. Material & Methods: 10 healthy male non-smokers were subjected to 4 different interventions (normocaloric diet or caloric restriction (CR) in upright position (UP) or HDT) for 14 days each (cross-over). DNA-damage in peripheral leukocytes (Comet Assay), trolox equivalent antioxidant capacity (TEAC) and uric acid in plasma were measured before, after 5, 10, and 13 days of intervention, and after 2 days recovery. T-cell apoptosis (Annexin V binding test) was assessed before and after intervention. Results: Preliminary results show that only endogenous, but not ex vivo H2O2-induced DNA strand breaks were reduced by CR compared to normocaloric diet. In upright position, endogenous DNA strand breaks decreased continuously during CR, reaching significance after recovery. During HDT, caloric restriction seems to counteract a temporary increase in DNA strand breaks observed in subjects receiving normocaloric diet. TEAC was reduced during HDT compared to UP in subjects under caloric restriction. An increase in plasma uric acid related to intervention occurred only after 5 days HDT in CR vs. normocaloric diet. T-cell apoptosis was not affected by any kind of intervention. Conclusion: Neither HDT nor CR with sufficient supply of micronutrients seem to induce oxidative stress or T-cell apoptosis in healthy young men. In contrast, CR might prevent endogenous DNA-damage in peripheral leukocytes. As DNA-damage is a risk factor for carcinogenesis, protective effects of energy reduction are

  16. Entry and release of transmissible gastroenteritis coronavirus are restricted to apical surfaces of polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Bekker, C P; Voorhout, W F; Strous, G J; van der Ende, A; Rottier, P J

    1994-01-01

    The transmissible gastroenteritis coronavirus (TGEV) infects the epithelial cells of the intestinal tract of pigs, resulting in a high mortality rate in piglets. This study shows the interaction of TGEV with a porcine epithelial cell line. To determine the site of viral entry, LLC-PK1 cells were gro

  17. Restricted distribution of mrg-1 mRNA in C. elegans primordial germ cells through germ granule-independent regulation.

    Science.gov (United States)

    Miwa, Takashi; Takasaki, Teruaki; Inoue, Kunio; Sakamoto, Hiroshi

    2015-11-01

    The chromodomain protein MRG-1 is an essential maternal factor for proper germline development that protects germ cells from cell death in C. elegans. Unlike germ granules, which are exclusively segregated to the germline blastomeres at each cell division from the first cleavage of the embryo, MRG-1 is abundant in all cells in early embryos and is then gradually restricted to the primordial germ cells (PGCs) by the morphogenesis stage. Here, we show that this characteristic spatiotemporal expression pattern is dictated by the mrg-1 3'UTR and is differentially regulated at the RNA level between germline and somatic cells. Asymmetric segregation of germ granules is not necessary to localize MRG-1 to the PGCs. We found that MES-4, an essential chromatin regulator in germ cells, also accumulates in the PGCs in a germ granule-independent manner. We propose that C.elegans PGCs have a novel mechanism to accumulate at least some chromatin-associated proteins that are essential for germline immortality. PMID:26537333

  18. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  19. É importante restringir a movimentação cefálica após a manobra de Epley? Is it important to restrict head movement after Epley maneuver?

    Directory of Open Access Journals (Sweden)

    Fernando Freitas Ganança

    2005-12-01

    head movements and to use a cervical collar and group 2 patients were not informed about these postmaneuver restrictions. The patients from both groups were reevaluated one week after Epley maneuver, regarding the presence of symptoms and positional nystagmus. RESULTS: One week after Epley maneuver 82.1% of the patients from group 1 and 73.3% from group 2 didn't present positional nystagmus (p=0.421. There was a clinical improvement in 96.0% of the patients from group 1 and in 94.0% from group 2 (p=0.781. CONCLUSION: The use of postural restrictions in patients with benign paroxysmal positional vertigo of posterior canal didn't interfere in their clinical evaluation, one week after a unique Epley maneuver.

  20. Tuning nano electric field to affect restrictive membrane area on localized single cell nano-electroporation

    Science.gov (United States)

    Santra, Tuhin Subhra; Wang, Pen-Cheng; Chang, Hwan-You; Tseng, Fan-Gang

    2013-12-01

    Interaction of electric field with biological cells is an important phenomenon for field induced drug delivery system. We demonstrate a selective and localized single cell nano-electroporation (LSCNEP) by applying an intense electric field on a submicron region of the single cell membrane, which can effectively allow high efficient molecular delivery but low cell damage. The delivery rate is controlled by adjusting transmembrane potential and manipulating membrane status. Thermal and ionic influences are deteriorated from the cell membrane by dielectric passivation. Either reversible or irreversible by LSCNEP can fully controlled with potential applications in medical diagnostics and biological studies.

  1. The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression

    Directory of Open Access Journals (Sweden)

    Mo RuRan

    2007-11-01

    Full Text Available Abstract Background The mechanism explaining the increased disease susceptibility in aging is not well understood. CD8+ T cells are crucial in anti-viral and anti-tumor responses. Although the chemokine system plays a critical role in CD8+ T cell function, very little is known about the relationship between aging and the T cell chemokine system. Results In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression. Freshly isolated splenic CD8+ T cells from old C57BL/6 mice were found to have higher CCR1, CCR2, CCR4, CCR5 and CXCR5, and lower CCR7 gene expression compared to their younger cohort. Anti-CD3/anti-CD28 stimulation elicited a similar robust chemokine receptor response from young and old CD8+ T cells. Western blot analyses confirmed elevated protein level of CCR4 and CCR5 in aged CD8+ T cells. Increases in T cell CCR1 and CCR5 expression also correlate to increased in vitro chemotaxis response to macrophage-inflammatory protein-1 α(MIP-1α. Finally, caloric restriction selectively prevents the loss of CD8+ T cell CCR7 gene expression in aging to the level that is seen in young CD8+ T cells. Conclusion These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment. In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.

  2. Tobamoviral movement protein transiently expressed in a single epidermal cell functions beyond multiple plasmodesmata and spreads multicellularly in an infection-coupled manner.

    Science.gov (United States)

    Tamai, A; Meshi, T

    2001-02-01

    Cell-to-cell movement of a plant virus requires expression of the movement protein (MP). It has not been fully elucidated, however, how the MP functions in primary infected cells. With the use of a microprojectile bombardment-mediated DNA infection system for Tomato mosaic virus (ToMV), we found that the cotransfected ToMV MP gene exerts its effects in the initially infected cells and in their surrounding cells to achieve multicellular spread of movement-defective ToMV. Five other tobamoviral MPs examined also transcomplemented the movement-defective phenotype of ToMV, but the Cucumber mosaic virus 3a MP did not. Together with the cell-to-cell movement of the mutant virus, a fusion between the MP and an enhanced green fluorescent protein variant (EGFP) expressed in trans was distributed multicellularly and localized primarily in plasmodesmata between infected cells. In contrast, in noninfected sites the MP-EGFP fusion accumulated predominantly inside the bombarded cells as irregularly shaped aggregates, and only a minute amount of the fusion was found in plasmodesmata. Thus, the behavior of ToMV MP is greatly modulated in the presence of a replicating virus and it is highly likely that the MP spreads in the infection sites, coordinating with the cell-to-cell movement of the viral genome. PMID:11204775

  3. Cells in the monkey ponto-medullary reticular formation modulate their activity with slow finger movements

    OpenAIRE

    Soteropoulos, Demetris S.; Williams, Elizabeth R.; Baker, Stuart N.

    2012-01-01

    Recent work has shown that the primate reticulospinal tract can influence spinal interneurons and motoneurons involved in control of the hand. However, demonstrating connectivity does not reveal whether reticular outputs are modulated during the control of different types of hand movement. Here, we investigated how single unit discharge in the pontomedullary reticular formation (PMRF) modulated during performance of a slow finger movement task in macaque monkeys. Two animals performed an inde...

  4. A restricted set of apical proteins recycle through the trans-Golgi network in MDCK cells.

    OpenAIRE

    Brändli, A W; Simons, K

    1989-01-01

    Sorting of newly synthesized proteins destined for the apical plasma membrane takes place in the trans-Golgi network (TGN) in MDCK cells. This process is most likely receptor mediated and requires components that recycle between both compartments. We have developed an assay to detect apical proteins that recycle through the sialyltransferase-containing TGN. Cell surface glycoproteins were exogalactosylated apically using a mutant cell line derived from MDCK, MDCKII-RCAr. The mutant exhibits i...

  5. Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens

    OpenAIRE

    Suffia, Isabelle J.; Reckling, Stacie K.; Piccirillo, Ciriaco A; Goldszmid, Romina S.; Belkaid, Yasmine

    2006-01-01

    Natural regulatory T (T reg) cells are involved in control of the immune response, including response to pathogens. Previous work has demonstrated that the repertoire of natural T reg cells may be biased toward self-antigen recognition. Whether they also recognize foreign antigens and how this recognition contributes to their function remain unknown. Our studies addressed the antigenic specificity of natural T reg cells that accumulate at sites of chronic infection with Leishmania major in mi...

  6. Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression

    International Nuclear Information System (INIS)

    Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects. To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis. In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A. These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity

  7. Cell-to-cell movement of Alfalfa mosaic virus can be mediated by the movement proteins of Ilar-, bromo-, cucumo-, tobamo- and comoviruses and does not require virion formation.

    Science.gov (United States)

    Sánchez-Navarro, Jesús A; Carmen Herranz, María; Pallás, Vicente

    2006-03-01

    RNA 3 of Alfalfa mosaic virus (AMV) encodes the movement protein (MP) and coat protein (CP). Chimeric RNA 3 with the AMV MP gene replaced by the corresponding MP gene of Prunus necrotic ringspot virus, Brome mosaic virus, Cucumber mosaic virus or Cowpea mosaic virus efficiently moved from cell-to-cell only when the expressed MP was extended at its C-terminus with the C-terminal 44 amino acids of AMV MP. MP of Tobacco mosaic virus supported the movement of the chimeric RNA 3 whether or not the MP was extended with the C-terminal AMV MP sequence. The replacement of the CP gene in RNA 3 by a mutant gene encoding a CP defective in virion formation did not affect cell-to-cell transport of the chimera's with a functional MP. A GST pull-down technique was used to demonstrate for the first time that the C-terminal 44 amino acids of the MP of a virus belonging to the family Bromoviridae interact specifically with AMV virus particles. Together, these results demonstrate that AMV RNA 3 can be transported from cell-to-cell by both tubule-forming and non-tubule-forming MPs if a specific MP-CP interaction occurs. PMID:16316673

  8. Severe cell reduction in the future brain cortex in human growth-restricted fetuses and infants

    DEFF Research Database (Denmark)

    Samuelsen, Grethe B; Pakkenberg, Bente; Bogdanović, Nenad;

    2007-01-01

    controls. The daily increase in brain cells in the future cortex was only half of that of the controls. In the 3 other developmental zones, no significant differences in cell numbers could be demonstrated. CONCLUSIONS: IUGR in humans is associated with a severe reduction in cortical growth and a...... estimated in 9 severely affected IUGR fetuses and 15 controls using the optical fractionator. Cell numbers were estimated within 4 developmental zones. The gestational ages were 19-41 weeks. RESULTS: The total cell number in the future cortex was significantly reduced in the IUGR fetuses, compared with...

  9. Real-time detection of α1A-AR movement stimulated by phenylephrine in single living cells

    Institute of Scientific and Technical Information of China (English)

    Ning XU; Zhang-yi LIANG; Ming XU; Ying-hua GUAN; Qi-hua HE; Qi-de HAN; Xin-sheng ZHAO; You-yi ZHANG

    2007-01-01

    Aim: To investigate the movement of α1A-adrenergic receptors(α1A-AR) stimu-lated by agonist, phenylephrine (PE), and the dynamics of receptor movement in real time in single living cells with millisecond resolution.Methods: We labeled α1A-AR using the monoclonal, anti-FLAG (a kind of tag) antibody and Cy3-conju-gated goat anti-mouse IgG and recorded the trajectory of their transport process in living HEK293A cells stimulated by agonist, PE, and then analyzed their dy-namic properties.Results: The specific detection of α1A-AR on the surface of living HEK293A-α1A cells was achieved. α1A-AR internalize under the stimulation of PE. After the cells were stimulated with PE for 20 rain, apparent colocalization was found between α1A-AR and F-actins. After 40 min stimulation of PE, trajecto-ries of approximate linear motion in HEK293A-α1A cells were recorded, and their velocity was calculated. Condusion: The specific labeling method on the living cell surface provides a convenient means of real-time detection of the behavior of surface receptors. By this method we were able to specifically detectα1A-AR and record the behavior of individual particles of receptors with 50 ms exposure time in real time in single living cells.

  10. Actin Cytoskeleton and Golgi Involvement in Barley stripe mosaic virus Movement and Cell Wall Localization of Triple Gene Block Proteins

    Directory of Open Access Journals (Sweden)

    Hyoun-Sub Lim

    2013-03-01

    Full Text Available Barley stripe mosaic virus (BSMV induces massive actin filament thickening at the infection front of infected Nicotiana benthamiana leaves. To determine the mechanisms leading to actin remodeling, fluorescent protein fusions of the BSMV triple gene block (TGB proteins were coexpressed in cells with the actin marker DsRed: Talin. TGB ectopic expression experiments revealed that TGB3 is a major elicitor of filament thickening, that TGB2 resulted in formation of intermediate DsRed:Talin filaments, and that TGB1 alone had no obvious effects on actin filament structure. Latrunculin B (LatB treatments retarded BSMV cell-to-cell movement, disrupted actin filament organization, and dramatically decreased the proportion of paired TGB3 foci appearing at the cell wall (CW. BSMV infection of transgenic plants tagged with GFP-KDEL exhibited membrane proliferation and vesicle formation that were especially evident around the nucleus. Similar membrane proliferation occurred in plants expressing TGB2 and/or TGB3, and DsRed: Talin fluorescence in these plants colocalized with the ER vesicles. TGB3 also associated with the Golgi apparatus and overlapped with cortical vesicles appearing at the cell periphery. Brefeldin A treatments disrupted Golgi and also altered vesicles at the CW, but failed to interfere with TGB CW localization. Our results indicate that actin cytoskeleton interactions are important in BSMV cell-to-cell movement and for CW localization of TGB3.

  11. Feedback, receptor clustering, and receptor restriction to single cells yield large Turing spaces for ligand-receptor-based Turing models

    Science.gov (United States)

    Kurics, Tamás; Menshykau, Denis; Iber, Dagmar

    2014-08-01

    Turing mechanisms can yield a large variety of patterns from noisy, homogenous initial conditions and have been proposed as patterning mechanism for many developmental processes. However, the molecular components that give rise to Turing patterns have remained elusive, and the small size of the parameter space that permits Turing patterns to emerge makes it difficult to explain how Turing patterns could evolve. We have recently shown that Turing patterns can be obtained with a single ligand if the ligand-receptor interaction is taken into account. Here we show that the general properties of ligand-receptor systems result in very large Turing spaces. Thus, the restriction of receptors to single cells, negative feedbacks, regulatory interactions among different ligand-receptor systems, and the clustering of receptors on the cell surface all greatly enlarge the Turing space. We further show that the feedbacks that occur in the FGF10-SHH network that controls lung branching morphogenesis are sufficient to result in large Turing spaces. We conclude that the cellular restriction of receptors provides a mechanism to sufficiently increase the size of the Turing space to make the evolution of Turing patterns likely. Additional feedbacks may then have further enlarged the Turing space. Given their robustness and flexibility, we propose that receptor-ligand-based Turing mechanisms present a general mechanism for patterning in biology.

  12. Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

    DEFF Research Database (Denmark)

    Blomqvist, Maria; Rhost, Sara; Teneberg, Susann;

    2009-01-01

    relevant isoforms C24:1 and C24:0, major constituents of the myelin sheet of the nervous system, and C16:0, prominent in the pancreatic islet beta-cells. The most potent sulfatide isoform was lysosulfatide (lacking a fatty acid). Shortened fatty acid chain length (C24:1 versus C18:1), or saturation of the...... mixture of sulfatide isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Here, we demonstrate that sulfatide-specific CD1d-restricted murine NKT hybridomas recognized several different sulfatide isoforms. These included the physiologically...... long fatty acid (C24:0), resulted in reduced stimulatory capacity, and fatty acid hydroxylation abolished the response. Moreover, sulfatide was not responsible for the natural autoreactivity toward splenocytes by XV19 T hybridoma cells. Our results reveal a promiscuity in the recognition of sulfatide...

  13. A novel envelope mediated post entry restriction of murine leukaemia virus in human cells is Ref1/TRIM5α independent

    Directory of Open Access Journals (Sweden)

    McKnight Áine

    2010-10-01

    Full Text Available Abstract Background 'Intrinsic' resistance to retroviral infection was first recognised with the Friend virus susceptibility gene (Fv1, which determines susceptibility to murine leukaemia virus (MLV infection in different murine species. Similarly, the tripartite motif (TRIM family of proteins determine lentiviral restriction in a primate host-species specific manner. For example rhesus TRIM5α (rhTRIM5α can potently restrict HIV-1 infection while human TRIM5α (huTRIM5α only has a mild effect on SIVmac and HIV-1 infectivity (Lv1. Human TRIM5α is able to restrict MLV-N virus replication, but is ineffective against MLV-B or MLV-NB virus infection. Lv2 restriction of some HIV-2 viruses is seen in human cells. Like Lv1, Lv2 is a post-entry restriction factor, whose viral determinants have been mapped to the viral capsid (CA. Unlike Lv1, however, Lv2 is determined by envelope (Env in addition to CA. Here we present evidence of a novel Env determined post entry restriction to infection in human cells of pseudotyped MLV-B and MLV-NB cores. Results We generated retroviral vectors pseudotyped with various gamma and lentiviral Envs on MLV-B and -NB CAs containing a green fluorescent protein (GFP reporter. Flow cytometry was used to determine transduction efficiencies in NP2/CD4/CXCR4 (glioma cell line stably transduced with the HIV receptors and HeLa/CD4 cell lines. The HeLa/CD4 cell line restricted both MLV CAs in an Env dependent manner, compared to NP2/CD4/CXCR4 cells. Quantitative polymerase chain reaction (QT-PCR analysis of reverse transcription (RT transcripts demonstrates that this restriction occurs at a post entry and RT level. siRNA knockdown of huTRIM5α ruled out a direct role for this cellular component in mediating this restriction. We describe a previously unobserved Env determined restriction of MLV-B and MLV-NB CAs in HeLa/CD4 cells when pseudotyped with HIV-2 and RD114 Envs, but not gibbon ape leukaemia virus (GALV, HIV-1 or

  14. Down-regulation of the cyprinid herpesvirus-3 annotated genes in cultured cells maintained at restrictive high temperature.

    Science.gov (United States)

    Ilouze, Maya; Dishon, Arnon; Kotler, Moshe

    2012-10-01

    Cyprinid herpesvirus-3 (CyHV-3) is a member of the Alloherpesviridae, in the order Herpesvirales. It causes a fatal disease in carp and koi fish. The disease is seasonal and is active when water temperatures ranges from 18 to 28 °C. Little is known about how and where the virus is preserved between the permissive seasons. The hallmark of the herpesviruses is their ability to become latent, persisting in the host in an apparently inactive state for varying periods of time. Hence, it could be expected that CyHV-3 enter a latent period. CyHV-3 has so far been shown to persist in fish maintained under restrictive temperatures, while shifting the fish to permissive conditions reactivates the virus. Previously, we demonstrated that cultured cells infected with CyHV-3 at 22 °C and subsequently transferred to a restrictive temperature of 30 °C preserve the virus for 30 days. The present report shows that cultured carp cells maintained and exposed to CyHV-3 at 30 °C are abortively infected; that is, autonomous viral DNA synthesis is hampered and the viral genome is not multiplied. Under these conditions, 91 of the 156 viral annotated ORFs were initially transcribed. These transcripts were down-regulated and gradually shut off over 18 days post-infection, while two viral transcripts encoded by ORFs 114 and 115 were preserved in the infected cells for 18 days p.i. These experiments, carried out in cultured cells, suggest that fish could be infected at a high non-permissive temperature and harbor the viral genome without producing viral particles. PMID:22841492

  15. Hibiscus chlorotic ringspot virus coat protein is essential for cell-to-cell and long-distance movement but not for viral RNA replication.

    Directory of Open Access Journals (Sweden)

    Shengniao Niu

    Full Text Available Hibiscus chlorotic ringspot virus (HCRSV is a member of the genus Carmovirus in the family Tombusviridae. In order to study its coat protein (CP functions on virus replication and movement in kenaf (Hibiscus cannabinus L., two HCRSV mutants, designated as p2590 (A to G in which the first start codon ATG was replaced with GTG and p2776 (C to G in which proline 63 was replaced with alanine, were constructed. In vitro transcripts of p2590 (A to G were able to replicate to a similar level as wild type without CP expression in kenaf protoplasts. However, its cell-to-cell movement was not detected in the inoculated kenaf cotyledons. Structurally the proline 63 in subunit C acts as a kink for β-annulus formation during virion assembly. Progeny of transcripts derived from p2776 (C to G was able to move from cell-to-cell in inoculated cotyledons but its long-distance movement was not detected. Virions were not observed in partially purified mutant virus samples isolated from 2776 (C to G inoculated cotyledons. Removal of the N-terminal 77 amino acids of HCRSV CP by trypsin digestion of purified wild type HCRSV virions resulted in only T = 1 empty virus-like particles. Taken together, HCRSV CP is dispensable for viral RNA replication but essential for cell-to-cell movement, and virion is required for the virus systemic movement. The proline 63 is crucial for HCRSV virion assembly in kenaf plants and the N-terminal 77 amino acids including the β-annulus domain is required in T = 3 assembly in vitro.

  16. Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2012-12-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

  17. Restricted ultraviolet mutational spectrum in a shuttle vector propagated in xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    A shuttle vector plasmid, pZ189, carrying a bacterial suppressor tRNA marker gene, was treated with ultraviolet radiation and propagated in cultured skin cells from a patient with the skin-cancer-prone, DNA repair-deficient disease xeroderma pigmentosum and in repair-proficient cells. After replication in the human cells, progeny plasmids were purified. Plasmid survival and mutations inactivating the marker gene were scored by transforming an indicator strain of Escherichia coli carrying a suppressible amber mutation in the beta-galactosidase gene. Plasmid survival in the xeroderma pigmentosum cells was less than that of pZ189 harvested from repair-proficient human cells. The point-mutation frequency in the 150-base-pair tRNA marker gene increased up to 100-fold with ultraviolet dose. Sequence analysis of 150 mutant plasmids revealed that mutations were infrequent at potential thymine-thymine dimer sites. Ninety-three percent of the mutant plasmids from the xeroderma pigmentosum cells showed G X C----A X T transitions, compared to 73% in the normal cells (P less than 0.002). There were significantly fewer transversions (P less than 0.002) (especially G X C----T X A) and multiple base substitutions (P less than 0.00001) than when pZ189 was passaged in repair-proficient cells. The subset of mutational changes that are common to ultraviolet-treated plasmids propagated in both repair-proficient and xeroderma pigmentosum skin cells may be associated with the development of ultraviolet-induced skin cancer in humans

  18. Fast cellular automata with restricted inter-cell communication: computational capacity

    OpenAIRE

    Kutrib, Martin; Malcher, Andreas

    2006-01-01

    A d-dimensional cellular automaton with sequential input mode is a d-dimensional grid of interconnected interacting finite automata. The distinguished automaton at the origin, the communication cell, is connected to the outside world and fetches the input sequentially. Often in the literature this model is referred to as iterative array. We investigate d-dimensional iterative arrays and one-dimensional cellular automata operating in real and linear time, whose inter-cell communicati...

  19. Drosophila Rabex-5 restricts Notch activity in hematopoietic cells and maintains hematopoietic homeostasis

    OpenAIRE

    Reimels, Theresa A.; Cathie M. Pfleger

    2015-01-01

    ABSTRACT Hematopoietic homeostasis requires the maintenance of a reservoir of undifferentiated blood cell progenitors and the ability to replace or expand differentiated blood cell lineages when necessary. Multiple signaling pathways function in these processes, but how their spatiotemporal control is established and their activity is coordinated in the context of the entire hematopoietic network are still poorly understood. We report here that loss of the gene Rabex-5 in Drosophila causes se...

  20. Human CD1-restricted T cell recognition of lipids from pollens.

    Science.gov (United States)

    Agea, Elisabetta; Russano, Anna; Bistoni, Onelia; Mannucci, Roberta; Nicoletti, Ildo; Corazzi, Lanfranco; Postle, Anthony D; De Libero, Gennaro; Porcelli, Steven A; Spinozzi, Fabrizio

    2005-07-18

    Plant pollens are an important source of environmental antigens that stimulate allergic responses. In addition to acting as vehicles for foreign protein antigens, they contain lipids that incorporate saturated and unsaturated fatty acids, which are necessary in the reproduction of higher plants. The CD1 family of nonpolymorphic major histocompatibility complex-related molecules is highly conserved in mammals, and has been shown to present microbial and self lipids to T cells. Here, we provide evidence that pollen lipids may be recognized as antigens by human T cells through a CD1-dependent pathway. Among phospholipids extracted from cypress grains, phosphatidyl-choline and phosphatidyl-ethanolamine were able to stimulate the proliferation of T cells from cypress-sensitive subjects. Recognition of phospholipids involved multiple cell types, mostly CD4(+) T cell receptor for antigen (TCR)alphabeta(+), some CD4(-)CD8(-) TCRgammadelta(+), but rarely Valpha24i(+) natural killer-T cells, and required CD1a(+) and CD1d(+) antigen presenting cell. The responding T cells secreted both interleukin (IL)-4 and interferon-gamma, in some cases IL-10 and transforming growth factor-beta, and could provide help for immunoglobulin E (IgE) production. Responses to pollen phospholipids were maximally evident in blood samples obtained from allergic subjects during pollinating season, uniformly absent in Mycobacterium tuberculosis-exposed health care workers, but occasionally seen in nonallergic subjects. Finally, allergic, but not normal subjects, displayed circulating specific IgE and cutaneous weal and flare reactions to phospholipids. PMID:16009719

  1. Engraftment potential of human fetal hematopoietic cells in NOD/SCID mice is not restricted to mitotically quiescent cells.

    Science.gov (United States)

    Wilpshaar, Jannine; Bhatia, Mickie; Kanhai, Humphrey H H; Breese, Robert; Heilman, Doug K; Johnson, Cynthia S; Falkenburg, J H Frederik; Srour, Edward F

    2002-07-01

    During fetal development, there is a continued demand for large numbers of primitive and mature hematopoietic cells. This demand may require that all potential hematopoietic stem cells (HSCs) migrate effectively to emerging hematopoietic sites and subsequently contribute to blood cell production, regardless of their cell cycle status. We recently established that umbilical cord blood cells in the G(1) phase of the cell cycle have a repopulating potential similar to cells in G(0), suggesting that cycling prenatal and neonatal HSCs may have the same functional capabilities described for quiescent, but not cycling, cells from adult sources. To establish the relationship between cell cycle status and hematopoietic potential at early stages of human ontogeny, the in vivo engraftment potential of mitotically defined fetal liver (FL) and fetal bone marrow (FBM) cells were examined in NOD/SCID recipients. Following transplantation of the same numbers of G(0), G(1), or S/G(2)+M CD34(+) cells from FL, equivalent percentages of recipient mice were chimeric (55%, 60%, and 60%, respectively). FBM-derived CD34(+) cells in all phases of the cell cycle engrafted in conditioned recipients and sustained human hematopoiesis, albeit at lower levels than their FL-derived counterparts. Multilineage differentiation was evident in all transplanted mice independent of the source or cell cycle status of graft cells. In addition, levels of chimerism in mice transplanted with fetal blood-derived G(0) or G(1) CD34(+) lineage-depleted cells were similar. These results support the assertion that mitotically quiescent and cycling fetal hematopoietic cells contain marrow-repopulating stem cells capable of multilineage engraftment in NOD/SCID mouse recipients. PMID:12070016

  2. Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells.

    Science.gov (United States)

    Chen, Chin; Fang, Rixun; Davis, Corrine; Maravelias, Charalambos; Sibley, Eric

    2009-12-01

    Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1(flox/flox);VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1(flox/flox);VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1(flox/flox);VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine. PMID:19808654

  3. Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals.

    Science.gov (United States)

    Boudinot, Pierre; Mondot, Stanislas; Jouneau, Luc; Teyton, Luc; Lefranc, Marie-Paule; Lantz, Olivier

    2016-05-24

    Whereas major histocompatibility class-1 (MH1) proteins present peptides to T cells displaying a large T-cell receptor (TR) repertoire, MH1Like proteins, such as CD1D and MR1, present glycolipids and microbial riboflavin precursor derivatives, respectively, to T cells expressing invariant TR-α (iTRA) chains. The groove of such MH1Like, as well as iTRA chains used by mucosal-associated invariant T (MAIT) and natural killer T (NKT) cells, respectively, may result from a coevolution under particular selection pressures. Herein, we investigated the evolutionary patterns of the iTRA of MAIT and NKT cells and restricting MH1Like proteins: MR1 appeared 170 Mya and is highly conserved across mammals, evolving more slowly than other MH1Like. It has been pseudogenized or independently lost three times in carnivores, the armadillo, and lagomorphs. The corresponding TRAV1 gene also evolved slowly and harbors highly conserved complementarity determining regions 1 and 2. TRAV1 is absent exclusively from species in which MR1 is lacking, suggesting that its loss released the purifying selection on MR1. In the rabbit, which has very few NKT and no MAIT cells, a previously unrecognized iTRA was identified by sequencing leukocyte RNA. This iTRA uses TRAV41, which is highly conserved across several groups of mammals. A rabbit MH1Like gene was found that appeared with mammals and is highly conserved. It was independently lost in a few groups in which MR1 is present, like primates and Muridae, illustrating compensatory emergences of new MH1Like/Invariant T-cell combinations during evolution. Deciphering their role is warranted to search similar effector functions in humans. PMID:27170188

  4. Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients.

    Science.gov (United States)

    Toma, Andréa; Haddouk, Samy; Briand, Jean-Paul; Camoin, Luc; Gahery, Hanne; Connan, Francine; Dubois-Laforgue, Danielle; Caillat-Zucman, Sophie; Guillet, Jean-Gérard; Carel, Jean-Claude; Muller, Sylviane; Choppin, Jeannine; Boitard, Christian

    2005-07-26

    Proinsulin is a key autoantigen in type 1 diabetes. Evidence in the mouse has underscored the importance of the insulin B chain region in autoimmunity to pancreatic beta cells. In man, a majority of proteasome cleavage sites are predicted by proteasome cleavage algorithms within this region. To study CD8+ T cell responses to the insulin B chain and adjacent C peptide, we selected 8- to 11-mer peptides according to proteasome cleavage patterns obtained by digestion of two peptides covering proinsulin residues 28 to 64. We studied their binding to purified HLA class I molecules and their recognition by T cells from diabetic patients. Peripheral blood mononuclear cells from 17 of 19 recent-onset and 12 of 13 long-standing type 1 diabetic patients produced IFN-gamma in response to proinsulin peptides as shown by using an ELISPOT assay. In most patients, the response was against several class I-restricted peptides. Nine peptides were recognized within the proinsulin region covering residues 34 to 61. Four yielded a high frequency of recognition in HLA-A1 and -B8 patients. Three peptides located in the proinsulin region 41-51 were shown to bind several HLA molecules and to be recognized in a high percentage of diabetic patients. PMID:16030147

  5. miRNA Profiles of Monocyte-Lineage Cells Are Consistent with Complicated Roles in HIV-1 Restriction

    Directory of Open Access Journals (Sweden)

    Janice E. Clements

    2012-09-01

    Full Text Available Long-lived HIV-1 reservoirs include tissue macrophages. Monocyte-derived macrophages are more susceptible to infection and more permissive to HIV-1 replication than monocytes for reasons that may include the effects of different populations of miRNAs in these two cell classes. Specifically, miRs-28-3p, -150, -223, -198, and -382 exert direct or indirect negative effects on HIV-1 and are reportedly downmodulated during monocyte-to-macrophage differentiation. Here, new experimental results are presented along with reviews and analysis of published studies and publicly available datasets, supporting a broader role of miRNAs in HIV-1 restriction than would be suggested by a simple and uniform downregulation of anti-HIV miRNAs during monocyte-to-macrophage differentiation. Although miR-223 is downregulated in macrophages, other putatively antiviral miRNAs are more abundant in macrophages than in monocytes or are rare and/or variably present in both cell classes. Our analyses point to the need for further studies to determine miRNA profiles of monocytes and macrophages, including classic and newly identified subpopulations; examine the sensitivity of miRNA profiling to cell isolation and differentiation protocols; and characterize rigorously the antiviral effects of previously reported and novel predicted miRNA-HIV-1 interactions in cell-specific contexts.

  6. Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532

    OpenAIRE

    Wardi, Layal; Alaaeddine, Nada; Raad, Issam; Sarkis, Riad; Serhal, Rim; Khalil, Charbel; Hilal, George

    2014-01-01

    Background Considerable progress has been made to understand the association between lifestyle and diet in cancer initiation and promotion. Because excessive glucose consumption is a key metabolic hallmark of cancer cells, glucose restriction (GR) decreases the proliferation, and promotes the differentiation and transformation of cancer cells to quiescent cells. The immortality of cancerous cells is largely assured by telomerase, which is an interesting target for inhibition by BIBR 1532. In ...

  7. XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Monica Yabal

    2014-06-01

    Full Text Available X-linked inhibitor of apoptosis protein (XIAP has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2 in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1β secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap−/− mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1β secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2.

  8. Extra-Low-Frequency Magnetic Fields alter Cancer Cells through Metabolic Restriction

    CERN Document Server

    Li, Ying

    2012-01-01

    Background: Biological effects of extra-low-frequency (ELF) magnetic fields (MF) have lacked a credible mechanism of interaction between MFs and living material. Objectives: Examine the effect of ELF-MFs on cancer cells. Methods: Five cancer cell lines were exposed to ELF-MFs within the range of 0.025 to 5 microT, and the cells were examined for karyotype changes after 6 days. Results: All cancer cells lines lost chromosomes from MF exposure, with a mostly flat dose-response. Constant MF exposures for three weeks allow a rising return to the baseline, unperturbed karyotypes. From this point, small MF increases or decreases are again capable of inducing karyotype contractions. Our data suggests that the karyotype contractions are caused by MF interference with mitochondria's ATP synthase (ATPS), compensated by the action of AMP-activated Protein Kinase (AMPK). The effects of MFs are similar to those of the ATPS inhibitor oligomycin. They are amplified by metformin, an AMPK stimulator, and attenuated by resisti...

  9. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

    DEFF Research Database (Denmark)

    Knudsen, Kasper Jermiin; Rehn, Matilda Carolina; Hasemann, Marie Sigurd;

    2015-01-01

    The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors...

  10. Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1994-01-01

    Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate...

  11. APM_GUI: analyzing particle movement on the cell membrane and determining confinement

    Directory of Open Access Journals (Sweden)

    Menchón Silvia A

    2012-02-01

    Full Text Available Abstract Background Single-particle tracking is a powerful tool for tracking individual particles with high precision. It provides useful information that allows the study of diffusion properties as well as the dynamics of movement. Changes in particle movement behavior, such as transitions between Brownian motion and temporary confinement, can reveal interesting biophysical interactions. Although useful applications exist to determine the paths of individual particles, only a few software implementations are available to analyze these data, and these implementations are generally not user-friendly and do not have a graphical interface,. Results Here, we present APM_GUI (Analyzing Particle Movement, which is a MatLab-implemented application with a Graphical User Interface. This user-friendly application detects confined movement considering non-random confinement when a particle remains in a region longer than a Brownian diffusant would remain. In addition, APM_GUI exports the results, which allows users to analyze this information using software that they are familiar with. Conclusions APM_GUI provides an open-source tool that quantifies diffusion coefficients and determines whether trajectories have non-random confinements. It also offers a simple and user-friendly tool that can be used by individuals without programming skills.

  12. Food Restriction-Induced Changes in Gonadotropin-Inhibiting Hormone Cells are Associated with Changes in Sexual Motivation and Food Hoarding, but not Sexual Performance and Food Intake.

    Science.gov (United States)

    Klingerman, Candice M; Williams, Wilbur P; Simberlund, Jessica; Brahme, Nina; Prasad, Ankita; Schneider, Jill E; Kriegsfeld, Lance J

    2011-01-01

    We hypothesized that putative anorectic and orexigenic peptides control the motivation to engage in either ingestive or sex behaviors, and these peptides function to optimize reproductive success in environments where energy fluctuates. Here, the putative orexigenic peptide, gonadotropin-inhibiting hormone (GnIH, also known as RFamide-related peptide-3), and the putative anorectic hormones leptin, insulin, and estradiol were examined during the course of food restriction. Groups of female Syrian hamsters were restricted to 75% of their ad libitum food intake or fed ad libitum for 4, 8, or 12 days. Two other groups were food-restricted for 12 days and then re-fed ad libitum for 4 or 8 days. After testing for sex and ingestive behavior, blood was sampled and assayed for peripheral hormones. Brains were immunohistochemically double-labeled for GnIH and the protein product of the immediate early gene, c-fos, a marker of cellular activation. Food hoarding, the number of double-labeled cells, and the percent of GnIH-Ir cells labeled with Fos-Ir were significantly increased at 8 and 12 days after the start of food restriction. Vaginal scent marking and GnIH-Ir cell number significantly decreased after the same duration of restriction. Food hoarding, but not food intake, was significantly positively correlated with cellular activation in GnIH-Ir cells. Vaginal scent marking was significantly negatively correlated with cellular activation in GnIH-Ir cells. There were no significant effects of food restriction on plasma insulin, leptin, estradiol, or progesterone concentrations. In the dorsomedial hypothalamus (DMH) of energetically challenged females, strong projections from NPY-Ir cells were found in close apposition to GnIH-Ir cells. Together these results are consistent with the idea that metabolic signals influence sexual and ingestive motivation via NPY fibers that project to GnIH cells in the DMH. PMID:22649396

  13. Food restriction-induced changes in gonadotropin-inhibiting hormone-immunoreactive cells are associated with sexual motivation and food hoarding, but not sexual performance and food intake

    Directory of Open Access Journals (Sweden)

    CandiceMKlingerman

    2011-12-01

    Full Text Available We hypothesized that putative anorectic and orexigenic peptides control the motivation to engage in either ingestive or sex behaviors, and these peptides function to optimize reproductive success in environments where energy fluctuates. Here, the putative orexigenic peptide, gonadotropin-inhibiting hormone (GnIH, also known as RFamide-related peptide-3 and the putative anorectic hormones leptin, insulin and estradiol were examined during the course of food restriction. Groups of female Syrian hamsters were restricted to 75% of their ad libitum food intake or fed ad libitum for 4, 8, or 12 days. Two other groups were food restricted for 12 days and then re-fed ad libitum for 4 or 8 days. After testing for sex and ingestive behavior, blood was sampled and assayed for peripheral hormones. Brains were immunohistochemically double-labeled for GnIH and the protein product of the immediate early gene, c-fos, a marker of cellular activation. Food hoarding, the number of double-labeled cells, and the percent of GnIH-Ir cells labeled with Fos-Ir were significantly increased at 8 and 12 days after the start of food restriction. Vaginal scent marking and GnIH-Ir cell number significantly decreased after the same duration of restriction. Food hoarding, but not food intake, was significantly positively correlated with cellular activation in GnIH-Ir cells. Vaginal scent marking was significantly negatively correlated with cellular activation in GnIH-Ir cells. There were no significant effects of food restriction on plasma insulin, leptin, estradiol, or progesterone concentrations. In the dorsomedial hypothalamus (DMH of energetically-challenged females, strong projections from NPY-Ir cells were found in close apposition to GnIH-Ir cells. Together these results are consistent with the idea that metabolic signals influence sexual and ingestive motivation via NPY fibers that project to GnIH cells in the DMH.

  14. Initial presentation of CNS-restricted acute lymphoblastic B cell leukaemia as peripheral polyneuropathy.

    Science.gov (United States)

    Piovezani Ramos, Guilherme; Villasboas Bisneto, Jose C; Chen, Dong; Pardanani, Animesh

    2016-01-01

    We report a case of a 58-year-old woman who presented with a 1-month course of progressive lower and upper extremity weakness in addition to binocular diplopia. Diagnostic lumbar puncture revealed atypical lymphoid cells with 28% blasts. Immunophenotype was consistent with B cell acute lymphoblastic leukaemia (B-ALL). Further work up showed no systemic involvement but extensive thoracolumbar-sacral leptomeningeal disease. The patient was treated with several courses of intrathecal and systemic chemotherapy followed by craniospinal irradiation for consolidation. There was initial steady improvement in neurological symptoms and leptomeningeal disease, the latter being ascertained through radiological studies and cerebrospinal fluid examination. After 10 months of response, the patient relapsed with central nervous system (CNS) and systemic disease. B-ALL is a rare precursor lymphoid neoplasm that generally presents with systemic disease. While CNS involvement is not uncommon, isolated involvement of this compartment without systemic disease is exceedingly rare. PMID:27095809

  15. SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions.

    Science.gov (United States)

    Pucci, Ferdinando; Garris, Christopher; Lai, Charles P; Newton, Andita; Pfirschke, Christina; Engblom, Camilla; Alvarez, David; Sprachman, Melissa; Evavold, Charles; Magnuson, Angela; von Andrian, Ulrich H; Glatz, Katharina; Breakefield, Xandra O; Mempel, Thorsten R; Weissleder, Ralph; Pittet, Mikael J

    2016-04-01

    Tumor-derived extracellular vesicles (tEVs) are important signals in tumor-host cell communication, yet it remains unclear how endogenously produced tEVs affect the host in different areas of the body. We combined imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular, and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169(+) macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169(+) macrophage layer physically blocks tEV dissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the lymph node cortex, interact with B cells, and foster tumor-promoting humoral immunity. Thus, CD169(+) macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity. PMID:26989197

  16. Drosophila Pez acts in Hippo signaling to restrict intestinal stem cell proliferation

    DEFF Research Database (Denmark)

    Poernbacher, Ingrid; Baumgartner, Roland; Marada, Suresh K;

    2012-01-01

    The conserved Hippo signaling pathway acts in growth control and is fundamental to animal development and oncogenesis. Hippo signaling has also been implicated in adult midgut homeostasis in Drosophila. Regulated divisions of intestinal stem cells (ISCs), giving rise to an ISC and an enteroblast...... (EB) that differentiates into an enterocyte (EC) or an enteroendocrine (EE) cell, enable rapid tissue turnover in response to intestinal stress. The damage-related increase in ISC proliferation requires deactivation of the Hippo pathway and consequential activation of the transcriptional coactivator...... pathway activity specifically in the fly midgut epithelium. Thus, Pez displays a tissue-specific requirement and functions as a negative upstream regulator of Yki in the regulation of ISC proliferation....

  17. Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell

    OpenAIRE

    Barbato, Daniele Lettieri; Tatulli, Giuseppe; Aquilano, Katia; Ciriolo, Maria R.

    2015-01-01

    Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the ex...

  18. E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction

    OpenAIRE

    Yang, Qi; Esplin, Brandt; Borghesi, Lisa

    2011-01-01

    The immune system is replenished by self-renewing hematopoietic stem cells (HSCs) that produce multipotent progenitors (MPPs) with little renewal capacity. E-proteins, the widely expressed basic helix-loop-helix transcription factors, contribute to HSC and MPP activity, but their specific functions remain undefined. Using quantitative in vivo and in vitro approaches, we show that E47 is dispensable for the short-term myeloid differentiation of HSCs but regulates their long-term capabilities. ...

  19. Dexamethasone-induced cell death is restricted to specific molecular subgroups of multiple myeloma

    OpenAIRE

    Kervoëlen, Charlotte; Ménoret, Emmanuelle; Gomez-Bougie, Patricia; Bataille, Régis; Godon, Catherine; Marionneau-Lambot, Séverine; Moreau, Philippe; Pellat-Deceunynck, Catherine; Amiot, Martine

    2015-01-01

    Due to its cytotoxic effect in lymphoid cells, dexamethasone is widely used in the treatment of multiple myeloma (MM). However, only a subset of myeloma patients responds to high-dose dexamethasone. Despite the undeniable anti-myeloma benefits of dexamethasone, significant adverse effects have been reported. We re-evaluate the anti-tumor effect of dexamethasone according to the molecular heterogeneity of MM. We demonstrated that the pro-death effect of dexamethasone is related to the genetic ...

  20. Oncogenic transformation of rat lung epithelioid cells by SV40 DNA and restriction enzyme fragments

    International Nuclear Information System (INIS)

    Rat epithelioid lung cells were transformed with various preparations of SV40 DNA using the Ca2+-precipitation technique. The amount of SV40 genetic information integrated into transformed clones was evaluated by DNA-DNA renaturation kinetics. The growth properties on plastic and in soft-agar were examined, as well as the ability to induce tumors in syngeneic newborn animals or in adult nude mice. One particular transformed line, which had received the HpaII/BamHIA (59 per cent) fragment, was found to contain about 3 integrated copies of this fragment per cell and no significant amount of the HpaII/BamHIB (41 per cent fragment). This line which grew to high saturatio densities and efficiently formed clones in low serum on plastic, produced tumors in both syngeneic rats and nude mice. Thus the HpaII/BamHIA fragment, which mainly includes early viral information, was sufficient to impart these properties to rat epithelioid lung cells. (author)

  1. Activation of Nonclassical CD1d-Restricted NK T Cells Induces Airway Hyperreactivity in β2-Microglobulin-Deficient Mice1

    Science.gov (United States)

    Meyer, Everett H.; Pichavant, Muriel; Akbari, Omid; Yasumi, Takahiro; Savage, Paul B.; DeKruyff, Rosemarie H.; Umetsu, Dale T.

    2016-01-01

    Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in β2-microglobulin (β2m)−/− mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1+ noninvariant TCR NKT cell population is present in β2m−/− mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of β2m−/− mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to α-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a β2m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR. PMID:18802058

  2. Restricted Airspace

    Data.gov (United States)

    Federal Laboratory Consortium — Redstone Technical Test Center has restricted airspace up to 30,000 feet ASL. Airspace encompasses R-2104 (Redstone). Airspace is used extensively for airborne/UAV...

  3. Restrictive glycosylphosphatidylinositol anchor synthesis in cwh6/gpi3 yeast cells causes aberrant biogenesis of cell wall proteins.

    OpenAIRE

    Vossen, J.H.; Müller, W. H.; Lipke, P N; Klis, F. M.

    1997-01-01

    We previously reported that the defects in the Saccharomyces cerevisiae cwh6 Calcofluor white-hypersensitive cell wall mutant are caused by a mutation in SPT14/GPI3, a gene involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Here we describe the effect of cwh6/spt14/gpi3 on the biogenesis of cell wall proteins. It was found that the release of precursors of cell wall proteins from the endoplasmic reticulum (ER) was retarded. This was accompanied by proliferation of ER structur...

  4. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    DEFF Research Database (Denmark)

    Longo Martins, Murillo; Ignazzi, Rosanna; Eckert, Juergen;

    2016-01-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer...... drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with...

  5. Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell.

    Science.gov (United States)

    Barbato, Daniele Lettieri; Tatulli, Giuseppe; Aquilano, Katia; Ciriolo, Maria R

    2015-10-01

    Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the expression of mitochondrial- and nuclear-encoded oxidative phosphorylation genes as well as mitochondrial stress defensive proteins (UCP1, SOD2). Such adaptation is placed in a canonical mitohormetic response that proceeds via mitochondrial reactive oxygen species ((mt)ROS) production and redistribution of FoxO1 transcription factor into nucleus. Nuclear FoxO1 ((n)FoxO1) mediates retrograde communication by inducing the expression of mitochondrial oxidative and stress defensive genes. Collectively, our findings describe an unusual white/beige fat cell response to nutrient availability highlighting another health-promoting mechanism of fasting. PMID:26540513

  6. Influence of dietary nucleotide restriction on bacterial sepsis and phagocytic cell function in mice.

    Science.gov (United States)

    Kulkarni, A D; Fanslow, W C; Drath, D B; Rudolph, F B; Van Buren, C T

    1986-02-01

    Although enzyme defects in purine metabolism have revealed the importance of these substrates to maintenance of a normal immune response, the role of exogenous nucleotides on the cells that mediate the host defense system has remained largely unexplored. Recent investigations have revealed that dietary nucleotides are vital to the maintenance of cell-mediated responses to antigen stimulation. To test the influence of dietary nucleotide deprivation on resistance to infection, Balb/c mice were maintained on chow, a nucleotide-free (NF) diet, or an NF diet repleted with adenine, uracil, or RNA. Mice on the NF diet suffered 100% mortality following intravenous challenge with Staphylococcus aureus, while chow-fed and RNA- or uracil-repleted mice demonstrated significantly greater resistance to this bacterial challenge. Macrophages from mice on the NF diet had decreased phagocytic activity as measured by uptake of radiolabeled bacteria compared with mice maintained on the NF diet supplemented with adenine, uracil, or RNA. No change in S aureus antibody response was noted on the various diets. Although the mechanism of this suppression of nonspecific immunity remains unclear, provision of nucleotides to defined diets appears vital to maintain host resistance to bacterial challenge. PMID:3947217

  7. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells.

    Science.gov (United States)

    Diehl, Gretchen E; Longman, Randy S; Zhang, Jing-Xin; Breart, Beatrice; Galan, Carolina; Cuesta, Adolfo; Schwab, Susan R; Littman, Dan R

    2013-02-01

    The intestinal microbiota has a critical role in immune system and metabolic homeostasis, but it must be tolerated by the host to avoid inflammatory responses that can damage the epithelial barrier separating the host from the luminal contents. Breakdown of this regulation and the resulting inappropriate immune response to commensals are thought to lead to the development of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. We proposed that the intestinal immune system is instructed by the microbiota to limit responses to luminal antigens. Here we demonstrate in mice that, at steady state, the microbiota inhibits the transport of both commensal and pathogenic bacteria from the lumen to a key immune inductive site, the mesenteric lymph nodes (MLNs). However, in the absence of Myd88 or under conditions of antibiotic-induced dysbiosis, non-invasive bacteria were trafficked to the MLNs in a CCR7-dependent manner, and induced both T-cell responses and IgA production. Trafficking was carried out by CX(3)CR1(hi) mononuclear phagocytes, an intestinal-cell population previously reported to be non-migratory. These findings define a central role for commensals in regulating the migration to the MLNs of CX(3)CR1(hi) mononuclear phagocytes endowed with the ability to capture luminal bacteria, thereby compartmentalizing the intestinal immune response to avoid inflammation. PMID:23334413

  8. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage

    DEFF Research Database (Denmark)

    Gold, Marielle C.; McLaren, James E.; Reistetter, Joseph A.;

    2015-01-01

    line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of...

  9. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage

    DEFF Research Database (Denmark)

    Gold, Marielle C.; McLaren, James E.; Reistetter, Joseph A.;

    2014-01-01

    line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of...

  10. Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell.

    OpenAIRE

    Langer, G. A.; Peskoff, A

    1996-01-01

    We model the space between the junctional sarcoplasmic reticulum (JSR) membrane and the inner leaflet of the transverse tubular ("T") sarcolemmal (SL) membrane, the diadic cleft, with respect to calcium (Ca) concentration and movement. The model predicts the following: 1) Ca influx via the "L" channel increases [Ca] to 1 microM within a distance of 50 nm from the channel mouth in < 500 microseconds. This is sufficient to trigger Ca release from a domain of 9 "feet." 2) By contrast, "reverse" ...

  11. Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicity.

    Science.gov (United States)

    Antoine, Daniel James; Williams, Dominic P; Kipar, Anja; Laverty, Hugh; Park, B Kevin

    2010-01-01

    Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-dependent cysteine 106 oxidation within high mobility group box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of immune activation. In fed mice treated with APAP, necrosis was the dominant form of hepatocyte death. However, apoptosis was also observed, indicated by K18 cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence of hepatocyte death was observed only in fasted mice treated with APAP or fed mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in the induction of inflammation was confirmed with an HMGB1-neutralizing antibody. The differential response between fasted and fed mice was a consequence of a significant reduction in basal hepatic ATP, which prevented caspase processing, rather than glutathione depletion or altered APAP metabolism. Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology. PMID:20811657

  12. Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production

    Directory of Open Access Journals (Sweden)

    Longo Dan L

    2011-03-01

    Full Text Available Abstract Background Intermittent fasting (IF improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects. Objective A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects. Design In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15 were maintained for 2 months on controlled on-site one meal per day (OMD or three meals per day (TMD isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay. Results There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets. Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet. Conclusions PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.

  13. Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens.

    Science.gov (United States)

    Meermeier, Erin W; Laugel, Bruno F; Sewell, Andrew K; Corbett, Alexandra J; Rossjohn, Jamie; McCluskey, James; Harriff, Melanie J; Franks, Tamera; Gold, Marielle C; Lewinsohn, David M

    2016-01-01

    Mucosal-associated invariant T (MAIT) cells are thought to detect microbial antigens presented by the HLA-Ib molecule MR1 through the exclusive use of a TRAV1-2-containing TCRα. Here we use MR1 tetramer staining and ex vivo analysis with mycobacteria-infected MR1-deficient cells to demonstrate the presence of functional human MR1-restricted T cells that lack TRAV1-2. We characterize an MR1-restricted clone that expresses the TRAV12-2 TCRα, which lacks residues previously shown to be critical for MR1-antigen recognition. In contrast to TRAV1-2(+) MAIT cells, this TRAV12-2-expressing clone displays a distinct pattern of microbial recognition by detecting infection with the riboflavin auxotroph Streptococcus pyogenes. As known MAIT antigens are derived from riboflavin metabolites, this suggests that TRAV12-2(+) clone recognizes unique antigens. Thus, MR1-restricted T cells can discriminate between microbes in a TCR-dependent manner. We postulate that additional MR1-restricted T-cell subsets may play a unique role in defence against infection by broadening the recognition of microbial metabolites. PMID:27527800

  14. Amelioration of neuronal cell death in a spontaneous obese rat model by dietary restriction through modulation of ubiquitin proteasome system.

    Science.gov (United States)

    Shruthi, Karnam; Reddy, S Sreenivasa; Reddy, P Yadagiri; Shivalingam, Potula; Harishankar, Nemani; Reddy, G Bhanuprakash

    2016-07-01

    Dietary restriction (DR) has been shown to increase longevity, delay onset of aging, reduce DNA damage and oxidative stress and prevent age-related decline of neuronal activity. We previously reported the role of altered ubiquitin proteasome system (UPS) in the neuronal cell death in a spontaneous obese rat model (WNIN/Ob rat). In this study, we investigated the effect of DR on obesity-induced neuronal cell death in a rat model. Two groups of 40-day-old WNIN/Ob rats were either fed ad libitum (Ob) or pair-fed with lean. The lean phenotype of WNIN/Ob rats served as ad libitum control. These animals were maintained for 6.5months on their respective diet regime. At the end of the study, cerebral cortex was collected and markers of UPS, endoplasmic reticulum (ER) stress and autophagy were analyzed by quantitative real-time polymerase chain reaction, immunoblotting and immunohistochemistry. Chymotrypsin-like activity of proteasome was assayed by the fluorimetric method. Apoptotic cells were analyzed by TUNEL assay. DR improved metabolic abnormalities in obese rats. Alterations in UPS (up-regulation of UCHL1, down-regulation of UCHL5, declined proteasomal activity), increased ER stress, declined autophagy and increased expression of α-synuclein, p53 and BAX were observed in obese rats and DR alleviated these changes in obese rats. Further, DR decreased TUNEL-positive cells. In conclusion, DR in obese rats could not only restore the metabolic abnormalities but also preserved neuronal health in the cerebral cortex by preventing alterations in the UPS. PMID:27260470

  15. Propranolol Restricts the Mobility of Single EGF-Receptors on the Cell Surface before Their Internalization

    Science.gov (United States)

    Otero, Carolina; Linke, Max; Sanchez, Paula; González, Alfonso; Schaap, Iwan A. T.

    2013-01-01

    The epidermal growth factor receptor is involved in morphogenesis, proliferation and cell migration. Its up-regulation during tumorigenesis makes this receptor an interesting therapeutic target. In the absence of the ligand, the inhibition of phosphatidic acid phosphohydrolase activity by propranolol treatment leads to internalization of empty/inactive receptors. The molecular events involved in this endocytosis remain unknown. Here, we quantified the effects of propranolol on the mobility of single quantum-dot labelled receptors before the actual internalization took place. The single receptors showed a clear stop-and-go motion; their diffusive tracks were continuously interrupted by sub-second stalling events, presumably caused by transient clustering. In the presence of propranolol we found that: i) the diffusion rate reduced by 22 %, which indicates an increase in drag of the receptor. Atomic force microscopy measurements did not show an increase of the effective membrane tension, such that clustering of the receptor remains the likely mechanism for its reduced mobility. ii) The receptor got frequently stalled for longer periods of multiple seconds, which may signal the first step of the internalization process. PMID:24349439

  16. Induction of DNA double-strand breaks by restriction enzymes in X-ray-sensitive mutant Chinese hamster ovary cells measured by pulsed-field gel electrophoresis

    International Nuclear Information System (INIS)

    This investigation was designed to determine whether the cytotoxic effects of different restriction endonucleases are related to the number and type of DNA double-strand breaks (DSBs) they produce. Chinese hamster ovary (CHO) K1 and xrs-5 cells, a radiosensitive mutant of CHO K1, were exposed to restriction endonucleases HaeIII, HinfI, PvuII and BamHI by electroporation. These enzymes represent both blunt and sticky end cutters with differing recognition sequence lengths. The number of DSBs was measured by pulsed-field gel electrophoresis (PFGE). Two forms of PFGE were employed: asymmetric field-inversion gel electrophoresis (AFIGE) for measuring the kinetics of DNA breaks by enzyme digestion and clamped homogeneous gel electrophoresis (CHEF) for examining the size distributions of damaged DNA. The amount of DNA damage induced by exposure to all four restriction enzymes was significantly greater in xrs-5 compared to CHO K1 cells, consistent with the reported DSB repair deficiency in these cells. Since restriction endonucleases produce DSBs alone as opposed to the various types of DNA damage induced by X rays, these results confirm that the repair defect in this mutant involves the rejoining of DSBs. Although the cutting frequency was directly related to the length of the recognition sequence for four restriction enzymes, there was no simple correlation between the cytotoxic effect and the amount of DNA damage produced by each enzyme in either cell line. This finding suggests that the type or nature of the cutting sequence itself may play a role in restriction enzyme-induced cell killing. 32 refs., 6 figs., 3 tabs

  17. Failure to detect a DNA repair-related defect in the transfection of ataxia-telangiectasia cells by enzymatically restricted plasmid

    International Nuclear Information System (INIS)

    Two SV40-transformed human fibroblast cell lines were transfected with plasmids in which double-strand breaks had been introduced by restriction enzymes, within or near the selected gene. Restriction of pSV2gpt with KpnI reduced the frequency of transfection more in the ionizing radiation-sensitive ataxia-telangiectasia line AT5BIVA than in the resistant line MRC5V1. When the related plasmid pSV2neo was restricted with SmaI, the reduction in transfection was less in the ataxia-telangiectasia than in the normal cells. The apparent defect in transfection of AT5BIVA by pSV2gpt appeared to be a result of the unusual sensitivity of the repair-deficient recipient to the selective agent. Loss of potential transfectants is exacerbated when transient gene expression is reduced by restriction of the plasmid. It is suggested that a reduction in yield of transfectants with restricted plasmid in ataxia-telangiectasia cells cannot readily be used as evidence of a defect in DNA repair. The results are also relevant to standard transfection experiments; they emphasize the importance of optimizing selection when transient expression may be reduced, to ensure that potential transfectants are not killed by the selection regime. (author)

  18. Oxygen restriction increases the infective potential of Listeria monocytogenes in vitro in Caco-2 cells and in vivo in guinea pigs

    Directory of Open Access Journals (Sweden)

    Licht Tine

    2007-06-01

    Full Text Available Abstract Background Listeria monocytogenes has been implicated in several food borne outbreaks as well as sporadic cases of disease. Increased understanding of the biology of this organism is important in the prevention of food borne listeriosis. The infectivity of Listeria monocytogenes ScottA, cultivated with and without oxygen restriction, was compared in vitro and in vivo. Fluorescent protein labels were applied to allow certain identification of Listeria cells from untagged bacteria in in vivo samples, and to distinguish between cells grown under different conditions in mixed infection experiments. Results Infection of Caco-2 cells revealed that Listeria cultivated under oxygen-restricted conditions were approximately 100 fold more invasive than similar cultures grown without oxygen restriction. This was observed for exponentially growing bacteria, as well as for stationary-phase cultures. Oral dosage of guinea pigs with Listeria resulted in a significantly higher prevalence (p Listeria in fecal samples was observed after dosage with oxygen-restricted bacteria. These differences were seen after challenge with single Listeria cultures, as well as with a mixture of two cultures grown with and without oxygen restriction. Conclusion Our results show for the first time that the environmental conditions to which L. monocytogenes is exposed prior to ingestion are decisive for its in vivo infective potential in the gastrointestinal tract after passage of the gastric barrier. This is highly relevant for safety assessment of this organism in food.

  19. Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels

    DEFF Research Database (Denmark)

    Poulsen, Kristian Arild; Andersen, E C; Hansen, C F;

    2010-01-01

    Changes in cell volume and ion gradients across the plasma membrane play a pivotal role in the initiation of apoptosis. Here we explore the kinetics of apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT...... was further reduced. AVD(1) and AVD(2) were coupled to net loss of Cl(-), K(+), Na(+), and amino acids (ninhydrin-positive substances), whereas during AVD(T), Na(+) and Cl(-) were accumulated. MDR EATC was resistant to cisplatin, showing increased viability and less caspase 3 activation. Compared with...... AVD, primarily via modulation of NaCl movements, contribute to protection against apoptosis in MDR EATC....

  20. The study of responses to 'model' DNA breaks induced by restriction endonucleases in cells and cell-free systems: achievements and difficulties

    International Nuclear Information System (INIS)

    The use of restriction endonucleases (RE) as a means of implicating DNA double-strand breaks (dsb) in cellular responses is reviewed. The introduction of RE into cells leads to many of the responses known to be characteristic of radiation damage -cell killing, chromosomal aberration, oncogenic transformation, gene mutation and amplification. Additionally, radiosensitive cell lines are hypersensitive to RE, including those from the human disorder ataxia-telangiectasia. However, quantitation of response and comparisons of the effectiveness of different RE are difficult, partly because of unknown activity and lifetime of RE in the cell. Re-induced dsb have also been used to reveal molecular mechanisms of repair and misrepair at specific sites in DNA. Dsb have been implicated in recombination processes including those leading to illegitimate rejoining (formation of deletions and rearrangements) at short sequence features in DNA. Also model dsb act as a signal to activate other cellular processes, which may influence or indirectly cause some responses, including cell death. In these signalling responses the detailed chemistry at the break site may not be very important, perhaps explaining why there is considerable overlap in responses to RE and to ionizing radiations. (author)

  1. The ability of PVX p25 to form RL structures in plant cells is necessary for its function in movement, but not for its suppression of RNA silencing.

    Directory of Open Access Journals (Sweden)

    Fei Yan

    Full Text Available The p25 triple gene block protein of Potato virus X (PVX is multifunctional, participating in viral movement and acting as a suppressor of RNA silencing. The cell-to-cell movement of PVX is known to depend on the suppression function of p25. GFP-fused p25 accumulates in rod-like (RL structures with intense fluorescence in cells. By monitoring the location of fluorescence at different times, we have now shown that the RL structure is composed of filaments. P25 mutants without the conditional ability to recover movement function could not form RL structures while the mutants that had the ability did form the structure, suggesting that the ability of p25 to form RL structures is necessary for its function in cell-to-cell movement, but not for its suppressor function. Moreover, chemical inhibition of microfilaments in cells destroyed the formation of the complete RL structure. Additionally, TGBp2 and TGBp3 were recruited into the RL structure, suggesting a relationship between the TGBps in virus movement.

  2. Restrictive dermopathy and fetal behaviour

    NARCIS (Netherlands)

    Mulder, EJH; Beemer, FA; Stoutenbeek, P

    2001-01-01

    We report three siblings from consecutive pregnancies affected with restrictive dermopathy (RD). During the second pregnancy, fetal behavioural development and growth were studied extensively using ultrasound at 1-4 week intervals. Dramatic and sudden changes occurred in fetal body movements and gro

  3. Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.

    Directory of Open Access Journals (Sweden)

    Anne Frentzen

    2011-04-01

    Full Text Available Hepatitis C virus (HCV is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.

  4. Caloric Restriction reduces inflammation and improves T cell-mediated immune response in obese mice but concomitant consumption of curcumin/piperine adds no further benefit

    Science.gov (United States)

    Obesity is associated with low-grade inflammation and impaired immune response. Caloric restriction (CR) has been shown to inhibit inflammatory response and enhance cell-mediated immune function. Curcumin, the bioactive phenolic component of turmeric spice, is proposed to have anti-obesity and anti-...

  5. Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen.

    Science.gov (United States)

    McCormack, Ryan; Bahnan, Wael; Shrestha, Niraj; Boucher, Justin; Barreto, Marcella; Barrera, Carlos M; Dauer, Edward A; Freitag, Nancy E; Khan, Wasif N; Podack, Eckhard R; Schesser, Kurt

    2016-04-01

    The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1,Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogenListeria monocytogenes Within a few hours of systemic infection, the massive proliferation ofL. monocytogenesinPerforin-2(-/-)mice leads to a rapid appearance of acute disease symptoms. We go on to show in culturedPerforin-2(-/-)cells that the vacuole-to-cytosol transitioning ofL. monocytogenesis greatly accelerated. Unexpectedly, we found that inPerforin-2(-/-)macrophages,Listeria-containing vacuoles quickly (≤15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation ofL. monocytogenesto its replicative niche in the cytosol. This hypothesis was supported by our finding that aL. monocytogenesstrain expressing virulence factors at a constitutively high level replicated equally well inPerforin-2(+/+)andPerforin-2(-/-)macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification ofListeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity. PMID:26831467

  6. Cell biology in orthodontic tooth movement: The known and the unknown

    Institute of Scientific and Technical Information of China (English)

    REN Yi-jin

    2005-01-01

    This review is aimed at providing, at the cellular level, a concise and complete overview of the important knowledge on the mechanism of orthodontic tooth movement to orthodontists and postgraduates who are involved or interested in basic research. The construction of this article was oriented to the following key questions: Where an osteoclast starts to its first resorption site? When the cascade of a resorption cycle starts? What are the factors involved in bone remodeling and how they orchestrate? What happens before and after the formation of a resorption pit? Major findings in these aspects were summarized and discussed. In addition, related biological phenomenon such as orthodontically induced root resorption was intensively reviewed. By means of an updated and systematic review, the author intended to introduce more biological evidence to orthodontic intervention and to encourage evidence-based treatment in daily orthodontic practice.

  7. Rapid Antigen Processing and Presentation of a Protective and Immunodominant HLA-B*27-restricted Hepatitis C Virus-specific CD8+ T-cell Epitope

    OpenAIRE

    Julia Schmidt; Iversen, Astrid K N; Stefan Tenzer; Emma Gostick; Price, David A.; Volker Lohmann; Ute Distler; Paul Bowness; Hansjörg Schild; Blum, Hubert E.; Paul Klenerman; Christoph Neumann-Haefelin; Robert Thimme

    2012-01-01

    HLA-B*27 exerts protective effects in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. While the immunological and virological features of HLA-B*27-mediated protection are not fully understood, there is growing evidence that the presentation of specific immunodominant HLA-B*27-restricted CD8+ T-cell epitopes contributes to this phenomenon in both infections. Indeed, protection can be linked to single immunodominant CD8+ T-cell epitopes and functional constraints on e...

  8. Shadowing on Apollo 12 Solar Cells and Possible Movement of the ALSEP Central Station

    Science.gov (United States)

    Berman, Paul A.; Williams, David R.

    2014-01-01

    A fortuitous arrangement of a west-facing solar cell and a bracket on the Apollo 12 ALSEP (Apollo Lunar Surface Experiments Package) has allowed us to precisely determine the relative position of the Sun near sunset relative to the Apollo 12 central station over a period of nearly 8 years. The small bracket, mounted on the central station due west of the cell, casts a shadow on the cell near sunset, decreasing the output of the cell proportional to the area of shadow covering the cell. The pattern of shadowing by the bracket gives good agreement with the known change of solar azimuth on a yearly timescale, but the pattern gradually but constantly changed from year-to-year, in a manner inconsistent with the known and changing position of the Sun.

  9. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    OpenAIRE

    1984-01-01

    The presence in athymic nude mice of precursor T cells with self- recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate ...

  10. Entamoeba histolytica cell movement: A central role for self-generated chemokines and chemorepellents

    OpenAIRE

    Zaki, Mehreen; Andrew, Natalie; Insall, Robert H.

    2006-01-01

    Entamoeba histolytica cells, the cause of amoebic dysentery, are highly motile, and this motility is an essential feature of the pathogenesis and morbidity of amoebiasis. However, the control of E. histolytica motility within the gut and during invasion is poorly understood. We have used an improved chemotaxis assay to identify the key extracellular signals mediating Entamoeba chemotaxis. The dominant responses we observe are caused by factors generated by E. histolytica cells themselves. Med...

  11. Movement as utopia.

    Science.gov (United States)

    Couton, Philippe; López, José Julián

    2009-10-01

    Opposition to utopianism on ontological and political grounds has seemingly relegated it to a potentially dangerous form of antiquated idealism. This conclusion is based on a restrictive view of utopia as excessively ordered panoptic discursive constructions. This overlooks the fact that, from its inception, movement has been central to the utopian tradition. The power of utopianism indeed resides in its ability to instantiate the tension between movement and place that has marked social transformations in the modern era. This tension continues in contemporary discussions of movement-based social processes, particularly international migration and related identity formations, such as open borders transnationalism and cosmopolitanism. Understood as such, utopia remains an ongoing and powerful, albeit problematic instrument of social and political imagination. PMID:20027697

  12. Molecular mapping of interactions between a Mycobacterium leprae-specific T cell epitope, the restricting HLA-DR2 molecule, and two specific T cell receptors.

    Science.gov (United States)

    Anderson, D C; van Schooten, W C; Janson, A; Barry, M E; de Vries, R R

    1990-04-01

    A systematic series of 89 single residue substitution analogs of the Mycobacterium leprae 65-kDa protein-derived peptide LQAAPALDKL were tested for stimulation of two HLA-DR2 restricted 65 kDa-reactive T cell clones from a tuberculoid leprosy patient. Some analogs with substitutions outside a "core" region showed enhanced stimulation of the T cell clones. This core region of seven or eight residues was essential for recognition, whereas substitution of amino acids outside this region did not affect T cell recognition although these residues could not be omitted. Thus these core residues interact directly with the presenting HLA-DR2 molecule and/or the TCR. Except for analogs of position 419 for clone 2B6, the majority of the nonstimulatory substitution analogs did not inhibit the presentation of LQAAPALDKL and thus probably failed to bind to the HLA-DR2 molecule. Unless all of the core residues are physically involved in binding to DR2, substitution at a position not directly involved in binding appears to have an influence on other residues that do bind to the DR2 molecule. Active peptide analogs with two or more internal prolines suggest that not all analogs need be helical for activity with clone 2F10. PMID:1690768

  13. Live-Cell Imaging of Dual-Labeled Golgi Stacks in Tobacco BY-2 Cells Reveals Similar Behaviors for Different Cisternae during Movement and Brefeldin A Treatment

    Institute of Scientific and Technical Information of China (English)

    Stephanie L. Madison; Andreas Nebenführ

    2011-01-01

    In plant cells,the Golgi apparatus consists of numerous stacks that,in turn,are composed of several flattened cisternae with a clear cis-to-trans polarity.During normal functioning within living cells,this unusual organelle displays a wide range of dynamic behaviors such as whole stack motility,constant membrane flux through the cisternae,and Golgi enzyme recycling through the ER.In order to further investigate various aspects of Golgi stack dynamics and integrity,we co-expressed pairs of established Golgi markers in tobacco BY-2 cells to distinguish sub-compartments of the Golgi during monensin treatments,movement,and brefeldin A (BFA)-induced disassembly.A combination of cis and trans markers revealed that Golgi stacks remain intact as they move through the cytoplasm.The Golgi stack orientation during these movements showed a slight preference for the cis side moving ahead,but trans cisternae were also found at the leading edge.During BFA treatments,the different sub-compartments of about half of the observed stacks fused with the ER sequentially; however,no consistent order could be detected.In contrast,the ionophore monensin resulted in swelling of trans cisternae while medial and particularly cis cisternae were mostly unaffected.Our results thus demonstrate a remarkable equivalence of the different cisternae with respect to movement and BFA-induced fusion with the ER.In addition,we propose that a combination of dual-label fluorescence microscopy and drug treatments can provide a simple alternative approach to the determination of protein localization to specific Golgi sub-compartments.

  14. Caloric restriction.

    Science.gov (United States)

    Speakman, John R; Mitchell, Sharon E

    2011-06-01

    Restricting the intake of calories has been practiced as a method for increasing both the length and quality of life for over 500 years. Experimental work confirming the success of this approach in animals has accumulated over the last 100 years. Lifelong caloric restriction (CR) may extend life by up to 50% in rodents, with progressively less impact the later in life it is started. This effect is matched by profound impacts on age related diseases including reduced risk of cancer, neurodegenerative disorders, autoimmune disease, cardiovascular disease and type II diabetes mellitus. The disposable soma theory of ageing suggests that CR evolved as a somatic protection response to enable animals to survive periods of food shortage. The shutdown of reproductive function during CR is consistent with this suggestion, but other features of the phenomenon are less consistent with this theory, and some have suggested that in rodents it may be mostly an artifact of domestication. CR induces profound effects on animals at all levels from the transcriptome to whole animal physiology and behavior. Animals under CR lose weight which is disproportionately contributed to by white adipose tissue. Generally animals on CR change their activity patterns so that they are more active prior to food delivery each day but total activity may be unchanged or reduced. Considerable debate has occurred over the effects of CR on resting metabolic rate (RMR). Total RMR declines, but as body mass and body composition also change it is unclear whether metabolism at the tissue level also declines, is unchanged or even increases. Body temperature universally decreases. Hunger is increased and does not seem to abate even with very long term restriction. Circulating adipokines are reduced reflecting the reduction in white adipose tissue (WAT) mass under restriction and there is a large reduction in circulating insulin and glucose levels. There are profound tissue level changes in metabolism with a

  15. In vitro and in vivo analyses of a genetically—restricted antigen specific factor from mixed cell cultures of macrophage,T and B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    CHAURMW; LAUASK

    1990-01-01

    An immunostimulatory factor was identified to be secreted by antigen-pulsed macrophages.This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo.Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a geneticallyrestricted antigen specific factor (ASF).The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-qulsed macrophages with T lymphocytes,and then spleen cells,and finally the TNP-coated sheep red blood cells.

  16. Coupling of protein localization and cell movements by a dynamically localized response regulator in Myxococcus xanthus

    DEFF Research Database (Denmark)

    Leonardy, Simone; Freymark, Gerald; Hebener, Sabrina;

    2007-01-01

    Myxococcus xanthus cells harbor two motility machineries, type IV pili (Tfp) and the A-engine. During reversals, the two machineries switch polarity synchronously. We present a mechanism that synchronizes this polarity switching. We identify the required for motility response regulator (RomR) as ...

  17. Periodic Colony Formation of Bacteria Due to their Cell Reproduction and Movement

    Science.gov (United States)

    Itoh, H.; Wakita, J.; Watanabe, K.; Matsuyama, T.; Matsushita, M.

    We have experimentally investigated periodic pattern formation produced by bacterial species Proteus mirabilis, which forms concentric-ring-like colonies by repeating migration and rest alternately on the surface of a solid agar medium. We distinguish three phases (initial lag phase, the following migration and consolidation phases that appear alternately) for the colony growth. Here we mainly used physical approaches in order to try to understand the formation of concentric-ring-like colonies, such as cutting the part of a colony during its growth. Global chemical signals governing the colony formation from the center were not found. We also checked phase entrainment quantitatively by letting two colonies collide with each other and confirmed that it does not take place in macroscopic scales. When we cut a colony just behind the migrating front shortly after the migration started, the migration ended earlier and the following consolidation lasted longer. However, the following cycles were not influenced by the cut, i.e., the following migration and consolidation phases were both found to return normal. The cut results in the stop of supply of cell population to the migrating front by internal waves. In fact the cell population on the new terrace during the first migration after the cut was less than that without cut. Furthermore, the cell population density was found to be recovered to the ordinary value by the end of the consolidation. All these experimental results suggest that the most important factor for the repetition of migration and consolidation phases is the cell population density.

  18. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    International Nuclear Information System (INIS)

    To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

  19. A Model for Cell Wall Dissolution in Mating Yeast Cells: Polarized Secretion and Restricted Diffusion of Cell Wall Remodeling Enzymes Induces Local Dissolution

    OpenAIRE

    Huberman, Lori B.; Murray, Andrew W.

    2014-01-01

    Mating of the budding yeast, Saccharomyces cerevisiae, occurs when two haploid cells of opposite mating types signal using reciprocal pheromones and receptors, grow towards each other, and fuse to form a single diploid cell. To fuse, both cells dissolve their cell walls at the point of contact. This event must be carefully controlled because the osmotic pressure differential between the cytoplasm and extracellular environment causes cells with unprotected plasma membranes to lyse. If the cell...

  20. Nitric Oxide Inducing Function and Intracellular Movement of Chicken Interleukin-18 in Cultured Cells

    Institute of Scientific and Technical Information of China (English)

    Jian XU; Tong-Le DENG; Long LI; Zhen-Qiang YOU; Wang-Jun WAN; Lian YU

    2005-01-01

    To evaluate the characteristics of chicken interleukin-18 (ChIL-18) in different forms in vitro,the ChIL-18 full-length gene (ChIL-18-F) and the ChIL-18 presumed mature protein gene (ChIL-18-M) were cloned and inserted into the eukaryotic expression vector pCI, to construct recombinant pCI-ChIL-18-F and pCI-ChIL-18-M. The recombinant plasmids were then transferred into chicken splenic lymphocytes (CSLs). Western blot showed that ChIL-18-F, with a molecular weight of 23.0 kDa, was produced in CSLs transfected by pCI-ChIL-18-F; ChIL-18-M, with a molecular weight of 19.5 kDa, was produced in CSLs transfected by pCI-ChIL-18-M. The nitric oxide (NO) level in the transfected CSLs and the culture medium at different time points was further examined under confocal microscopy using 4,5-diaminofluorescein staining. The results showed that both pCI-ChIL-18-F and pCI-ChIL-18-M groups showed significant increase in intracellular and extracellular NO production compared with pCI transfected control cells. These results suggest that both ChIL-18-F and ChIL-18-M could stimulate NO secretion in CSLs. To characterize the intracellular distribution of ChIL-18, ChIL-18-F and ChIL-18-M were each fused to the enhanced green fluorescent protein gene, and expressed in Vero cells. The results showed that the ChIL-18-F tended to the membranous region in Vero cells, while ChIL-18-M did not. This indicates that the N-terminal 27 amino acid peptide helped ChIL-18 target to Vero cell membranes.

  1. The Research of Movement Simulation in Bianzhong Choreography

    Institute of Scientific and Technical Information of China (English)

    CHEN QIXIANG; SUN JUNYI; CHEN XIAOWEI; SHENG JIANHUI

    2007-01-01

    This paper introduces the process of producing movement database on a virtual model for the Bianzhong choreography. It focuses on analyzing the movement taxonomy and corresponding relationship under the dancing syntax. We study the movement style identification theory based on the emotion model, present a movement connection method by defining the attributes of characteristically movement units and their related restriction, and give the application framework of the method in Movement Compilation System.

  2. Optical high-resolution analysis of rotational movement: testing circular spatial filter velocimetry (CSFV) with rotating biological cells

    Science.gov (United States)

    Schaeper, M.; Schmidt, R.; Kostbade, R.; Damaschke, N.; Gimsa, J.

    2016-07-01

    Circular spatial filtering velocimetry (CSFV) was tested during the microscopic registration of the individual rotations of baker’s yeast cells. Their frequency-dependent rotation (electrorotation; ER) was induced in rotating electric fields, which were generated in a glass chip chamber with four electrodes (600 μm tip-to-tip distance). The electrodes were driven with sinusoidal quadrature signals of 5 or 8 V PP with frequencies up to 3 MHz. The observed cell rotation was of the order of 1–100 s per revolution. At each measuring frequency, the independent rotations of up to 20 cells were simultaneously recorded with a high-speed camera. CSFV was software-implemented using circular spatial filters with harmonic gratings. ER was proportional to the phase shift between the values of the spatial filtering signal of consecutive frames. ER spectra obtained by CSFV from the rotation velocities at different ER-field frequencies agreed well with manual measurements and theoretical spectra. Oscillations in the rotation velocity of a single cell in the elliptically polarized field near an electrode, which were resolved by CSFV, could not be visually discerned. ER step responses after field-on were recorded at 2500 frames per second. Analysis proved the high temporal resolution of CSFV and revealed a largely linear torque-friction relation during the acceleration phase of ER. Future applications of CSFV will allow for the simple and cheap automated high-resolution analysis of rotational movements where mechanical detection has too low a resolution or is not possible, e.g. in polluted environments or for gas and fluid vortices, microscopic objects, etc.

  3. Ca²⁺ Movement Induced by Deltamethrin in PC3 Human Prostate Cancer Cells.

    Science.gov (United States)

    Lee, Hai-Hsiang; Chou, Chiang-Ting; Liang, Wei-Zhe; Chen, Wei-Chuan; Wang, Jue-Long; Yeh, Jeng-Hsien; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Chen, Fu-An; Jan, Chung-Ren

    2016-06-30

    This study explored the effect of deltamethrin, a pesticide, on intracellular free Ca²⁺ concentration ([Ca²⁺]i) in PC3 human prostate cancer cells. Deltamethrin at concentrations between 5 μM and 20 μM evoked [Ca²⁺]i rises in a concentration-dependent manner. This Ca²⁺ signal was inhibited by 22% by removal of extracellular Ca²⁺. Nifedipine, econazole, and SKF96365 also inhibited the Ca²⁺ signal. Treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) in Ca²⁺-free medium nearly abolished deltamethrin-induced [Ca²⁺]i rises. Treatment with deltamethrin also inhibited most of BHQ-induced [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter deltamethrin-evoked [Ca²⁺]i rises. Deltamethrin killed cells at concentrations of 20-100 μM in a concentration-dependent fashion. Chelation of cytosolic Ca²⁺ with 1,2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid/acetoxymethyl ester (BAPTA/AM) did not prevent deltamethrin's cytotoxicity. Together, in PC3 human prostate cancer cells, deltamethrin induced [Ca²⁺]i rises that involved Ca²⁺ entry through store-operated Ca²⁺ channels and PLC-independent Ca²⁺ release from the endoplasmic reticulum. Deltamethrin induced cytotoxicity in a Ca²⁺-independent manner. PMID:27188467

  4. Pseudopod growth and evolution during cell movement is controlled through SCAR/WAVE dephosphorylation

    Science.gov (United States)

    Ura, Seiji; Pollitt, Alice Y.; Veltman, Douwe M.; Morrice, Nicholas A.; Machesky, Laura M.; Insall, Robert H.

    2016-01-01

    Background SCAR/WAVE is a principal regulator of pseudopod growth in crawling cells. It exists in a stable pentameric complex, which is regulated at multiple levels that are only beginning to be understood. SCAR/WAVE is phosphorylated at multiple sites, but how this affects its biological activity is unclear. Here we show that dephosphorylation of Dictyostelium SCAR controls normal pseudopod dynamics. Results We demonstrate that the C-terminal acidic domain of most Dictyostelium SCAR is basally phosphorylated at four serine residues. A small amount of singly phosphorylated SCAR is also found. SCAR phosphorylation site mutants cannot replace SCAR’s role in the pseudopod cycle, though they rescue cell size and growth. Unphosphorylatable SCAR is hyperactive – excessive recruitment to the front gives large pseudopods that fail to bifurcate because they continually grow forwards. Conversely, phosphomimetic SCAR is weakly active, causing frequent small, disorganised pseudopods. Even in its regulatory complex, SCAR is normally held inactive by an interaction between the phosphorylated acidic and basic domains. Loss of basic residues complementary to the acidic phosphosites yields a hyperactive protein similar to unphosphorylatable SCAR. Conclusions Regulated dephosphorylation of a fraction of the cellular SCAR pool is a key step in SCAR activation during pseudopod growth. Phosphorylation increases autoinhibition of the intact complex. Dephosphorylation weakens this interaction and facilitates SCAR activation, but also destabilizes the protein. We show that SCAR is specifically dephosphorylated in pseudopods, increasing activation by Rac and lipids and supporting positive feedback of pseudopod growth. PMID:22386315

  5. Induction of Cytotoxic T Lymphocytes Specific to Malignant Glioma Using T2 Cells Pulsed with HLA-A2-restricted Interleukin-13 Receptor α2 Peptide in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Interleukin-13 receptor α2 (IL-13Rα2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. The present study is a report of a novel approach of targeting malignant glioma with IL-13Rα2-specific cytotoxic T lymphocyte (CTL) induced from the peripheral blood mononuclear cells of healthy donors by multiple stimulations with human leukocyte antigen(HLA)-A2-restricted IL-13Rα2345-353 peptide-pulsed T2 cells. The induced CTL showed specific lysis against T2 cells pulsed with the peptide and HLA-A2+ glioma cells expressing IL-13Rα2345-353, while HLA-A2 glioma cell lines that express IL-13Rα2345-353 could not be recognized by CTL. The peptide-specific activity was inhibited by anti-HLA class Ⅰ monoclonal antibody. These results suggest that the induced CTL specific for IL-13Rα2345-353 peptide could be a potential target of specific immunotherapy for HLA-A2 patients with malignant glioma.

  6. Pigment cell movement is not required for generation of Turing patterns in zebrafish skin

    Science.gov (United States)

    Bullara, D.; De Decker, Y.

    2015-01-01

    The zebrafish is a model organism for pattern formation in vertebrates. Understanding what drives the formation of its coloured skin motifs could reveal pivotal to comprehend the mechanisms behind morphogenesis. The motifs look and behave like reaction–diffusion Turing patterns, but the nature of the underlying physico-chemical processes is very different, and the origin of the patterns is still unclear. Here we propose a minimal model for such pattern formation based on a regulatory mechanism deduced from experimental observations. This model is able to produce patterns with intrinsic wavelength, closely resembling the experimental ones. We mathematically prove that their origin is a Turing bifurcation occurring despite the absence of cell motion, through an effect that we call differential growth. This mechanism is qualitatively different from the reaction–diffusion originally proposed by Turing, although they both generate the short-range activation and the long-range inhibition required to form Turing patterns. PMID:25959141

  7. Intra-operative intravenous fluid restriction reduces perioperative red blood cell transfusion in elective cardiac surgery, especially in transfusion-prone patients: a prospective, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Georgopoulou Stavroula

    2010-02-01

    Full Text Available Abstract Background Cardiac surgery is a major consumer of blood products, and hemodilution increases transfusion requirements during cardiac surgery under CPB. As intraoperative parenteral fluids contribute to hemodilution, we evaluated the hypothesis that intraoperative fluid restriction reduces packed red-cell (PRC use, especially in transfusion-prone adults undergoing elective cardiac surgery. Methods 192 patients were randomly assigned to restrictive (group A, 100 pts, or liberal (group B, 92 pts intraoperative intravenous fluid administration. All operations were conducted by the same team (same surgeon and perfusionist. After anesthesia induction, intravenous fluids were turned off in Group A (fluid restriction patients, who only received fluids if directed by protocol. In contrast, intravenous fluid administration was unrestricted in group B. Transfusion decisions were made by the attending anesthesiologist, based on identical transfusion guidelines for both groups. Results 137 of 192 patients received 289 PRC units in total. Age, sex, weight, height, BMI, BSA, LVEF, CPB duration and surgery duration did not differ between groups. Fluid balance was less positive in Group A. Fewer group A patients (62/100 required transfusion compared to group B (75/92, p Conclusions Our data suggest that fluid restriction reduces intraoperative PRC transfusions without significantly increasing postoperative transfusions in cardiac surgery; this effect is more pronounced in transfusion-prone patients. Trial registration NCT00600704, at the United States National Institutes of Health.

  8. Nephrotoxicity of Bence-Jones proteins: correlation with endocytosis by BHK cells and intracellular movement

    Directory of Open Access Journals (Sweden)

    Ana Lucia Nicastri

    2001-06-01

    Full Text Available The aim of this investigation was to evaluate the endocytosis of two Bence-Jones proteins by renal cells in order to elucidate the interference of their physical and chemical characteristics on nephrotoxicity. Bence-Jones proteins (AK and GL were purified and isolated from the urine of two patients with multiple myeloma. The isotype of both proteins was characterised as being human monoclonal lambda light chain. The AK protein presented mainly an Ip>7.0, a high content of galactose and a low amount of sialic acid molecules. On the other hand, the GL protein presented a single band with an Ip of 4.3, a higher level of sialic acid and a reduced amount of galactose, in comparison with the AK protein. Baby Hamster Kidney (BHK cells were maintained in culture in bottles at 37ºC, using DMEM culture media supplemented with 10% of calf serum with a pH of 7.4. Once the monolayer was observed to be confluent, the BHK cells were incubated with the two proteins, dissolved in a serum-free medium for 1, 5, 15, 30, 60 minutes and 24 hours. Control cells were established omitting the incubation with Bence-Jones proteins, but maintaining all of the other conditions. After, this the cells were washed, trypsinised, centrifuged and fixed in a solution of 4% paraformaldehyde and 0.5% glutaraldehyde on a 0.1 M, pH 7.4 phosphate buffer. Cells were processed for immunocytochemical reactions by using protein A coupled with colloidal gold and further silver enhancement. Semi-thin sections of the pellets were obtained and submitted to the cytochemical reactions. Detection of labelling was made by using light microscopy. It was observed that GL protein tended to be directed towards a perinuclear position, whereas the AK protein tended to suffer lysosomal deviation, suggesting that there is a direct contribution of physical and chemical characteristics on intracellular direction taken by Bence-Jones proteins.O objetivo deste trabalho foi avaliar a endocitose de duas prote

  9. Calorie restriction and stroke

    Directory of Open Access Journals (Sweden)

    Manzanero Silvia

    2011-09-01

    Full Text Available Abstract Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR or intermittent fasting (IF, extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF and basic fibroblast growth factor (bFGF; protein chaperones, including heat shock protein 70 (Hsp70 and glucose regulated protein 78 (GRP78; antioxidant enzymes, such as superoxide dismutases (SOD and heme oxygenase-1 (HO-1, silent information regulator T1 (SIRT1, uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke.

  10. Differential binding of the Bombyx silk gland-specific factor SGFB to its target DNA sequence drives posterior-cell-restricted expression.

    OpenAIRE

    Horard, B; Julien, E; Nony, P; Garel, A; Couble, P

    1997-01-01

    The gene encoding the silk protein P25 in Bombyx mori is expressed in the posterior silk gland (PSG) cells and repressed in the middle silk gland (MSG) cells. To identify the factors involved in this transcription-dependent spatial restriction, we examined the P25 chromatin in PSG and MSG nuclei by DNase I-aided ligation-mediated PCR and analyzed the expression of various P25-lacZ constructs in biolistically treated silk glands. P25 promoter activation depends on two cis-acting elements. One ...

  11. Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8+ T Cells

    OpenAIRE

    Payne, Rebecca P.; Kløverpris, Henrik; Sacha, Jonah B.; Brumme, Zabrina; Brumme, Chanson; Buus, Søren; Sims, Stuart; Hickling, Stephen; Riddell, Lynn; Chen, Fabian; Luzzi, Graz; Edwards, Anne; Phillips, Rodney; Prado, Julia G.; Goulder, Philip J. R.

    2010-01-01

    The association between HLA-B*2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B*2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8+ T cells. In order to better define the mechanisms of the HLA-B*2705 immune control of HIV, we first characterized the CD8+ T-cell responses of nine highly active antiretroviral therapy (HAART)-naïve B*2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B*...

  12. Development of an MHC class I Ld-restricted PSA peptide-loaded tetramer for detection of PSA-specific CD8+ T cells in the mouse

    OpenAIRE

    Lemke, Caitlin D.; Graham, Jessica B.; Lubaroff, David M.; Salem, Aliasger K.

    2011-01-01

    Objectives We set out to develop a prostate specific antigen (PSA) peptide-loaded tetramer for enumeration of PSA-specific CD8+ T cells in the Balb/c mouse model. Methods A candidate MHC class I PSA peptide (HPQKVTKFML188–197) was selected based on its ability to restimulate PSA-specific CD8+ T cells to secrete IFN-γ in our assays. Next, H-2Ld-restricted peptide-loaded and fluorescently labeled tetramers were produced in conjunction with the NIH Tetramer Core Facility. This tetramer was then ...

  13. Inefficient boosting of antitumor CD8+ T cells by dendritic-cell vaccines is rescued by restricting T-cell cytotoxic functions

    OpenAIRE

    Zhi-Iong Ma, Joel; Yang, Jianping; Qin, Jim S.; Richter, Antonia; PERRET, Rachel; El-Deiry, Wafik S.; Finnberg, Niklas; Ronchese, Franca

    2012-01-01

    Dendritic cells (DCs) are powerful activators of primary and secondary immune responses and have promising activity as anticancer vaccines. However, various populations of immune cells, including natural killer cells, regulatory T cells and especially cytotoxic T lymphocytes (CTLs), can inhibit DC function through cytotoxic clearance. Spontaneous tumor-specific CTL responses are frequently observed in patients before immunotherapy, and it is unclear how such pre-existing responses may affect ...

  14. Analysis of antigen-specific, Ig-restricted cell-free material made by I-J+ Ly-1 cells (Ly-1 TsiF) that induces Ly-2+ cells to express suppressive activity.

    Science.gov (United States)

    Yamauchi, K; Murphy, D; Cantor, H; Gershon, R K

    1981-11-01

    A set of T cells defined by a unique profile of cell surface alloantigens (phenotype Ly-1+2-; Qa-1+; I-J+) produces biologically active cell-free material(s) (Ly-1 TsiF) which induces another T cell set (cell surface phenotype Ly-1,2+; I-J/; Qa-1+) to participate in the suppression of primary immune responses to heterologous erythrocytes. The suppression is specific for the inducing antigen, and the Ly-1 TsiF binds antigen in a specific way. The activity of Ly-1 TsiF can be removed by anti-I-J immunosorbents and will not be expressed if the functional producer and acceptor cells do not share gene products that are encoded in or are tightly linked to the VH portion of the Ig complex. There is no requirement for the Ly-1 TsiF and its acceptor cell(s) to share major histocompatibility complex gene products. Thus, for optimal induction of antigen-specific suppression by cell-gree materials from Ly-1 T cells, three necessary conditions must be met: (a) antigen recognition by Ly-1 TsiF; (b) the expression of I-J gene products and (c) identify of VH-linked Ig locus gene products (or other products influenced by those genes) on both the inducer molecule and its acceptor cell. The role of the Ig-linked restriction is particularly intriguing, and its possible meaning is considered in detail. PMID:6173228

  15. Gene Expression Analysis of a Panel of Cell Lines That Differentially Restrict HIV-1 CA Mutants Infection in a Cyclophilin A-Dependent Manner

    Science.gov (United States)

    Shah, Vaibhav B.; Aiken, Christopher

    2014-01-01

    HIV-1 replication is dependent on binding of the viral capsid to the host protein cyclophilin A (CypA). Interference with cyclophilin A binding, either by mutations in the HIV-1 capsid protein (CA) or by the drug cyclosporine A (CsA), inhibits HIV-1 replication in cell culture. Resistance to CsA is conferred by A92E or G94D substitutions in CA. The mutant viruses are also dependent on CsA for their replication. Interestingly, infection of some cell lines by these mutants is enhanced by CsA, while infection of others is not affected by the drug. The cells are thus termed nonpermissive and permissive, respectively, for infection by CsA-dependent mutants. The mechanistic basis for the cell type dependence is not well understood, but has been hypothesized to result from a dominant-acting host factor that blocks HIV-1 infection by a mechanism that requires CypA binding to the viral capsid. In an effort to identify a CypA-dependent host restriction factor, we adopted a strategy involving comparative gene expression analysis in three permissive and three non-permissive cell types. We ranked the genes based on their relative overexpression in non-permissive cell types compared to the permissive cell types. Based on specific selection criteria, 26 candidate genes were selected and targeted using siRNA in nonpermissive (HeLa) cells. Depletion of none of the selected candidate genes led to the reversal of CsA-dependent phenotype of the A92E mutant. Our data suggest that none of the 26 genes tested is responsible for the dependence of the A92E mutant on CsA. Our study provides gene expression data that may be useful for future efforts to identify the putative CypA-dependent HIV-1 restriction factor and in studies of other cell-specific phenotypes. PMID:24663101

  16. Live cell imaging of the assembly, disassembly, and actin cable–dependent movement of endosomes and actin patches in the budding yeast, Saccharomyces cerevisiae

    OpenAIRE

    Huckaba, Thomas M.; Gay, Anna Card; Pantalena, Luiz Fernando; Yang, Hyeong-Cheol; Liza A Pon

    2004-01-01

    Using FM4-64 to label endosomes and Abp1p-GFP or Sac6p-GFP to label actin patches, we find that (1) endosomes colocalize with actin patches as they assemble at the bud cortex; (2) endosomes colocalize with actin patches as they undergo linear, retrograde movement from buds toward mother cells; and (3) actin patches interact with and disassemble at FM4-64–labeled internal compartments. We also show that retrograde flow of actin cables mediates retrograde actin patch movement. An Arp2/3 complex...

  17. Protest movements

    International Nuclear Information System (INIS)

    The author describes the development of protest movements in postwar Germay and outlines two essential overlapping 'flow cycles'. The first of these was characterised by the restaurative postwar years. It culminated and ended in the students' revolt. This revolt is at the same time the start of a second cycle of protest which encompasses all subsequent individual movement and is initated by an economic, political and sociocultural procrastination of modernisation. This cycle culminates in the late 70s and early 80s and clearly lost momentum over the last few years. The follwoing phases and themes are described profoundly: against restauration and armament in the 1950; the revolutionary impatience of the students' movement, politisation of everyday life by the womens' movement and citizens' action groups, antinuclear- and ecological movement, differentiation and stabilisation of the movement in the 70s and 80s; break-up and continuity in the German protest behaviour. The paper contains a detailed chronicle of protest activities since 1945. (orig.)

  18. Telomere Restriction Fragment (TRF) Analysis

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al., 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al., 1990; Ouellette et al., 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  19. Induction of an antitumor response using dendritic cells transfected with DNA constructs encoding the HLA-A*02:01-restricted epitopes of tumor-associated antigens in culture of mononuclear cells of breast cancer patients.

    Science.gov (United States)

    Sennikov, Sergey Vital'evich; Shevchenko, Julia Alexandrovna; Kurilin, Vasilii Vasil'evich; Khantakova, Julia Nikolaevna; Lopatnikova, Julia Anatol'evna; Gavrilova, Elena Vasil'evna; Maksyutov, Rinat Amirovich; Bakulina, Anastasiya Yur'evna; Sidorov, Sergey Vasil'evich; Khristin, Alexander Alexandrovich; Maksyutov, Amir Zakievich

    2016-02-01

    Advances in oncoimmunology related to the definition of the basic mechanisms of the formation of antitumor immune response, as well as the opening of tumor-associated antigens recognized by immune cells, allowed to start developing ways to influence the effector cells of the immune system to generate effective antitumor cytotoxic response. We investigated the possibility to stimulate an antitumor response in a culture of mononuclear cells of breast cancer patients by dendritic cells transfected with HLA-A*02:01-restricted DNA constructs. We isolated dendritic cells from peripheral blood monocytes and delivered our constructs to these cells by magnetic transfection. Additionally, a series of experiments with loading of dendritic cells with autologous tumor cell lysate antigens was conducted. We have shown that dendritic cells transfected with the HLA-A*02:01-restricted DNA constructs are effective in inducing an antitumor response in a culture of mononuclear cells of breast cancer patients. Dendritic cells transfected with DNA constructor dendritic cells loaded with lysate antigens revealed a comparable stimulated cytotoxic response of mononuclear cells to these two ways of antigen delivery. We conclude that using DNA constructs in conjunction with patient stratification by HLA type allows the application of transfected DCs as an effective method to stimulate antitumor immunity in vitro. PMID:26590947

  20. Cell-to-cell movement of Potato virus X: the role of p12 and p8 encoded by the second and third open reading frames of the triple gene block.

    Science.gov (United States)

    Tamai, A; Meshi, T

    2001-10-01

    Potato virus X (PVX) requires three proteins, p25, p12, and p8, encoded by the triple gene block plus the coat protein (CP) for cell-to-cell movement. When each of these proteins was co-expressed with a cytosolic green fluorescent protein (GFP) in the epidermal cells of Nicotiana benthamiana by the microprojectile bombardment-mediated gene delivery method, only p12 enhanced diffusion of co-expressed GFP, indicating an ability to alter plasmodesmal permeability. p25, p12, and CP, expressed transiently in the initially infected cells, transcomplemented the corresponding movement-defective mutants to spread through two or more cell boundaries. Thus, these proteins probably move from cell to cell with the genomic RNA. In contrast, p8 only functioned intracellularly and was not absolutely required for cell-to-cell movement. Since overexpression of p12 overcame the p8 deficiency, p8 appears to facilitate the functioning of p12, presumably by mediating its intracellular trafficking. Considering the likelihood that p12 and p8 are membrane proteins, it is suggested that intercellular as well as intracellular movement of PVX involves a membrane-mediated process. PMID:11605955

  1. A dynamic pressure view cell for acoustic stimulation of fluids—Micro-bubble generation and fluid movement in porous media

    Science.gov (United States)

    Stewart, Robert A.; Shaw, J. M.

    2015-09-01

    The development and baseline operation of an acoustic view cell for observing fluids, and fluid-fluid and fluid-solid interfaces in porous media over the frequency range of 10-5000 Hz is described. This range includes the industrially relevant frequency range 500-5000 Hz that is not covered by existing devices. Pressure waveforms of arbitrary shape are generated in a 17.46 mm ID by 200 mm and 690.5 mm long glass tubes at flow rates up to 200 ml/min using a syringe pump. Peak-to-peak amplitudes exceeding 80 kPa are readily realized at frequencies from 10 to 5000 Hz in bubble free fluids when actuated with 20 Vpp as exemplified using castor oil. At resonant frequencies, peak-to-peak pressure amplitudes exceeding 500 kPa were obtained (castor oil at 2100 Hz when actuated with 20 Vpp). Impacts of vibration on macroscopic liquid-liquid and liquid-vapour interfaces and interface movement are illustrated. Pressure wave transmission and attenuation in a fluid saturated porous medium, randomly packed 250-330 μm spherical silica beads, is also demonstrated. Attenuation differences and frequency shifts in resonant peaks are used to detect the presence and generation of dispersed micro-bubbles (micro-bubbles comprise subjects of special interest.

  2. DNA double-strand break measurement in mammalian cells by pulsed-field gel electrophoresis: an approach using restriction enzymes and gene probing

    International Nuclear Information System (INIS)

    DNA samples prepared from human SP3 cells, which had not been exposed to various doses of X-ray, were treated with NotI restriction endonuclease before being run in a contour-clamped homogeneous electrophoresis system. The restriction enzyme cuts the DNA at defined positions delivering DNA sizes which can be resolved by pulsed-field gel electrophoresis (PFGE). In order to investigate only one of the DNA fragments, a human lactoferrin cDNA, pHL-41, was hybridized to the DNA separated by PFGE. As a result, only the DNA fragment which contains the hybridized gene was detected resulting in a one-band pattern. The decrease of this band was found to be exponential with increasing radiation dose. From the slope, a double-strand break induction rate of (6.3±0.7) x 10-3/Mbp/Gy was deduced for 80 kV X-rays. (Author)

  3. Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Kløverpris, Henrik; Jensen, Kristoffer Jarlov; Buus, Anette Stryhn; Buus, Søren; Karlsson, Annika; Vinner, Lasse; Goulder, Philip; Fomsgaard, Anders

    2012-01-01

    The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design of a...... universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted...... from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide...

  4. Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood-flow restriction

    DEFF Research Database (Denmark)

    Nielsen, Jakob Lindberg; Aagaard, Per; Bech, Rune Dueholm; Nygaard, Tobias; Hvid, Lars Grøndahl; Wernbom, Mathias; Suetta, Charlotte Arneboe; Frandsen, Ulrik

    2012-01-01

    Low-load resistance training with blood-flow restriction has been shown to elicit substantial increases in muscle mass and muscle strength; however the effect on myogenic stem cells (MSC) and myonuclei number remains unexplored. Ten male subjects (22.8±2.3 yrs) performed 4 sets of knee extensor...... exercise (20% 1RM) to concentric failure during blood-flow restriction (BFR) of the proximal thigh (100 mmHg), while eight work-matched controls (21.9±3.0 yrs) trained without BFR (CON). 23 training sessions were performed within 19 days. Maximal isometric knee extensor strength (MVC) was examined pre and...... post training, while muscle biopsies were obtained at baseline (Pre), after 8 days intervention (Mid8) and 3 (Post3) and 10 days (Post10) post training to examine changes in myofibre area (MFA), MSC and myonuclei number. MVC increased by 7.1% (Post5) and 10.6% (Post12) (P...

  5. Oxygen restriction increases the infective potential of Listeria monocytogenes in vitro in Caco-2 cells and in vivo in guinea pigs

    DEFF Research Database (Denmark)

    Andersen, Jens Bo; Roldgaard, Bent; Christensen, Bjarke Bak; Licht, Tine Rask

    2007-01-01

    Background: Listeria monocytogenes has been implicated in several food borne outbreaks as well as sporadic cases of disease. Increased understanding of the biology of this organism is important in the prevention of food borne listeriosis. The infectivity of Listeria monocytogenes ScottA, cultivated...... first time that the environmental conditions to which L. monocytogenes is exposed prior to ingestion are decisive for its in vivo infective potential in the gastrointestinal tract after passage of the gastric barrier. This is highly relevant for safety assessment of this organism in food........ Results: Infection of Caco-2 cells revealed that Listeria cultivated under oxygen-restricted conditions were approximately 100 fold more invasive than similar cultures grown without oxygen restriction. This was observed for exponentially growing bacteria, as well as for stationary-phase cultures. Oral...

  6. Early-age feed restriction affects viability and gene expression of satellite cells isolated from the gastrocnemius muscle of broiler chicks

    Directory of Open Access Journals (Sweden)

    Li Yue

    2012-11-01

    Full Text Available Abstract Background Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0–14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. However, how satellite cells respond to such nutritional insult has not been adequately elucidated. Results One-day-old broiler chicks were allocated to control (Con, ad libitum feeding, intermittent feeding (IF, feed provided on alternate days and re-feeding (RF, 2 days ad libitum feeding after 12 days of intermittent feeding groups. Chickens were killed on Day 15 and satellite cells were isolated. When cultured, satellite cells from the IF group demonstrated significant retardation in proliferation and differentiation potential, while RF partly restored the proliferation rate and differentiation potential of the satellite cells. Significant up-regulation of insulin like growth factor I receptor (IGF-IR (P0.05 and thyroid hormone receptor α (TRα (P0.05, and down-regulation of growth hormone receptor (GHR (P0.01 and IGF-I (P0.01 mRNA expression was observed in freshly isolated IF satellite cells when compared with Con cells. In RF cells, the mRNA expression of IGF-I was higher (P0.05 and of TRα was lower (P0.01 than in IF cells, suggesting that RF restored the mRNA expression of TRα and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio tended to increase in the IF group, which was reversed in the RF group (P0.05, indicating that RF reduced the pro-apoptotic influence of IF. Moreover, no significant effect of T3 was detected on cell survival in IF cells compared with Con (PP0.05 cells. Conclusions These data suggest that early-age feed restriction inhibits the proliferation and differentiation of satellite cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone receptors in satellite cells, as well as blunted sensitivity of satellite cells to T3, and that RF partially reverses these effects. Thus

  7. Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Rufener, Nora; Nielsen, Jens J;

    2008-01-01

    .05) in blood flow without a significant enhancement in oxygen uptake. Muscle interstitial fluid was sampled with microdialysis technique and analyzed for vascular endothelial growth factor (VEGF) protein and for the effect on endothelial cell proliferation. Biopsies obtained from the musculus vastus...... lateralis were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase (P < 0.05) in interstitial VEGF protein concentration above rest (73 +/- 21 vs. 344 +/- 83 pg/ml). Addition of muscle dialysate to......The present study used passive limb movement as an experimental model to study the effect of increased blood flow and passive stretch, without enhanced metabolic demand, in young healthy male subjects. The model used was 90 min of passive movement of the leg leading to a 2.8-fold increase (P < 0...

  8. Isolation and Characterization of an HLA-DPB1*04: 01-restricted MAGE-A3 T-Cell Receptor for Cancer Immunotherapy.

    Science.gov (United States)

    Yao, Xin; Lu, Yong-Chen; Parker, Linda L; Li, Yong F; El-Gamil, Mona; Black, Mary A; Xu, Hui; Feldman, Steven A; van der Bruggen, Pierre; Rosenberg, Steven A; Robbins, Paul F

    2016-06-01

    Long-term tumor regressions have been observed in patients following the adoptive transfer of autologous tumor-infiltrating lymphocytes or genetically modified T cells expressing MHC class I-restricted T-cell receptors (TCRs), but clinical trials have not evaluated responses to genetically modified T cells expressing antitumor MHC class II-restricted TCRs. As studies carried out in a murine tumor model system have demonstrated that the adoptive transfer of CD4 T cells could lead to the regression of established tumors, we plan to test the hypothesis that CD4 T cells can also induce tumor regressions in cancer patients. In this study, 2 MAGE-A3-specific TCRs were isolated from a regulatory T-cell clone (6F9) and an effector clone (R12C9), generated from the peripheral blood of 2 melanoma patients after MAGE-A3 vaccination. The results indicated that T cells transduced with 6F9 TCR mediated stronger effector functions than R12C9 TCR. The 6F9 TCR specifically recognized MAGE-A3 and the closely related MAGE-A6 gene product, but not other members of the MAGE-A family in the context of HLA-DPB1*04:01. To test the feasibility of a potential clinical trial using this TCR, a clinical-scale procedure was developed to obtain a large number of purified CD4 T cells transduced with 6F9 TCR. Because HLA-DPB1*04:01 is present in ∼60% of the Caucasian population and MAGE-A3 is frequently expressed in a variety of cancer types, this TCR immunotherapy could potentially be applicable for a significant portion of cancer patients. PMID:27163739

  9. The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection

    Science.gov (United States)

    Sullivan, Lucy C.; Westall, Glen P.; Widjaja, Jacqueline M. L.; Mifsud, Nicole A.; Nguyen, Thi H. O.; Meehan, Aislin C.; Kotsimbos, Tom C.; Brooks, Andrew G.

    2015-01-01

    The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical peptide sequence with that found in the leader sequence of many human leukocyte antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40 specific T cells by tetramer staining of peripheral blood mononuclear cells (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however the magnitude of the response varied significantly between patients. Moreover, unlike healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that minor histocompatibility antigens presented by HLA-E can represent an additional risk factor following lung transplantation. PMID:26302084

  10. H-2 restriction specificity of T cells from H-2 incompatible radiation bone marrow chimeras: further evidence for the absence of crucial influence of the host/thymus environment on the generation of H-2 restricted TNP-specific T lymphocyte precursors

    International Nuclear Information System (INIS)

    Experiments were conducted to answer the questions related to (a) the role played by the antigen-presenting cells (APCs) present within the thymus and (b) the effect of radiation dose to the recipients on the H-2 restriction profile of TNP-specific cytotoxic T lymphocyte precursors (CTLP) recovered from spleens and/or thymuses of H-2 incompatible radiation bone marrow chimeras (BMC). The H-2 restriction profile of intrathymically differentiating TNP-specific CTLPs was also analyzed in order to test an argument that donor-H-2 restricted CTLP detected in spleens of H-2 incompatible BMC were due to the extrathymically differentiated T cells under the influence of donor-derived lymphoreticular cells. The results indicated the following: (i) splenic T cells from B10(H-2b) leads to (B10(H-2b) leads to B10.BR(H-2k)) chimeras, which were constructed by irradiating primary B10 leads to B10.BR chimeras with 1100 R and reconstituting them with donor-type (B10) bone marrow cells as long as 8 months after their construction, manifested restriction specificities for both donor- and host-type H-2, (ii) splenic T cells from two types of (B10 X B10.BR)F1 leads to B10 chimeras which were reconstituted after exposure of the recipients with either 900 or 1100 R with donor-type bone marrow cells generated both donor- and host-H-2 restricted TNP-specific cytotoxic T cells, and (iii) the TNP-specific CTLPs present in the regenerating thymuses of B10.BR leads to B10 and (B10 X B10.BR)F1 leads to B10 chimeras 4 weeks after their construction were also shown to manifest both donor- and host-H-2 restriction specificities. The significance of these findings on the H-2 restriction profile of CTLP generated in BMCs is discussed

  11. Nossa notação m' na prova de Rorschach: ampliação e restrição do fator m de Klopfer Our m' determinant in the Rorschach's test, enlarging and restricting "inanimate movement" score

    Directory of Open Access Journals (Sweden)

    Aníbal Silveira

    1972-06-01

    Full Text Available Julgamos oportuna e necessária a diferenciação de fatores "movimento" efetuada por Klopfer, entre os quais a categoria a que denominou "movimento inanimado", como integrante do grupo "movimentos menores". O significado particular de semelhantes fatores foi claramente acentuado por Piotrowski quando redefiniu todos os elementos psicodiagnósticos. E acreditamos que o próprio Rorschach faria essa diversificação de determinantes. Pessoalmente, utilizamos a categoria m de Klopfer e de Piotrowski de modo algo diverso. Por um lado, não incluimos aí máscara, nem mímica expressiva, nem expressões emocionais, nem movimentos parciais. Por outro, classificamos nesse grupo movimento humano ou de animal, toda vez que não resulte diretamente da configuração da mancha como elemento formal, mas da reação subjetiva do examinando ante a cinestesia percebida. Como condição básica para a classificação, é indispensável que esteja clara a sensação de tensão muscular — como é exigido desde Rorschach para M;e como traço comum a todas as interpretações da rubrica — sejam abstrações, sejam seres inanimados: (a intenção, bloqueio, incapacidade, por exemplo, ou (b atividade de elementos da natureza. Devido a esse caráter subjetivo, anotamos m'em vez de m. Essas duas maneiras (a e (b de o probando interpretar movimento, já encontramos em Rorschach, respectivamente nos Exemplosdo Psychodiagnostik e da Contribuição póstuma. E tanto uma como outra podem decorrer, em última análise, quer de fuga ante estímulos emocionais, quer de capacidade mental muito elevada.Klopfer's differentiation of movement scores, among which "inanimate movement" integrating the "minor movements" group, was no doubt opportune and needed. Their peculiar meaning has been clearly stressed and enriched by Piotrowski in his reformulation of Rorschach variables. It is our belief that Rorschach himself would take such step. Our criteria for scoring this

  12. MHC-I-restricted epitopes conserved among variola and other related orthopoxviruses are recognized by T cells 30 years after vaccination

    DEFF Research Database (Denmark)

    Tang, Sheila Tuyet; Wang, M.; Lamberth, K.; Harndahl, M.; Dziegiel, M.H.; Claesson, M.H.; Buus, Søren; Lund, Ole

    2008-01-01

    It is many years since the general population has been vaccinated against smallpox virus. Here, we report that human leukocyte antigen (HLA) class I restricted T cell epitopes can be recognized more than 30 years after vaccination. Using bioinformatic methods, we predicted 177 potential cytotoxic T...... lymphocyte epitopes. Eight epitopes were confirmed to stimulate IFN-gamma release by T cells in smallpox-vaccinated subjects. The epitopes were restricted by five supertypes (HLA-A1, -A2, -A24 -A26 and -B44). Significant T cell responses were detected against 8 of 45 peptides with an HLA class I affinity of...... K(D) less than or equal to 5 nM, whereas no T cell responses were detected against 60 peptides with an HLA affinity of K(D) more than 5 nM. All epitopes were fully conserved in seven variola, vaccinia and cowpox strains. Knowledge of the long-term response to smallpox vaccination may lead to a...

  13. Single cell analysis of G1 check points-the relationship between the restriction point and phosphorylation of pRb

    International Nuclear Information System (INIS)

    Single cell analysis allows high resolution investigation of temporal relationships between transition events in G1. It has been suggested that phosphorylation of the retinoblastoma tumor suppressor protein (pRb) is the molecular mechanism behind passage through the restriction point (R). We performed a detailed single cell study of the temporal relationship between R and pRb phosphorylation in human fibroblasts using time lapse video-microscopy combined with immunocytochemistry. Four principally different criteria for pRb phosphorylation were used, namely (i) phosphorylation of residues Ser795 and Ser780 (ii) degree of pRb-association with the nuclear structure, a property that is closely related with pRb phosphorylation status, (iii) release of the transcription factor E2F-1 from pRb, and (iv) accumulation of cyclin E, which is dependent on phosphorylation of pRb. The analyses of individual cells revealed that passage through R preceded phosphorylation of pRb, which occurs in a gradually increasing proportion of cells in late G1. Our data clearly suggest that pRb phosphorylation is not the molecular mechanism behind the passage through R. The restriction point and phosphorylation of pRb thus seem to represent two separate check point in G1

  14. Interdisciplinary Evaluation of Broadly-Reactive HLA Class II Restricted Epitopes Eliciting HIV-Specific CD4+T Cell Responses

    DEFF Research Database (Denmark)

    Buggert, M.; Norström, M.; Lundegaard, Claus; Lund, Ole; Nielsen, Morten; Karlsson, A. C.

    2011-01-01

    Background: CD4+ T cells orchestrate immune protection by ‘‘helping’’ other cells of our immune system to clear viral infections. It is well known that the preferential infection and depletion of CD4+ T cells contributes to hampered systemic T cell help following HIV infection. However, the funct...

  15. IgE production after antigen-specific and cognate activation of HLA-DPw4-restricted T-cell clones, by 78% of randomly selected B-cell donors

    NARCIS (Netherlands)

    Baselmans, PJ; Pollabauer, EM; van Reijsen, FC; Heystek, HC; Hren, A; Stumptner, P; Tilanus, MGJ; Vooijs, WC; Mudde, GC

    2000-01-01

    The frequency of expression of the MHC class II antigen, HLA-DPw4, in the caucasoid population is approximately 78%, and is unmatched by phenotypic frequencies of other HLA class II molecules. Here we describe three human Der-P1-specific T-cell clones (TCC), restricted by the HLA-DPw4-variant HLA-DP

  16. Restriction beyond the restriction point: mitogen requirement for G2 passage

    Directory of Open Access Journals (Sweden)

    te Riele Hein

    2006-05-01

    Full Text Available Abstract Cell proliferation is dependent on mitogenic signalling. When absent, normal cells cannot pass the G1 restriction point, resulting in cell cycle arrest. Passage through the G1 restriction point involves inactivation of the retinoblastoma protein family. Consequently, loss of the retinoblastoma protein family leads to loss of the G1 restriction point. Recent work in our lab has revealed that cells possess yet another mechanism that restricts proliferation in the absence of mitogens: arrest in the G2 phase of the cell cycle. Here, we discuss the similarities and differences between these restriction points and the roles of cyclin-dependent kinase inhibitors (CKIs herein.

  17. Mixed Movements

    DEFF Research Database (Denmark)

    Brabrand, Helle

    2010-01-01

    levels than those related to building, and this exploration is a special challenge and competence implicit artistic development work. The project Mixed Movements generates drawing-material, not primary as representation, but as a performance-based media, making the body being-in-the-media felt and appear......Mixed Movements is a research project engaged in performance-based architectural drawing. Architectonic implementation questions relations between the human body and a body of architecture by the different ways we handle drawing materials. A drawing may explore architectonic problems at other...

  18. Striking movements

    DEFF Research Database (Denmark)

    Dahl, Sofia

    2011-01-01

    note onsets and short interaction times between player and instrument do not allow for much adjustment once a stroke is initiated. The paper surveys research that shows a close relationship between movement and sound production, and how playing conditions such as tempo and the rebound after impact......Like all music performance, percussion playing requires high control over timing and sound properties. Specific to percussionists, however, is the need to adjust the movement to different instruments with varying physical properties and tactile feedback to the player. Furthermore, the well defined...

  19. T cell potentiation in normal and autoimmune-prone mice after extended exposure to low doses of ionizing radiation and/or caloric restriction

    International Nuclear Information System (INIS)

    In order to better understand the apparent physiologic up-regulation in response to low levels of potentially lethal insults, murine T lymphocytes were analysed for functional and phenotypic alterations after exposure to 0.005 Gy/day, 0.01 Gy/day and 0.04 Gy/day in groups of ad-libitum-fed and calorie-restricted mice. Studies were conducted in two strains of mice: long-lived and immunologically normal C57B1/6 +/+ and congenic short-lived immunologically depressed C57B1/6 1pr/1pr. Whole-body exposure to 0.01 Gy/day and 0.04 Gy/day for an extended period of 20 days was associated with an increase in splenic proliferative response and shifts in proportions of T cell subpopulations in the thymus and spleen of both strains. Caloric restriction independently altered functional activity and T cell subpopulations in the same direction as low dose rates of ionizing radiation. Although dose-response augmentation in proliferative activity was similar in the strains, observed alterations in thymic and splenic T cell subpopulations were clearly different, suggesting different mechanisms were responsible for immune enhancement in each strain. (author)

  20. Caveolae Restrict Tiger Frog Virus Release in HepG2 cells and Caveolae-Associated Proteins Incorporated into Virus Particles.

    Science.gov (United States)

    He, Jian; Zheng, Yi-Wen; Lin, Yi-Fan; Mi, Shu; Qin, Xiao-Wei; Weng, Shao-Ping; He, Jian-Guo; Guo, Chang-Jun

    2016-01-01

    Caveolae are flask-shaped invaginations of the plasma membrane. Caveolae play important roles in the process of viruses entry into host cells, but the roles of caveolae at the late stage of virus infection were not completely understood. Tiger frog virus (TFV) has been isolated from the diseased tadpoles of the frog, Rana tigrina rugulosa, and causes high mortality of tiger frog tadpoles cultured in Southern China. In the present study, the roles of caveolae at the late stage of TFV infection were investigated. We showed that TFV virions were localized with the caveolae at the late stage of infection in HepG2 cells. Disruption of caveolae by methyl-β-cyclodextrin/nystatin or knockdown of caveolin-1 significantly increase the release of TFV. Moreover, the interaction between caveolin-1 and TFV major capsid protein was detected by co-immunoprecipitation. Those results suggested that caveolae restricted TFV release from the HepG2 cells. Caveolae-associated proteins (caveolin-1, caveolin-2, cavin-1, and cavin-2) were selectively incorporated into TFV virions. Different combinations of proteolytic and/or detergent treatments with virions showed that caveolae-associated proteins were located in viral capsid of TFV virons. Taken together, caveolae might be a restriction factor that affects virus release and caveolae-associated proteins were incorporated in TFV virions. PMID:26887868

  1. A dynamic pressure view cell for acoustic stimulation of fluids--Micro-bubble generation and fluid movement in porous media.

    Science.gov (United States)

    Stewart, Robert A; Shaw, J M

    2015-09-01

    The development and baseline operation of an acoustic view cell for observing fluids, and fluid-fluid and fluid-solid interfaces in porous media over the frequency range of 10-5000 Hz is described. This range includes the industrially relevant frequency range 500-5000 Hz that is not covered by existing devices. Pressure waveforms of arbitrary shape are generated in a 17.46 mm ID by 200 mm and 690.5 mm long glass tubes at flow rates up to 200 ml/min using a syringe pump. Peak-to-peak amplitudes exceeding 80 kPa are readily realized at frequencies from 10 to 5000 Hz in bubble free fluids when actuated with 20 Vpp as exemplified using castor oil. At resonant frequencies, peak-to-peak pressure amplitudes exceeding 500 kPa were obtained (castor oil at 2100 Hz when actuated with 20 Vpp). Impacts of vibration on macroscopic liquid-liquid and liquid-vapour interfaces and interface movement are illustrated. Pressure wave transmission and attenuation in a fluid saturated porous medium, randomly packed 250-330 μm spherical silica beads, is also demonstrated. Attenuation differences and frequency shifts in resonant peaks are used to detect the presence and generation of dispersed micro-bubbles (<180 μm diameter), and bubbles within porous media that are not readily visualized. Envisioned applications include assessment of the impacts of vibration on reaction, mass transfer, and flow/flow pattern outcomes. This knowledge will inform laboratory and pilot scale process studies, where nuisance vibrations may affect the interpretation of process outcomes, and large scale or in situ processes in aquifers or hydrocarbon reservoirs where imposed vibration may be deployed to improve aspects of process performance. Future work will include miscible interface observation and quantitative measurements in the bulk and in porous media where the roles of micro-bubbles comprise subjects of special interest. PMID:26429474

  2. Movement disorders

    International Nuclear Information System (INIS)

    This thesis describes the measurement of brain-tissue functions in patients with movement disorders using positron emission tomography (PET). This scanning technique is a method for direct in vivo quantitation of the regional tissue content of positron emitting radionuclides in brain (or other organs) in an essentially non-invasive way. Ch. 2 outlines some general features of PET and describes the scanner which has been used for the studies in this thesis. Also the tracer methodology, as applied to data investigations of movement disorders, are discussed. Ch. 3 contains the results of the PET investigations which were performed in the study of movement disorders. The results are presented in the form of 12 papers. The main goals of these studies were the understanding of the pathophysiology of Parkinson's disease, Huntington's chorea, Steele-Richardson-Olzewski syndrome and special case reports. Ch. 4 summarizes the results of these publications and Ch. 5 concludes the main part of this thesis with a general discussion of movement disorders in relation to PET investigations. 697 refs.; 60 figs.; 31 tabs

  3. Psychodynamic Movement

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This chapter/article describes the historical development of the disciplin Psychodynamic Movement. The importance of this disciplin for self-experience and for training in developing a therapist identy for the music therapy students are emphasized. Prototypeexercises developed and simplified...

  4. Bacillus anthracis lethal toxin disrupts TCR signaling in CD1d-restricted NKT cells leading to functional anergy.

    Directory of Open Access Journals (Sweden)

    Sunil K Joshi

    2009-09-01

    Full Text Available Exogenous CD1d-binding glycolipid (alpha-Galactosylceramide, alpha-GC stimulates TCR signaling and activation of type-1 natural killer-like T (NKT cells. Activated NKT cells play a central role in the regulation of adaptive and protective immune responses against pathogens and tumors. In the present study, we tested the effect of Bacillus anthracis lethal toxin (LT on NKT cells both in vivo and in vitro. LT is a binary toxin known to suppress host immune responses during anthrax disease and intoxicates cells by protective antigen (PA-mediated intracellular delivery of lethal factor (LF, a potent metalloprotease. We observed that NKT cells expressed anthrax toxin receptors (CMG-2 and TEM-8 and bound more PA than other immune cell types. A sub-lethal dose of LT administered in vivo in C57BL/6 mice decreased expression of the activation receptor NKG2D by NKT cells but not by NK cells. The in vivo administration of LT led to decreased TCR-induced cytokine secretion but did not affect TCR expression. Further analysis revealed LT-dependent inhibition of TCR-stimulated MAP kinase signaling in NKT cells attributable to LT cleavage of the MAP kinase kinase MEK-2. We propose that Bacillus anthracis-derived LT causes a novel form of functional anergy in NKT cells and therefore has potential for contributing to immune evasion by the pathogen.

  5. CONTROLS ON CAPITAL MOVEMENTS

    Directory of Open Access Journals (Sweden)

    Petris Sorina

    2012-12-01

    Full Text Available Until recently, capital mobility was encouraged across national borders, because it was considered that such capital can seek the highest rate of return. However, recent global financial developments have shown that, due to contagion, the mobility of capital flows can cause severe financial imbalances. In the context of globalization, liberalization or maintaining controls on capital flows is a current topic, more debated by economists. This topic is very important, due to the impact of liberalization decision or maintaining controls on capital flows has on the overall macroeconomic framework. The paper analyzes the relationship between capital flows’ control and the income per capita, the degree of central bank independence, democracy country, the foreign exchange regime. Also, it analyzes the effectiveness in time of capital controls, taking account of financial system development and potential risks of instability. Over time, it was observed that a period in which they have imposed restrictions on capital movements was followed by a removal of such restrictions, and vice versa. Cyclic change of capital movements regime corresponds to the cyclic evolution of the global economy. Full capital account liberalization led to the emergence of currency and financial crises, so that the idea of maintaining controls on capital is not rejected by economists. After a full liberalization of capital flows, there is a change in the mentality of an increasing number of economists, who support the maintenance of controls, in a gradual liberalization.

  6. The pathophysiology of restricted repetitive behavior

    OpenAIRE

    Lewis, Mark; Kim, Soo-Jeong

    2009-01-01

    Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, l...

  7. CD8(+) T cells specific to a single Yersinia pseudotuberculosis epitope restrict bacterial replication in the liver but fail to provide sterilizing immunity.

    Science.gov (United States)

    Shen, Haiqian; Gonzalez-Juarbe, Norberto; Blanchette, Krystle; Crimmins, Gregory; Bergman, Molly A; Isberg, Ralph R; Orihuela, Carlos J; Dube, Peter H

    2016-09-01

    CD8(+) T cells use contact-dependent cytolysis of target cells to protect the host against intracellular pathogens. We have previously shown that CD8(+) T cells and perforin are required to protect against the extracellular pathogen Yersinia pseudotuberculosis. Here we establish an experimental system where CD8(+) T cells specific to a single model antigen are the only memory response present at time of challenge. Using mice immunized with a vaccine strain of Listeria monocytogenes that expresses secreted ovalbumin (Lm-OVA), we show that OVA-specific CD8(+) T cells are generated and provide limited protection against challenge with virulent OVA(+)Y. pseudotuberculosis. Perforin expression by OVA-specific CD8(+) T cells was required, as Lm-OVA-immunized perforin-deficient mice showed higher bacterial burden as compared to Lm-OVA-immunized perforin-sufficient mice. Surprisingly, antigen-specific T cell protection waned over time, as Lm-OVA-immune mice eventually succumbed to Yersinia infection. Kinetic analysis of infection in mice with and without OVA-specific CD8(+) T cells revealed that bacterial numbers increased sharply in OVA-naïve mice until death, while OVA-immune mice held bacterial burden to a lower level throughout the duration of illness until death. Clonal analysis of bacterial populations in OVA-naïve and OVA-immune mice at distinct time points revealed equivalent and severe bottle-neck effects for bacteria in both sets of mice immediately after intravenous challenge, demonstrating a dominant role for other aspects of the immune system regardless of CD8(+) T cell status. These studies indicate that CD8(+) T cells against a single antigen can restrict Y. pseudotuberculosis colonization in a perforin-dependent manner, but ultimately are insufficient in their ability to provide sterilizing immunity and protect against death. PMID:27268148

  8. Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Brandt, Lea; Vinner, Lasse;

    2013-01-01

    -cell responses specific for one or more vaccine epitopes were induced in 10/10 vaccinees. The responses were dominated by CD107a and MIP1β expression. There were no significant changes in HIV-1 viral load or CD4 T-cell counts. Our study demonstrates that the peptide/CAF01 vaccine is safe and that it is possible...

  9. Progressive developmental restriction, acquisition of left-right identity and cell growth behavior during lobe formation in mouse liver development.

    Science.gov (United States)

    Weiss, Mary C; Le Garrec, Jean-Francois; Coqueran, Sabrina; Strick-Marchand, Helene; Buckingham, Margaret

    2016-04-01

    To identify cell-based decisions implicated in morphogenesis of the mammalian liver, we performed clonal analysis of hepatocytes/hepatoblasts in mouse liver development, using a knock-in allele of Hnf4a/laacZ This transgene randomly undergoes a low frequency of recombination that generates a functional lacZ gene that produces β-galactosidase in tissues in which Hnf4a is expressed. Two types of β-galactosidase-positive clones were found. Most have undergone three to eight cell divisions and result from independent events (Luria-Delbrück fluctuation test); we calculate that they arose between E8.5 and E13.5. A second class was mega-clones derived from early endoderm progenitors, generating many descendants. Some originated from multi-potential founder cells, with labeled cells in the liver, pancreas and/or intestine. A few mega-clones populate only one side of the liver, indicating hepatic cell chirality. The patterns of labeled cells indicate cohesive and often oriented growth, notably in broad radial stripes, potentially implicated in the formation of liver lobes. This retrospective clonal analysis gives novel insights into clonal origins, cell behavior of progenitors and distinct properties of endoderm cells that underlie the formation and morphogenesis of the liver. PMID:26893346

  10. Gracious Movement

    Directory of Open Access Journals (Sweden)

    Lev Kreft

    2012-07-01

    Full Text Available In 1984 Christopher Cordner offered a critical view on theories of graceful movement in sport developed by Ng. G. Wulk, David Best and Joseph Kupfer. In 2001 Paul Davis criticized his view. Cordner responded, rejecting all the criticism. More than a century before, Herbert Spencer and Jean-Marie Guyau had a similar controversy over grace. Both exchanges of opinion involve three positions: that grace is the most efficient movement and therefore something quantitative and measurable; that grace is expression of the wholeness of person and the world; and that grace is something which neither science nor philosophy can explain. To clarify these conflicting issues, this article proposes to examine the history of the notion which goes back to the Latin gratia and has root in the Ancient Greek charis, and to apply the concepts of cultural anchor and thin coherence, following John R. Searle’s explanation that we produce epistemically objective accounts of ontologically subjective reality.

  11. Expression of the human immunodeficiency virus envelope glycoprotein is restricted to basolateral surfaces of polarized epithelial cells

    International Nuclear Information System (INIS)

    Polarized epithelial cells exhibit apical (lumenal) and basolateral (serosal) membrane domains that are separated by circumferential tight junctions. In such cells, enveloped viruses that mature by budding at cell surfaces are released at particular membrane domains. The authors have used a vaccinia virus recombinant to investigate the site of surface expression of the human immunodeficiency virus type 1 envelope glycoprotein in Madin-Darby canine kidney cells. Cells were infected with the vaccinia virus recombinant, and surface expression of the glycoprotein was analyzed by indirect immunofluorescence, 125I-protein A binding, and immunoelectron microscopy. The glycoprotein appeared exclusively at the basolateral surface as early as 2 h postinfection and reached a maximum level at 8 h postinfection. The gp120 glycoprotein was found to be secreted efficiently into culture medium, and this secretion occurred exclusively at the basolateral surface

  12. Host range restriction of vaccinia virus in Chinese hamster ovary cells: relationship to shutoff of protein synthesis

    International Nuclear Information System (INIS)

    Chinese hamster ovary cells were found to be nonpermissive for vaccinia virus. Although early virus-induced events occurred in these cells (RNA and polypeptide synthesis), subsequent events appeared to be prevented by a very rapid and nonselective shutoff of protein synthesis. Within less than 2 h after infection, both host and viral protein syntheses were arrested. At low multiplicities of infection, inhibition of RNA synthesis with cordycepin resulted in failure of the virus to block protein synthesis. Moreover, infection of the cells in the presence of cycloheximide prevented the immediate onset of shutoff after reversal of cycloheximide. Inactivation of virus particles by uv irradiation also impaired the capacity of the virus to inhibit protein synthesis. These results suggested that an early vaccinia virus-coded product was implicated in the shutoff of protein synthesis. Either the nonpermissive Chinese hamster ovary cells were more sensitive to this inhibition than permissive cells, or a regulatory control of the vaccinia shutoff function was defective

  13. IL-27 receptor signalling restricts the formation of pathogenic, terminally differentiated Th1 cells during malaria infection by repressing IL-12 dependent signals.

    Directory of Open Access Journals (Sweden)

    Ana Villegas-Mendez

    Full Text Available The IL-27R, WSX-1, is required to limit IFN-γ production by effector CD4⁺ T cells in a number of different inflammatory conditions but the molecular basis of WSX-1-mediated regulation of Th1 responses in vivo during infection has not been investigated in detail. In this study we demonstrate that WSX-1 signalling suppresses the development of pathogenic, terminally differentiated (KLRG-1⁺ Th1 cells during malaria infection and establishes a restrictive threshold to constrain the emergent Th1 response. Importantly, we show that WSX-1 regulates cell-intrinsic responsiveness to IL-12 and IL-2, but the fate of the effector CD4⁺ T cell pool during malaria infection is controlled primarily through IL-12 dependent signals. Finally, we show that WSX-1 regulates Th1 cell terminal differentiation during malaria infection through IL-10 and Foxp3 independent mechanisms; the kinetics and magnitude of the Th1 response, and the degree of Th1 cell terminal differentiation, were comparable in WT, IL-10R1⁻/⁻ and IL-10⁻/⁻ mice and the numbers and phenotype of Foxp3⁺ cells were largely unaltered in WSX-1⁻/⁻ mice during infection. As expected, depletion of Foxp3⁺ cells did not enhance Th1 cell polarisation or terminal differentiation during malaria infection. Our results significantly expand our understanding of how IL-27 regulates Th1 responses in vivo during inflammatory conditions and establishes WSX-1 as a critical and non-redundant regulator of the emergent Th1 effector response during malaria infection.

  14. E1A,E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Hua; Makoto Satoh; CHEN Gui-ping; LI De-chuan; Hirofumi Hamada; Yoichi Arai

    2011-01-01

    Background Our previous studies have demonstrated potent oncolysis efficacy of the E1A,E1B double-restricted replication-competent oncolytic adenovirus AxdAdB-3 for treatment of bladder cancer. Here,we reported the feasibility and efficacy of AxdAdB-3 alone,or in combination with gemcitabine for treating renal cell carcinoma.Methods Cytopathic effects of AxdAdB-3 were evaluated in human renal cell carcinoma cell lines TOS-1,TOS-2,TOS-3,TOS-3LN,SMKT-R3,SMKT-R4 and ACHN,and in normal human renal proximal tubule epithelial cells (RPTEC).AxdAdB-3 induced down-regulation of the cell cycle was determined by flow cytometry. Combination therapies of AxdAdB-3 with gemcitabine were evaluated in vitro and in vivo on subcutaneous TOS-3LN tumors in a severe combined immunodeficiency disease (SCID) mouse model.Results AxdAdB-3 was potently cytopathic against the tested most renal cell carcinoma cell lines including TOS-2,TOS-3,TOS-3LN,SMKT-R3 and SMKT-R4,while normal human RPTEC were not destroyed. AxdAdB-3 effectively induced cell cycle S-phase entry. Combined therapy of AxdAdB-3 with gemcitabine demonstrated stronger antitumor effects in vitro and in vivo compared with either AxdAdB-3 or gemcitabine alone.Conclusion AxdAdB-3 alone,or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.

  15. Carbohydrate restriction and dietary cholesterol modulate the expression of HMG-CoA reductase and the LDL receptor in mononuclear cells from adult men

    Directory of Open Access Journals (Sweden)

    Volek Jeff S

    2007-11-01

    Full Text Available Abstract The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10–15% energy from carbohydrate, 30–35% energy from protein and 55–60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C compared to baseline (P > 0.10 or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 ± 1.26 to 1.32 ± 0.92 arbitrary units P

  16. Social movements and human rights rhetoric in tobacco control

    OpenAIRE

    Jacobson, P.; Banerjee, A.

    2005-01-01

    After achieving breathtaking successes in securing state and local restrictions on smoking in public places and restricting youth access to tobacco products, the tobacco movement faces difficult decisions on its future strategic directions. The thesis of this article is that the tobacco control movement is at a point of needing to secure its recent successes and avoiding any public retrenchment. To do so requires rethinking the movement's strategic direction. We use the familiar trans-theoret...

  17. A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells

    DEFF Research Database (Denmark)

    Andersen, P S; Stryhn, A; Hansen, B E; Fugger, L; Engberg, J; Buus, S

    1996-01-01

    lead to novel approaches in immunotherapy. However, it has proven difficult to generate antibodies with the specificity of T cells by conventional hybridoma techniques. Here we report that the phage display technology is a feasible alternative to generate antibodies recognizing specific, predetermined......Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might...

  18. Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes

    DEFF Research Database (Denmark)

    Román, Victor Raúl Gómez; Jensen, Kristoffer Jarlov; Jensen, Sanne Skov;

    2013-01-01

    were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts...... is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected...... against HIV-1 using IFN-γ ELISpot in this chronically infected African population....

  19. High-throughput sequencing reveals restricted TCR Vβ usage and public TCRβ clonotypes among pancreatic lymph node memory CD4(+) T cells and their involvement in autoimmune diabetes.

    Science.gov (United States)

    Marrero, Idania; Aguilera, Carlos; Hamm, David E; Quinn, Anthony; Kumar, Vipin

    2016-06-01

    Islet-reactive memory CD4(+) T cells are an essential feature of type 1 diabetes (T1D) as they are involved in both spontaneous disease and in its recurrence after islet transplantation. Expansion and enrichment of memory T cells have also been shown in the peripheral blood of diabetic patients. Here, using high-throughput sequencing, we investigated the clonal diversity of the TCRβ repertoire of memory CD4(+) T cells in the pancreatic lymph nodes (PaLN) of non-obese diabetic (NOD) mice and examined their clonal overlap with islet-infiltrating memory CD4T cells. Both prediabetic and diabetic NOD mice exhibited a restricted TCRβ repertoire dominated by clones expressing TRBV13-2, TRBV13-1 or TRBV5 gene segments. There is a limited degree of TCRβ overlap between the memory CD4 repertoire of PaLN and pancreas as well as between the prediabetic and diabetic group. However, public TCRβ clonotypes were identified across several individual animals, some of them with sequences similar to the TCRs from the islet-reactive T cells suggesting their antigen-driven expansion. Moreover, the majority of the public clonotypes expressed TRBV13-2 (Vβ8.2) gene segment. Nasal vaccination with an immunodominat peptide derived from the TCR Vβ8.2 chain led to protection from diabetes, suggesting a critical role for Vβ8.2(+) CD4(+) memory T cells in T1D. These results suggest that memory CD4(+) T cells bearing limited dominant TRBV genes contribute to the autoimmune diabetes and can be potentially targeted for intervention in diabetes. Furthermore, our results have important implications for the identification of public T cell clonotypes as potential novel targets for immune manipulation in human T1D. PMID:27161799

  20. Expression of photosynthesis-related gene fusions is restricted by cell type in transgenic plants and in transfected protoplasts.

    OpenAIRE

    Harkins, K R; Jefferson, R A; Kavanagh, T A; Bevan, M W; Galbraith, D W

    1990-01-01

    We have analyzed the expression of chimeric genes in populations of protoplasts isolated from the photosynthetic and nonphotosynthetic tissues within leaves of transgenic tobacco plants and separated by fluorescence-activated cell sorting. Expression of transcriptional gene fusions controlled by promoters from photosynthesis-associated genes showed a striking dependence on cell type. These patterns of expression were preserved when the gene fusions were transfected into normal (nontransgenic)...

  1. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

    OpenAIRE

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2011-01-01

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends o...

  2. Structural Basis for the Presentation of Tumor-Associated MHC Class II-Restricted Phosphopeptides to CD4+ T Cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Depontieu, F; Sidney, J; Salay, T; Engelhard, V; Hunt, D; Sette, A; Topalian, S; Mariuzza, R

    2010-01-01

    Dysregulated protein phosphorylation is a hallmark of malignant transformation. Transformation can generate major histocompatibility complex (MHC)-bound phosphopeptides that are differentially displayed on tumor cells for specific recognition by T cells. To understand how phosphorylation alters the antigenic identity of self-peptides and how MHC class II molecules present phosphopeptides for CD4{sup +} T-cell recognition, we determined the crystal structure of a phosphopeptide derived from melanoma antigen recognized by T cells-1 (pMART-1), selectively expressed by human melanomas, in complex with HLA-DR1. The structure revealed that the phosphate moiety attached to the serine residue at position P5 of pMART-1 is available for direct interactions with T-cell receptor (TCR) and that the peptide N-terminus adopts an unusual conformation orienting it toward TCR. This structure, combined with measurements of peptide affinity for HLA-DR1 and of peptide-MHC recognition by pMART-1-specific T cells, suggests that TCR recognition is focused on the N-terminal portion of pMART-1. This recognition mode appears to be distinct from that of foreign antigen complexes but is remarkably reminiscent of the way autoreactive TCRs engage self- or altered self-peptides, consistent with the tolerogenic nature of tumor-host immune interactions.

  3. The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style.

    Science.gov (United States)

    Margheri, Francesca; Luciani, Cristina; Taddei, Maria Letizia; Giannoni, Elisa; Laurenzana, Anna; Biagioni, Alessio; Chillà, Anastasia; Chiarugi, Paola; Fibbi, Gabriella; Del Rosso, Mario

    2014-03-30

    The receptor for the urokinase plasminogen activator (uPAR) is up-regulated in malignant tumors. Historically the function of uPAR in cancer cell invasion is strictly related to its property to promote uPA-dependent proteolysis of extracellular matrix and to open a path to malignant cells. These features are typical of mesenchymal motility. Here we show that the full-length form of uPAR is required when prostate and melanoma cancer cells convert their migration style from the "path generating" mesenchymal to the "path finding" amoeboid one, thus conferring a plasticity to tumor cell invasiveness across three-dimensional matrices. Indeed, in response to a protease inhibitors-rich milieu, prostate and melanoma cells activated an amoeboid invasion program connoted by retraction of cell protrusions, RhoA-mediated rounding of the cell body, formation of a cortical ring of actin and a reduction of Rac-1 activation. While the mesenchymal movement was reduced upon silencing of uPAR expression, the amoeboid one was almost completely abolished, in parallel with a deregulation of small Rho-GTPases activity. In melanoma and prostate cancer cells we have shown uPAR colocalization with β1/β3 integrins and actin cytoskeleton, as well integrins-actin co-localization under both mesenchymal and amoeboid conditions. Such co-localizations were lost upon treatment of cells with a peptide that inhibits uPAR-integrin interactions. Similarly to uPAR silencing, the peptide reduced mesenchymal invasion and almost abolished the amoeboid one. These results indicate that full-length uPAR bridges the mesenchymal and amoeboid style of movement by an inward-oriented activity based on its property to promote integrin-actin interactions and the following cytoskeleton assembly. PMID:24681666

  4. Correlation between chloride flux via the mitochondria-rich cells and transepithelial water movement in isolated frog skin (Rana esculenta)

    DEFF Research Database (Denmark)

    Nielsen, Robert

    Antidiuretic hormone; chloride transport; electroosmosis; Frog skin; Intercalated cells; Local osmosis; Mitochondria-rich cells.......Antidiuretic hormone; chloride transport; electroosmosis; Frog skin; Intercalated cells; Local osmosis; Mitochondria-rich cells....

  5. Computational movement analysis

    CERN Document Server

    Laube, Patrick

    2014-01-01

    This SpringerBrief discusses the characteristics of spatiotemporal movement data, including uncertainty and scale. It investigates three core aspects of Computational Movement Analysis: Conceptual modeling of movement and movement spaces, spatiotemporal analysis methods aiming at a better understanding of movement processes (with a focus on data mining for movement patterns), and using decentralized spatial computing methods in movement analysis. The author presents Computational Movement Analysis as an interdisciplinary umbrella for analyzing movement processes with methods from a range of fi

  6. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells

    International Nuclear Information System (INIS)

    The authors have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. The analysis indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson two-hit hypothesis. In addition, the analysis has shown that inactivations of the RB gene are nearly as frequent in a more common human tumor, small cell lung carcinoma. One-third of bladder carcinomas surveyed also carry altered or absent p105-Rb. Other human tumors by contrast demonstrate only infrequent inactivation of the RB gene. These results suggest that inactivation of the RB gene is a critical step in the pathogenesis of a subset of human tumors

  7. The repair fidelity of restriction enzyme-induced double strand breaks in plasmid DNA correlates with radioresistance in human tumor cell lines

    International Nuclear Information System (INIS)

    The accuracy of DNA repair may play a role in determining the cytotoxic effect of ionizing radiation. Repair, as measured by DNA strand breakage, often shows little difference between tumor cell lines of widely different radiosensitivity. The mechanism by which DNA fragments are rejoined is poorly understood. This study used plasmid transfection as a probe to assess the balance between correct repair and misrepair. A general trend for sensitive cells to show lower repair fidelity relative to resistant cells was observed. The type of double-strand cleavage of the plasmid (staggered or blunt) made little difference to the measured repair fidelity, in contrast to published studies in which restriction-enzyme breaks had been introduced into DNA within chromatin. Specific comparison of parent lines and their radiosensitive clones showed significant differences in repair fidelity for a relatively small change in radiation response, which was in line with the overall correlation. These same pairs have previously been shown to have no difference in the loss of DNA fragmentation with time after irradiation, and Southern analysis had confirmed the integrated plasmid copy number was similar in the cell lines compared. The number of intact copies of the damaged gene relative to the undamaged gene mirrored the observed repair fidelity. However, in one cell line out of the 10 studied, an exception to the observed trend was found. In comparison of two equally radioresistant bladder cancer cell lines, large differences in repair fidelity were observed. Again, no difference in the integrated copy number was found, and the damaged gene was highly rearranged or deleted in the cell line with low repair fidelity. It is suggested that repair fidelity can be, but is not invariably, a measure of correct repair relative to misrepair, resulting from the processing of double-strand breaks and, hence, the response to ionizing radiation. 24 refs., 2 figs., 2 tabs

  8. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.

    Science.gov (United States)

    Salerno-Gonçalves, Rosângela; Fernandez-Viña, Marcelo; Lewinsohn, David M; Sztein, Marcelo B

    2004-11-01

    Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net frequency of IFN-gamma spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections. PMID:15494539

  9. A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis

    OpenAIRE

    Calvo, Dominica; Victor, Martin; Gay, Frédérique; Sui, Guangchao; Luke, Margaret Po-Shan; Dufourcq, Pascale; Wen, Gengyun; Maduro, Morris; Rothman, Joel; Shi, Yang

    2001-01-01

    In Caenorhabditis elegans, histone acetyltransferase CBP-1 counteracts the repressive activity of the histone deacetylase HDA-1 to allow endoderm differentiation, which is specified by the E cell. In the sister MS cell, the endoderm fate is prevented by the action of an HMG box-containing protein, POP-1, through an unknown mechanism. In this study, we show that CBP-1, HDA-1 and POP-1 converge on end-1, an initial endoderm-determining gene. In the E lineage, an essential function of CBP-1 appe...

  10. Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4+ T cells

    OpenAIRE

    Yik Lim Kok; Valentina Vongrad; Mohaned Shilaih; Francesca Di Giallonardo; Herbert Kuster; Roger Kouyos; Günthard, Huldrych F.; Metzner, Karin J.

    2016-01-01

    The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integ...

  11. Cell size and fat content of dietary-restricted Caenorhabditis elegans are regulated by ATX-2, an mTOR repressor.

    Science.gov (United States)

    Bar, Daniel Z; Charar, Chayki; Dorfman, Jehudith; Yadid, Tam; Tafforeau, Lionel; Lafontaine, Denis L J; Gruenbaum, Yosef

    2016-08-01

    Dietary restriction (DR) is a metabolic intervention that extends the lifespan of multiple species, including yeast, flies, nematodes, rodents, and, arguably, rhesus monkeys and humans. Hallmarks of lifelong DR are reductions in body size, fecundity, and fat accumulation, as well as slower development. We have identified atx-2, the Caenorhabditis elegans homolog of the human ATXN2L and ATXN2 genes, as the regulator of these multiple DR phenotypes. Down-regulation of atx-2 increases the body size, cell size, and fat content of dietary-restricted animals and speeds animal development, whereas overexpression of atx-2 is sufficient to reduce the body size and brood size of wild-type animals. atx-2 regulates the mechanistic target of rapamycin (mTOR) pathway, downstream of AMP-activated protein kinase (AMPK) and upstream of ribosomal protein S6 kinase and mTOR complex 1 (TORC1), by its direct association with Rab GDP dissociation inhibitor β, which likely regulates RHEB shuttling between GDP-bound and GTP-bound forms. Taken together, this work identifies a previously unknown mechanism regulating multiple aspects of DR, as well as unknown regulators of the mTOR pathway. They also extend our understanding of diet-dependent growth retardation, and offers a potential mechanism to treat obesity. PMID:27457958

  12. A HLA-A2 restricted human CTL line recognizes a novel tumor cell expressed p53 epitope

    DEFF Research Database (Denmark)

    Würtzen, Peter A; Claesson, Mogens H

    2002-01-01

    , the CTL line, which expressed relatively low affinity for the HLA-A2/peptide complex, was able to kill 3 different HLA-A2(+) p53 mutated tumor cell lines. The present and our previous observations expand the number of p53-derived peptides suitable for vaccination protocols for cancer patients with p53......A p53 peptide-specific CTL line was generated through stimulation with autologous monocyte-derived dendritic cells (DC) pulsed with wild-type HLA-A2 binding p53 derived peptides. A p53 peptide-specific CD8(+) CTL line was established from a healthy HLA-A2 positive donor. The CTL line was...... characterized with respect to specificity, affinity and killing of cell lines derived from p53 mutated spontaneous tumors. The CTL line demonstrated lysis of p53(139-147) pulsed target cells and cold target inhibition experiments as well as antibody blocking confirmed that the killing was epitope-specific, HLA...

  13. High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.

    Science.gov (United States)

    Nair, Smita K; Tomaras, Georgia D; Sales, Ana Paula; Boczkowski, David; Chan, Cliburn; Plonk, Kelly; Cai, Yongting; Dannull, Jens; Kepler, Thomas B; Pruitt, Scott K; Weinhold, Kent J

    2014-01-01

    Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide epitopes is necessary for peptide-based vaccine strategies. We present a three-tiered strategy for identifying and validating immunogenic peptides: first, identify peptides that form stable complexes with class I MHC molecules; second, determine whether cytotoxic T lymphocytes (CTLs) raised against the whole protein antigen recognize and lyse target cells pulsed with peptides that passed step 1; third, determine whether peptides that passed step 2, when administered in vivo as a vaccine in HLA-A2 transgenic mice, elicit CTLs that lyse target cells expressing the whole protein antigen. Our innovative approach uses dendritic cells transfected with Mtb antigen-encoding mRNA to drive antigen expression. Using this strategy, we have identified five novel peptide epitopes from the Mtb proteins Apa, Mtb8.4 and Mtb19. PMID:24755960

  14. Discovery of a novel restriction endonuclease by genome comparison and application of a wheat-germ-based cell-free translation assay: PabI (5′-GTA/C) from the hyperthermophilic archaeon Pyrococcus abyssi

    OpenAIRE

    Ishikawa, Ken; Watanabe, Miki; Kuroita, Toshihiro; Uchiyama, Ikuo; Bujnicki, Janusz M.; Kawakami, Bunsei; Tanokura, Masaru; Kobayashi, Ichizo

    2005-01-01

    To search for restriction endonucleases, we used a novel plant-based cell-free translation procedure that bypasses the toxicity of these enzymes. To identify candidate genes, the related genomes of the hyperthermophilic archaea Pyrococcus abyssi and Pyrococcus horikoshii were compared. In line with the selfish mobile gene hypothesis for restriction–modification systems, apparent genome rearrangement around putative restriction genes served as a selecting criterion. Several candidate restricti...

  15. Selective Targeting and Restrictive Damage for Nonspecific Cells by Pulsed Laser-Activated Hyaluronan-Gold Nanoparticles.

    Science.gov (United States)

    Rau, Lih-Rou; Tsao, Shu-Wei; Liaw, Jiunn-Woei; Tsai, Shiao-Wen

    2016-08-01

    Herein, we describe an approach that immobilizes low-molecular-weight hyaluronic acid (low-MW HA) on the surface of gold nanoparticles (GNPs), which can serve as a cellular probe and photodamage media, to evaluate the selectivity and efficiency of HA-based GNPs (HGNPs) as a mediator of laser-induced photothermal cell damage. In addition, it is known that solid tumors contain a higher content of low-MW HA than normal tissues. Thus, we used low-MW HA rather than high-MW HA used in other studies. In the present study, we conjugated low-MW HA, which is a linear polysaccharide with a disaccharide repeat unit, to prevent a reduction of the ligand-receptor binding efficiency in contrast to the conjugation of protein or peptides, which have unique three-dimensional structures. Three cell lines-MDA-MB-435 S (with CD44), MDA-MB-453 and NIH/3T3 (both are without CD44)-were investigated in the study, and qualitative observations were conducted by dark-field microscopy and laser scanning confocal microscopy (LSCM). In addition, quantitative measurements calculated using inductively coupled plasma emissions were taken for comparison. Our results showed that within the same treatment time, the uptake dosage of HGNPs by the MDA-MB-435 S cells was higher than that by the MDA-MB-453 and NIH 3T3 cells. Meanwhile, HGNPs uptake by the untreated MDA-MB-435 S cells was higher than that of MDA-MB-435 S cells with CD44 blocked by antibodies or silencing CD44 expression. This result implies that receptor-mediated endocytosis can enhance the cellular uptake of HGNPs. In addition, when exposed to a low-power pulsed laser, the former cell morphologies showed a more laser-induced giant plasma membrane vesicles (GPMV) than the latter morphologies. Therefore, this study utilized the specific photothermal property of HA-modified GNPs with laser-induced blebs to create a possible new method for medical applications. PMID:27439142

  16. Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

    Science.gov (United States)

    Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

    2013-06-01

    Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

  17. Detection and Quantification of CD4+ T Cells with Specificity for a New Major Histocompatibility Complex Class II-Restricted Influenza A Virus Matrix Protein Epitope in Peripheral Blood of Influenza Patients

    OpenAIRE

    Linnemann, Thomas; Jung, Günther; Walden, Peter

    2000-01-01

    FVFTLTVPS was identified as the core sequence of a new major histocompatibility complex class II-restricted T-cell epitope of influenza virus matrix protein. Epitope-specific CD4+ T cells were detected in the peripheral blood of patients with frequencies of up to 0.94%, depending on the number of additional terminal amino acids.

  18. Acute response of peripheral CCr5 chemoreceptor and NK cells in individuals submitted to a single session of low-intensity strength exercise with blood flow restriction.

    Science.gov (United States)

    Dorneles, Gilson Pires; Colato, Alana Schraiber; Galvão, Simone Lunelli; Ramis, Thiago Rozales; Ribeiro, Jerri Luiz; Romão, Pedro Roosevelt; Peres, Alessandra

    2016-07-01

    The purpose of this study was to compare the peripheral expression of natural killers and CCR5 in a session of low-intensity strength training with vascular occlusion and in high-intensity training. Young males were randomized into session groups of a high-intensity strength training (HI) and a session group of low-intensity strength training with vascular occlusion (LI-BFR). The exercise session consisted in knee extension and bicep curl in 80% 1RM (HI) and 30% 1RM (LI-BFR) with equalized volumes. Blood collection was made before, immediately after and 24 h after each training session. Immunophenotyping was carried out through CD195+ (CCR5) e CD3-CD16+CD56+ (NK) in peripheral blood and analysed by flow cytometry and presented in frequency (%). Peripheral frequency of NK cells showed no significant difference in LI-BFR group in time effect, while a gradual reduction of NK cells was identified in HI group in before-24 h postexercise and after-24 h postexercise comparison. However, significant differences have been found in relative change of NK cells immediately after exercise between sessions. In addition, HI and LI-BFR groups showed a significant reduction in the cells expressed CCR5 during 24 h postsession compared to the postsession, but CCR5 also differed when comparing before-24 h after session in the HI group. No differences were observed amongst the groups. LIO induced CCR5 response similar to the HI session, while the NK cells remained in similar frequency during the studied moments in LI-BFR, but not in HI group, suggesting that local hypoxia created by the blood flow restriction was able to prevent a change in the frequency of peripheral cells and a possible immunosuppression. PMID:25643617

  19. Engineering of Isogenic Cells Deficient for MR1 with a CRISPR/Cas9 Lentiviral System: Tools To Study Microbial Antigen Processing and Presentation to Human MR1-Restricted T Cells.

    Science.gov (United States)

    Laugel, Bruno; Lloyd, Angharad; Meermeier, Erin W; Crowther, Michael D; Connor, Thomas R; Dolton, Garry; Miles, John J; Burrows, Scott R; Gold, Marielle C; Lewinsohn, David M; Sewell, Andrew K

    2016-08-01

    The nonclassical HLA molecule MHC-related protein 1 (MR1) presents metabolites of the vitamin B synthesis pathways to mucosal-associated invariant T (MAIT) cells and other MR1-restricted T cells. This new class of Ags represents a variation on the classical paradigm of self/non-self discrimination because these T cells are activated through their TCR by small organic compounds generated during microbial vitamin B2 synthesis. Beyond the fundamental significance, the invariant nature of MR1 across the human population is a tantalizing feature for the potential development of universal immune therapeutic and diagnostic tools. However, many aspects of MR1 Ag presentation and MR1-restricted T cell biology remain unknown, and the ubiquitous expression of MR1 across tissues and cell lines can be a confounding factor for experimental purposes. In this study, we report the development of a novel CRISPR/Cas9 genome editing lentiviral system and its use to efficiently disrupt MR1 expression in A459, THP-1, and K562 cell lines. We generated isogenic MR1(-/-) clonal derivatives of the A549 lung carcinoma and THP-1 monocytic cell lines and used these to study T cell responses to intracellular pathogens. We confirmed that MAIT cell clones were unable to respond to MR1(-/-) clones infected with bacteria whereas Ag presentation by classical and other nonclassical HLAs was unaffected. This system represents a robust and efficient method to disrupt the expression of MR1 and should facilitate investigations into the processing and presentation of MR1 Ags as well as into the biology of MAIT cells. PMID:27307560

  20. B-cell responses to pregnancy-restricted and -unrestricted Plasmodium falciparum erythrocyte membrane protein 1 antigens in Ghanaian women naturally exposed to malaria parasites

    DEFF Research Database (Denmark)

    Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F;

    2014-01-01

    Protective immunity to Plasmodium falciparum malaria acquired after natural exposure is largely antibody mediated. IgG-specific P. falciparum EMP1 (PfEMP1) proteins on the infected erythrocyte surface are particularly important. The transient antibody responses and the slowly acquired protective...... immunity probably reflect the clonal antigenic variation and allelic polymorphism of PfEMP1. However, it is likely that other immune-evasive mechanisms are also involved, such as interference with formation and maintenance of immunological memory. We measured PfEMP1-specific antibody levels by enzyme......-linked immunosorbent assay (ELISA) and memory B-cell frequencies by enzyme-linked immunosorbent spot (ELISPOT) assay in a cohort of P. falciparum-exposed nonpregnant Ghanaian women. The antigens used were a VAR2CSA-type PfEMP1 (IT4VAR04) with expression restricted to parasites infecting the placenta, as well as two...

  1. Restricting lignin and enhancing sugar deposition in secondary cell walls enhances monomeric sugar release after low temperature ionic liquid pretreatment

    OpenAIRE

    Scullin, Chessa; Cruz, Alejandro G; Chuang, Yi-De; Simmons, Blake A.; Loque, Dominique; Singh, Seema

    2015-01-01

    Background Lignocellulosic biomass has the potential to be a major source of renewable sugar for biofuel production. Before enzymatic hydrolysis, biomass must first undergo a pretreatment step in order to be more susceptible to saccharification and generate high yields of fermentable sugars. Lignin, a complex, interlinked, phenolic polymer, associates with secondary cell wall polysaccharides, rendering them less accessible to enzymatic hydrolysis. Herein, we describe the analysis of engineere...

  2. miRNA Profiles of Monocyte-Lineage Cells Are Consistent with Complicated Roles in HIV-1 Restriction

    OpenAIRE

    Clements, Janice E.; Sisk, Jeanne M.; Witwer, Kenneth W.

    2012-01-01

    Long-lived HIV-1 reservoirs include tissue macrophages. Monocyte-derived macrophages are more susceptible to infection and more permissive to HIV-1 replication than monocytes for reasons that may include the effects of different populations of miRNAs in these two cell classes. Specifically, miRs-28-3p, -150, -223, -198, and -382 exert direct or indirect negative effects on HIV-1 and are reportedly downmodulated during monocyte-to-macrophage differentiation. Here, new experimental results are ...

  3. Studies of a nuclear matrix protein restricted to normal brain cells and lead-induced intranuclear inclusion bodies of kidney

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, K.; Egle, P.; Redford, K.; Bigbee, J.

    1986-05-01

    A nuclear matrix protein, p32/6.3, with an unusual tissue distribution, has been identified. Protein from 21 tissues was surveyed by immunoprobing Western blots. In normal adult rats p32/6.3 is found only in grey matter from the cerebrum and the cerebellum, occurring in both neurons and astrocytes. Other brain cell types have not been examined. The protein appears to be developmentally regulated. It is detectable in the brain within a few days after birth and reaches adult levels within one to two weeks. Brain p32/6.3 has been found in all animals tested including rat, mouse, dog, cow, pig, chicken and human. This conservation indicates a fundamental role for p32/6.3 in the nucleus of brain cells. Possible functions for p32/6.3 may be indicated by a second novel occurrence. Chronic lead poisoning characteristically induces intranuclear inclusion bodies in the cells lining kidney proximal tubules. p32/6.3 is a major constituent of these inclusion bodies. They are also rich in lead and other metals including calcium, iron, zinc, copper and cadmium. These diverse observations suggest that p32/6.3 may have a role in metal homeostasis in the brain of normal animals.

  4. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    International Nuclear Information System (INIS)

    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F1 hybrid bone marrow. The F1 → C3H chimera but not the F1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F1 → C57BL/6 chimera but not the F1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  5. Virulent Mycobacterium fortuitum restricts NO production by a gamma interferon-activated J774 cell line and phagosome-lysosome fusion.

    Science.gov (United States)

    Da Silva, Tânia Regina Marques; De Freitas, Juliana Ribeiro; Silva, Queilan Chagas; Figueira, Cláudio Pereira; Roxo, Eliana; Leão, Sylvia Cardoso; De Freitas, Luiz Antônio Rodrigues; Veras, Patrícia Sampaio Tavares

    2002-10-01

    The virulence of different isolates of Mycobacterium has been associated with two morphologically distinguishable colonial variants: opaque (SmOp) and transparent (SmTr). In this report we used an in vitro assay to compare macrophage (Mphi) responses to SmOp and SmTr Mycobacterium fortuitum variants, taking advantage of the fact that these variants were derived from the same isolate. Cells preactivated or not with gamma interferon (IFN-gamma) were infected with SmOp or SmTr M. fortuitum. We showed that SmOp and SmTr induced different levels of nitric oxide (NO) production by IFN-gamma-stimulated Mphi. Indeed, the amount of IFN-gamma-induced NO production by J774 cells was 4.8 to 9.0 times higher by SmOp (23.1 to 37.7 micro M) compared to SmTr infection (3.9 to 4.8 micro M) (P = 0.0332), indicating that virulent SmTr bacilli restricted NO production. In addition, IFN-gamma-induced NO production by Mphi was higher when correlated with reduction of only avirulent SmOp bacillus viability. SNAP (S-nitroso-N-acetyl-DL-penicillamine)-induced NO production did not modify SmTr viability, indicating its resistance to nitrogen radicals. Electron microscopy studies were performed to evaluate the capacity of phagosomes to fuse with lysosomes labeled with bovine serum albumin-colloidal gold particles. By 24 h postinfection, 69% more phagosome-containing SmOp variant had fused with lysosomes compared to the SmTr-induced phagosomes. In conclusion, these data indicate that virulent SmTr bacilli may escape host defense by restricting IFN-gamma-induced NO production, resisting nitrogen toxic radicals, and limiting phagosome fusion with lysosomes. PMID:12228291

  6. Pregnane × Receptor (PXR expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation

    Directory of Open Access Journals (Sweden)

    Lumbroso Serge

    2010-03-01

    Full Text Available Abstract Background Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11 is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR, we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. Results PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies

  7. Alphavirus Restriction by IFITM Proteins.

    Science.gov (United States)

    Weston, Stuart; Czieso, Stephanie; White, Ian J; Smith, Sarah E; Wash, Rachael S; Diaz-Soria, Carmen; Kellam, Paul; Marsh, Mark

    2016-09-01

    Interferon inducible transmembrane proteins (IFITMs) are broad-spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by either virus. IFITM3 inhibits release of the SFV capsid into the cytosol, without inhibiting binding, internalization, trafficking to endosomes or low pH-induced conformational changes in the envelope glycoprotein. Infection by SFV fusion at the cell surface was inhibited by IFITM1, but was equally inhibited by IFITM3. Furthermore, an IFITM3 mutant (Y20A) that is localized to the plasma membrane inhibited infection by cell surface fusion more potently than IFITM1. Together, these results indicate that IFITMs, in particular IFITM3, can restrict alphavirus infection by inhibiting viral fusion with cellular membranes. That IFITM3 can restrict SFV infection by fusion at the cell surface equivalently to IFITM1 suggests that IFITM3 has greater antiviral potency against SFV. PMID:27219333

  8. Dual MHC class I and class II restriction of a single T cell receptor: distinct modes of tolerance induction by two classes of autoantigens.

    Science.gov (United States)

    Arsov, I; Vukmanović, S

    1999-02-15

    In the final stages of thymic development, immature T cells undergo three distinct processes (positive selection, negative selection, and lineage commitment) that all depend on interactions of thymocyte TCRs with MHC molecules. It is currently thought that TCRs are preferentially restricted by either MHC class I or class II molecules. In this report, we present direct evidence that the TCR previously described as H-Y/H-2Db specific cross-reacts with H-2IAb if expressed in CD4+ cells. We also demonstrate an increase in thymocyte numbers in H-Y TCR-trangenic mice deficient in MHC class II, suggesting a relatively discrete form of negative selection by MHC class II compared with that induced by H-Y/H-2Db. We propose that inability to generate CD4+ T cells expressing H-Y TCR in different experimental settings may be due to tolerance to self-MHC class II. These results, therefore, support an intriguing possibility that tolerance to self may influence and/or interfere with the outcome of the lineage commitment. PMID:9973472

  9. 3′ UTR-Dependent, miR-92-Mediated Restriction of Tis21 Expression Maintains Asymmetric Neural Stem Cell Division to Ensure Proper Neocortex Size

    Directory of Open Access Journals (Sweden)

    Ji-Feng Fei

    2014-04-01

    Full Text Available Mammalian neocortex size primarily reflects the number and mode of divisions of neural stem and progenitor cells. Cortical stem cells (apical progenitors switching from symmetric divisions, which expand their population, to asymmetric divisions, which generate downstream neuronal progenitors (basal progenitors, start expressing Tis21, a so-called antiproliferative/prodifferentiative gene. Tis21 encodes a small (17.5 kDa, functionally poorly characterized protein and a relatively large (2 kb, highly conserved 3′ UTR. Here, we show that mice lacking the Tis21 3′ UTR develop a microcephalic neocortex with fewer neurons, notably in the upper layers. This reflects a progressive decrease in basal progenitors, which in turn is due to a fraction of apical progenitors prematurely switching from asymmetric self-renewing to symmetric self-consuming divisions. This switch is caused by the markedly increased Tis21 protein level resulting from lack of microRNA-, notably miR-92-, dependent restriction of Tis21 expression. Our data show that a premature onset of consumptive neural stem cell divisions can lead to microcephaly.

  10. Improved restriction landmark cDNA scanning and its application to global analysis of genes regulated by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Mayumi, K; Yaoi, T; Kawai, J; Kojima, S; Watanabe, S; Suzuki, H

    1998-07-30

    Restriction landmark cDNA scanning (RLCS) is a novel method by which more than 1000 genes can be simultaneously and quantitatively displayed as two-dimensional gel spots. Here we present an adaptation that allows an individual spot to correspond to a unique gene species without redundancy in more than two gel patterns. Using this improved RLCS, we examined global changes on the gene expression of PC12 cells before and after treatment with nerve growth factor. Among a total of 3000 spots, 21 (0.70%) and 91 (3.03%) spots newly appeared and became more intense with treatment. On the other hand, 15 (0.50%) and 44 (1.47%) spots disappeared, becoming less intense with treatment. These observations suggest that approx. 6% of the detected PC12 genes are up-(3.73%) or down-(1.97%) regulated when the cells differentiate to neuronal cells. In comparison with the results obtained using the expressed-sequence-tag approach, previously reported by Lee et al. (Proc. Natl. Acad. Sci. USA 92 (1995) 8303-8307), RLCS should be useful for quantitatively examining the global change of differentially expressed genes of various expression levels. PMID:9714711

  11. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-01-01

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated. PMID:26986509

  12. Changes in the Responses of Purkinje Cells in the Floccular Complex of Monkeys After Motor Learning in Smooth Pursuit Eye Movements

    OpenAIRE

    Kahlon, Maninder; Lisberger, Stephen G.

    2000-01-01

    We followed simple- and complex-spike firing of Purkinje cells (PCs) in the floccular complex of the cerebellum through learned modifications of the pursuit eye movements of two monkeys. Learning was induced by double steps of target speed in which initially stationary targets move at a “learning” speed for 100 ms and then change to either a higher or lower speed in the same direction. In randomly interleaved control trials, targets moved at the learning speed in the opposite direction. When ...

  13. Movement in Architecture: A Spacial Movement Theory

    OpenAIRE

    Mitchell, Lauren Coleen

    2010-01-01

    As the body moves through space ephemeral lines of movement are created. These lines of movement are influenced by body tendencies. We learn from the body by watching the path and patterning of movement. From the study of the movement of the body, theories of spacial movement were developed. The goal of my project is to draw from spacial movement theory to create an architectural expression that motivates movement of the body on my site and through my building. The focus of my thesis is ...

  14. Phloem restriction of viroids in three citrus hosts is overcome by grafting with Etrog citron: potential involvement of a translocatable factor.

    Science.gov (United States)

    Bani-Hashemian, Seyed Mehdi; Pensabene-Bellavia, Giovanni; Duran-Vila, Nuria; Serra, Pedro

    2015-08-01

    Viroid systemic spread involves cell-to-cell movement from initially infected cells via plasmodesmata, long-distance movement within the phloem and again cell-to-cell movement to invade distal tissues including the mesophyll. Citrus exocortis viroid (CEVd), hop stunt viroid, citrus bent leaf viroid, citrus dwarfing viroid, citrus bark cracking viroid and citrus viroid V remained phloem restricted when singly infecting Citrus karna, Citrus aurantium and Poncirus trifoliata, but not Etrog citron, where they were additionally detected in mesophyll protoplasts. However, when CEVd-infected C. karna was side-grafted with Etrog citron--with the resulting plants being composed of a C. karna stock and an Etrog citron branch--the viroid was detected in mesophyll protoplasts of the former, thus indicating that the ability of Etrog citron to support viroid invasion of non-vascular tissues was transferred to the stock. Further results suggest that a translocatable factor from Etrog citron mediates this viroid trafficking. PMID:25888624

  15. Restricting retrotransposons: a review.

    Science.gov (United States)

    Goodier, John L

    2016-01-01

    Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic "parasites", focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation. Some factors act in the nucleus and involve DNA repair enzymes or epigenetic processes of DNA methylation and histone modification. RISC and piRNA pathway proteins protect the germline. Retrotransposon control is relaxed in some cell types, such as neurons in the brain, stem cells, and in certain types of disease and cancer, with implications for human health and disease. This review also considers potential pitfalls in interpreting retrotransposon-related data, as well as issues to consider for future research. PMID:27525044

  16. Activation of CD1d-restricted natural killer T cells can inhibit cancer cell proliferation during chemotherapy by promoting the immune responses in murine mesothelioma.

    Science.gov (United States)

    Wu, Licun; Yun, Zhihong; Tagawa, Tetsuzo; De la Maza, Luis; Wu, Matthew Onn; Yu, Julie; Zhao, Yidan; de Perrot, Marc

    2014-12-01

    We studied the impact of natural killer T (NKT) cell activation by alpha-galactocysylceramide (α-GalCer, α-GC) on cancer cell repopulation during chemotherapy in murine mesothelioma. The number of NKT cells was found to be increased during the development of murine mesothelioma. NKT cells specifically recognize α-GC through CD1d resulting in their activation and expansion. Tumor-bearing mice were treated with chemotherapy once weekly, and α-GC was followed after each cycle of chemotherapy. Anti-tumor effect was evaluated on wild-type (WT) and CD1d knockout (CD1dKO) mice. Cancer cell proliferation and apoptosis were evaluated by Ki67 and TUNEL immunohistochemistry. CD4(+) and CD8(+) T cell proportion and activation in tumor, spleen, draining lymph node and peripheral blood were determined by flow cytometry, and gene expression of activated T cell-related cytokines was quantified by reverse transcription PCR. NKT cells were identified by CD1d-α-GC-tetramer staining. In WT mice, tumor growth delay was achieved by cisplatin (Cis), and this effect was improved in combination with α-GC, but α-GC alone had little effect. Cancer cell proliferation during chemotherapy was significantly inhibited by α-GC, while cancer cell death was significantly upregulated. α-GC following chemotherapy resulted in NKT cell expansion and an increase of interferon-γ production in the draining lymph node, blood and spleen. Gene expression of immune-associated cytokines was upregulated. Strikingly, the percentage of inducible T cell co-stimulator(+)CD4 T cells, Th17/Tc17 cells increased in splenocytes. In CD1d KO mice, however, Cis alone was less effective and Cis + α-GC provided no additional benefit over Cis alone. α-GC alone had minimal effect in both mice. NKT activation between cycles of chemotherapy could improve the outcome of mesothelioma treatment. PMID:25183171

  17. Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development.

    Science.gov (United States)

    Ahuja, Suchit; Dogra, Deepika; Stainier, Didier Y R; Reischauer, Sven

    2016-04-01

    The atrioventricular canal (AVC) connects the atrial and ventricular chambers of the heart and its formation is critical for the development of the cardiac valves, chamber septation and formation of the cardiac conduction system. Consequently, problems in AVC formation can lead to congenital defects ranging from cardiac arrhythmia to incomplete cardiac septation. While our knowledge about early heart tube formation is relatively comprehensive, much remains to be investigated about the genes that regulate AVC formation. Here we identify a new role for the basic helix-loop-helix factor Id4 in zebrafish AVC valve development and function. id4 is first expressed in the AVC endocardium and later becomes more highly expressed in the atrial chamber. TALEN induced inactivation of id4 causes retrograde blood flow at the AV canal under heat induced stress conditions, indicating defects in AV valve function. At the molecular level, we found that id4 inactivation causes misexpression of several genes important for AVC and AV valve formation including bmp4 and spp1. We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. PMID:26892463

  18. Markers of early endothelial dysfunction in intrauterine growth restriction-derived human umbilical vein endothelial cells revealed by 2D-DIGE and mass spectrometry analyses.

    Science.gov (United States)

    Caniuguir, Andres; Krause, Bernardo J; Hernandez, Cherie; Uauy, Ricardo; Casanello, Paola

    2016-05-01

    Intrauterine growth restriction (IUGR) associates with fetal and placental vascular dysfunction, and increased cardiovascular risk later on life. We hypothesize that endothelial cells derived from IUGR umbilical veins present significant changes in the proteome which could be involved in the endothelial dysfunction associated to this conditions. To address this the proteome profile of human umbilical endothelial cells (HUVEC) isolated from control and IUGR pregnancies was compared by 2D-Differential In Gel Electrophoresis (DIGE) and further protein identification by MALDI-TOF MS. Using 2D-DIGE 124 spots were identified as differentially expressed between control and IUGR HUVEC, considering a cut-off of 2 fold change, which represented ∼10% of the total spots detected. Further identification by MALDI-TOF MS and in silico clustering of the proteins showed that those differentially expressed proteins between control and IUGR HUVEC were mainly related with cytoskeleton organization, proteasome degradation, oxidative stress response, mRNA processing, chaperones and vascular function. Finally Principal Component analysis of the identified proteins showed that differentially expressed proteins allow distinguishing between control and IUGR HUVEC based on their proteomic profile. This study demonstrates for the first time that IUGR-derived HUVEC maintained in primary culture conditions present an altered proteome profile, which could reflect an abnormal programming of endothelial function in this fetal condition. PMID:27208404

  19. Movement disorders.

    Science.gov (United States)

    Stoessl, A Jon; Mckeown, Martin J

    2016-01-01

    Movement disorders can be hypokinetic (e.g., parkinsonism), hyperkinetic, or dystonic in nature and commonly arise from altered function in nuclei of the basal ganglia or their connections. As obvious structural changes are often limited, standard imaging plays less of a role than in other neurologic disorders. However, structural imaging is indicated where clinical presentation is atypical, particularly if the disorder is abrupt in onset or remains strictly unilateral. More recent advances in magnetic resonance imaging (MRI) may allow for differentiation between Parkinson's disease and atypical forms of parkinsonism. Functional imaging can assess regional cerebral blood flow (functional MRI (fMRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT)), cerebral glucose metabolism (PET), neurochemical and neuroreceptor status (PET and SPECT), and pathologic processes such as inflammation or abnormal protein deposition (PET) (Table 49.1). Cerebral blood flow can be assessed at rest, during the performance of motor or cognitive tasks, or in response to a variety of stimuli. In appropriate situations, the correct imaging modality and/or combination of modalities can be used to detect early disease or even preclinical disease, and to monitor disease progression and the effects of disease-modifying interventions. Various approaches are reviewed here. PMID:27430452

  20. Expression of Interferon γ by Decidual Cells and Natural Killer Cells at the Human Implantation Site: Implications for Preeclampsia, Spontaneous Abortion, and Intrauterine Growth Restriction.

    Science.gov (United States)

    Chen, Chie-Pein; Piao, Longzhu; Chen, Xilin; Yu, Jianhua; Masch, Rachel; Schatz, Frederick; Lockwood, Charles J; Huang, S Joseph

    2015-11-01

    Human first-trimester decidual cells (FTDCs) chemoattract CXCR3-expressing circulating CD56(bright)CD16(-) natural killer (NK) cells, which increase uteroplacental blood flow by remodeling spiral arteries and arterioles. This recruitment reflects elevated FTDC expression of NK cell-recruiting induced protein 10 and interferon (IFN)-inducible T-cell-α chemoattractant produced in response to the synergistic effects of tumor necrosis factor α (TNF-α) and IFN-γ stimulation. Decidual macrophages express TNF-α, whereas the cellular origin of IFN-γ is unclear. Therefore, this study aims to identify the cell source(s) of IFN-γ in human first trimester decidua. Immunostaining of decidual sections revealed that both FTDCs and decidual NK (dNK) cells express IFN-γ. Although individual dNK cells express higher IFN-γ levels, the more numerous FTDCs account for greater proportion of total IFN-γ immunostaining. Freshly isolated FTDCs express greater IFN-γ staining than dNK cells as measured by flow cytometry, whereas incubation of dNK cells with documented NK cell activators significantly increases IFN-γ above FTDC levels. Confluent FTDCs intrinsically produce, but paradoxically respond to, exogenous IFN-γ. PMID:25963913

  1. Selectional Restrictions in HPSG

    OpenAIRE

    Androutsopoulos, Ion; Dale, Robert

    2000-01-01

    Selectional restrictions are semantic sortal constraints imposed on the participants of linguistic constructions to capture contextually-dependent constraints on interpretation. Despite their limitations, selectional restrictions have proven very useful in natural language applications, where they have been used frequently in word sense disambiguation, syntactic disambiguation, and anaphora resolution. Given their practical value, we explore two methods to incorporate selectional restrictions...

  2. Peptide-loaded dendritic cells prime and activate MHC-class I-restricted T cells more efficiently than protein-loaded cross-presenting DC

    DEFF Research Database (Denmark)

    Met, Ozcan; Buus, Søren; Claesson, Mogens H

    2003-01-01

    Undifferentiated and differentiated dendritic cells (uDC and dDC, respectively), derived from the bone marrow, were studied in vitro and in vivo. Ovalbumin (OVA) and two OVA-derived peptides binding to H-2K(b) and I-A(b), respectively, were used. Two IL-2 secreting T cell hybridomas specific for...

  3. A highly restricted T-cell receptor dominates the CD8+ T-cell response to parvovirus B19 infection in HLA-A*2402-positive individuals

    DEFF Research Database (Denmark)

    Kasprowicz, V; Jeffery, K; Broliden, K;

    2006-01-01

    Six of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF. All responders showed highly focused T-cell receptor (TCR) usage, using almost exclusively BV5.1. The BV5.1 TCR dominated the...

  4. A HEV-restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is induced by lymphotoxin-α/β and TNF-α in cultured endothelial cells

    Directory of Open Access Journals (Sweden)

    Palao Guillermo

    2005-03-01

    Full Text Available Abstract Background The recruitment of lymphocytes to secondary lymphoid organs relies on interactions of circulating cells with high endothelial venules (HEV. HEV are exclusive to these organs under physiological conditions, but they can develop in chronically-inflamed tissues. The interaction of L-selectin on lymphocytes with sulfated glycoprotein ligands on HEV results in lymphocyte rolling, which represents the initial step in lymphocyte homing. HEV expression of GlcNAc6ST-2 (also known as HEC-GlcNAc6ST, GST-3, LSST or CHST4, an HEV-restricted sulfotransferase, is essential for the elaboration of L-selectin functional ligands as well as a critical epitope recognized by MECA-79 mAb. Results We examined the expression of GlcNAc6ST-2 in relationship to the MECA-79 epitope in rheumatoid arthritis (RA synovial vessels. Expression of GlcNAc6ST-2 was specific to RA synovial tissues as compared to osteoarthritis synovial tissues and localized to endothelial cells of HEV-like vessels and small flat-walled vessels. Double MECA-79 and GlcNAc6ST-2 staining showed colocalization of the MECA-79 epitope and GlcNAc6ST-2. We further found that both TNF-α and lymphotoxin-αβ induced GlcNAc6ST-2 mRNA and protein in cultured human umbilical vein endothelial cells. Conclusion These observations demonstrate that GlcNAc6ST-2 is induced in RA vessels and provide potential cytokine pathways for its induction. GlcNAc6ST-2 is a novel marker of activated vessels within RA ectopic lymphoid aggregates. This enzyme represents a potential therapeutic target for RA.

  5. Comparison Between Truview EVO2 and Macintosh Laryngoscopes in Endotreacheal Intubation for Patients with Restricted Neck Movement%Truview EVO 2喉镜与 Macintosh 喉镜用于颈椎活动受限患者气管插管的对比研究

    Institute of Scientific and Technical Information of China (English)

    张耕; 韩永正; 李民; 王军; 郭向阳

    2014-01-01

    目的:评价Truview EVO2喉镜与Macintosh喉镜用于颈椎活动受限患者气管插管的临床应用情况。方法择期颈椎活动受限经口气管插管全麻手术49例,静脉麻醉诱导后,随机先后使用Truview EVO2喉镜与Macintosh喉镜显露喉部,并采用喉部暴露条件好的喉镜行气管插管。比较2种喉镜Cormack-Lehane(C-L)分级,喉部结构显露时间和声门显露时血流动力学改变。结果 Truview EVO2喉镜组C-L分级显著优于Macintosh喉镜组(Z=-5.488,P=0.000),喉部结构显露时间明显长于Macintosh喉镜组[(15.9±6.7)s vs.(12.3±4.5)s,t=4.304,P=0.000]。2种喉镜声门显露时HR、SBP、MAP变化无统计学差异(P>0.05)。结论 Truview EVO2喉镜用于颈椎活动受限患者气管插管效果明显优于Macintosh喉镜,可提高气管插管成功率,对于部分困难气道患者具有较好的应用价值。%Objective To compare the clinical application between Truview EVO 2 and Macintosh laryngoscopes in endotreachal intubation for patients with restricted neck movement. Methods Forty-nine patients scheduled for elective surgery under general anesthesia requiring orotracheal intubation were enrolled. After intravenous anesthetic induction, orotracheal intubation was randomly performed by an experienced anesthesiologist with both Truview EVO 2 and Macintosh laryngoscopes. Then the patient was intubated with the laryngoscope with better view. Parameters were recorded, including Cormack-Lehane ( C-L) grade of laryngeal view, the laryngeal exposuring time, and hemodynamic changes during intubation. Results Better C-L grade of laryngeal view was achieved in the Truview EVO2 laryngoscope as compared with the Macintosh laryngoscope (Z=-5.488, P=0.000).The laryngeal exposuring time of Truview EVO2 laryngoscopy was longer than that of Macintosh laryngoscope [(15.9 ±6.7) s vs.(12.3 ±4.5) s, t=4.304, P =0.000].There was no

  6. T cells from fully H-2 allogeneic (A replaced by B) radiation bone marrow chimeras are functionally competent and host restricted but are alloreactive against hybrid Ia determinants expressed on (A x B)F1 cells

    International Nuclear Information System (INIS)

    In this communication it is demonstrated that T cells from fully allogeneic A replaced by B radiation bone marrow chimeras are alloreactive against the hybrid Ia molecules expressed on the surface of heterozygous A X B cells. These results suggested that previous failures to generate cytotoxic T lymphocyte (CTL) responses from fully allogeneic chimeras by sensitizing the chimeric T cells to antigen in an (A X B)F1-priming environment might have been confounded by an ongoing alloreaction against determinants created by hybrid Ia molecules expressed on F1 cells. Consequently, the ability to generate CTL responses from fully allogeneic chimeras was re-examined by sensitizing the chimeric T cells to antigen presented by homozygous rather that F1 stimulator cells. It was found that T cells of donor bone marrow origin that mediate cytotoxic responses to trinitrophenyl-modified self determinants do differentiate into functional competence in an H-2-incompatible host environment and are restricted to the host H-2 haplotype

  7. CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

    OpenAIRE

    Le Borgne, Sylvie; Février, Michèle; Callebaut, Christian; Lee, Steven P.; Rivière, Yves

    2000-01-01

    CD8+ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4+ T cells by a noncytolytic mechanism involving secreted CD8+-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4+ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector pha...

  8. AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene.

    Science.gov (United States)

    Gopal, Anjali R; Fugmann, Sebastian D

    2008-04-01

    Somatic hypermutation (SHM) and gene conversion (GCV) are closely related processes that increase the diversity the primary immunoglobulin repertoire. In both processes the activation-induced cytidine deaminase (AID) converts cytosine residues to uracils within the DNA of the immunoglobulin (Ig) genes in a transcription-dependent manner, and subsequent error-prone repair processes lead to changes in the antigen recognition site of the encoded receptors. This activity is specifically recruited to the Ig loci by unknown mechanisms. Our analyses of the chicken B-cell line DT40, and derivatives thereof, now revealed that even the closest neighbors of the Ig light chain (IgL) gene are protected from AID activity, albeit being transcribed and thus acting as potential targets of AID. Our findings are in support of a model in which cis-acting DNA boundary elements restrict AID activity to the IgL locus and guard the genome in the vicinity of the IgL gene from deleterious mutations. PMID:18023479

  9. The broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.

    Science.gov (United States)

    Sandoz, Kelsi M; Valiant, William G; Eriksen, Steven G; Hruby, Dennis E; Allen, Robert D; Rockey, Daniel D

    2014-07-01

    Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process. PMID:24777097

  10. Free vs. Restricted Immigration: Bilateral Country Study

    OpenAIRE

    Razin, Assaf; Wahba, Jackline

    2011-01-01

    This paper tests the differential effects of the generosity of the welfare state under free migration and under policy-controlled migration, distinguishing between source developing and developed countries. We utilize free-movement within the EU to examine the free migration regime and compare that to immigration into the EU from two other groups, developed and developing source countries, to capture immigration-restricted regimes. We standardize cross-country education quality differences by...

  11. Routization Problem Complicated by the Dependence of Costs Functions and «Current» Restrictions From the Tasks List

    OpenAIRE

    Chentsov, A. G.; Chentsov, A. A.

    2016-01-01

    The problem of a routization of the movements complicated by the restrictions of different type (preceding conditions, the restrictions on the attainability of states by each movement and others) is considered. A multivariance at the movement step is permitted, it is naturally resulted in the problem about the visiting of megalopolises. The costs of movements and jobs executed when visiting megalopolises may depend on the list of tacks. This list may correspond to performed or unperformed tas...

  12. Antinuclear movement in Middle Tennessee

    International Nuclear Information System (INIS)

    This is a social anthropological analysis of the antinuclear movement in Middle Tennessee. This social movement was determined to halt the construction of proposed nuclear power plants in Tennessee, especially one the Tennessee Valley Authority (TVA) intended to build in Middle Tennessee. The data for the study were gathered by participant-observation interviewing, and the examination of documents from February 1973 through March 1975. The treatment of the data is based on transactional analysis and portions of the network model. This social movement was composed of a series of informally organized cells connected by a loose network of people who visited and talked with one another. Individual cells tended to be organized on a geographical basis, as was communication. Activity-initiators, however, often contacted antinuclear personnel in other Middle Tennessee cells. Movement activity for many of the antinuclear activists was short-lived. The strategic maneuvers of the movement utilized all the structurally and legally possible alternatives and the nuclear opponents hoped that the public would pressure public officials to oppose nuclear plants. Although the antinuclear activists worked very hard, they did not succeed in halting the planned construction of the Middle Tennessee nuclear plant. Indeed, they had not succeeded in the summer of 1977

  13. The importance of foetal movement for co-ordinated cartilage and bone development in utero

    Science.gov (United States)

    Shea, C. A.; Rolfe, R. A.; Murphy, P.

    2015-01-01

    Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105–116 PMID:26142413

  14. Threshold for ion movements in wood cell walls below fiber saturation observed by X-ray fluorescence microscopy (XFM)

    Energy Technology Data Exchange (ETDEWEB)

    Zelinka, Samuel L.; Gleber, Sophie-Charlotte; Vogt, Stefan; Rodriguez Lopez, Gabriela M.; Jakes, Joseph E.

    2015-05-01

    Diffusion of chemicals and ions through the wood cell wall plays an important role in wood damage mechanisms. In the present work, free diffusion of ions through wood secondary walls and middle lamellae has been investigated as a function of moisture content (MC) and anatomical direction. Various ions (K, Cl, Zn, Cu) were injected into selected regions of 2 mu m thick wood sections with a microinjector and then the ion distribution was mapped by means of X-ray fluorescence microscopy with submicron spatial resolution. The MC of the wood was controlled in situ by means of climatic chamber with controlled relative humidity (RH). For all ions investigated, there was a threshold RH below which the concentration profiles did not change. The threshold RH depended upon ionic species, cell wall layer, and wood anatomical orientation. Above the threshold RH, differences in mobility among ions were observed and the mobility depended upon anatomical direction and cell wall layer. These observations support a recently proposed percolation model of electrical conduction in wood. The results contribute to understanding the mechanisms of fungal decay and fastener corrosion that occur below the fiber saturation point.

  15. Cytoskeletal dependence of insulin granule movement dynamics in INS-1 beta-cells in response to glucose.

    Directory of Open Access Journals (Sweden)

    Aoife T Heaslip

    Full Text Available For pancreatic β-cells to secrete insulin in response to elevated blood glucose, insulin granules retained within the subplasmalemmal space must be transported to sites of secretion on the plasma membrane. Using a combination of super-resolution STORM imaging and live cell TIRF microscopy we investigate how the organization and dynamics of the actin and microtubule cytoskeletons in INS-1 β-cells contribute to this process. GFP-labeled insulin granules display 3 different modes of motion (stationary, diffusive-like, and directed. Diffusive-like motion dominates in basal, low glucose conditions. Upon glucose stimulation no gross rearrangement of the actin cytoskeleton is observed but there are increases in the 1 rate of microtubule polymerization; 2 rate of diffusive-like motion; and 3 proportion of granules undergoing microtubule-based directed motion. By pharmacologically perturbing the actin and microtubule cytoskeletons, we determine that microtubule-dependent granule transport occurs within the subplasmalemmal space and that the actin cytoskeleton limits this transport in basal conditions, when insulin secretion needs to be inhibited.

  16. Up-regulation of Fas Ligand Expression by Sirtuin 1 in both Flow-restricted Vessels and Serum-stimulated Vascular Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    Li Li; Peng Gao; Hou-zao Chen; Zhu-qin Zhang; Ting-ting Xu; Yu-yan Jia; Hui-na Zhang; Guan-hua Du; De-pei Liu

    2013-01-01

    Objective To study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation duringvascular lesion formation and to elucidate the potential mechanisms.Methods SIRT1 and FasL protein levels were detected byWestern blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell (VSMC) lysate. Smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) C57BL/6 mice and their littermate wild-type (WT) controlsunderwent complete carotid artery ligation (ligation groups) or the ligation-excluded operation (sham groups). The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays wereperformed todetect the effect of WT-SIRT1, a dominant-negative form of SIRT1 (SIRT1H363Y), andGATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploidDNA content of VSMC so as to monitor cellular apoptosis.Results SIRT1 was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expressionincreased FasL expression both in injured mouse carotid arteries 1 day after ligation (P<0.001) and VSMCs treated with serum (P<0.05 at the transcriptional level, P<0.001 at the protein level). No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL (P<0.001).The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 (P<0.001), whileSIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 (P<0.001).ConclusionsOverexpression of SIRT1 up-regulates FasL expression in both flow-restricted mousecarotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in thetranscriptional regulation of FasL expression by SIRT1.

  17. Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl− Movements in Salivary Acinar Cells

    OpenAIRE

    Sugita, Makoto; Hirono, Chikara; Shiba, Yoshiki

    2004-01-01

    Elevations of cytoplasmic free calcium concentrations ([Ca2+]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl− through Ca2+-activated Cl− channels, while Cl− enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl− cotransporter (NKCC) and/or parallel operations of Cl−-HCO3 − and Na+-H+ exchangers, located in the basolateral membrane. To characterize the con...

  18. Effects of the group I metabotropic glutamate receptor agonist, DHPG, and injection stress on striatal cell signaling in food-restricted and ad libitum fed rats

    Directory of Open Access Journals (Sweden)

    Carr Kenneth D

    2004-12-01

    Full Text Available Abstract Background Chronic food restriction augments the rewarding effect of centrally administered psychostimulant drugs and this effect may involve a previously documented upregulation of D-1 dopamine receptor-mediated MAP kinase signaling in nucleus accumbens (NAc and caudate-putamen (CPu. Psychostimulants are known to induce striatal glutamate release, and group I metabotropic glutamate receptors (mGluR have been implicated in the cellular and behavioral responses to amphetamine. The purpose of the present study was to evaluate whether chronic food restriction increases striatal MAP kinase signaling in response to the group I mGluR agonist, DHPG. Results Western immunoblotting was used to demonstrate that intracerebroventricular (i.c.v. injection of DHPG (500 nmol produces greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted as compared to ad libitum fed rats. Fos-immunostaining induced by DHPG was also stronger in CPu and NAc core of food-restricted relative to ad libitum fed rats. However, i.c.v. injection of saline-vehicle produced greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted relative to ad libitum fed rats, and this difference was not seen when subjects received no i.c.v. injection prior to sacrifice. In addition, although DHPG activated Akt, there was no difference in Akt activation between feeding groups. To probe whether the augmented ERK1/2 and CREB activation in vehicle-injected food-restricted rats are mediated by one or more GluR types, effects of an NMDA antagonist (MK-801, 100 nmol, AMPA antagonist (DNQX, 10 nmol, and group I mGluR antagonist (AIDA, 100 nmol were compared to saline-vehicle. Antagonist injections did not diminish activation of ERK1/2 or CREB. Conclusions These results indicate that a group I mGluR agonist induces phosphorylation of Akt, ERK1/2 and CREB in both CPu and NAc. However, group I mGluR-mediated signaling may not be upregulated in food-restricted rats

  19. HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome.

    Directory of Open Access Journals (Sweden)

    Ying Ma

    Full Text Available BACKGROUND: Hantaan virus (HTNV infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and the role of epitope-specific T cell response after HTNV infection remain largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Five well-conserved novel CD8(+ T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. Two epitopes aa129-aa137 and aa131-aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8(+ T-cell response. HLA-peptide pentamer complex staining showed that the frequency of single epitope-specific CD8(+ T cell could be detected in patients (95% confidence interval for aa129-aa137: 0.080%-0.208%; for aa131-aa139: 0.030%-0.094%. The frequency of epitope-specific pentamer(+ CD8(+ T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. Moreover, the frequency of epitope-specific CD8(+ T cells at acute stage was inversely associated with the peak level of serum creatinine and was positively associated with the nadir platelet counts during the hospitalization. The intracellular cytokine staining and the proliferation assay showed that the effective epitope-specific CD8(+ T cells were characterized with the production of interferon-γ, expression of CD69 and the strong capacity of proliferation. CONCLUSION/SIGNIFICANCE: The novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8(+ T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine

  20. Movement and Space

    DEFF Research Database (Denmark)

    Riisgaard Hansen, Thomas; Eriksson, Eva; Lykke-Olesen, Andreas

    2005-01-01

    In this paper we explore the space in which movement based interaction takes place. We have in several projects explored how fixed and mobile cameras can be used in movement based interaction and will shortly describe these projects. Based on our experience with working with movement-based intera......In this paper we explore the space in which movement based interaction takes place. We have in several projects explored how fixed and mobile cameras can be used in movement based interaction and will shortly describe these projects. Based on our experience with working with movement...

  1. Restrictions of stable bundles

    CERN Document Server

    Balaji, V

    2011-01-01

    The Mehta-Ramanathan theorem ensures that the restriction of a stable vector bundle to a sufficiently high degree complete intersection curve is again stable. We improve the bounds for the "sufficiently high degree" and propose a possibly optimal conjecture.

  2. Exogenous progesterone exacerbates running response of adolescent female mice to repeated food restriction stress by changing α4-GABAA receptor activity of hippocampal pyramidal cells.

    Science.gov (United States)

    Wable, G S; Chen, Y-W; Rashid, S; Aoki, C

    2015-12-01

    Adolescent females are particularly vulnerable to mental illnesses with co-morbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel-running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain resistance

  3. Intermediation under Trade Restrictions.

    OpenAIRE

    Winkler, G Michael

    1989-01-01

    Intermediation is the activity of buying and selling simultaneously in one market. In this paper, intermediation in the market for an arbitrary good is derived from trade restrictions in a general equilibrium exchange model. The trade restrictions are given by a trade feasibility relation defined on the set of households, and they necessitate dropping the one price assumption of standard general equilibrium theory. It is shown that, in this setting, equilibria need not exist in spite of well-...

  4. Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

    International Nuclear Information System (INIS)

    The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

  5. Tectonic Plate Movement.

    Science.gov (United States)

    Landalf, Helen

    1998-01-01

    Presents an activity that employs movement to enable students to understand concepts related to plate tectonics. Argues that movement brings topics to life in a concrete way and helps children retain knowledge. (DDR)

  6. Eye Movement Disorders

    Science.gov (United States)

    ... t work properly. There are many kinds of eye movement disorders. Two common ones are Strabismus - a disorder ... of the eyes, sometimes called "dancing eyes" Some eye movement disorders are present at birth. Others develop over ...

  7. Research on virtual actor action editing and movement control

    Institute of Scientific and Technical Information of China (English)

    Wenhu QIN; Yuhui WU; Zhengxu ZHAO

    2008-01-01

    To directly use a virtual surface model for action editing and movement control, a general method for creating virtual actor skeleton models and controlling movement is presented. The method includes judging borderlines of the block virtual surface model, calculat-ing the joints, confirming the above block, and using the block hierarchical layout to create the skeleton model. Then, according to the virtual actor model and move-ment restriction, the study focuses on the generation of movement animation using the key frame technique and smoothing movement technique by automatically adding animation and adjusting the actor's pose by different weights on movement amplitude. Finally, movement control of the actor in the virtual environment is implemented by real-time control and path point control, which achieve a good result.

  8. Identification of an HLA-A*0201-Restricted T-Cell Epitope on the MPT51 Protein, a Major Secreted Protein Derived from Mycobacterium tuberculosis, by MPT51 Overlapping Peptide Screening▿

    OpenAIRE

    Aoshi, Taiki; Nagata, Toshi; Suzuki, Mina; Uchijima, Masato; Hashimoto, Dai; Rafiei, Alireza; Suda, Takafumi; Chida, Kingo; Koide, Yukio

    2008-01-01

    CD8+ T cells play a pivotal role in protection against Mycobacterium tuberculosis infection. We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice. HHD mice were immunized with plasmid DNA encoding MPT51 with gene gun bombardment, and gamma interferon (IFN-γ) production by the immune splenocytes was analyzed. In response to overlapping synthetic peptides covering the mature MPT51 sequence, th...

  9. The proviral genome of radiation leukemia virus (RadLV): molecular cloning, restriction analysis and integration sites in tumor cell DNA

    International Nuclear Information System (INIS)

    An infectious clone of the linear, unintegrated RadLV provirus was obtained by insertion in the plasmid pBR322. Its restriction map was indistinguishable from that of the majority of the multiple proviral copies, which are found apparently at random sites in the DNA of RadLV-induced rat thymic lymphomas

  10. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

    Science.gov (United States)

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-cen...

  11. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating...

  12. Social movements and science

    DEFF Research Database (Denmark)

    Jamison, Andrew

    2006-01-01

    The article examines the role of social movements in the development of scientific knowledge. Interactions between social movements and science in broad, historical terms are discussed. The relations between the new social movements of the 1960s and 1970s and changes in the contemporary scientific...

  13. Bilinear Fourier restriction theorems

    CERN Document Server

    Demeter, Ciprian

    2012-01-01

    We provide a general scheme for proving $L^p$ estimates for certain bilinear Fourier restrictions outside the locally $L^2$ setting. As an application, we show how such estimates follow for the lacunary polygon. In contrast with prior approaches, our argument avoids any use of the Rubio de Francia Littlewood--Paley inequality.

  14. Neuroaesthetics: range and restrictions.

    Science.gov (United States)

    Chatterjee, Anjan

    2013-04-01

    Bullot & Reber (B&R) should be commended for highlighting tensions between scientific aesthetics and art history. The question of how each tradition can learn from the other is timely. While I am sympathetic to their views, their diagnosis of the problem appears exaggerated and their solution partial. They underestimate the reach of scientific aesthetics while failing to identify its inherent restrictions. PMID:23507092

  15. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...

  16. [Sleep related movement disorders].

    Science.gov (United States)

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2015-06-01

    Sleep related movement disorders (SRMD) are characterized by simple, stereotyped movements occur during sleep, with the exception of restless legs syndrome (RLS). RLS has the following essential features; an urge to move the legs usually accompanied by uncomfortable sensation in the legs, improvement of symptoms after movement (non-stereotypical movements, such as walking and stretching, to reduce symptoms), and symptoms occur or worsen during periods of rest and in the evening and night. However, RLS is closely associated with periodic limb movement, which shows typical stererotyped limb movements. In the International Classification of Sleep Disorders, 3rd edition, sleep disturbances or daytime symptoms are prerequiste for a diagnosis of SRMD. We here review diagnosis and treatment of SRMD. PMID:26065126

  17. MOVEMENT DISORDERS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Sujitnath

    2016-01-01

    Full Text Available Involuntary movements of different types are associated with many diseases in children. Movement disorders in adult have been published in different journals, but in children these disorders have been ignored, even in most of the paediatric neurology books. Here is a brief attempt to describe different types of movement disorders and their various names in different diseases. Possible investigations and treatment of the disorders have been described in short.

  18. Leishmania major-specific, CD4+, major histocompatibility complex class II-restricted T cells derived in vitro from lymphoid tissues of naive mice

    OpenAIRE

    1993-01-01

    Several studies indicate that the outcome of experimental murine cutaneous leishmaniasis caused by Leishmania major (Lm) is determined by immunological events occurring shortly after infection. These events lead to outgrowth of either protective CD4+ T cells in the C57BL/6 mouse, which cures, or exacerbative cells in the BALB/c mouse, which succumbs to disease. Potential factors influencing the outgrowth of protective or exacerbative T cells include antigen-presenting cells (APC), cytokines, ...

  19. Gravity effects on endogenous movements

    Science.gov (United States)

    Johnsson, Anders; Antonsen, Frank

    Gravity effects on endogenous movements A. Johnsson * and F. Antonsen *+ * Department of Physics, Norwegian University of Science and Technology,NO-7491, Trond-heim, Norway, E-mail: anders.johnsson@ntnu.no + Present address: Statoil Research Center Trondheim, NO-7005, Trondheim, Norway Circumnutations in stems/shoots exist in many plants and often consists of more or less regular helical movements around the plumb line under Earth conditions. Recent results on circumnu-tations of Arabidopsis in space (Johnsson et al. 2009) showed that minute amplitude oscilla-tions exist in weightlessness, but that centripetal acceleration (mimicking the gravity) amplified and/or created large amplitude oscillations. Fundamental mechanisms underlying these results will be discussed by modeling the plant tissue as a cylinder of cells coupled together. As a starting point we have modeled (Antonsen 1998) standing waves on a ring of biological cells, as first discussed in a classical paper (Turing 1952). If the coupled cells can change their water content, an `extension' wave could move around the ring. We have studied several, stacked rings of cells coupled into a cylinder that together represent a cylindrical plant tissue. Waves of extensions travelling around the cylinder could then represent the observable circumnutations. The coupling between cells can be due to cell-to-cell diffusion, or to transport via channels, and the coupling can be modeled to vary in both longitudinal and transversal direction of the cylinder. The results from ISS experiments indicate that this cylindrical model of coupled cells should be able to 1) show self-sustained oscillations without the impact of gravity (being en-dogenous) and 2) show how an environmental factor like gravity can amplify or generate the oscillatory movements. Gravity has been introduced in the model by a negative, time-delayed feed-back transport across the cylinder. This represents the physiological reactions to acceler

  20. The mathematics of movement

    Science.gov (United States)

    Johnson, D.H.

    1999-01-01

    Review of: Quantitative Analysis of Movement: Measuring and Modeling Population Redistribution in Animals and Plants. Peter Turchin. 1998. Sinauer Associates, Sunderland, MA. 306 pages. $38.95 (paper).

  1. Calibrating the X-ray attenuation of liquid water and correcting sample movement artefacts during in operando synchrotron X-ray radiographic imaging of polymer electrolyte membrane fuel cells.

    Science.gov (United States)

    Ge, Nan; Chevalier, Stéphane; Hinebaugh, James; Yip, Ronnie; Lee, Jongmin; Antonacci, Patrick; Kotaka, Toshikazu; Tabuchi, Yuichiro; Bazylak, Aimy

    2016-03-01

    Synchrotron X-ray radiography, due to its high temporal and spatial resolutions, provides a valuable means for understanding the in operando water transport behaviour in polymer electrolyte membrane fuel cells. The purpose of this study is to address the specific artefact of imaging sample movement, which poses a significant challenge to synchrotron-based imaging for fuel cell diagnostics. Specifically, the impact of the micrometer-scale movement of the sample was determined, and a correction methodology was developed. At a photon energy level of 20 keV, a maximum movement of 7.5 µm resulted in a false water thickness of 0.93 cm (9% higher than the maximum amount of water that the experimental apparatus could physically contain). This artefact was corrected by image translations based on the relationship between the false water thickness value and the distance moved by the sample. The implementation of this correction method led to a significant reduction in false water thickness (to ∼0.04 cm). Furthermore, to account for inaccuracies in pixel intensities due to the scattering effect and higher harmonics, a calibration technique was introduced for the liquid water X-ray attenuation coefficient, which was found to be 0.657 ± 0.023 cm(-1) at 20 keV. The work presented in this paper provides valuable tools for artefact compensation and accuracy improvements for dynamic synchrotron X-ray imaging of fuel cells. PMID:26917148

  2. In vitro analysis of a primary, major histocompatibility complex (MHC)-restricted, cytotoxic T-lymphocyte response to avian leukosis virus (ALV), using target cells expressing MHC class I cDNA inserted into a recombinant ALV vector.

    Science.gov (United States)

    Thacker, E L; Fulton, J E; Hunt, H D

    1995-10-01

    The interaction between the major histocompatibility complex (MHC) and cytotoxic T lymphocytes (CTLs) is an important component of the host's resistance to viral infections and tumor formation. In this study, an avian leukosis virus (ALV) vector system, RCASBP, expressing MHC chicken class I (B-F) cDNA was used to develop target cells expressing the chicken class I glycoproteins complexed with ALV antigens on the cell surface. Peripheral blood from chickens inoculated with ALV was shown to contain antigen-specific, MHC-restricted, CD8+ effector CTLs, using a 51Cr release assay utilizing the RCASBP B-F target cells. The stimulated effector cells were also predominantly alpha beta T-cell receptor-positive (TCR2) T cells. The CTL response varied between two haplotypes of chickens which differed in their response to Rous sarcoma virus (RSV)-induced tumors. Chickens with the B21 haplotype which regress RSV-induced tumors showed maximal cytolytic activity, while chickens with the B13 haplotype which do not regress RSV-induced tumors had minimal to no cytolytic activity. In addition to assessing the CTL response to ALV, the creation of MHC-specific immortal target cell lines will be extremely useful in evaluating CTL responses to other viral disease in chickens. PMID:7666545

  3. Restriction of Helmholtz Model

    Directory of Open Access Journals (Sweden)

    V.M. Polunin

    2014-07-01

    Full Text Available The results of the experimental studies of physical mechanisms of energy dissipation in the oscillating system in which air cavity held by the forces of magnetic levitation is used as the elastic element, and magnetic fluid prepared on the basis of dispersing media with different viscosity level is used as the inertial element are considered in the article. Based on the obtained results the conclusion on the restriction of the applicability of Helmholtz equation, caused by boundary effects is made.

  4. License restrictions at Barnwell

    Energy Technology Data Exchange (ETDEWEB)

    Autry, V.R. [S.C. Dept. of Health and Environmental Control, Columbia, SC (United States). Bureau of Radiological Health

    1991-12-31

    The State of South Carolina was delegated the authority by the US Nuclear Regulatory Commission to regulate the receipt, possession, use and disposal of radioactive material as an Agreement State. Since 1970, the state has been the principal regulatory authority for the Barnwell Low-Level Waste Disposal Facility operated by Chem-Nuclear Systems, Inc. The radioactive material license issued authorizing the receipt and disposal of low-level waste contains numerous restrictions to ensure environmental protection and compliance with shallow land disposal performance criteria. Low-level waste has evolved from minimally contaminated items to complex waste streams containing high concentrations of radionuclides and processing chemicals which necessitated these restrictions. Additionally, some waste with their specific radionuclides and concentration levels, many classified as low-level radioactive waste, are not appropriate for shallow land disposal unless additional precautions are taken. This paper will represent a number of these restrictions, the rationale for them, and how they are being dealt with at the Barnwell disposal facility.

  5. Boosting the MHC class II-restricted tumor antigen presentation to CD4+ T helper cells: a critical issue for triggering protective immunity and re-orienting the tumor microenvironment toward an anti-tumor state

    Directory of Open Access Journals (Sweden)

    RobertoAccolla

    2014-02-01

    Full Text Available Although the existence of an immune response against tumor cells is well documented, the fact that tumors take off in cancer patients indicates that neoplastic cells can circumvent this response. Over the years many investigators have described strategies to rescue the anti-tumor immune response with the aim of creating specific and long lasting protection against the disease. When exported to human clinical settings, these strategies have revealed in most cases a very limited, if any, positive outcome.We believe that the failure is mostly due to the inadequate triggering of the CD4+ T helper cell (TH arm of the adaptive immunity, as TH cells are necessary to trigger all the immune effector mechanisms required to eliminate tumor cells. In this review we focus on novel strategies that by stimulating MHC class II-restricted activation of TH cells generate a specific and persistent adaptive immunity against the tumor.This point is of critical importance for both preventive or therapeutic anti-tumor vaccination protocols, because adaptive immunity with its capacity to produce specific, long lasting protection and memory responses, is indeed the final goal of vaccination. We will discuss data from our as well as other laboratories which strongly suggest that triggering a specific and persistent anti-tumor CD4+ TH cell response stably modify not only the tumor microenvironment but also tumor-dependent extratumor microenvironments eliminating and/or reducing the blood-derived tumor infiltrating cells that may have a pro-tumor growth function such as regulatory CD4+/CD25+ T cells (Tregs and myeloid-derived suppressor cells (MDSC. Within this frame therefore, we believe that the establishment of a pro-tumor environment is not the cause but simply the consequence of the tumor strategy to primarily counteract components of the adaptive cellular immunity, particularly TH lymphocytes.

  6. The Circular Camera Movement

    DEFF Research Database (Denmark)

    Hansen, Lennard Højbjerg

    2014-01-01

    It has been an accepted precept in film theory that specific stylistic features do not express specific content. Nevertheless, it is possible to find many examples in the history of film in which stylistic features do express specific content: for instance, the circular camera movement is used...... circular camera movement. Keywords: embodied perception, embodied style, explicit narration, interpretation, style pattern, television style...

  7. 85 Engaging Movement Activities.

    Science.gov (United States)

    Weikart, Phyllis S.; Carlton, Elizabeth B.

    This book presents activities to keep K-6 students moving in a variety of ways as they learn. The movement experiences are planned around key curriculum concepts in movement and music as well as in academic curriculum areas. The experiences develop students' basic timing, language abilities, vocabulary, concentration, planning skills, and…

  8. Dynamics of human movement

    NARCIS (Netherlands)

    Koopman, Bart H.F.J.M.

    2010-01-01

    The part of (bio)mechanics that studies the interaction of forces on the human skeletal system and its effect on the resulting movement is called rigid body dynamics. Some basic concepts are presented: A mathematical formulation to describe human movement and how this relates on the mechanical loads

  9. [Dance/Movement Therapy.

    Science.gov (United States)

    Fenichel, Emily, Ed.

    1994-01-01

    This newsletter theme issue focuses on dance, play, and movement therapy for infants and toddlers with disabilities. Individual articles are: "Join My Dance: The Unique Movement Style of Each Infant and Toddler Can Invite Communication, Expression and Intervention" (Suzi Tortora); "Dynamic Play Therapy: An Integrated Expressive Arts Approach to…

  10. IFNγ and IL-12 Restrict Th2 Responses during Helminth/Plasmodium Co-Infection and Promote IFNγ from Th2 Cells

    OpenAIRE

    Coomes, Stephanie M.; Pelly, Victoria S.; Kannan, Yashaswini; Okoye, Isobel S.; Czieso, Stephanie; Entwistle, Lewis J.; Perez-Lloret, Jimena; Nikolov, Nikolay; Potocnik, Alexandre J.; Biró, Judit; Langhorne, Jean; Wilson, Mark S.

    2015-01-01

    Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFNγ or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with ...

  11. T cell retargeting with MHC class I-restricted antibodies: the CD28 costimulatory domain enhances antigen-specific cytotoxicity and cytokine production

    OpenAIRE

    Willemsen, Ralph; Ronteltap, C.; Chames, P.; Debets, Reno; Bolhuis, Reinder

    2005-01-01

    textabstractT cells require both primary and costimulatory signals for optimal activation. The primary Ag-specific signal is delivered by engagement of the TCR. The second Ag-independent costimulatory signal is mediated by engagement of the T cell surface costimulatory molecule CD28 with its target cell ligand B7. However, many tumor cells do not express these costimulatory molecules. We previously constructed phage display derived F(AB), G8, and Hyb3, Ab-based receptors with identical specif...

  12. C/EBPα is dispensable for the ontogeny of PD-1+ CD4+ memory T cells but restricts their expansion in an age-dependent manner

    DEFF Research Database (Denmark)

    Norrie, Ida Christine; Ohlsson, Ewa; Nielsen, Olaf;

    2014-01-01

    Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the atte...

  13. Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Johansen, L E; Nielsen, O;

    2006-01-01

    , and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct...

  14. Allogeneic HLA-A*02-Restricted WT1-Specific T Cells from Mismatched Donors Are Highly Reactive but Show Off-Target Promiscuity

    NARCIS (Netherlands)

    Falkenburg, Willem J. J.; Melenhorst, J. Joseph; van de Meent, Marian; Kester, Michel G. D.; Hombrink, Pleun; Heemskerk, Mirjam H. M.; Hagedoorn, Renate S.; Gostick, Emma; Price, David A.; Falkenburg, J. H. Frederik; Barrett, A. John; Jedema, Inge

    2011-01-01

    T cells recognizing tumor-associated Ags such as Wilms tumor protein (WT1) are thought to exert potent antitumor reactivity. However, no consistent high-avidity T cell responses have been demonstrated in vaccination studies with WT1 as target in cancer immunotherapy. The aim of this study was to inv

  15. RNA silencing movement in plants

    Institute of Scientific and Technical Information of China (English)

    Glykeria Mermigka; Frederic Verret; Kriton Kalantidis

    2016-01-01

    Multicellular organisms, like higher plants, need to coordinate their growth and development and to cope with environmental cues. To achieve this, various signal molecules are transported between neighboring cells and distant organs to control the fate of the recipient cells and organs. RNA silencing produces cell non-autonomous signal molecules that can move over short or long distances leading to the sequence specific silencing of a target gene in a well defined area of cells or throughout the entire plant, respectively. The nature of these signal molecules, the route of silencing spread, and the genes involved in their production, movement and reception are discussed in this review. Additionally, a short section on features of silencing spread in animal models is presented at the end of this review.

  16. 海洋无脊椎动物细胞培养的制约因素及改进方法%Restrictive Factor and Improved Strategy of Cell Culture from Marine Invertebrates

    Institute of Scientific and Technical Information of China (English)

    张晓燕; 王昌留; 李琳

    2015-01-01

    Attempts to development cell culture from marine invertebrates dated back to 1970s. The cell culture from marine invertebrates lags far behind that from vertebrates,there is no single immortal cell line available from marine invertebrates yet. This review outlines the progress of marine invertebrates’ cell culture,points out restrictive factor,and proposes improved strategy. This article provides the reference on the establishment of im-mortal cell lines from marine invertebrates.%海洋无脊椎动物细胞培养的研究始于20世纪70年代,至今未得到永生化细胞系,远远落后于脊椎动物细胞培养的研究。本文概述了海洋无脊椎动物细胞培养的进展,指出了制约因素,参考脊椎动物的研究成果进而提出了海洋无脊椎动物细胞培养的改进方法,为进一步建立起海洋无脊椎动物的永生化细胞系提供参考。

  17. The Development of Coordinated Movement.

    Science.gov (United States)

    Montanaro, Silvana Quattrocchi

    2002-01-01

    Discusses stages of movement in the first 3 years of life with a philosophical dimension regarding evolutionary aspects of movement as first manifestation of "will." Describes how the early childhood environment is prepared to allow for movement and the connection between movement and brain development. Discusses the contribution of movement to…

  18. Proteomic Characterization of Stomatal Movement

    Institute of Scientific and Technical Information of China (English)

    Sixue Chen

    2012-01-01

    Stomata on leaf epidermis formed by pairs of guard cells control CO2 intake and water transpiration,and respond to different environmental conditions.Stress induced stomatal closure is mediated via an intricate hormone network in guard cells.Here we report absicic acid (ABA) and methyl jasmonate (MeJA) responsive proteins and redox sensitive proteins.Both ABA and MeJA cause stomatal movement and H2O2 production.Using an isobaric tags for relative and absolute quantitation approach,we have identified many ABA and/or MeJA responsive proteins in B.napus guard cells.Most of the genes encoding these proteins contain hormone responsive elements in the promoters,indicating that they are potentially regulated at the transcriptional level.The protein level changes were validated using Western blot analysis.We have also identified redox responsive proteins in the above signaling processes.The identification of the hormone responsive proteins and redox state changes has revealed interesting molecular mechanisms underlying guard cell functions in stomatal movement.The knowledge has great potential to be applied to crop engineering for enhanced yield and stress tolerance.

  19. Do Economic Restrictions Improve Forecasts?

    OpenAIRE

    Murphy, Elizabeth A.; Norwood, F. Bailey; Wohlgenant, Michael K.

    2003-01-01

    A previous study showed that imposing economic restrictions improves the forecasting ability of food demand systems, thus warranting their use even when they are rejected in-sample. This article evaluates whether this result is due to economic restrictions enhancing degrees of freedom or containing nonsample information. Results indicate that restrictions improve forecasting ability even when they are not derived from economic theory, but theoretical restrictions forecast best.

  20. Cytotoxic T lymphocyte control during ectromelia (mousepox) virus infection: Interaction between MHC-restricted cells analyzed by non-radioactive-fluorimetry

    International Nuclear Information System (INIS)

    Cytotoxic T lymphocyte activity of draining lymph node cells isolated from BALB/c mice infected with ectromelia virus (EV) was examined using a fluorometric cell-mediated cytotoxicity (CMC) assay. Specific lysis of target cells A20 and EMT-6 primed with EV was demonstrated. The classical CD8+ cytolytic pathway (72.7%) as compared to that of CD4+ (27.3%) in the cellular response during acute infection. Also an alternative method for determining CMC, employing a bis-benzamide dye for labelling target cells, is described. Coefficient variations of relative fluorescence were below 6%, that makes the method sensitive and reliable. Comparison of the assay demonstrated with to that of the 51Cr-release assay is discussed

  1. Music and movement

    OpenAIRE

    Nasev, Lence

    2012-01-01

    Rhythm is one of the fundamental elements without which music would not exist. In plays with singing, a child learns to synchronize its movements with the rhythm of music from a very early age. The skill of movement plays a major role in the learning of music and thus deserves an important place in the school curriculum. In this paper, an overview is made of the most important music pedagogues who introduced movement, and at the same time perceived its importance in learning musical conte...

  2. The Irish Women's Movement

    OpenAIRE

    Cullen, Pauline

    2015-01-01

    Ireland’s long history of patriarchy is matched by the ongoing evolution of its women’s movements. Today’s complex, transnational feminism finds its precursor in the colonial era. The first wave of the Irish women’s movement dates from the mid-19th century, with the franchise secured for women in 1918 while still under British colonial rule. First-wave feminists played a role in the nationalist movement, but their demands were sidelined later, during the construction of a conserva...

  3. NEW RELIGIOUS MOVEMENTS

    OpenAIRE

    SURAJ KUMAR SUMAN

    2013-01-01

    Several of the new religious movements (NRMs) of modern times have become global movements. Among these are the Soka Gakkai of Japan; the Brahma Kumaris, Sathya Sai Baba, and Hare Krishna of India; the Tzu Chi Buddhist Compassion and Relief Society of Taiwan; and Scientology, which began in the United States in the early 1950s. In order to become global movements, NRMs must often depend heavily on one particular ethnic group as they expand beyond their home base. On arrival in new cultural co...

  4. Deconfinement from action restriction

    International Nuclear Information System (INIS)

    The effect of restricting the plaquette to be greater than a certain cutoff value is studied. The action considered is the standard Wilson action with the addition of a plaquette restriction, which should not affect the continuum limit of the theory. In this investigation, the strong coupling limit is also taken. It is found that a deconfining phase transition occurs as the cutoff is increased, on all lattices studied (up to 204). The critical cutoff on the infinite lattice appears to be around 0.55. For cutoffs above this, a fixed point behavior is observed in the normalized fourth cumulant of the Polyakov loop, suggesting the existence of a line of critical points corresponding to a massless gluon phase, not unlike the situation in compact U(1). The Polyakov loop susceptibility also appears to be diverging with lattice size at these cutoffs. A strong finite volume behavior is observed in the pseudo-specific heat. It is discussed whether these results could still be consistent with the standard crossover picture which precludes the existence of a deconfining phase transition on an infinite symmetric lattice. (orig.)

  5. Derivation from an alloreactive T-cell line of a clone which cross-reacts with a self H2-E-restricted minor alloantigen

    DEFF Research Database (Denmark)

    Owens, T; Liddell, M E; Crispe, I N

    1984-01-01

    An alloreactive T-helper-cell line [(A.TH X Balb/c) anti-A.TL] was shown to recognize both H2-Ek and H2-Ed. Both proliferation and polyclonal B-cell activation (protein A plaques) were used in the analyses of specificity. On cloning, the H2-Ek/Ed cross-reaction was shown by one clonotype. This cr...

  6. Non–lineage/stage-restricted effects of a gain-of-function mutation in tyrosine phosphatase Ptpn11 (Shp2) on malignant transformation of hematopoietic cells

    OpenAIRE

    Xu, Dan; Liu, Xia; Yu, Wen-Mei; Meyerson, Howard J.; Guo, Caiying; Gerson, Stanton L.; Qu, Cheng-Kui

    2011-01-01

    Activating mutations in protein tyrosine phosphatase 11 (Ptpn11) have been identified in childhood acute leukemias, in addition to juvenile myelomonocytic leukemia (JMML), which is a myeloproliferative disorder (MPD). It is not clear whether activating mutations of this phosphatase play a causal role in the pathogenesis of acute leukemias. If so, the cell origin of leukemia-initiating stem cells (LSCs) remains to be determined. Ptpn11E76K mutation is the most common and most active Ptpn11 mut...

  7. Self and non-self discrimination by "restriction proteases".

    OpenAIRE

    Lefkovits, I

    1986-01-01

    I propose that an organism possesses a set of specific enzymes ("restriction proteases") that cleave self proteins at defined amino acid sequences unless these sequences are rendered inaccessible by glycosylation. Intracellular proteins are degraded by restriction proteases when cells die. In this way, intracellular proteins remain undetected by the immune system. I propose that some autoimmune diseases are caused by the absence of a specific restriction protease.

  8. Human cytomegalovirus pp65- and immediate early 1 antigen-specific HLA class I-restricted cytotoxic T cell responses induced by cross-presentation of viral antigens.

    Science.gov (United States)

    Tabi, Z; Moutaftsi, M; Borysiewicz, L K

    2001-05-01

    Dendritic cells (DCs) play a pivotal role in the development of anti-viral CD8(+) CTL responses. This is straightforward if they are directly infected with virus, but is less clear in response to viruses that cannot productively infect DCS: Human CMV (HCMV) shows strain-specific cell tropism: fibroblast (Fb)-adapted laboratory strains (AD169) and recent clinical isolates do not infect DCs, whereas endothelial cell-adapted strains (TB40/E) result in productive lytic DC infection. However, we show here that uninfected DCs induce CD8(+) T cell cytotoxicity and IFN-gamma production against HCMV pp65 and immediate early 1 Ags following in vitro coculture with HCMV-AD169-infected Fbs, regardless of the HLA type of these FBS: CD8(+) T cell stimulation was inhibited by pretreatment of DCs with cytochalasin B or brefeldin A, indicating a phagosome/endosome to cytosol pathway. HCMV-infected Fbs were not apoptotic as measured by annexin V binding, and induction of apoptosis of infected Fbs in vitro did not augment CTL induction by DCs, suggesting a mechanism other than apoptosis in the initiation of cross-presentation. Furthermore, HCMV-infected Fbs provided a maturation signal for immature DCs during coculture, as evidenced by increased CD83 and HLA class II expression. Cross-presentation of HCMV Ags by host DCs enables these professional APCs to bypass some of the evasion mechanisms HCMV has developed to avoid T cell recognition. It may also serve to explain the presence of immediate early 1 Ag-specific CTLs in the face of pp65-induced inhibition of Ag presentation at the level of the infected cell. PMID:11313411

  9. The French ecological movement

    International Nuclear Information System (INIS)

    The analysis of the ecological Movement in France is presented: its organisation, its topics, its position with respect to the main political trends. The accent is put in particular on the antinuclear contestation

  10. Stereotypic movement disorder

    Science.gov (United States)

    ... with normal activity or have the potential to cause bodily harm. ... Stereotypic movement disorder is more common among boys than ... occur with other conditions, is unknown. Stimulant drugs such ...

  11. Movement and Coordination

    Science.gov (United States)

    ... in Action Medical Editor & Editorial Advisory Board Sponsors Sponsorship Opporunities Spread the Word Shop AAP Find a Pediatrician ... Movement and Coordination Page Content Article Body At this age, your child will seem to be continually on the go— ...

  12. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. PMID:25691247

  13. Rooted in Movement

    DEFF Research Database (Denmark)

    The result of the synergy between four doctoral projects and an advanced MA-level course on Bronze Age Europe, this integrated assemblage of articles represents a variety of different subjects united by a single theme: movement. Ranging from theoretical discussion of the various responses to and ...... period of European prehistory. In so doing, the text not only addresses transmission and reception, but also the conceptualization of mobility within a world which was literally Rooted in Movement....

  14. Organizations, coalitions, and movements

    OpenAIRE

    Diani, Mario; Bison, Ivano

    2004-01-01

    This article uses empirical evidence on networks of voluntary organizations mobilizing on ethnic minority, environmental, and social exclusion issues in two British cities, to differentiate between social movement processes and other, cognate collective action dynamics. Social movement processes are identified as the building and reproducing of dense informal networks between a multiplicity of actors, sharing a collective identity, and engaged in social and/or political conflict. They are con...

  15. Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells.

    OpenAIRE

    Steinsbø, Øyvind; Dunand, Carole J. Henry; Huang, Min; Mesin, Luka; Salgado-Ferrer, Marlene; Lundin, Knut E. A; Jahnsen, Jørgen; Wilson, Patrick C.; Sollid, Ludvig M.

    2014-01-01

    Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is characterized by CD4+ T cells recognizing deamidated gluten and by antibodies reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident PCs share this feature. Monoclonal antibodies were expression cloned from single PCs of patients either ...

  16. Equivalence of human and mouse CD4 in enhancing antigen responses by a mouse class II-restricted T cell hybridoma

    OpenAIRE

    1989-01-01

    We have examined the ability of hCD4 to interact functionally with mouse class II MHC molecules using the mouse T cell hybridoma BI-141, specific for beef insulin. We have previously shown that expression of mouse CD4 results in a marked enhancement of IL-2 release by BI-141 cells in response to beef insulin or, in a cross-reactive response, to pork insulin, on the appropriate mouse APCs. We now demonstrate that expression of hCD4 results in an equivalent stimulation of antigen responses by t...

  17. Gene Expression Analysis of a Panel of Cell Lines That Differentially Restrict HIV-1 CA Mutants Infection in a Cyclophilin A-Dependent Manner

    OpenAIRE

    Shah, Vaibhav B.; Aiken, Christopher

    2014-01-01

    HIV-1 replication is dependent on binding of the viral capsid to the host protein cyclophilin A (CypA). Interference with cyclophilin A binding, either by mutations in the HIV-1 capsid protein (CA) or by the drug cyclosporine A (CsA), inhibits HIV-1 replication in cell culture. Resistance to CsA is conferred by A92E or G94D substitutions in CA. The mutant viruses are also dependent on CsA for their replication. Interestingly, infection of some cell lines by these mutants is enhanced by CsA, w...

  18. MRI of restrictive cardiomyopathy

    International Nuclear Information System (INIS)

    Objective: To evaluate the diagnostic value of MRI in combination of delayed gadolinium-enhanced MR imaging for the identification of restrictive cardiomyopathy (RCM). Methods: One hundred sixteen patients with RCM underwent ECG, thoracic radiography, echocardiography and MRI. The final diagnosis was made on comprehensive evaluation in consideration of patient history, clinical symptoms and imaging appearances. Fifty-five normal subjects were used as the controls. All patients were divided into two groups according to contrast-enhanced MRI patterns: RCM with delayed enhancement (RCM with DE, n=35) and RCM without delayed enhancement (RCM without DE, n=81). Bi-atrial and bi-ventricular size, ventricular septal and left free wall thickness were measured. A paired t-test was used for statistic analysis. Results: Bi-atrial size, right ventricular diastolic diameter (RVDD), ventricular septal and left free wall thickness were significantly larger in RCM patients than in normal subjects (P0.05). Visual observation showed mild mitral regurgitation (50 cases), moderate mitral regurgitation (24 cases ), mild tricuspid regurgitation (32 cases) and severe tricuspid regurgitation (46 cases). Thirty-five RCMs with DE presented diffuse (15 cases) or segmental (20 cases) enhancement. Twelve RCMs with diffuse delayed enhancement showed powdery, enhancement, and 3 showed petaline enhancement. Three cases with powdery enhancement were histologically proven as myocardial amyloidosis. Ventricular septum was the most vulnerable segment in patients with segmental enhancement. Six cases presented subendocardial enhancement that corresponded to apical obliteration, of which one case was confirmed as hypereosinophilia by bone marrow biopsy and the other 14 cases didn't present any regular enhancement. In 81 RCMs without DE, marked bi-atrial dilation, near-normal ventricular chambers and near-normal ventricular thickness were presented. Conclusion: MRI is an excellent imaging modality for

  19. Patterns of movement for youth within an integrated continuum of residential services

    OpenAIRE

    Huefner, Jonathan C.; James, Sigrid; Ringle, Jay; Thompson, Ronald W.; Daly, Daniel L.

    2010-01-01

    This study examined patterns of movement for youth receiving services within a continuum of intensive and restrictive residentially-based programs. Data were collected for 701 completed episodes of care within a three-program residential continuum of care over a 5 year period, and examined time within program, movement between programs, in-program disruptive behavior, and discharge status. Results showed that most youth either remained in a stable placement in the least restrictive of the pro...

  20. RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG

    NARCIS (Netherlands)

    Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N.; Le Bras, Alexandra; Zwiers, Peter J.; Spokes, Katherine; Bhasin, Manoj; Shih, Shou-ching; Nagy, Janice A.; Molema, Grietje; Aird, William C.; Davis, George E.; Oettgen, Peter

    2011-01-01

    ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely inter

  1. Human leukocyte antigen-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies

    NARCIS (Netherlands)

    Kremer, A.N.; Meijden, E.D. van der; Honders, M.W.; Pont, M.J.; Goeman, J.J.; Falkenburg, J.H.F.; Griffioen, M.

    2014-01-01

    Hematological malignancies often express surface HLA class II, making them attractive targets for CD4+ T cell therapy. We previously demonstrated that HLA class II ligands can be divided into DM-resistant and DM-sensitive antigens. In contrast to presentation of DM-resistant antigens, presentation o

  2. The minimal sequence essential for replication and movement of Cotton leaf curl Multan betasatellite DNA by a helper virus in plant cells.

    Science.gov (United States)

    Eini, Omid; Behjatnia, S A Akbar

    2016-10-01

    Betasatellites are single-stranded circular DNAs associated with a number of monopartite begomoviruses. Betasatellites rely on the helper begomoviruses for replication and movement in plant tissues and plant-to-plant transmission by vectors. Their genomes are approximately half the size of the helper viruses and consist of three main regions including the βC1 gene, an adenine-rich (A-rich) region, and the satellite conserved region (SCR). In this study, we investigated the minimal sequences required for Cotton leaf curl Multan betasatellite (CLCuMB) replication and movement. Mutational analysis of CLCuMB DNA genome indicated that βC1 gene and A-rich region were not required for trans-replication and movement of CLCuMB in host plants by a helper virus. Deletion of βC1 gene and a fragment (135 nt in length) upstream of this gene impaired CLCuMB replication. However, CLCuMB mutant with deletion of βC1 gene and a further 163 nucleotides replicated at a lower level as compared to the wild-type betasatellite. This suggests that there are essential elements in the fragment upstream of βC1 gene, which are required for the replication of CLCuMB rather than the size limitation of CLCuMB DNA. PMID:27193570

  3. IRF1 and NF-kB Restore MHC Class I-Restricted Tumor Antigen Processing and Presentation to Cytotoxic T Cells in Aggressive Neuroblastoma

    Science.gov (United States)

    Cifaldi, Loredana; Antonucci, Chiara; Citti, Arianna; Boldrini, Renata; Pezzullo, Marco; Castellano, Aurora; Russo, Vincenzo; van der Bruggen, Pierre; Giacomini, Patrizio; Locatelli, Franco; Fruci, Doriana

    2012-01-01

    Neuroblastoma (NB), the most common solid extracranial cancer of childhood, displays a remarkable low expression of Major Histocompatibility Complex class I (MHC-I) and Antigen Processing Machinery (APM) molecules, including Endoplasmic Reticulum (ER) Aminopeptidases, and poorly presents tumor antigens to Cytotoxic T Lymphocytes (CTL). We have previously shown that this is due to low expression of the transcription factor NF-kB p65. Herein, we show that not only NF-kB p65, but also the Interferon Regulatory Factor 1 (IRF1) and certain APM components are low in a subset of NB cell lines with aggressive features. Whereas single transfection with either IRF1, or NF-kB p65 is ineffective, co-transfection results in strong synergy and substantial reversion of the MHC-I/APM-low phenotype in all NB cell lines tested. Accordingly, linked immunohistochemistry expression patterns between nuclear IRF1 and p65 on the one hand, and MHC-I on the other hand, were observed in vivo. Absence and presence of the three molecules neatly segregated between high-grade and low-grade NB, respectively. Finally, APM reconstitution by double IRF1/p65 transfection rendered a NB cell line susceptible to killing by anti MAGE-A3 CTLs, lytic efficiency comparable to those seen upon IFN-γ treatment. This is the first demonstration that a complex immune escape phenotype can be rescued by reconstitution of a limited number of master regulatory genes. These findings provide molecular insight into defective MHC-I expression in NB cells and provide the rational for T cell-based immunotherapy in NB variants refractory to conventional therapy. PMID:23071666

  4. DISTRIBUTION AND MOVEMENTS OF INTERTIDAL BUTTERFISH PHOLIS-GUNNELLUS

    NARCIS (Netherlands)

    KOOP, JH; GIBSON, RN

    1991-01-01

    The distribution and movements of intertidal butterfish Pholis gunnellus were studied on the west coast of Scotland in relation to the foraging tactics of one of its major predators, the otter. Fish were individually tagged and released at low tide in restricted areas of 5 m wide running from the to

  5. Caveolae Restrict Tiger Frog Virus Release in HepG2 cells and Caveolae-Associated Proteins Incorporated into Virus Particles

    OpenAIRE

    Jian He; Yi-Wen Zheng; Yi-Fan Lin; Shu Mi; Xiao-Wei Qin; Shao-Ping Weng; Jian-Guo He; Chang-Jun Guo

    2016-01-01

    Caveolae are flask-shaped invaginations of the plasma membrane. Caveolae play important roles in the process of viruses entry into host cells, but the roles of caveolae at the late stage of virus infection were not completely understood. Tiger frog virus (TFV) has been isolated from the diseased tadpoles of the frog, Rana tigrina rugulosa, and causes high mortality of tiger frog tadpoles cultured in Southern China. In the present study, the roles of caveolae at the late stage of TFV infection...

  6. Inefficient fusion due to a lack of attachment receptor/co-receptor restricts productive human immunodeficiency virus type 1 infection in human hepatoma Huh7.5 cells.

    Science.gov (United States)

    Fromentin, Rémi; Tardif, Mélanie R; Tremblay, Michel J

    2011-03-01

    Since the widespread use of the highly active antiretroviral therapy, the incidence of liver disease has increased to become a leading cause of death among human immunodeficiency virus type 1 (HIV-1)-infected individuals. It can be proposed that the ability of HIV-1 to infect hepatocytes could influence liver diseases. Although the presence of HIV-1 was identified in hepatocytes from HIV-1 seropositive patients, the susceptibility of hepatocytes to HIV-1 infection in vitro remains controversial. We present evidence here that human hepatoma cells are not productively infected with CD4-dependent HIV-1 strains because of inefficient fusion related to an absence of cell surface CD4 and CXCR4. However, these cells display an increased susceptibility to infection with a CD4-independent viral isolate through an interaction with galactosyl ceramide, an alternate receptor for HIV-1. This study provides further understanding of the susceptibility of human hepatocytes to HIV-1 infection. However, in vivo investigations are recommended to consolidate these data. PMID:21123542

  7. Cardiac-Restricted IGF-1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Enrique Gallego-Colon

    2015-01-01

    Full Text Available Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9, their inhibitors (TIMP-1 and TIMP-2, and collagen types (Col 1α1 and Col 1α3 in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.

  8. Structural Basis for the Recognition of Mutant Self by a Tumor-Specific, MHC Class II-Restricted T Cell Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Deng,L.; Langley, R.; Brown, P.; Xu, G.; Teng, L.; Wang, Q.; Gonzales, M.; Callender, G.; Nishimura, M.; et al.

    2007-01-01

    Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.

  9. Fetal movements as a predictor of health.

    Science.gov (United States)

    Lai, Jonathan; Nowlan, Niamh C; Vaidyanathan, Ravi; Shaw, Caroline J; Lees, Christoph C

    2016-09-01

    The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes, including reduced fetal growth, occur to favor survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity while reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision-making. In high-risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there has been little evolution in the development of technologies to objectively evaluate fetal movement behavior for clinical application. This review explores the available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and demonstrates how interdisciplinary developments in this area may aid in the improvement of clinical outcomes. PMID:27374723

  10. NEW RELIGIOUS MOVEMENTS

    Directory of Open Access Journals (Sweden)

    SURAJ KUMAR SUMAN

    2013-04-01

    Full Text Available Several of the new religious movements (NRMs of modern times have become global movements. Among these are the Soka Gakkai of Japan; the Brahma Kumaris, Sathya Sai Baba, and Hare Krishna of India; the Tzu Chi Buddhist Compassion and Relief Society of Taiwan; and Scientology, which began in the United States in the early 1950s. In order to become global movements, NRMs must often depend heavily on one particular ethnic group as they expand beyond their home base. On arrival in new cultural contexts, movements are most likely to appeal to first- or second-generation economic migrants from the same ethnic background as the missionaries who brought the movement to the region in the first place. While being themselves part of the process of ever-increasing globalization, NRMs also throw light on the dynamics and mechanics of this process, on how it plays itself out. This article discusses the globalization and “glocalization” of NRMs, as well as NRMs as vehicles of a new spirituality.

  11. Professionalization and the Null Curriculum: The Case of the Popular Eugenics Movement and American Educational Studies.

    Science.gov (United States)

    Selden, Steven

    1987-01-01

    Presents an essay review of three recent books on eugenics, a once popular quasiscientific and politically conservative social movement devoted to the improvement of humankind through programs of selective breeding and marriage restriction. States that educators must study and come to grips with the meaning of this movement in order to appreciate…

  12. Restricted diffusion of calretinin in cerebellar granule cell dendrites implies Ca²⁺-dependent interactions via its EF-hand 5 domain

    OpenAIRE

    Arendt, Oliver; Schwaller, Beat; Brown, Edward B.; Eilers, Jens; Schmidt, Hartmut

    2013-01-01

    Ca²⁺-binding proteins (CaBPs) are important regulators of neuronal Ca²⁺ signaling, acting either as buffers that shape Ca²⁺ transients and Ca²⁺ diffusion and/or as Ca²⁺ sensors. The diffusional mobility represents a crucial functional parameter of CaBPs, describing their range-of-action and possible interactions with binding partners. Calretinin (CR) is a CaBP widely expressed in the nervous system with strong expression in cerebellar granule cells. It is involved in regulating excitability a...

  13. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally the......Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...

  14. Antiretroviral Restriction Factors in Mice

    OpenAIRE

    Nair, Smita; Rein, Alan

    2014-01-01

    One of the most exciting areas in contemporary retrovirus research is the discovery of “restriction factors”. These are cellular proteins that act after virus entry to inhibit infection by or replication of retroviruses (and other viruses and intracellular pathogens). We briefly discuss here three antiretroviral restriction factors in mice: Fv1, APOBEC3, and tetherin, touching on both biological and molecular aspects of these restriction systems.

  15. A Survey of Geographic Restriction Mobility Models

    Directory of Open Access Journals (Sweden)

    Ibrahim Khider

    2007-01-01

    Full Text Available In this study, we present and visit the limitation of Random mobility model, the unconstraint motion of mobile node. Mobile nodes, in the Random Waypoint and Random walk mobility models, are allowed to move freely and randomly anywhere in the simulation field. However, in most real life applications, we observe that a node’s movement is subject to the environment. In particular, the motions of vehicles are bounded to the freeways or local streets in the urban area and on campus the pedestrians may be blocked by the buildings and other obstacles. Therefore, the nodes may move in a pseudo-random way on predefined pathways in the simulation field. Some recent works address this characteristic and integrate the paths and obstacles into mobility models. We call this kind of mobility model a mobility model with geographic restriction.

  16. Specific killing of P53 mutated tumor cell lines by a cross-reactive human HLA-A2-restricted P53-specific CTL line

    DEFF Research Database (Denmark)

    Würtzen, P A; Pedersen, L O; Poulsen, H S;

    2001-01-01

    p53 is upregulated in the majority of spontaneous tumors and the HLA class I molecule HLA-A2 is expressed by approximately 50% of the caucasians. Potentially, these facts make HLA-A2-binding p53 peptides for CTL-inducing immunotherapy applicable to a broad range of cancer patients. In our study, we...... investigated the CTL-inducing capacity of autologous monocyte-derived dendritic cells (DC) maturated by exposure to CD40L and pulsed with a pool of 4 wild-type, HLA-A2-binding p53 peptides, and the p53-specific CD8(+) CTL lines established from healthy HLA-A2-positive donors were characterized. Reactivity to p......53(65-73) and p53(187-197) peptides was obtained in the T-cell lines. Interestingly, cold target inhibition experiments demonstrated that the simultaneous recognition of the 2 peptides was the result of cross-reactivity, which was confirmed by killing experiments at the clonal CTL level. Furthermore...

  17. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn;

    2013-01-01

    BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS: The Transfusion Re...... after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P......BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS: The Transfusion...... Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin...

  18. Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes

    OpenAIRE

    Breit, T.M.; Mol, E.J.; Wolvers-Tettero, I.L.; Ludwig, W. D.; Wering, E.R. van; van Dongen, J.J.

    1993-01-01

    Site-specific deletions in the tal-1 gene are reported to occur in 12- 26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T- ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion reg...

  19. A movement ecology paradigm for unifying organismal movement research.

    Science.gov (United States)

    Nathan, Ran; Getz, Wayne M; Revilla, Eloy; Holyoak, Marcel; Kadmon, Ronen; Saltz, David; Smouse, Peter E

    2008-12-01

    Movement of individual organisms is fundamental to life, quilting our planet in a rich tapestry of phenomena with diverse implications for ecosystems and humans. Movement research is both plentiful and insightful, and recent methodological advances facilitate obtaining a detailed view of individual movement. Yet, we lack a general unifying paradigm, derived from first principles, which can place movement studies within a common context and advance the development of a mature scientific discipline. This introductory article to the Movement Ecology Special Feature proposes a paradigm that integrates conceptual, theoretical, methodological, and empirical frameworks for studying movement of all organisms, from microbes to trees to elephants. We introduce a conceptual framework depicting the interplay among four basic mechanistic components of organismal movement: the internal state (why move?), motion (how to move?), and navigation (when and where to move?) capacities of the individual and the external factors affecting movement. We demonstrate how the proposed framework aids the study of various taxa and movement types; promotes the formulation of hypotheses about movement; and complements existing biomechanical, cognitive, random, and optimality paradigms of movement. The proposed framework integrates eclectic research on movement into a structured paradigm and aims at providing a basis for hypothesis generation and a vehicle facilitating the understanding of the causes, mechanisms, and spatiotemporal patterns of movement and their role in various ecological and evolutionary processes. "Now we must consider in general the common reason for moving with any movement whatever." (Aristotle, De Motu Animalium, 4th century B.C.). PMID:19060196

  20. Migration policy: from restriction to regulation.

    Science.gov (United States)

    Wu, Z

    1996-12-01

    This article describes the extent of rural-urban migration, the flows by province in 1992, and social policies relating to migration in China. Population movements followed several patterns: increased flows from rural-urban areas during 1945-66, reversed flows back to rural areas during the Cultural Revolution of 1966-77, and relaxed controls during 1978-87 and increased rural-urban migration. Migration policy began on a strict household registration system. Restrictions were eased to allow for regulation and allocation of surplus rural workers. Rapid industrial development helped China recover from the war. Peak movements were in 1958 during the "Great Leap Forward." An estimated 19 million rural workers were recruited during 1958-60. Supply of labor exceeded needs, and urban governments reversed this strategy in 1961. During the 1960s, the household registration system was strictly enforced. Urban population declined during 1965-76. Youth were required to reeducate themselves in farming areas. During 1978-87, China's central leadership established the household land-contract responsibility system and grain production increased. Limits on arable land resulted in surplus labor. In the mid-1980s, policy focused on nonagricultural wage labor in local factories. After 1988, the government encouraged development of cities and towns and village enterprises under the socialist market economy. It is likely that now the labor market rather than the household registration system will control the size, direction, and selectivity of migration. PMID:12320642

  1. Mungiki as Youth Movement

    DEFF Research Database (Denmark)

    Rasmussen, Jacob

    2010-01-01

    Like many other African countries, Kenya has a large and growing youth population. Some of the youths are mobilized into militant and political networks; one of these is the Mungiki movement. The article explores Mungiki’s combination of politics, religion and Kikuyu traditions. Using the examples...

  2. Fluid Movement and Creativity

    Science.gov (United States)

    Slepian, Michael L.; Ambady, Nalini

    2012-01-01

    Cognitive scientists describe creativity as fluid thought. Drawing from findings on gesture and embodied cognition, we hypothesized that the physical experience of fluidity, relative to nonfluidity, would lead to more fluid, creative thought. Across 3 experiments, fluid arm movement led to enhanced creativity in 3 domains: creative generation,…

  3. Posture and Movement

    Science.gov (United States)

    1997-01-01

    Session TP3 includes short reports on: (1) Modification of Goal-Directed Arm Movements During Inflight Adaptation to Microgravity; (2) Quantitative Analysis of Motion control in Long Term Microgravity; (3) Does the Centre of Gravity Remain the Stabilised Reference during Complex Human Postural Equilibrium Tasks in Weightlessness?; and (4) Arm End-Point Trajectories Under Normal and Microgravity Environments.

  4. Music, Movement, and Poetry.

    Science.gov (United States)

    Carmichael, Karla D.

    This paper's premise is that music, movement, and poetry are unique and creative methods to be used by the counselor in working with both children and adults. Through these media, the counselor generates material for the counseling session that may not be available through more traditional "talk therapies." The choice of music as a counseling…

  5. Stroke and restricted sensory syndromes

    International Nuclear Information System (INIS)

    There have been sporadic case reports of a restricted sensory syndrome caused by stroke, most often as a cheiro-oral syndrome. We describe 14 patients with stroke who showed various restricted sensory syndromes and correlated their symptoms with the radiological findings. (orig./MG)

  6. Movement: A Clinical Investigation

    Directory of Open Access Journals (Sweden)

    Kazem Dalaie

    2015-10-01

    Full Text Available Objectives: One major drawback of orthodontic treatment is its long duration due to slow tooth movement and the pain at the onset of treatment following application of forces. There is controversy regarding the efficacy of laser for decreasing the treatment time and pain of orthodontic treatment. The purpose of this study was to investigate the effect of low level diode laser on the rate of orthodontic tooth movement and the associated pain.Materials and Methods: In this double blind randomized controlled clinical trial, 12 or- thodontic patients referring to Shahid Beheshti School of Dentistry for first premolar ex- traction were randomly selected and allocated to gallium aluminum-arsenide laser (Ga,Al,As diode laser, 880 nm, 100 mW, 5 j/cm2, 8 points, 80 seconds, continuous mode or control group. The patients initially underwent leveling and alignment using the sectional system. Force (150 gr was applied to each canine tooth via sectional closing loops. The loops were activated every month. The rate of tooth movement and pain were monitored over the treatment period and recorded on days 1, 3, 7, 30, 33, 37, 60, 63 and 67. Two-way ANOVA was used for comparison of groups.Results: There was no significant difference in terms of tooth movement and pain scores between the irradiated and non-irradiated sides at any time point (P>0.05.Conclusion: Although laser enhanced orthodontic tooth movement in the upper jaw, we failed to provide solid evidence to support the efficacy of laser for expediting tooth move- ment or reducing the associated pain.

  7. Design implications of extremely restricted patterning

    Science.gov (United States)

    Vaidyanathan, Kaushik; Liu, Renzhi; Liebmann, Lars; Lai, Kafai; Strojwas, Andzrej J.; Pileggi, Larry

    2014-07-01

    Escalating manufacturing cost and complexity is challenging the premise of affordable scaling. With lithography accounting for a large fraction of wafer costs, researchers are actively exploring several cost-effective alternative lithographic techniques, such as directed self-assembly, self-aligned multiple patterning, etc. However, most of the alternative lithographic techniques are restrictive, and it is important to understand the impact of such pattering restrictions on system-on-chip (SoC) design. To this end, we artificially restricted all layers in a 14 nm process to be pure gratings and observed that the pure gratings approach results in an inefficient SoC design with several process integration concerns. To come up with a technology definition that is mindful of designer requirements, it is essential to undertake a holistic design technology co-optimization (DTCO) considering several SoC design elements, such as standard cell logic, static random access memory bitcells, analog blocks, and physical synthesis. Our DTCO on the IBM 14 nm process with additional 10- and 7-nm node-like pattern restrictions leads us to converge on a set of critical pattern constructs that are required for an efficient and affordable SoC design.

  8. In silico Analysis of HIV-1 Env-gp120 Reveals Structural Bases for Viral Adaptation in Growth-Restrictive Cells

    Science.gov (United States)

    Yokoyama, Masaru; Nomaguchi, Masako; Doi, Naoya; Kanda, Tadahito; Adachi, Akio; Sato, Hironori

    2016-01-01

    Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1) envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co-receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness. PMID:26903989

  9. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

    Directory of Open Access Journals (Sweden)

    Liu Lei

    2008-12-01

    Full Text Available Abstract Background Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites" in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD can utilize directly infused or systemic neurotoxins. Results We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+ and UB-(+ aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes. Conclusion Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a

  10. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  11. A movement ecology paradigm for unifying organismal movement research

    OpenAIRE

    Nathan, Ran; Getz, Wayne M.; Revilla, Eloy; Holyoak, Marcel; Kadmon, Ronen; Saltz, David; Smouse, Peter E.

    2008-01-01

    Movement of individual organisms is fundamental to life, quilting our planet in a rich tapestry of phenomena with diverse implications for ecosystems and humans. Movement research is both plentiful and insightful, and recent methodological advances facilitate obtaining a detailed view of individual movement. Yet, we lack a general unifying paradigm, derived from first principles, which can place movement studies within a common context and advance the development of a mature scientific discip...

  12. Dissection of Silencing Signal Movement in Arabidopsis

    OpenAIRE

    Smith, Lisa M.; Baulcombe, David C.

    2007-01-01

    In our recent paper in Plant Cell, we examined the phenomenon of non-cell autonomous RNA silencing through a genetic screen of the requirements for cell-to-cell signal movement.1 We found a requirement for components of the nuclear and trans-acting RNA silencing pathways in blocking or enhancing the spread of silencing and identified a new SNF2 domain-containing protein, CLSY1, in the nuclear RNA silencing pathway. Here we discuss our data from a broader perspective of other recently publishe...

  13. Interaction between the Alfalfa mosaic virus movement protein and plasmodesmata

    NARCIS (Netherlands)

    Wel, van der N.N.

    2000-01-01

    For a full infection of a host, plant viruses should be able to multiply in the initially infected cell and to spread to neighbouring cells as to eventually invade the entire plant. The viral transport pathway can in principle be divided into two steps, i.e. cell-to-cell movement within tissues, and

  14. COMBINING MODULES FOR MOVEMENT

    OpenAIRE

    Bizzi, E; Cheung, V.C.K.; d’Avella, A.; Saltiel, P.; Tresch, M.

    2007-01-01

    We review experiments supporting the hypothesis that the vertebrate motor system produces movements by combining a small number of units of motor output. Using a variety of approaches such as microstimulation of the spinal cord, NMDA iontophoresis, and an examination of natural behaviors in intact and deafferented animals we have provided evidence for a modular organization of the spinal cord. A module is a functional unit in the spinal cord that generates a specific motor output by imposing ...

  15. Japan's growing environmental movement

    Energy Technology Data Exchange (ETDEWEB)

    Hase, T.

    1981-03-01

    Serious problems from overdevelopment and pollution along with a relaxation of restrictions on political protest are behind an active environmental movement in Japan. The historical development and structure of this movement is traced from the late 19th Century, when Japan was forced to admit western powers to avoid colonialization and set a path of industrial growth coupled with military strength. Serious health hazards began developing after World War II, but pro-growth policies limited public protest and government response. Polluting industries ignore their liability, while company-owned labor unions show little sympathy. Individual protests, especially among the young, increased and have organized into groups demanding compensation for injury from pollution, groups opposing development plans, and groups promoting altenative life styles. The strategies used by these groups fall into four categories: negotiation with polluter or developer, distribution of pamphlets, mass demonstration, and lawsuits. The movement is unique in its regional character, its independence from political parties, its weak political influence, and its limited impact on decision making. Its greatest contribution to date has been to alert an over-industrialized nation of the danger. 12 references, 6 figures. (DCK)

  16. Anti-nuclear movements

    International Nuclear Information System (INIS)

    Nuclear power, heralded in the years after World War II as the answer to the world's energy needs, has in more recent times become the focus of intense ecological, political and economic debate. In this study, the current worldwide opposition to nuclear power is examined from its origins in expert dissent to the widespread development of grassroots activity. Chapter headings include: Social Movements: A Theoretical Framework; Creating the Preconditions for Public Protest; Local and Regional Opposition: Mobilizing the Grass Roots; Local Opposition and the Politicization of Nuclear Power; The Use of Local Opposition as a Political Resource; Local Opposition and Social Movement Analysis; The Removal of Political Stimuli: The Unpolitics of Nuclear Siting; Analyzing Host Community Attitudes: The Survey Evidence; Attitudes and Political Action of Nuclear Host Communities: Approaches and Explanations; Novel Siting Approaches and their Political Implications; Siting and Social Movement Analysis; Patterns and Outcomes of Nuclear Energy Conflicts; The Future of the Nuclear Energy Conflict. Throughout the text, analysis and theory are blended with detailed accounts of the growth and activities of individual anti-nuclear organizations in different countries. (author)

  17. Monitoring underground movements

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    On 16 September 2015 at 22:54:33 (UTC), an 8.3-magnitude earthquake struck off the coast of Chile. 11,650 km away, at CERN, a new-generation instrument – the Precision Laser Inclinometer (PLI) – recorded the extreme event. The PLI is being tested by a JINR/CERN/ATLAS team to measure the movements of underground structures and detectors.   The Precision Laser Inclinometer during assembly. The instrument has proven very accurate when taking measurements of the movements of underground structures at CERN.    The Precision Laser Inclinometer is an extremely sensitive device capable of monitoring ground angular oscillations in a frequency range of 0.001-1 Hz with a precision of 10-10 rad/Hz1/2. The instrument is currently installed in one of the old ISR transfer tunnels (TT1) built in 1970. However, its final destination could be the ATLAS cavern, where it would measure and monitor the fine movements of the underground structures, which can affect the precise posi...

  18. Human preference for air movement

    DEFF Research Database (Denmark)

    Toftum, Jørn; Melikov, Arsen Krikor; Tynel, A.;

    2002-01-01

    Human preference for air movement was studied at slightly cool, neutral, and slightly warm overall thermal sensations and at temperatures ranging from 18 deg.C to 28 deg.C. Air movement preference depended on both thermal sensation and temperature, but large inter-individual differences existed...... between subjects. Preference for less air movement was linearly correlated with draught discomfort, but the percentage of subjects who felt draught was lower than the percentage who preferred less air movement....

  19. Creativity and Embodied Fluid Movements

    OpenAIRE

    Broadhead, Alastair

    2015-01-01

    There is an increasing body of evidence suggesting that the embodiment of certain movements can stimulate creative idea formation. Embodied Creativity suggests that embodying particular movements, often fluid, free movements can improve creative thinking over the embodiment of nonfluid movements. In the first of two experiments participants were required to navigate a character through a bespoke virtual environment while (a) following a fluid, free flowing pathway, (b) a nonfluid pathway, or ...

  20. Eye movements when viewing advertisements

    OpenAIRE

    Emily eHiggins; Mallorie eLeinenger; Keith eRayner

    2014-01-01

    In this selective review, we examine key findings on eye movements when viewing advertisements. We begin with a brief, general introduction to the properties and neural underpinnings of saccadic eye movements. Next, we provide an overview of eye movement behavior during reading, scene perception, and visual search, since each of these activities is, at various times, involved in viewing ads. We then review the literature on eye movements when viewing print ads and warning labels (of the kind ...

  1. How Social Movements Do Culture

    OpenAIRE

    Roy, William G.

    2010-01-01

    While much social science literature has analyzed the cultural bases of social movement, activity, and the content of cultural production by social movements, relatively little has been written about the concrete social relations within which social movements do culture. This paper addresses the issue of what social movements are doing when they produce culture. Four dimensions of social relations within which culture is enacted are identified: the division of labor, the relations of power, t...

  2. How harmful are adaptation restrictions

    OpenAIRE

    Bruin, de, B.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  3. Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells.

    Science.gov (United States)

    Wallingford, Mary C; Gammill, Hilary S; Giachelli, Cecilia M

    2016-03-01

    The essential nutrient phosphorus must be taken up by the mammalian embryo during gestation. The mechanism(s) and key proteins responsible for maternal to fetal phosphate transport have not been identified. Established parameters for placental phosphate transport match those of the type III phosphate transporters, Slc20a1 and Slc20a2. Both members are expressed in human placenta, and their altered expression is linked to preeclampsia. In this study, we tested the hypothesis that Slc20a2 is required for placental function. Indeed, complete deficiency of Slc20a2 in either the maternal or embryonic placental compartment results in fetal growth restriction. We found that Slc20a2 null mice can reproduce, but are subviable; ∼50% are lost prior to weaning age. We also observed that 23% of Slc20a2 deficient females develop pregnancy complications at full term, with tremors and placental abnormalities including abnormal vascular structure, increased basement membrane deposition, abundant calcification, and accumulation of novel CD13 and lamininα1 positive cells. Together these data support that Slc20a2 deficiency impacts both maternal and neonatal health, and Slc20a2 is required for normal placental function. In humans, decreased levels of placental Slc20a1 and Slc20a2 have been correlated with early onset preeclampsia, a disorder that can manifest from placental dysfunction. In addition, preterm placental calcification has been associated with poor pregnancy outcomes. We surveyed placental calcification in human preeclamptic placenta samples, and detected basement membrane-associated placental calcification as well as a comparable lamininα1 positive cell type, indicating that similar mechanisms may underlie both human and mouse placental calcification. PMID:26952749

  4. Management of heterotopic ossification and restricted forearm rotation after tension band wiring for olecranon fracture

    OpenAIRE

    Karthik, Karuppaiah; Tahmassebi, Ramon; Tavakkolizadeh, Adel; Compson, Jonathan

    2014-01-01

    A 32-year-old lady presented to our clinic with persistent painful restriction of her dominant forearm movements for three months after tension band wiring of olecranon. She had full elbow flexion and extension; however, her forearm rotations were restricted and painful. Investigations revealed prominent tips of the wire, eroding the radial tuberosity with heterotopic ossification between the radius and ulna. As there was no synostosis, the patient had implant exit. During surgery, before imp...

  5. Laser-Based Trespassing Prediction in Restrictive Environments: A Linear Approach

    OpenAIRE

    Gustavo Scaglia; Fernando Auat Cheein

    2012-01-01

    Stationary range laser sensors for intruder monitoring, restricted space violation detections and workspace determination are extensively used in risky environments. In this work we present a linear based approach for predicting the presence of moving agents before they trespass a laser-based restricted space. Our approach is based on the Taylor's series expansion of the detected objects' movements. The latter makes our proposal suitable for embedded applications. In the experimental results ...

  6. TRIM5 Acts as More Than a Retroviral Restriction Factor

    OpenAIRE

    Li Wu; Suresh De Silva

    2011-01-01

    The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiq...

  7. Energy and movement

    CERN Document Server

    2009-01-01

    Energy and Movement, is one book in the Britannica Illustrated Science Library Series that is correlated to the science curriculum in grades 5-8. The Britannica Illustrated Science Library is a visually compelling set that covers earth science, life science, and physical science in 16 volumes.  Created for ages 10 and up, each volume provides an overview on a subject and thoroughly explains it through detailed and powerful graphics-more than 1,000 per volume-that turn complex subjects into information that students can grasp.  Each volume contains a glossary with full definitions for vocabular

  8. Energy and Movement

    CERN Document Server

    90, Sol

    2011-01-01

    Updated for 2011, Energy and Movement, is one book in the Britannica Illustrated Science Library Series that covers today's most popular science topics, from digital TV to microchips to touchscreens and beyond. Perennial subjects in earth science, life science, and physical science are all explored in detail. Amazing graphics-more than 1,000 per title-combined with concise summaries help students understand complex subjects. Correlated to the science curriculum in grades 5-9, each title also contains a glossary with full definitions for vocabulary.

  9. Knowledge through movement

    DEFF Research Database (Denmark)

    Jensen, Søren Kjær; Moser, T.

    2003-01-01

    In: Children and adolescents in movement - perspectives and ideas. The Danish Ministry of Culture, pages 150 - 162. 2003 Short description: the article debunks a lot of the myths surrounding body and learning, and replace them with a vision about another kind of learning. The aim is to reintroduce...... the bodily aspect to the educational system in a highly effective and useful way. Abstract: Children and adolescents are raised to passivity. Lack of motion in kindergartens and schools promote obesity and life style-related diseases, but another and just as dire consequence is the impact on learning...

  10. The Evidence Movement

    DEFF Research Database (Denmark)

    Hansen, Hanne Foss; Rieper, Olaf

    2009-01-01

    The evidence movement and the idea of systematic reviews, defined as summaries of the results of already existing evaluation and research projects, have gained considerable support in recent years as many international as well as national evidence-producing organizations have been established. This...... article analyses how the idea is practised in the areas of health, social welfare and education and shows that evidence-producing organizations work differently. Some subscribe to the hierarchy of evidence, others to a typology of evidence. The consequences of these variations are discussed....

  11. Antenatal taurine supplementation reduces cerebral cell apoptosis in fetal rats with growth restriction%孕鼠补充牛磺酸减少胎儿生长受限胎鼠脑细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    王晓凤; 滕慧云; 刘敬; 杨娜; 任晓暾

    2013-01-01

    目的 通过建立胎儿生长受限(fetal growth restriction,FGR)大鼠模型,探讨孕鼠补充牛磺酸对FGR胎鼠脑细胞凋亡以及胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)和半胱氨酸蛋白酶-3(caspase 3)表达的影响. 方法 将15只Sprague-Dawley (SD)孕鼠随机分为对照组、FGR模型组(模型组)、FGR+孕鼠补充牛磺酸组(牛磺酸组),每组5只.通过低蛋白饮食法建立FGR模型,牛磺酸组自妊娠第12天开始于饲料中添加牛磺酸300 mg/(kg·d)直至自然分娩.对照组每窝随机取2只适于胎龄胎鼠,牛磺酸组与模型组每窝随机取2只FGR胎鼠,应用原位末端脱氧核苷酸转移酶标记(terminal deoxynucleotidyl transferase mediated nick end labeling,TUNEL)法检测各组胎鼠脑神经细胞凋亡情况.用免疫组织化学方法检测GDNF和caspase-3表达情况.统计学方法采用单因素方差分析、Kruskal-Wallis秩和检验、SNK检验和Tamhane's检验. 结果 (1)对照组、模型组及牛磺酸组胎鼠总数分别为65、60和59只,胎鼠平均体重为(6.36±0.44)、(4.55±0.45)和(5.11±0.67)g.模型组胎鼠均发生FGR,牛磺酸组胎鼠FGR发生率为76.3% (45/59),成功建立FGR模型.(2)对照组胎鼠脑组织内偶见TUNEL阳性细胞;模型组明显增多,在大脑皮质、海马、白质区均有分布;牛磺酸组较模型组则明显减少.3组TUNEL阳性细胞数分别为(0.46±0.11)、(14.76±3.42)和(6.78±1.93)个(H=429.80,P=0.000).(3)对照组胎鼠大脑皮质内仅有少量GDNF阳性细胞分布,模型组明显增多,牛磺酸组则进一步增多.3组GDNF阳性细胞数分别为(93.56±6.73)、(120.36±6.23)和(139.56±5.28)个(H=715.17,P=0.000).(4)对照组胎鼠大脑皮质内仅见少数caspase 3阳性细胞分布,模型组明显增多,牛磺酸组较模型组显著减少,但仍多于对照组.3组caspase 3阳性细胞数分别为(7.50±2.31)、(151.32±24.43)和(37.28±11.21)个(F=132.54,P=0.000).

  12. Genetics Home Reference: familial restrictive cardiomyopathy

    Science.gov (United States)

    ... Home Health Conditions familial restrictive cardiomyopathy familial restrictive cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Familial restrictive cardiomyopathy is a genetic form of heart disease. For ...

  13. A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Spiess, S;

    1995-01-01

    We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were...... present in spleen, mesenteric lymph nodes, peritoneal cavity, lamina propria and epithelial layer of the small and large intestine of 6- to 10-month-old, male and female tg scid mice. Only low numbers of CD3+ T cells were recovered from inguinal, popliteal, or axillary lymph nodes. We studied CD4+ T cells...... in these tg scid mice. CD4+ T cells were found in the peritoneal cavity, in the mesenteric lymph nodes and in the intraepithelial layer and lamina propria of the gut. All CD4+ T cells were CD44+ (i.e. showed evidence of antigen-driven differentiation) and expressed the tg V beta 8.2 TcR beta...

  14. Entanglement with restricted measurement setups

    CERN Document Server

    Meznaric, Sebastian

    2010-01-01

    We consider what is the effective amount of entanglement when the measurement operators one has at their disposal are restricted. Such a scenario occurs when superselection rules are in effect or when there are imperfections in our measurement setup. Given a quantum state and the restrictions on measurements, we consider the following scenario. Imagine we have an ideal, or non-restricted, measurement setup and a state $\\rho_1$ and a non-ideal, or restricted, measurement setup and a state $\\rho_2$. Then the minimum amount of entanglement in $\\rho_1$ so that all quantum communication protocols still perform with the same fidelity as with $\\rho_2$ is effectively the entanglement with restricted measurement setup. For indistinguishable particles, we find that any quantum communication protocol that can be performed with indistinguishable particles, can thus be performed with a ``normal'' state of no more than $E_P$ of entanglement. For the imperfect measurement apparatus we find an upper bound for the effective e...

  15. A STUDY OF COMMITTEES ON THE DEVELOPMENT OF COOPERATIVE MOVEMENT

    OpenAIRE

    ANIL KUMAR SONI; HARJINDER PAL SINGH SALUJA

    2013-01-01

    The cooperatives which are the life blood of the state economy and the mechanism for any development programs. The cooperative credit structure is serving the Indian society since 1904 and since then it has seen several ups and downs. Despite of several limitations such as restriction of area of operations, limited clients, small volume of business, political interference, this movement is standing since last 108 years and serving the societies. The cooperative sector is one of the main partn...

  16. PKC and neurofibromin in the molecular pathology of urinary bladder carcinoma:the effect of PKC inhibitors on carcinoma cell junctions, movement and death

    OpenAIRE

    Aaltonen, V. (Vesa)

    2007-01-01

    Abstract This study examined the role of tumor suppressor neurofibromin and Protein kinase C (PKC) in urinary bladder cancer, and the effect of PKC inhibitors on cancer cell behaviour. Tumor suppressor protein neurofibromin is a product of the NF1 gene, a mutation of which causes the most common hereditary tumor syndrome, type 1 neurofibromatosis. NF1 gene mutations and changes in expression have been demonstrated in malignancies, unrelated to type 1 neurofibromatosis. The best known ...

  17. Localized movement and morphology of UBF1-positive nucleolar regions are changed by -irradiation in G2 phase of the cell cycle

    Czech Academy of Sciences Publication Activity Database

    Sorokin, D.V.; Stixová, Lenka; Sehnalová, Petra; Legartová, Soňa; Suchánková, Jana; Šimara, P.; Kozubek, Stanislav; Matula, Pavel; Skalníková, M.; Raška, I.; Bártová, Eva

    2015-01-01

    Roč. 6, č. 4 (2015), s. 301-313. ISSN 1949-1034 R&D Projects: GA ČR GBP302/12/G157; GA ČR GA13-07822S; GA MŠk 7F14369; GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : DNA damage * live cells * nucleolus Subject RIV: BO - Biophysics Impact factor: 3.033, year: 2014

  18. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Siddharth Gautam; S Mitra; R Mukhopadhyay

    2008-10-01

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time scales involved in the motion and the geometry of motion can be studied using QENS. Molecular dynamics (MD) simulation not only provides insight into the details of the different types of motion possible but also does not suffer limitations of the experimental set-up. Here we report the effect of confinement on molecular dynamics in various restricted geometries as studied by QENS and MD simulations: An example where the QENS technique provided direct evidence of phase transition associated with change in the dynamical behaviour of the molecules is also discussed.

  19. Bridge Decomposition of Restriction Measures

    CERN Document Server

    Alberts, Tom

    2009-01-01

    Motivated by Kesten's bridge decomposition for two-dimensional self-avoiding walks in the upper half plane, we show that the conjectured scaling limit of the half-plane SAW, the SLE(8/3) process, also has an appropriately defined bridge decomposition. This continuum decomposition turns out to entirely be a consequence of the restriction property of SLE(8/3), and as a result can be generalized to the wider class of restriction measures. Specifically we show that the restriction hulls with index less than one can be decomposed into a Poisson Point Process of irreducible bridges in a way that is similar to Ito's excursion decomposition of a Brownian motion according to its zeros.

  20. Polycythemia vera presenting with left hemichoreiform movements

    International Nuclear Information System (INIS)

    A 65-year-old man developed abruptly choreiform movements involving the left face, arm and leg one day prior to admission. Physical examination revealed red face and palms, hyperemic conjunctivae and atrial fibrillations. Blood pressure was 168/90. Spleen was not palpable. Hemichoreiform movements of the left face and limbs were observed. There was no other neurological abnormalities. Laboratory studies showed RBC 880x104, Hb 22.4g/dl, Hct 63%, WBC 8,100, platelets 22.9x104, ESR 0mm/hr, RBC oxygen saturation 97%, serum iron 67 μg/dl, LDH 593 units, uric acid 14mg/dl, and erythropoietine (HI method) 19mIU/ml (normal 28-88). Bone marrow showed myeloid nucleated cell count 38.6x104. ECG showed atrial fibrillations. Chest X-ray and scintigrams of liver and spleen were normal. CSF was normal. Brain CT scan on admission disclosed a low density area in right caudate nucleus. The choreiform movements were rapidly mitigated by venesection and by oral administration of haloperidol(3mg daily). There weeks after discontinuing haloperidol, the hemichorea returned. The routine hematology showed RBC 870x104, Hb 19.8g/dl, Hct 62%, WBC 10,200, and plateret 37.4x104. Another venesection reduced the chorea. Pipobroman was administered to control the polycythemia vera. He has been free of choreic movements thereafter. Choreiform movement is rarely observed in polycythemia vera. The pathogenesis is still unknown. The venous congestion, however, may play a role in this case because the choreic movements disappeared by venesection. (author)

  1. CDRL - company dose restriction level

    International Nuclear Information System (INIS)

    For a number of year's close constraints and controls have been used as effective measures in aiding restricting exposure to ionising radiation. Predecessor companies to British Energy Generation (BEG) originally established the Company Dose Restriction Level (CDRL) as a consequence of the revision of risk estimates, then with the revised Ionising Radiations Regulations 1999 (IRR99) the CDRL for BEG was also revised. The background, influences and consequences of CDRL appliance in a commercial organisation in calendar year 2000/1 are presented below. (author)

  2. HFB in a restricted space

    International Nuclear Information System (INIS)

    A restricted Hartree-Fock-Bogoliubov method is developed with a restriction on the angular momenta of the Cooper pairs that conform the vacuum (SD or SDG). The method is applied to 176Yb. The quadrupole moment in the SD subspace is found to be 80% for neutrons and 91% for protons of its value in the full space. The inclusion of the G part of the Cooper pairs improves that agreement. The descriptions in terms of boson condensate and coherent states are discussed. (author)

  3. Material and Affective Movements

    DEFF Research Database (Denmark)

    Rasmussen, Lisa Rosén

    2014-01-01

    This chapter offers a study of life at school as remembered by groups of people who finished secondary school in the 1950s, 1970s and 1990s. The article draws up three generational portraits based on in-depth interviews that demonstrate how school life is remembered in complex and textural ways....... The chapter traces the former pupil’s memories of physical and affective movements within the larger context of school and discovers surprisingly diverse modes of knowing, relating, and attending to things, teachers and classmates among and between the three generations. It thus taps into the rich...... demonstrates how the use of spoken memories is a rewarding source for the writing about school from the pupils’ perspective....

  4. Contrasting movement strategies among juvenile albatrosses and petrels.

    Science.gov (United States)

    de Grissac, Sophie; Börger, Luca; Guitteaud, Audrey; Weimerskirch, Henri

    2016-01-01

    Animal movement is a fundamental eco-evolutionary process yet the behaviour of juvenile animals is largely unknown for many species, especially for soaring seabirds which can range widely over the oceans at low cost. We present an unprecedented dataset of 98 juvenile albatrosses and petrels (nine species), tracked for the first three months after independence. There was a startling diversity within and among species in the type and scale of post-natal movement strategies, ranging from area-restricted to nomadic patterns. Spatial scales were clustered in three groups that ranged from 6000 km from the natal nest. In seven of the nine species, the orientation of flight paths and other movement statistics showed strong similarities between juveniles and adults, providing evidence for innate orientation abilities. Our results have implications for understanding the development of foraging behaviour in naïve individuals and the evolution of life history traits such as survival, lifespan and breeding strategy. PMID:27189182

  5. Contrasting movement strategies among juvenile albatrosses and petrels

    Science.gov (United States)

    de Grissac, Sophie; Börger, Luca; Guitteaud, Audrey; Weimerskirch, Henri

    2016-01-01

    Animal movement is a fundamental eco-evolutionary process yet the behaviour of juvenile animals is largely unknown for many species, especially for soaring seabirds which can range widely over the oceans at low cost. We present an unprecedented dataset of 98 juvenile albatrosses and petrels (nine species), tracked for the first three months after independence. There was a startling diversity within and among species in the type and scale of post-natal movement strategies, ranging from area-restricted to nomadic patterns. Spatial scales were clustered in three groups that ranged from 6000 km from the natal nest. In seven of the nine species, the orientation of flight paths and other movement statistics showed strong similarities between juveniles and adults, providing evidence for innate orientation abilities. Our results have implications for understanding the development of foraging behaviour in naïve individuals and the evolution of life history traits such as survival, lifespan and breeding strategy. PMID:27189182

  6. Air movement - good or bad?

    DEFF Research Database (Denmark)

    Toftum, Jørn

    2004-01-01

    Air movement - good or bad? The question can only be answered by those who are exposed when they are exposed. Human perception of air movement depends on environmental factors including air velocity, air velocity fluctuations, air temperature, and personal factors such as overall thermal sensation...... and activity level. Even for the same individual, sensitivity to air movement may change from day to day as a result of e.g. different levels of fatigue. Based on existing literature, the current paper summarizes factors influencing the human perception of air movement and attempts to specify in...... general terms when air movement is desirable and when it is not. At temperatures up to 22-23oC, at sedentary activity and with occupants feeling neutral or cooler there is a risk of air movement being perceived as unacceptable, even at low velocities. In particular, a cool overall thermal sensation...

  7. Modelling group dynamic animal movement

    OpenAIRE

    Langrock, Roland; Hopcraft, Grant; Blackwell, Paul; Goodall, Victoria; King, Ruth; Niu, Mu; Patterson, Toby; Pedersen, Martin; Skarin, Anna; Schick, Robert Schilling

    2013-01-01

    1). Group dynamics are a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognized, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However, to date, practical statistical methods, which can include group dynamics in animal movement models, have been lacking. 2). We consider a flexible modelling framework that distinguishes a group-level ...

  8. Characterization of Borrelia burgdorferi isolates by restriction endonuclease analysis and DNA hybridization.

    OpenAIRE

    LeFebvre, R B; Perng, G C; Johnson, R C

    1989-01-01

    Genomes of several Borrelia burgdorferi isolates from North America and Europe were characterized by restriction endonuclease analysis and DNA hybridization using labeled B. burgdorferi whole-cell DNA (strain ATCC 35210). Several different restriction and homology patterns were observed among these isolates, indicating genotypic heterogeneity within this genus and species. It was concluded from this study that restriction endonuclease analysis of B. burgdorferi whole-cell DNA may be a reliabl...

  9. Space-restricted attribute grammars

    DEFF Research Database (Denmark)

    Schmidt, Erik Meineche

    1980-01-01

    Restricting the size of attribute values, relative to the length of the string under consideration, leads to a model of attribute grammars in which grammars with both inherited and synthesized attributes can be significantly more economical than grammars with synthesized attributes only....

  10. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  11. Arousal facilitates involuntary eye movements.

    Science.gov (United States)

    DiGirolamo, Gregory J; Patel, Neha; Blaukopf, Clare L

    2016-07-01

    Attention plays a critical role in action selection. However, the role of attention in eye movements is complicated as these movements can be either voluntary or involuntary, with, in some circumstances (antisaccades), these two actions competing with each other for execution. But attending to the location of an impending eye movement is only one facet of attention that may play a role in eye movement selection. In two experiments, we investigated the effect of arousal on voluntary eye movements (antisaccades) and involuntary eye movements (prosaccadic errors) in an antisaccade task. Arousal, as caused by brief loud sounds and indexed by changes in pupil diameter, had a facilitation effect on involuntary eye movements. Involuntary eye movements were both significantly more likely to be executed and significantly faster under arousal conditions (Experiments 1 and 2), and the influence of arousal had a specific time course (Experiment 2). Arousal, one form of attention, can produce significant costs for human movement selection as potent but unplanned actions are benefited more than planned ones. PMID:26928432

  12. Immigration and freedom of movement

    Directory of Open Access Journals (Sweden)

    Adam Hosein

    2013-03-01

    Full Text Available In this paper I focus on one very influential argument for open borders, the freedom of movement argument, which says that if we value freedom of movement we must demand open borders. I begin the paper the paper by discussing Joseph Carens’ well known version of the argument. I then consider, and reject, David Miller's response to that argument. Finally, I develop my own reply to Carens. Both Carens and Miller, I argue, are mistaken about the proper grounds for freedom of movement. Once we see this, it is clear how we can value freedom of movement without being committed to open borders.

  13. Co-movement in Inflation

    OpenAIRE

    Hugo Gerard

    2012-01-01

    Inflation rates across countries tend to exhibit a degree of co-movement. In this paper we use a panel vector autoregression (panel VAR) model to investigate possible explanations of this co-movement for the G7 economies. Shocks to commodity prices are found to be more important than common movements in real activity as a driver of 'global inflation' dynamics. However, commodity prices and common real activity cannot explain all of the co-movement in inflation. Even when controlling for these...

  14. The Explanatory Range of Movement

    DEFF Research Database (Denmark)

    Thrane, Torben

    2005-01-01

    Drawing a distinction between systemic and functional explanations of movement in general, I shall argue that the Chomskyan view of movement in language is originally functional. With the advent of the Minimimalist Program, however, it has become systemic, but no argument for this change has been...... forthcoming. I'll then present data (from Danish) to sustain the view that only functional type explanations of movement can be empirically motivated, and these only if movement is reinterpreted as transition states between representations of different kinds....

  15. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li

    2011-11-01

    Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

  16. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than...

  17. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  18. Social-movement analysis of the American antinuclear movement

    International Nuclear Information System (INIS)

    Utilizing data from a survey of participants at the May 6, 1979 antinuclear rally in Washington, DC (N = 420), this dissertation explored some of the major structural and ideological characteristics of the American Antinuclear Movement. By organizing the data around three of the key analytical concepts in the study of social movements - mobilization, recruitment, and ideology - the author was able to derive from the demonstration sample a descriptive and illustrative analysis of those individuals, organizations, and processes involved in the national antinuclear crusade. Given that few researchers have actively studied the antinuclear movement beyond the scope of local or regional protests, this work constitutes the only empirical study to date examining a cross section of the movement's participants from a sociological perspective. It is also one of the few attempts to use a national demonstration as a social laboratory for the study of a social movement in general. In terms of the mobilization variables examined in the study, it was found that organizational networks, past movement activism, and individual resources were important factors in the May 6 mobilization effort. While less than one-half of the demonstrators were part of the antinuclear organizational network per se, most of them had been active in the major protest movements of the 1960's and 1970's. The demonstrators were relatively high in socio-economic resources and had occupational or educational schedules conducive to creating the necessary discretionary time for movement participation

  19. Reaching movement onset- and end-related characteristics of EEG spectral power modulations

    Directory of Open Access Journals (Sweden)

    Evariste eDemandt

    2012-05-01

    Full Text Available The spectral power of intracranial field potentials shows movement-related modulations during reaching movements to different target positions that in frequencies up to the high-γ range (approximately 50 to above 200 Hz can be reliably used for single-trial inference of movement parameters. However, identifying spectral power modulations suitable for single-trial analysis for non-invasive approaches remains a challenge. We recorded non-invasive electroencephalography (EEG during a self-paced center-out and center-in arm movement task, resulting in 8 reaching movement classes (4 center-out, 4 center-in. We found distinct slow (≤ 5 Hz, μ (7.5 to 10 Hz, β (12.5 to 25 Hz, low-γ (27.5 to approximately 50Hz and high-γ (above 50 Hz movement onset- and end-related responses. Movement class-specific spectral power modulations were restricted to the β band at approximately 1 s after movement end and could be explained by the sensitivity of this response to different static, post-movement electromyography (EMG levels. Based on the β band, significant single-trial inference of reaching movement endpoints was possible. The findings of the present study support the idea that single-trial decoding of different reaching movements from non-invasive EEG spectral power modulations is possible, but also suggest that the informative time window is after movement end and that the informative frequency range is restricted to the β band.

  20. Improved performance of dye sensitized solar cells using Cu-doped TiO2 as photoanode materials: Band edge movement study by spectroelectrochemistry

    Science.gov (United States)

    Zhou, Li; Wei, Liguo; Yang, Yulin; Xia, Xue; Wang, Ping; Yu, Jia; Luan, Tianzhu

    2016-08-01

    Cu-doped TiO2 nanoparticles are prepared and used as semiconductor materials of photoanode to improve the performance of dye sensitized solar cells (DSSCs). UV-Vis spectroscopy and variable temperature spectroelectrochemistry study are used to characterize the influence of copper dopant with different concentrations on the band gap energies of TiO2 nanoparticles. The prepared Cu-doped TiO2 semiconductor has avoided the formation of CuO during hydrothermal process and lowered the conduction band position of TiO2, which contribute to increase the short circuit current density of DSSCs. At the optimum Cu concentration of 1.0 at.%, the short circuit current density increased from 12.54 to 14.98 mA cm-2, full sun solar power conversion efficiencies increased from 5.58% up to 6.71% as compared to the blank DSSC. This showed that the presence of copper in DSSCs leads to improvements of up to 20% in the conversion efficiency of DSSCs.